1 IN THE UNITED STATES DISTRICT COURT FOR THE ... - Zoloft …zoloftmdl.com › documents › Hearing Transcripts › Zoloft... · mdl called zoloft and it is an important stage and

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IN THE UNITED STATES DISTRICT COURT

FOR THE EASTERN DISTRICT OF PENNSYLVANIA

IN RE: ZOLOFT : MDL NO. 2342

(SERTRALINE HYDROCHLORIDE) : 12-MD-2342

PRODUCTS LIABILITY LITIGATION :

MONDAY, 4-7-14

COURTROOM 12-A

PHILADELPHIA, PA 19106

________________________________________________________

BEFORE THE HONORABLE CYNTHIA M. RUFE, J.

_______________________________________________________

DAUBERT HEARING

________________________________________________________

APPEARANCES:

DIANNE M. NAST, ESQUIRE

NASTLAW LLC

1101 MARKET STREET, SUITE 2801

PHILADELPHIA, PA. 19107

LEAD ATTORNEY

MARK P. ROBINSON, JR., ESQ.

ROBINSON CALCAGNIE ROBINSON SHAPIRO DAVIS INC.

19 CORPORATE PLAZA DRIVE

NEWPORT BEACH, CA 92660

FOR PLAINTIFFS

SEAN PATRICK TRACEY, ESQ

TRACEY LAW FIRM

440 LOUISIANA, SUITE 1901

HOUSTON, TX 77003

FOR PLAINTIFFS

SUZANNE R. WHITE

OFFICIAL COURT REPORTER

FIRST FLOOR U. S. COURTHOUSE

601 MARKET STREET

PHILADELPHIA, PA 19106

(215)627-1882

PROCEEDINGS RECORDED BY STENOTYPE-COMPUTER,

TRANSCRIPT PRODUCED BY COMPUTER-AIDED TRANSCRIPTION

Case 2:12-md-02342-CMR Document 881 Filed 05/15/14 Page 1 of 241

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APPEARANCES CONTINUED:

BRYAN F. AYLSTOCK, ESQ.

AYLSTOCK WITKIN KREIS & OVERHOLTZ, PLLC

17 EAST MAIN STREET, SUITE 200

PENSACOLA, FL 32502-5998

FOR PLAINTIFFS

JOSEPH J. ZONIES, ESQ.

REILLY POZNER LLP

1900 16TH STREET, SUITE 1700

DENVER, CO 80202

FOR PLAINTIFFS

MARK CHEFFO, ESQ.

SHEILA L. BIRNBAUM, ESQ.

QUINN EMANUEL URQUHART & SULLIVAN LLP

51 MADISON AVENUE, 22ND FLOOR

NEW YORK, NY 10010

FOR PFIZER, INC.

JAMES E. HOOPER, ESQ.

WHEELER TRIGG O'DONNELL LLP

370 SEVENTEENTH ST., SUITE 4500

DENVER, CO 80202

FOR PFIZER, INC.

PAMELA YATES, ESQ.

KAYE SCHOLER

1999 AVENUE OF THE STARS, SUITE 1700

LOS ANGELES, CA 90067-6048

FOR GREENSTONE, LLC

ROBERT HEIM, ESQ.

DECHERT

4000 BELL ATLANTIC TOWER

1717 ARCH STREET

PHILADELPHIA, PA 19103-7301

FOR GREENSTONE, LLC

- - -


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(THE CLERK OPENS COURT.)

THE COURT: GOOD MORNING.

ALL COUNSEL: GOOD MORNING, YOUR HONOR.

THE COURT: PLEASE BE SEATED, EVERYONE.

I'M HAPPY TO WELCOME MY COLLEAGUE FROM

STATE COURT, THE PHILADELPHIA COURT OF COMMON PLEAS,

JUDGE LISA RAU, WHO DID RESPOND TO THE COURT'S OVERTURES

TO ALL THE STATE JUDGES TO DETERMINE WHETHER OR NOT THEY

WISHED TO PARTICIPATE IN THE SCIENCE HEARINGS THAT ARE

HELD TODAY. WE DID HAVE SOME RESPONSES FROM JUDGES WHO

WOULD LIKE A COPY OF THE TRANSCRIPT AND OTHERS THAT

MIGHT WANT TO VIDEO CONFERENCE LATER IN THE WEEK AS THEY

WERE NOT AVAILABLE THE ENTIRE WEEK. AND I'M NOT EVEN

SURE THAT JUDGE RAU WILL BE ABLE TO MAINTAIN THAT ENTIRE

WEEK SCHEDULE, BUT SHE IS WELCOME TO.

AND I ALSO WANTED TO MAKE IT CLEAR THAT

THERE IS NO PENDING MOTION BEFORE JUDGE RAU IN ANY OF

HER CASES THAT INVOLVE THE ZOLOFT PHARMACEUTICAL.

THEREFORE WE KNOW THAT YOUR BRIEFING AND YOUR ARGUMENTS

AND YOUR EVIDENCE ARE NOT TAILORED TO A FRYE STANDARD.

SO THAT IS NOT EXPECTED. NO ONE IS ASKING YOU TO DO

THAT TODAY. IF THAT BECOMES AN ISSUE IN ONE OF HER

LATER CASES, THEN YOU CAN BRIEF THAT AS SHE WOULD LIKE

IT. BUT I DID THINK IT WAS IMPORTANT TO MAKE SURE THAT

ALL OF THE JUDGES KNEW THAT WE ARE AT THIS STAGE IN THE


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MDL CALLED ZOLOFT AND IT IS AN IMPORTANT STAGE AND THEY

WERE INVITED TO LEARN AS MUCH AS THEY COULD. SO I'M

JUST GOING TO ASK JUDGE RAU IF SHE HAS ANYTHING THAT SHE

WOULD LIKE TO SAY AT THIS TIME.

JUDGE RAU: GOOD MORNING, EVERYONE. I

JUST WANTED TO THANK YOU FOR THE INVITATION TO COME AND

I'M REALLY JUST HERE TO LEARN. SO, THANK YOU.

THE COURT: AND I'M HAPPY TO HAVE YOU

HERE.

ALL RIGHT. WITH THAT BEING OUT OF THE

WAY, AND BY THE WAY I THINK THE CASES THAT REMAIN ON THE

PHILADELPHIA DOCKET CONCERNING ZOLOFT ARE ALL ASSIGNED

TO JUDGE RAU. I'M NOT AWARE OF ANY OTHERS. SO I THINK

SHE IS IN CHARGE OF THOSE CASES, AND I THINK SHE HAS

ALREADY REACHED OUT TO ONE OF THE ATTORNEYS, PLAINTIFF'S

COUNSEL, ABOUT IT?

JUDGE RAU: WE SENT LETTERS TO BOTH

SIDES.

THE COURT: ALL RIGHT. SO WE ARE GOING

TO LEAVE THAT AND MOVE ON. I'M GOING TO TRY TO USE MY

IPAD WITHOUT THE EXPLETIVE OF HAVING DIFFICULTY WITH

SERVICE IN HERE. I THINK THAT IT WILL SAVE ME FROM

GOING THROUGH ALL OF THE PAPER BECAUSE I HAVE ALL OF

YOUR REPORTS DOWNLOADED. THAT WAS VERY HELPFUL BECAUSE

I READ THEM ON THE PLANE TWICE, GOING AND COMING.


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AND WHERE ARE ALL THE WIGS? I THOUGHT

YOU WERE ALL GOING TO BE WEARING YOUR WIGS. FOR THOSE

THAT DON'T KNOW THIS INSIDE JOKE, THAT WAS ACTUALLY ON

THE RECORD. I SPENT TIME IN LONDON VISITING THE COURTS

AND LAWYERS AND THAT WAS OF COURSE A WONDERFUL INNS OF

COURT TRIP. IT WAS MOST OF THE WEEK. BUT I FOUND THAT

WHEN I INQUIRED AS TO THE COST OR THE PRICE OF WIGS, I

WAS NOT GOING TO BE ABLE TO WEAR ONE MYSELF TODAY. SO

ALL OF YOU VERY SUCCESSFUL LAWYERS CAN AFFORD IT, BUT

THE PUBLIC SERVANT THAT IS ME CANNOT.

WITH THAT, I WOULD LIKE TO HEAR HOW

COUNSEL WISH TO PROCEED HERE. I KNOW THAT WE EXPECT

OPENING STATEMENTS AND WE WOULD LIKE TO JUST ASK HOW YOU

WOULD LIKE TO GO ABOUT THIS.

MS. NAST: GOOD MORNING, YOUR HONOR.


MS. NAST: GOOD MORNING, JUDGE RAU.

JUDGE RAU: GOOD MORNING.

MS. NAST: WE ARE HAPPY TO GET TO THIS

STAGE, JUDGE. WE HAVE ANTICIPATED IT FOR A LONG TIME

AND BOTH SIDES HAVE WORKED VERY HARD IN PREPARING FOR

IT. SO IT'S GOOD THAT WE ARE FINALLY HERE.

AS THE COURT KNOWS, THE PSC IS DIVIDED

INTO SEVEN COMMITTEES. AND WE HAVE A BRIEFING

COMMITTEE, FOR EXAMPLE, WHICH IS CHAIRED BY ARNOLD LEVIN


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AND MYSELF. WE HAVE A SCIENCE COMMITTEE, CHAIRED BY

MARK ROBINSON AND JOE ZONIES -- NOT JOE ZONIES. I'M

SORRY, SEAN, BY MARK ROBINSON AND SEAN TRACEY.

MR. ZONIES: I WILL TAKE IT.

MS. NAST: JOE IS JUST WAITING IN THE

WINGS.

THE PSC HAS ASKED THE SCIENCE TEAM TO

CONDUCT THE HEARING AND MARK AND SEAN WILL DO SO,

ASSISTED BY TWO OTHER MEMBERS OF THE SCIENCE TEAM, BRIAN

AYLSTOCK AND JOE ZONIES.

WE INTEND TO CALL FOUR WITNESSES. IN

ALPHABETICAL ORDER THE FIRST IS DR. ANICK BERARD,

B-E-R-A-R-D. DR. BERARD HAS A PH.D. IN EPIDEMIOLOGY AND

BIOSTATISTICS FROM MCGILL UNIVERSITY IN CANADA. AND SHE

IS A NATIVE FRENCH SPEAKER. ENGLISH IS HER SECOND

LANGUAGE, AND SHE EMBARRASSES MANY OF US WHO SPEAK

ENGLISH AS OUR FIRST LANGUAGE. SHE CURRENTLY SERVES AS

PROFESSOR OF PERINATAL PHARMACOEPIDEMIOLOGY AND IS

HOLDER OF THE RESEARCH CHAIR ON MEDICATIONS, PREGNANCY

AND LACTATION AT THE FACULTY OF PHARMACY OF THE

UNIVERSITY OF MONTREAL.

AGAIN, IN ALPHABETICAL ORDER, OUR NEXT

WITNESS IN ALPHABETICAL ORDER IS DR. CABRERA, DR. ROBERT

CABRERA. DR. CABRERA HAS A PH.D. IN MEDICAL SCIENCE

FROM TEXAS A&M UNIVERSITY HEALTH SCIENCE CENTER. HE


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CURRENTLY SERVES AS PROJECT MANAGER FOR STEM CELL

RESEARCH AT THE DELL PEDIATRIC RESEARCH INSTITUTION AND

AS A SENIOR RESEARCH SCIENTIST IN THE DEPARTMENT OF

NUTRITIONAL SCIENCES AT THE UNIVERSITY OF TEXAS IN

AUSTIN.

THE THIRD PERSON IN ALPHABETICAL ORDER IS

DR. MICHAEL LEVIN. DR. LEVIN HAS A PH.D. FROM THE

HARVARD SCHOOL OF MEDICINE. HE IS CURRENTLY A PROFESSOR

IN THE DEPARTMENT OF BIOLOGY AT TUFTS UNIVERSITY,

HOLDING THE ENDOWED VANNEVAR BUSH CHAIR. HE IS DIRECTOR

OF THE TUFTS CENTER FOR REGENERATIVE AND DEVELOPMENTAL

BIOLOGY. HE IS KNOWN FOR HIS IDENTIFICATION OF GENETIC

MUTATIONS THAT DICTATE THE POSITION OF THE HEART AND

VISCERAL ORGANS.

DR. THOMAS SADLER HAS A PH.D. IN ANATOMY

AND EMBRYOLOGY FROM THE UNIVERSITY OF VIRGINIA. DR.

SADLER IS AN EMBRYOLOGIST AND A DEVELOPMENTAL BIOLOGIST

AND TERATOLOGIST WITH MORE THAN 40 YEARS OF EXPERIENCE.

HE IS CURRENTLY AN ADJUNCT PROFESSOR OF PEDIATRICS AT

THE UNIVERSITY OF UTAH. HE IS A VISITING PROFESSOR OF

CELL BIOLOGY AND ANATOMY AT THE QUILLEN COLLEGE OF

MEDICINE AT EAST TENNESSEE STATE UNIVERSITY, AND HE IS A

SENIOR SCHOLAR AT THE GREENWOOD GENETIC CENTER IN

GREENWOOD, SOUTH CAROLINA.

DR. BERARD WILL BE EXAMINED BY MARK


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ROBINSON. DR. CABRERA WILL BE EXAMINED BY SEAN TRACEY.

DR. LEVIN WILL BE EXAMINED BY MARK ROBINSON -- BY JOE

ZONIES. AND WHERE DID YOUR OTHER WITNESS GO? DR.

SADLER WILL BE EXAMINED BY MARK ROBINSON.

OUR PRELIMINARY THOUGHT, SUBJECT TO

OBVIOUSLY WHAT YOUR HONOR SAYS, IS I THINK THE

DEFENDANTS HAVE A BRIEF OPENING REMARK SIMILAR TO -- NOT

SIMILAR, BUT NONSUBSTANTIVE, IF YOU WILL. AND THEN

THERE WILL BE OPENINGS AND THEN THE TESTIMONY WILL

BEGIN. WE WILL START WITH -- WHEN THE TESTIMONY BEGINS,

WE WILL START WITH OUR FOUR WITNESSES, AND THERE WILL BE

CROSS-EXAMINATION AND REDIRECT AND THEN WE WILL GO TO

THE DEFENDANT'S CASE.

THE COURT: VERY WELL. THANK YOU.

MS. NAST: THANK YOU.

THE COURT: I MIGHT ASK COUNSEL AT THE

OUTSET, I THINK I'M JUST CONFIRMING WHAT I HAVE READ,

THAT THERE ARE NO OUTSTANDING OBJECTIONS TO

QUALIFICATIONS OF ANY OF THE EXPERTS ON EITHER SIDE THAT

WOULD BE CALLED TO TESTIFY.

MS. NAST: THAT IS CORRECT, YOUR HONOR.

THE COURT: THANK YOU.

MR. CHEFFO.

MR. CHEFFO: GOOD MORNING, YOUR HONORS, I

WILL BE BRIEF. SINCE DIANE WAS KIND ENOUGH TO COVER


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SOME OF THE HOUSEKEEPING. LET ME FIRST INTRODUCE TO YOU

TWO MEMBERS OF OUR TEAM, WHO I DON'T THINK YOU HAVE HAD

AN OPPORTUNITY TO MEET YET. FIRST IS JIM HOOPER. NEXT

TO MR. HOOPER IS PAM YATES. AND LET ME ALSO, WHILE I'M

ON IT, JUST INTRODUCE -- THERE'S TWO ATTORNEYS FROM OUR

CLIENT, MOLLY MORPHY AND CONNIE MATTEO YOU HAVE MET

BEFORE.

COUNSEL: GOOD MORNING.


MR. CHEFFO: YOUR HONOR, FOR THE SAKE OF

TIME, WE ARE GOING TO -- WITH THE COURT'S PERMISSION, WE

ARE GOING TO START OUR OPENINGS IN A MINUTE. I THINK WE

WILL GO THROUGH AND INTRODUCE ANY WITNESSES THAT WE

INTEND TO CALL FOLLOWING THE PLAINTIFFS' PRESENTATION

AND CROSS-EXAMINATION.

THE COURT: THAT IS FINE.

MR. CHEFFO: THANK YOU, YOUR HONOR.

THE COURT: SO, SHALL WE MOVE INTO

OPENINGS?

MS. BIRNBAUM: GOOD MORNING, YOUR HONORS.

MY NAME IS SHEILA BIRNBAUM. I'M GOING TO BE DELIVERING

THE OPENING STATEMENT WITH MR. CHEFFO FOR THE DEFENDANTS

IN THIS CASE.

I WILL PROCEED WITH AN OVERVIEW OF WHAT

IS GOING TO BE HAPPENING DURING THESE HEARINGS, HOW


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PLAINTIFFS HAVE FAILED TO SATISFY THEIR BURDEN UNDER

DAUBERT, THE IMPORTANCE OF ZOLOFT AS A LIFE SAVING

MEDICINE, AND THE IMPORTANCE OF THE PUBLIC HEALTH ISSUES

THAT ARE INVOLVED HERE BECAUSE WE ARE DEALING WITH A

POPULATION OF PREGNANT WOMEN WHO SUFFER FROM DEPRESSION.

AND THIS IS QUITE IMPORTANT TO MANY OF THE ARGUMENTS

THAT ARE GOING TO BE MADE HERE IN THE NEXT WEEK. MR.

CHEFFO WILL FOLLOW ME WITH A REALLY FOCUSED AND IN-DEPTH

ANALYSIS OF THE METHODOLOGICAL FLAWS AND ERRORS

CONTAINED IN PLAINTIFFS' EXPERT REPORTS.

NOW, PLAINTIFFS CAN'T SATISFY THEIR

BURDEN, AND THEY HAVE A HEAVY BURDEN HERE, OF PROVIDING

RELIABLE EXPERT TESTIMONY BASED ON RELIABLE SCIENTIFIC

EVIDENCE THAT ESTABLISHES THAT ZOLOFT CAUSES BIRTH

DEFECTS AND OTHER INJURIES, INCLUDING PPHN. THE

CAUSATION OPINIONS OF THESE EXPERTS ARE METHODOLOGICALLY

FLAWED FOR SEVERAL REASONS.

THE FIRST SLIDE. FIRST, I WOULD LIKE TO

CONCENTRATE ON DR. BERARD BECAUSE DR. BERARD IS THE ONLY

EPIDEMIOLOGIST THAT THE PLAINTIFFS ARE CALLING. ALL OF

THE OTHER WITNESSES ARE WHAT WE CALL MECHANICAL EXPERTS.

THEY DEAL IN TEST TUBE TESTING AND WE ARE NOT EVEN HERE

TALKING ABOUT ANIMAL TESTING. AND WE WILL TALK ABOUT

THAT VERY BRIEFLY AT THE END OF THIS OPENING. BUT DR.

BERARD IS THE MAIN EVENT. SHE IS THE EPIDEMIOLOGIST AND


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THE ONLY EPIDEMIOLOGIST THAT THE PLAINTIFFS HAVE.

WHAT DR. BERARD HAS DONE IN COMING TO HER

CONCLUSIONS IS SHE HAS RELIED ON INCONSISTENT FINDINGS

AND FALSE ASSOCIATIONS. AND WE WILL GO INTO THAT IN

MUCH DETAIL. SHE CHERRY PICKS THE DATA. WHAT DO WE

MEAN BY THAT? SHE ONLY PICKS DATA AND EXPLAINS DATA TO

THIS COURT THAT SUPPORTS HER OPINION. SHE DOES NOT TALK

ABOUT OR EXPLAIN OR ANALYZE THE DATA THAT DOES NOT

SUPPORT HER OPINION AND THERE ARE MANY, MANY STUDIES

THAT DO NOT SUPPORT HER OPINION.

THIRD, SHE MAKES CONCLUSIONS AND COMES TO

CONCLUSIONS THAT ARE NOT MADE BY THE AUTHORS OF THE

STUDIES SHE IS RELYING ON.

FOURTH, SHE RELIES ON NONZOLOFT DATA.

THERE IS GOING TO BE A LOT OF DISCUSSION HERE ABOUT

WHETHER THERE IS A CLASS EFFECT FOR SSRIS IN GENERAL AND

WHETHER YOU CAN LOOK AT DATA THAT IS NONZOLOFT DATA,

THAT IS SSRI DATA, SSRIS IN GENERAL. AND THAT WE ARE

GOING TO PROVE TO THIS COURT IS SOMETHING YOU CAN'T DO

AND SHOULD NOT DO.

SHE LUMPS SPECIFIC AND DISTINCT BIRTH

DEFECTS. WE CALL IT A LUMPING FALLACY. THAT IS WHAT IT

IS. IT'S WHAT THE SCIENTISTS CALL IT. WHEN SHE DOES

THAT AND SHE IS NOT SPECIFIC, AGAIN YOU ARE GOING TO SEE

THIS IS NOT THE METHODOLOGY THAT SCIENTISTS USE WHO ARE


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OUT IN THE FIELD OF EPIDEMIOLOGY OR TERATOGENICITY.

IMPORTANTLY, HER OPINIONS ARE NOT

GENERALLY ACCEPTED BY THE SCIENTIFIC COMMUNITY. NOW,

LET'S FOCUS FOR A MINUTE ON ACCEPTANCE IN THE SCIENTIFIC

COMMUNITY. ZOLOFT IS A DRUG THAT HAS BEEN STUDIED

EXTENSIVELY. THIS IS NOT A DRUG THAT DOES NOT HAVE A

LOT OF HISTORICAL STUDY THAT HAS GONE ON. IT'S USED BY

THOUSANDS AND THOUSANDS OF PEOPLE EVERY YEAR SINCE 1992.

IT'S BEEN ON THE MARKET SINCE 1992. WE ARE GOING TO

SHOW YOU -- MR. CHEFFO IS GOING TO TAKE YOU THROUGH THE

ORGANIZATIONS, THE SCIENTISTS, THE INDEPENDENT

SCIENTISTS, THE PEER REVIEW ARTICLES THAT ALL COME TO

THE CONCLUSION, AFTER REVIEWING THE ROBUST DATA ON

ZOLOFT, THEY COME TO THE CONCLUSION THAT THE DATA DO NOT

DEMONSTRATE THAT ZOLOFT CAUSES ANY BIRTH DEFECTS. AND

WHEN DR. BERARD WAS ASKED IN HER DEPOSITION TESTIMONY,

CAN YOU CITE TO ANY REGULATORY AGENCY, ANY REGULATORY

AGENCY, THE FDA, FOR EXAMPLE, PROFESSIONAL ORGANIZATION,

PEER REVIEWED MEDICAL TREATISE OR PUBLISHED STUDY THAT

STATES THAT ZOLOFT CAUSES MAJOR MALFORMATIONS, SHE SAYS,

NO. THERE IS NONE. WE WILL SHOW YOU THAT. NONE, NOT

ONE.

BUT DR. BERARD IS GOING TO TESTIFY THAT

THIS DRUG THAT IS ON THE MARKET, THAT HAS BEEN ON THE

MARKET, THAT HAS NOT BEEN REMOVED FROM THE MARKET CAUSES


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MYRIAD HEART DEFECTS -- MYRIAD DEFECTS, BIRTH DEFECTS,

HEART DEFECTS, IN EVERY SYSTEM OF THE BODY ALMOST. SHE

SAYS THIS DRUG CAUSES BIRTH DEFECTS IN ALL OF THOSE

SYSTEMS. MR. CHEFFO IS GOING TO TAKE YOU THROUGH THAT

TO SHOW THAT THIS IS JUST NOT POSSIBLE. THE LAW

PROHIBITS THAT RESULT. THE COURTROOM IS NOT THE PLACE

FOR SCIENTIFIC GUESSWORK, EVEN OF THE INSPIRED SORT.

LET'S TALK A LITTLE ABOUT ZOLOFT BECAUSE

IT'S IMPORTANT THAT YOU HAVE AN UNDERSTANDING OF THIS

DRUG AND WHAT IT DOES. IT WAS APPROVED BY THE FDA IN

DECEMBER OF 1991 AS SAFE AND EFFECTIVE FOR THE TREATMENT

OF DEPRESSION. IT'S ALSO SAFE AND EFFECTIVE FOR OTHER

THINGS, BUT WE ARE GOING TO BE TALKING HERE ABOUT

DEPRESSION.

THERE HAS BEEN, AS I HAVE SAID, AND AS I

THINK WE WILL ESTABLISH HERE, THERE HAS BEEN ROBUST

STUDIES, LOTS OF EVIDENCE. THIS IS NOT A DRUG THAT HAS

NOT BEEN STUDIED FREQUENTLY AND OFTEN. AND WHEN YOU

REVIEW THAT SCIENTIFIC DATA, THE FDA HAS REVIEWED IT,

THE FDA HAS FOUND THAT THERE IS NO CAUSATION BETWEEN

ZOLOFT AND ANY BIRTH DEFECTS. THERE ISN'T EVEN A

STATISTICAL ASSOCIATION, BUT THERE CLEARLY IS NOT

CAUSATION.

HOW DO WE KNOW WHAT THE FDA HAS DONE?

WELL, IN THIS -- I WOULD LIKE TO ALSO TALK ABOUT THIS


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WHEN WE TALK ABOUT THE CLASS EFFECT FALLACY. THE FDA

HAS PLACED PAXIL IN CATEGORY D IN THE PREGNANCY

CATEGORIES. THIS IS MEANINGFUL. CATEGORY D. BECAUSE

THE FDA, ACCORDING TO ITS REGULATIONS, FOUND POSITIVE

EVIDENCE OF HUMAN FETAL RISK BASED ON HUMAN DATA WITH

PAXIL. WHAT DID IT DO WITH ZOLOFT AND WHAT DID IT DO

WITH THE OTHER SSRIS? IT REMAINS IN CATEGORY C, NOT A

CATEGORY D, WHICH MEANS THAT THE FDA HAS NOT -- IT'S NOT

THAT THE FDA HAS NOT STUDIED THIS. IT MEANS THAT THE

FDA HAS NOT FOUND POSITIVE EVIDENCE OF HUMAN FETAL RISK

BASED ON HUMAN DATA FOR ZOLOFT. THIS IS IMPORTANT.

ZOLOFT TODAY REMAINS IN CATEGORY C, NOT D.

NOW THIS ACTION BY THE FDA IS ALSO

IMPORTANT BECAUSE IT REALLY TALKS ABOUT THE CLASS EFFECT

OF SSRIS. NOW THERE IS NO QUESTION THAT ZOLOFT AND

PAXIL ARE WITHIN THIS GENERAL CATEGORY, THIS CLASS OF

SSRIS. AND NO ONE IS ARGUING THAT IT ISN'T. BUT THE

REAL ISSUE FOR THIS COURT AND THE REAL ISSUE THAT IS

HOTLY DEBATED BY BOTH SIDES, AND THE COURT IS GOING TO

HAVE TO, WHEN REACHING ITS DECISION, I THINK, DETERMINE

WHETHER OR NOT WHEN WE ARE TALKING ABOUT BIRTH DEFECTS,

WHEN WE ARE TALKING ABOUT TERATOGENICITY, IS THERE A

DIFFERENCE IN THE VARIOUS SSRI DRUGS? AND THERE ARE

MANY SSRI DRUGS. CAN YOU JUST LUMP THEM ALL TOGETHER,

AND SAY ALL THE SSRI DATA COUNTS? WE CAN LOOK AT IT


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ALL.

THERE IS MUCH ZOLOFT DATA. WE SAY, LOOK

AT THE ZOLOFT DATA. WE LOOK AT THE ZOLOFT DATA. SO

WHAT THE FDA IS TELLING US IS THAT FOR TERATOGENICITY,

WE DON'T TREAT ALL SSRIS AS A CLASS, BECAUSE IF THEY DID

THEY WOULD HAVE PUT ALL SSRIS IN CATEGORY D, NOT LEAVE

MOST OF THEM IN CATEGORY C AND PUT PAXIL IN CATEGORY D.

SO SSRIS ARE DIFFERENT.

MR. CHEFFO WILL EXPLAIN WHAT THE

TERATOLOGY SOCIETY AND MANY OF US HAVE STATED. WHEN YOU

ARE LOOKING AT CAUSAL RELATIONSHIP, WHEN YOU ARE TALKING

AT BIRTH DEFECTS, YOU HAVE TO LOOK AT THE CHEMICAL AND

THE OUTCOME SPECIFIC, SPECIFIC TO THE CHEMICAL AT ISSUE,

AND THAT IS ZOLOFT. YOUR HONOR, WE ARE GOING TO GO INTO

THIS IN A LOT OF DETAILS, A LOT OF LITTLE, YOU KNOW,

MOLECULES HERE. BUT THIS JUST GIVES YOU THE DIFFERENCE

IN THE CHEMICAL COMPOUNDS OF THESE VARIOUS SSRIS. THEY

ARE NOT ALL THE SAME COMPOUND. THEY ARE VERY DIFFERENT

AND THOSE DIFFERENCES ARE MEANINGFUL WHEN IT COMES TO

THE DETERMINATION OF WHETHER ANY OF THESE CAN POSSIBLY

CAUSE BIRTH DEFECTS.

SO LET ME JUST POINT OUT, BECAUSE I THINK

THIS IS QUITE IMPORTANT TO TRY TO PUT THIS IN CONTEXT.

ZOLOFT HAS NOT BEEN WITHDRAWN FROM THE MARKET. THIS IS

NOT A LITIGATION ABOUT A PRODUCT THAT HAS BEEN WITHDRAWN


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BECAUSE IT'S UNSAFE. IT'S SOLD TO THOUSANDS OF WOMEN,

OR PRESCRIBED TO THOUSANDS OF WOMEN EVERY DAY. THERE IS

NO SUDDEN NEW STUDY THAT HAS BEEN PUBLISHED THAT CHANGES

THE SCIENTIFIC LANDSCAPE. THERE IS NO AHA MOMENT THAT

SAYS ZOLOFT NOW, AS AN SSRI, CAUSES ALL KIND OF BIRTH

DEFECTS. THE SCIENCE HAS REMAINED THE SAME, AND AS WE

WILL SHOW YOU, THAT SCIENCE SUPPORTS WHAT IS GENERALLY

ACCEPTED IS THAT ZOLOFT DOES NOT CAUSE BIRTH DEFECTS.

SO WHY ARE WE HERE ALL OF A SUDDEN? I

THINK MAYBE WE ARE HERE BECAUSE OF PAXIL, BECAUSE THERE

WAS A PAXIL LITIGATION. PAXIL, AT LEAST, ACCORDING TO

THE FDA, THERE WERE SOME RISKS OF BIRTH DEFECTS. BUT

OUR PRODUCT, ZOLOFT, IS DIFFERENT THAN PAXIL. IT HAS A

DIFFERENT CHEMICAL COMPOUND. IT HAS DIFFERENT

PHARMACOLOGICAL EVENTS, AND IT CAN'T BE ALL PUSHED

TOGETHER AS ONE.

SO NOT ONLY IS ZOLOFT WIDELY PRESCRIBED

FOR THE TREATMENT OF DEPRESSION DURING PREGNANCY, BUT AS

WE WILL SHOW YOU, DR. BERARD HERSELF HAS RECOGNIZED AND

CONTINUES TO RECOGNIZE AND HAS WRITTEN FOR THE PEER --

FOR PEER REVIEW SCIENTISTS AS LATE AS 2010 THAT ZOLOFT

IS A FIRST-LINE THERAPY FOR THE TREATMENT OF DEPRESSION

DURING PREGNANCY, A FIRST-LINE TREATMENT. AND WHAT IS

WIDELY RECOMMEND -- RECOGNIZED AMONG THE PROFESSIONAL

SCIENTIFIC GROUPS, AND I CAN'T, YOU KNOW, EMPHASIZE THIS


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TOO MUCH AND YOU WILL SEE WHAT WE MEAN WHEN MR. CHEFFO

POINTS IT OUT TO YOU, IS THAT THE EPIDEMIOLOGICAL

EVIDENCE DOES NOT DEMONSTRATE THAT ZOLOFT CAUSES ANY

BIRTH DEFECTS.

I'M JUST SHOWING ONE OF THESE HERE IN

THIS OVERVIEW, OTIS. OTIS IS THE ORGANIZATION OF

TERATOLOGY INFORMATION SPECIALISTS. THESE ARE PEOPLE

THAT LOOK AT BIRTH DEFECTS. THIS IS THEIR PURPOSE, TO

GIVE INFORMATION ABOUT IT. AND WHAT DOES IT SAY? AND

THIS IS IN 2010. ZOLOFT IS ONE OF THE BETTER STUDIED

ANTIDEPRESSANTS DURING PREGNANCY, AND OVERALL THE

AVAILABLE INFORMATION DOES NOT SUGGEST THAT ZOLOFT

INCREASES THE RISK OF BIRTH DEFECTS ABOVE THE BACKGROUND

RISK OF 3 TO 5 PERCENT.

WE ARE GOING TO SHOW YOU MANY MORE OF

THESE, BUT FOR THESE PURPOSES, WE WILL -- WE STRENUOUSLY

ARGUE THIS IS THE STATE OF THE MEDICAL KNOWLEDGE. THIS

IS WHAT SCIENTISTS, ASIDE FROM DR. BERARD, THINK ABOUT

THIS PRODUCT AND BIRTH DEFECTS.

LET ME BRIEFLY TALK ABOUT BIRTH DEFECTS

SO WE CAN PUT EVERYTHING TOGETHER HERE, ZOLOFT, BIRTH

DEFECTS AND DEPRESSION. WE KNOW THAT BIRTH DEFECTS ARE

COMMON. IT'S UNDISPUTED THAT MOST BIRTH DEFECTS ARE DUE

TO UNKNOWN CAUSES. EVERY TYPE OF BIRTH DEFECT THAT IS

IN THIS LITIGATION HAS BEEN AROUND FOR HUNDREDS OF


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YEARS. AND THERE IS A BACKGROUND RISK OF BIRTH DEFECTS

OF 3 TO 5 PERCENT IN THE GENERAL POPULATION.

BUT WHAT IS VERY IMPORTANT TO KEEP IN

MIND THAT FROM THE TIME ZOLOFT AND ALL THESE SSRIS HAVE

GONE ON TO THE MARKET AND HAVE BEEN PRESCRIBED FOR

THOUSANDS UPON THOUSANDS OF WOMEN, THE RISK OF BIRTH

DEFECTS REMAINS THE SAME. NOW, WHY IS THIS IMPORTANT?

WELL, IT'S IMPORTANT BECAUSE IF WE LOOK AT THE

PRESCRIPTIONS IN THE FIRST TRIMESTER FOR THE RISK OF

MAJOR BIRTH DEFECTS, YOU ARE GOING TO FIND THAT THOSE

BIRTH DEFECTS REMAIN CONSTANT.

THIS IS ZOLOFT FROM 1992 TO 2005. YOU

CAN SEE, JUST ZOLOFT, HOW THE PRESCRIPTIONS HAVE

DRAMATICALLY INCREASED FROM THE TIME IT FIRST WENT ON

THE MARKET. HERE WE ARE LOOKING AT MAJOR BIRTH DEFECTS.

MAJOR BIRTH DEFECTS REMAIN THE SAME, PRACTICALLY THE

SAME, BEFORE ZOLOFT WAS ON THE MARKET AND AFTER ZOLOFT

WENT ON THE MARKET. WHAT WOULD YOU EXPECT IF ZOLOFT WAS

REALLY A DRUG THAT CAUSED BIRTH DEFECTS?

WHAT WE WANT TO SHOW YOU NEXT IS WHAT IS

CALLED THE SECULAR TREND ANALYSIS. AND FROM THE

TERATOLOGY SOCIETY POSITION PAPER IN 2005, IF YOU LOOK

AT THE SECULAR TREND ANALYSIS, THAT MEANS WHAT YOU ARE

LOOKING AT ON ONE WAY IS THE USE OF A PRODUCT OR

CHEMICAL AND THE NUMBER OF BIRTH DEFECTS THAT WOULD BE


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IN THE SAME PERIOD OF TIME. IF YOU HAVE A REAL

TERATOGEN, YOU WOULD EXPECT THAT CURVE TO GO UP, NOT

REMAIN THE SAME.

WE ARE GOING TO SHOW YOU JUST THAT. THIS

IS THE RATE ALSO OF SEPTAL DEFECTS AND SSRI USE, YOU CAN

SEE THE SAME CURVE. SSRI USE GOES UP, SEPTAL

MALFORMATIONS HAVE REMAINED THE SAME.

LET'S LOOK AT A REAL TERATOGEN,

THALIDOMIDE. LOOK AT THAT, YOUR HONORS. THALIDOMIDE

SALES GO UP, LOOK AT THE BIRTH DEFECTS, THE

MALFORMATIONS GOING UP. TAKE IT OFF THE MARKET,

MALFORMATIONS COME DOWN.

ZOLOFT, A VERY DIFFERENT PICTURE. THE

REASON FOR THAT IS THAT THERE IS A SCIENTIFIC COMMUNITY.

THEY ALL RECOGNIZE THIS IS NOT, IS NOT A DRUG THAT

CAUSES BIRTH DEFECTS.

UNTREATED DEPRESSION. DEPRESSION IS

DEBILITATING, IT'S LIFE THREATENING, IT'S A TERRIBLE

DISEASE. IT STRIKES WOMEN AT A HIGHER RATE THAN MEN AND

IT PEAKS AT CHILD BEARING AGE. I WAS SURPRISED WHEN I

SAW THESE STATISTICS. NEARLY ONE IN FIVE WOMEN

EXPERIENCE DEPRESSION DURING PREGNANCY, DEPRESSION OR

SYMPTOMS OF DEPRESSION. AND THIS IS SERIOUS BECAUSE THE

RISK OF UNTREATED DEPRESSION REALLY CANNOT BE

OVERSTATED.


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FIRST, DEPRESSION CAN LEAD TO SUICIDE

ATTEMPTS AND SUICIDES. I WAS SURPRISED AT THIS

STATISTIC, TOO. SUICIDE IS THE LEADING CAUSE OF DEATH

IN PREGNANT WOMEN AND POST-PARTUM WOMEN. THIS HAS

SERIOUS IMPLICATIONS IF IT IS NOT TREATED. BEHAVIOR

CHANGES IN THESE WOMEN. THEY USE TOBACCO AGAIN. THEY

USE ILLICIT DRUGS. THEY USE ALCOHOL. THEY HAVE POOR

NUTRITION. THEY DON'T FOLLOW INSTRUCTIONS. AFTER THE

BABY IS BORN, THEY'RE IMPAIRED BONDING WITH THE BABIES.

SO AS THE TERATOLOGY PRIMER HAS SAID,

UNTREATED DEPRESSION DURING PREGNANCY IS ASSOCIATED WITH

SEVERAL ADVERSE REPRODUCTIVE OUTCOMES. SO IF YOU DON'T

TREAT THIS WITH SSRIS AND ZOLOFT, YOU ARE GOING TO HAVE

BIRTH PROBLEMS, BIRTH DEFECTS OF CERTAIN KINDS AND ALL

THE OTHER THINGS THAT COME FROM THIS.

AND DR. BERARD AGREES. SHE HAS WRITTEN

THAT UNTREATED DEPRESSION DURING PREGNANCY CAN LEAD TO

DELETERIOUS EFFECTS ON THE MOTHER AND THE UNBORN FETUS.

SHE HAS WRITTEN, AND THIS IS IN 2010, 2010, IN A PEER

REVIEWED ARTICLE, SHE HAS NOTED THAT WHILE PAXIL HAS

BEEN LINKED TO THE INCREASE IN THE RISK OF

CARDIOVASCULAR MALFORMATIONS, SSRIS SUCH AS ZOLOFT

SHOULD BE USED AS A FIRST-LINE THERAPY DURING PREGNANCY

AND PAXIL SHOULD NOT. THIS IS IN 2010 WRITING TO HER

PEERS.


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IF WOMEN STOP TAKING THESE IMPORTANT

MEDICATIONS, ZOLOFT AND OTHER SSRIS, BECAUSE OF THE

ADMISSION OF UNRELIABLE EXPERT OPINION THAT CLAIM THAT

BIRTH DEFECTS IN MANY BODY SYSTEMS IS CAUSED BY ZOLOFT,

THERE CAN BE VERY, VERY SIGNIFICANT ADVERSE HEALTH

CONSEQUENCES TO THE WOMEN AND THEIR CHILDREN AND THEY

CREATE PUBLIC HEALTH PROBLEMS.

I WOULD LIKE TO READ A QUOTE FROM JUSTICE

BREYER IN THE JOINER CASE -- I CAN'T SAY IT AS GOOD AS

JUSTICE BREYER CAN. AND IT'S IN OUR BRIEF, YOUR HONOR.

BUT I THINK IT REALLY PUTS IT INTO SOME SORT OF

PERSPECTIVE ABOUT GOOD SCIENCE AND BAD SCIENCE AND WHY

WE HAVE DAUBERT. HE WROTE: MODERN LIFE, INCLUDING GOOD

HEALTH AS WELL AS ECONOMIC WELL-BEING, DEPENDS UPON THE

USE OF ARTIFICIAL OR MANUFACTURED SUBSTANCES, SUCH AS

CHEMICALS. IT MAY THEREFORE PROVE PARTICULARLY

IMPORTANT TO SEE THAT JUDGES FULFILL THEIR DAUBERT

GATEKEEPING FUNCTIONS SO THAT THEY HELP ASSURE THAT THE

POWERFUL ENGINE OF TORT LIABILITY, WHICH CAN GENERATE

STRONG FINANCIAL INCENTIVES TO REDUCE OR TO ELIMINATE

PRODUCTION, POINTS TOWARD THE RIGHT SUBSTANCES AND DOES

NOT DESTROY THE WRONG ONES. AND THAT IS OUR CONCERN

HERE. THIS IS A PRODUCT. THIS IS A MEDICINE THAT IS

USED BY DOCTORS ALL OVER THIS COUNTRY FOR WOMEN WHO ARE

DEPRESSED DURING PREGNANCY. AND WRONG DECISIONS HERE


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CAN HAVE PUBLIC HEALTH CONSEQUENCES.

I AM GOING TO SPEND A LITTLE TIME TALKING

ABOUT THE LEGAL FRAMEWORK OF DAUBERT. YOU ALL KNOW

DAUBERT. YOU HAVE WRITTEN DECISIONS, THE AVANDIA

DECISION AND OTHERS. YOU'VE HAD DAUBERT HEARINGS. I'M

NOT GOING TO INFORM YOU ABOUT HOW DAUBERT WORKS. BUT

THERE ARE A COUPLE OF THINGS THAT I WOULD LIKE TO POINT

OUT THAT THE PLAINTIFFS MAKE MUCH OF OR THAT WE SHOULD

BE ANSWERING.

FIRST OF ALL, AS WE ALL KNOW, THIS

HEARING IS ABOUT SCIENCE, SCIENTIFIC METHOD AND THE

OPINIONS OF PLAINTIFFS' SCIENTIFIC EXPERTS. YET

PLAINTIFFS SPENT THE FIRST 15 PAGES OF THEIR OPPOSITION

BRIEF ON A DISCUSSION OF A HANDFUL OF DOCUMENTS OF THE

DEFENDANT FROM THE MILLIONS OF PAGES THAT HAVE BEEN

PRODUCED HERE. I'M NOT GOING TO TAKE THE TIME TO GO

THROUGH AND TELL YOU WHY THOSE DOCUMENTS HAVE NO MEANING

IN THIS DAUBERT HEARING AND WHY THEY ARE NOT RELEVANT,

BECAUSE WE SPELLED THAT OUT, I THINK, IN GREAT DETAIL IN

OUR BRIEFS. BUT I WOULD JUST ASK YOU TO READ THOSE AND

IF THE PLAINTIFFS ARE GOING TO TRY IN THIS HEARING TO

USE DOCUMENTS FROM -- THAT ARE NOT SCIENTIFIC DOCUMENTS,

BUT DOCUMENTS THAT TALK ABOUT NEW ZEALAND, NEW ZEALAND

AUTHORITIES TRYING TO CHANGE LABELS OR ANYTHING OF THAT

SORT, IT'S INAPPROPRIATE ON THIS HEARING. IT HAS


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NOTHING TO DO WITH DR. BERARD'S METHODOLOGY AS

PLAINTIFFS CLAIM. IT'S JUST ALL BESIDE THE POINT.

NOW, A COUPLE OF OTHER THINGS THAT THE

PLAINTIFFS HAVE TALKED ABOUT. FIRST, THEY SAY GENERAL

ACCEPTANCE, YOU CAN HAVE A SCIENTIST COME IN AND GIVE AN

OPINION AND EVEN IF IT'S NOT GENERALLY ACCEPTED, DAUBERT

DOES NOT REQUIRE GENERAL ACCEPTANCE. WELL, FIRST OF

ALL, DAUBERT DOES. IT'S ONE OF THE IMPORTANT FACTORS.

IT'S NOT THE SOLE FACTOR, WE ADMIT THAT. BUT GENERAL

ACCEPTANCE IN THE SCIENTIFIC COMMUNITY IS AN IMPORTANT

FACTOR IN THE DAUBERT ANALYSIS. JUDGE RAU, AS WE KNOW

IN PENNSYLVANIA UNDER FRYE, IT IS THE THEORY. IT HAS TO

BE GENERALLY ACCEPTED. WE ARE GOING TO ESTABLISH FOR

YOU DURING THIS HEARING THAT IT IS NOT GENERALLY

ACCEPTED AND -- THAT ZOLOFT CAUSES BIRTH DEFECTS.

SO WE SHOULD THEN CONSIDER THE

PLAINTIFF'S OTHER ARGUMENT. DON'T WORRY. DON'T WORRY.

YOU CAN TAKE CARE ALL OF THIS ON CROSS EXAMINATION. YOU

SHOULD NOT THROW THESE OPINIONS OUT. JUST CROSS

EXAMINE. THAT IS GOOD ENOUGH. IT GOES TO WEIGHT OF

EVIDENCE. THAT IS WHAT ALWAYS GETS SAID IN THIS -- IN

THIS CONTEXT OF A DAUBERT HEARING. BUT IN DAUBERT, THE

COURT RECOGNIZES, THE SUPREME COURT, THAT BEFORE YOU GET

TO THE ISSUE OF WHETHER YOU CAN CROSS EXAMINE AN EXPERT,

THE SCIENTIFIC TESTIMONY MUST MEET THE STANDARDS OF RULE


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702. IF YOU DON'T MEET THE STANDARDS OF RULE 702, CROSS

EXAMINATION DOES NOT EVEN COME INTO PLAY. SO YOUR

HONORS, THE AVAILABILITY OF CROSS EXAMINATION CANNOT

SUPPLANT THE THRESHOLD RELIABILITY REQUIREMENTS THAT

PLAINTIFFS MUST SATISFY AND DO NOT SATISFY IN THIS CASE.

NOW, ONE LAST THING, AND THAT IS THE

PLAINTIFFS SPEND A LOT OF TIME IN THEIR BRIEFS RELYING

ON THE MATRIX CASE. I THINK WE AGAIN IN OUR BRIEFS HAVE

POINTED OUT THAT THIS IS JUST TOTALLY IMPROPER. MATRIX

IS A SUPREME COURT CASE, DOES CONCERN ADVERSE REACTION

REPORTS, BUT IT DISCUSSES THE ISSUE IN A SECURITIES

FRAUD CASE ABOUT THE STANDARD OF MATERIALITY UNDER

DISCLOSURE REQUIREMENTS OF 10(B)(5) OF THE SEC. IT

CONCERNED WHAT INFORMATION AN INVESTOR WOULD WANT TO

HAVE WITH REGARD TO ITS TRAINING DECISIONS. IN FACT, IN

THAT CASE THE SUPREME COURT MADE IT QUITE CLEAR THAT IT

WAS NOT ATTEMPTING TO DEFINE A MATRIX, WHAT CONSTITUTES

RELIABLE EVIDENCE FOR CAUSATION. SO IT HAS NO BEARING

HERE AT ALL.

NOW, WHAT I WOULD LIKE TO TALK ABOUT NEXT

IS DR. BERARD'S TESTIMONY JUST BRIEFLY, BECAUSE WE KNOW

IN PERFORMING YOUR GATEKEEPING FUNCTION, THE COURT MUST

DISTINGUISH BETWEEN REAL AND COURTROOM SCIENCE. YOU

CAN'T SAY ONE THING OUTSIDE OF THE COURTROOM WHEN YOU

ARE TALKING TO YOUR PEERS AND SAY ANOTHER THING WHEN YOU


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ARE IN THE COURTROOM. YOU'VE GOT TO BE CONSISTENT. AND

HERE DR. BERARD ADVANCES OPINIONS THAT ARE CONTRARY TO

HER OWN PRIOR STATEMENTS THAT SHE MADE TO THE SCIENTIFIC

COMMUNITY.

LET'S GO THROUGH THIS FOR A MINUTE. IN

HER 2007 STUDY DR. BERARD FOUND THAT, IN CONTRAST TO

PAXIL, THERE IS NO INCREASED RISK IN MAJOR CONGENITAL

MALFORMATIONS OR MAJOR CARDIAC MALFORMATIONS THAT'S

FOUND FOR THE FIRST TRIMESTER EXPOSURE TO OTHER SSRIS.

NO, NO INCREASED RISK. OKAY. AND IN 2009 IN HER REPORT

IN THE PAXIL LITIGATION, DR. BERARD WROTE THAT CURRENT

DATA DOES NOT SUGGEST A CLASS EFFECT, AS OTHER SSRIS ARE

NOT ASSOCIATED WITH THE RISKS. ONLY PAXIL. ALL OTHER

SSRIS JUST FINE. NOT ONLY ARE THEY FINE, THEY ARE

FIRST-LINE TREATMENTS.

SO AFTER 2009 WHAT HAPPENS? THE

PLAINTIFFS CLAIM AND DR. BERARD CLAIMS THAT SINCE SHE

WROTE THIS REPORT ON PAXIL IN 2009, NEW DATA HAS COME

OUT. WELL, WE ARE GOING TO TAKE A VERY HARD LOOK AT

THAT. AND WHAT DOES THE NEW DATA DO BETWEEN 2009 AND

2013 OR TO DATE? WELL, FIRST, AS MR. CHEFFO WILL SHOW

YOU, THE NEW DATA SUPPORTS THE GENERAL SCIENTIFIC VIEW

THAT ZOLOFT DOES NOT CAUSE BIRTH DEFECTS. IT DOES NOT

CHANGE THE VIEW. IT'S SUPPORTIVE OF THE VIEW. BUT MORE

IMPORTANTLY, DR. BERARD SHOULD HAVE KNOWN THAT BECAUSE


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IN HER WRITINGS AFTER 2009, SHE DOES NOT SAY, WOW,

THINGS HAVE CHANGED, DON'T USE -- DON'T USE ZOLOFT AS A

FIRST LINE TREATMENT FOR PREGNANT WOMEN WITH DEPRESSION.

BUT WHAT DOES SHE DO? WHAT DOES SHE TELL HER

COLLEAGUES? IN HER 2010 PEER REVIEWED ARTICLE, DR.

BERARD NOTED THAT WHILE PAXIL HAS BEEN LINKED TO AN

INCREASE IN THE RISK OF CARDIOVASCULAR MALFORMATIONS,

SSRIS, SUCH AS ZOLOFT, SHOULD BE USED AS A FIRST-LINE

THERAPY DURING PREGNANCY AND PAXIL SHOULD NOT. OKAY.

THAT IS AFTER 2009.

WHAT DOES SHE SAY IN 2012 TO HER PEERS?

IN HER 2012 PEER REVIEWED ARTICLE, DR. BERARD STATED

THERE IS NO INDICATION -- NO INDICATION TO STOP

ANTIDEPRESSANT MEDICATION AS A MATTER OF ROUTINE

TREATMENT IN EARLY PREGNANCY WITH THE EXCEPTION OF

PAXIL. AGAIN, SHE IS TELLING HER COLLEAGUES, DON'T STOP

THIS TREATMENT. THIS IS PERFECTLY FINE. IT DOES NOT

CAUSE BIRTH DEFECTS. ONLY PAXIL DOES.

NOW HERE IN THIS COURTROOM SHE IS GOING

TO TELL YOU SOMETHING DIFFERENT. AND, YOUR HONORS, WE

BELIEVE THIS IS LITIGATION-DRIVEN OPINIONS AND NOT

SUPPORTED BY THE GENERAL SCIENTIFIC EVIDENCE. AND MORE

SO, YOU ARE GOING TO SEE THAT HER REPORTS CITE ONLY

SELECTED FINDINGS FROM SELECTED STUDIES AND BY DESIGN.

SHE DOES NOT DESCRIBE. SHE DOES NOT ANALYZE. SHE DOES


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NOT EXPLAIN THE LARGE NUMBER OF FINDINGS THAT ARE

INCONSISTENT WITH HER OPINIONS.

NOW VERY QUICKLY, AND I HAVE TAKEN MORE

TIME THAN I PROBABLY SHOULD, BUT THIS IS VERY

INTERESTING MATERIAL. VERY QUICKLY, I WOULD LIKE TO

JUST TALK ABOUT THE THREE MECHANISM EXPERTS THAT YOU ARE

GOING TO SEE AND HEAR A LOT ABOUT. AND IN THIS REGARD I

THINK WE WANT TO POINT OUT THAT THERE'S A HIERARCHY OF

SCIENTIFIC EVIDENCE THAT ANYBODY, ANY SCIENTIST WOULD

LOOK TO IN TRYING TO DETERMINE CAUSATION OF BIRTH

DEFECTS.

THIS IS NOT US, IT'S THE TERATOLOGY

SOCIETY POSITION PAPER OF 2005. OF COURSE, THE TOP ONE

IS HUMAN EPIDEMIOLOGICAL DATA. AS THIS COURT HAS SAID

IN AVANDIA, EXPERTS SHOULD RELY PRIMARILY ON

EPIDEMIOLOGICAL STUDIES TO TEST THEIR THEORY THAT THE

DRUG CAUSES A DISEASE. AND WE ARE GOING TO DO THAT AND

WE ARE GOING TO SHOW YOU THAT IT DOESN'T.

BUT AFTER HUMAN EPIDEMIOLOGICAL EVIDENCE,

YOU HAVE TO GO TO THE EVIDENCE OF LIVING ANIMAL DATA.

WHAT IS THE LIVING ANIMAL DATA HERE? YOU ARE NOT GOING

TO HEAR A LOT ABOUT LIVE ANIMALS. YOU ARE NOT GOING TO

HEAR ABOUT THE RABBITS AND THE MAMMAL-TYPE ANIMALS THAT

WE HAVE TO DO TESTING ON IN ORDER TO EVEN PASS THE FDA'S

FIRST STEPS AS TO WHETHER YOU CAN SELL A DRUG IN THE


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UNITED STATES ON THE MARKET. I THINK THIS IS

UNQUESTIONED, WE WILL SEE WHAT THE PLAINTIFFS SAY, WHAT

HAS THE FDA FOUND? THERE IS NO TERATOGENIC EFFECTS SEEN

IN ANY OF THE ANIMAL REPRODUCTION STUDIES. NO EVIDENCE

OF TERATOGENICITY AT ANY DOSE LEVEL, ANY DOSE LEVEL.

IF WE LOOK AT THE LABEL FOR ZOLOFT, THE

FDA APPROVED LABEL, REPRODUCTION STUDIES HAVE BEEN

PERFORMED IN RATS AND RABBITS AT DOSES THAT CORRESPOND

TO APPROXIMATELY FOUR TIMES THE MAXIMUM HUMAN DOSE. AND

WHAT HAPPENS? NO EVIDENCE OF TERATOLOGY AT ANY DOSE

LEVEL. OKAY. WE DON'T HAVE ANY ANIMAL STUDIES. ALL

RIGHT.

SO WHAT DO THESE EXPERTS TALK ABOUT?

THEY TALK ABOUT IN VITRO, TEST TUBE DATA. THE

PLAINTIFFS' EXPERTS RELY ON THIS. WE ARE GOING TO SHOW

YOU, YOUR HONORS, THAT THIS KIND OF TESTING IS NOT GOING

TO PASS DAUBERT MUSTER IN THIS PARTICULAR SITUATION.

AND THE REASON THEY HAVE TO RELY ON IT? THEY DON'T HAVE

ANIMAL TESTING AND THEY CAN'T GET SUPPORTIVE TESTING IN

THE EPIDEMIOLOGICAL.

I JUST WANT TO END BY JUST SAYING YOU ARE

GOING TO HEAR A LOT ABOUT BIOLOGICAL PLAUSIBILITY FROM

THESE EXPERTS. AND AS PLAINTIFFS' EXPERTS CONCEDE,

BIOLOGICAL PLAUSIBILITY MERELY MEANS THAT IT'S POSSIBLE,

POSSIBLE, BUT NOT SCIENTIFICALLY PROVEN. POSSIBILITIES


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DON'T FLY IN DAUBERT. YOU HAVE TO HAVE REAL PROOF. AND

THEORIES, HYPOTHESES, ARE NOT PROOF OF CAUSATION.

I THANK YOUR HONOR FOR LISTENING SO

INTENTLY, AND I'M GOING TO TURN IT OVER TO MR. CHEFFO

WHO'S GOING TO GIVE YOU A LOT OF THE DETAILS THAT I JUST

TRIED TO SET THE STAGE FOR. THANK YOU SO MUCH.

THE COURT: THANK YOU.

MR. CHEFFO: THANK YOU, SHEILA.

GOOD MORNING, AGAIN, YOUR HONORS.

I WILL BE ADDRESSING THE KEY

METHODOLOGICAL FLAWS IN THE PLAINTIFFS' EXPERT REPORTS

THAT RENDER THEIR OPINIONS UNRELIABLE AND AS A RESULT

INHERENTLY INADMISSIBLE. I'D FIRST LIKE TO START WITH

DR. BERARD AND THEN I WILL TURN TO DRS. SADLER, LEVIN

AND CABRERA.

YOUR HONOR WILL RECALL THAT PLAINTIFFS

INITIALLY HAD PROFFERED SEVEN EXPERTS AND REPORTS. THEY

HAVE DISMISSED THREE OF THEM, INCLUDING THEIR ONLY

MEDICAL DOCTOR TWO DAYS BEFORE HIS DEPOSITION.

SO DR. BERARD. DR. BERARD TEACHES AT THE

UNIVERSITY OF MONTREAL. SHE IS NOT A MEDICAL DOCTOR.

SHE DOES NOT PRESCRIBE SSRIS OR ZOLOFT OR ANY MEDICINE,

AND SHE DOES NOT SEE OR TREAT PATIENTS. HER REPORT IS

FOUNDED ON A CONSTELLATION OF METHODOLOGICAL FLAWS. SHE

ADVANCES VIEWS THAT ARE NOT GENERALLY ACCEPTED IN THE


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MEDICAL SCIENTIFIC COMMUNITY. MS. BIRNBAUM TALKED A

LITTLE BIT ABOUT THAT. CITES LIMITED DATA POINTS FROM

STUDIES WITHIN STUDIES TO REACH CONCLUSIONS THAT THE

AUTHORS OF THOSE STUDIES DON'T REACH OR IN FACT OFTEN

CAUTION AGAINST. SHE CHERRY-PICKS DATA THAT SHE SAYS

SUPPORTS HER OPINIONS WHILE COMPLETELY IGNORING OTHER

STUDIES OR DATA WITHIN THOSE STUDIES, INCLUDING HER OWN

PUBLISHED REPORTS. SHE OVERLOOKS CONSISTENT FINDINGS

AND CONCLUSIONS AND INSTEAD RELIES ON SELECTED FINDINGS

AND DOES NOT EVEN LOOK FOR, MUCH LESS ADDRESS, THE

CONCEPT OF FALSE ASSOCIATIONS, AS WE WILL TALK ABOUT.

SHE FAILS TO ADHERE TO THE PROFESSIONAL

SCIENTIFIC STANDARDS EMPLOYED OUTSIDE THE COURTROOM.

NOW, SHE IS AWARE OF THEM. SHE HAS EMPLOYED THOSE WHEN

SHE HAS WRITTEN IN HER PEER REVIEWED LITERATURE AND HER

ARTICLES. HOWEVER, SHE HAS NOT USED THOSE SAME

METHODOLOGIES HERE.

AND SHE HAS LUMPED DATA FROM A GROUP OF

BIRTH DEFECTS TO TRY TO ESTABLISH CAUSATION FOR SPECIFIC

BIRTH DEFECTS. NOW FROM THE BEGINNING OF THIS

LITIGATION THE PLAINTIFFS HAVE ESSENTIALLY SAID WE ARE

LUMPERS. WE ARE GOING TO LUMP EVERYTHING TOGETHER. IN

FACT, THEY ARE, TRUE TO FORM. AND FRANKLY, DR. BERARD

IS A LUMPER AS WELL. AND THEY HAVE LUMPED DATA

CONCERNING OTHER MEDICINES, NOT ZOLOFT, WITH RESPECT TO


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ZOLOFT AND NONZOLOFT RELATED DATA.

NOW, DR. BERARD CLAIMS THAT ZOLOFT IS A

BROAD BASED TERATOGEN THAT CAUSES A VAST ARRAY OF BIRTH

DEFECTS. I APOLOGIZE. THIS IS A ADMITTEDLY VERY BUSY

SLIDE AND HARD TO READ. BUT IT'S SO BUSY BECAUSE THESE

ARE ALL THE BIRTH DEFECTS THAT DR. BERARD ATTRIBUTES TO

ZOLOFT. YOU WILL SEE THAT THEY CROSS VIRTUALLY EVERY

BODY SYSTEM. I'M NOT SURE WE HAVE A TO Z, BUT WE

CERTAINLY HAVE ANAL ATRESIA TO VSD. WE HAVE HEAD TO

TOE, FROM CRANIOSYNOSTOSIS TO CLUB FOOT. AND WHAT I

THINK ALSO THIS AGAIN ADMITTEDLY BUSY CHART REPRESENTS

IS THAT THERE ARE DIFFERENT CATEGORIES. EVEN WITHIN

CARDIAC, YOUR HONOR WILL SEE THAT THERE ARE VERY

DIFFERENT POTENTIAL BIRTH DEFECT OUTCOMES. YET WHAT THE

PLAINTIFFS HAVE DONE, THEY HAVE LUMPED WITHIN CARDIO,

THEY HAVE LUMPED WITHIN BODY SYSTEMS, AND THEN THEY HAVE

LUMPED WITHIN SSRIS GENERALLY.

NOW MS. BIRNBAUM HIGHLIGHTED THE POINT

THAT THERE IS NO AHA MOMENT HERE. IN OTHER WORDS, THIS

IS NOT A MEDICINE WHERE ALL OF A SUDDEN IT WAS WITHDRAWN

FROM FOR THE MARKET OR WE HAD A BLACK BOX WARNING. WHAT

IS PARTICULARLY TROUBLING -- WELL, TROUBLING AND

INSTRUCTIVE HERE IS THAT DR. BERARD HAS LOOKED AT THE

SAME DATA. SHE LOOKED AT THE SAME DATA THAT THE WORLD

SCIENTISTS AND PROFESSIONAL ORGANIZATIONS AND REGULATORY


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AGENCIES HAVE LOOKED AT. THERE IS NOTHING NEW. YET SHE

HAS COME TO THE CONCLUSION THAT ZOLOFT CAUSES ALL OF

THESE BIRTH DEFECTS, WHERE ALL OF THE OTHER SCIENTISTS

AND PROFESSIONAL ORGANIZATIONS AND REGULATORY

ASSOCIATIONS, REGULATORY AGENCIES, HAVE DETERMINED THAT

IT DOES NOT EVEN CAUSE ONE OF THESE BIRTH DEFECTS. IT'S

DR. BERARD AGAINST THE WORLD, YOUR HONOR. NOW, DR.

BERARD'S OPINIONS ARE NOT GENERALLY ACCEPTED AND THEY

ARE CONTRARY TO THE CONCLUSIONS IN THE INDEPENDENT

SCIENTIFIC AND MEDICAL COMMUNITY. AND THIS IS TRUE FOR

ALL OF THE GROUPED OR LUMPED BODY SYSTEM DEFECTS THAT

DR. BERARD HAS IDENTIFIED.

WHAT I WOULD FIRST LIKE TO ADDRESS IS THE

ZOLOFT SPECIFIC DATA. NOW, OTIS, MS. BIRNBAUM TALKED

ABOUT OTIS, A WELL REGARDED TERATOLOGY ORGANIZATION. IN

FACT DR. BERARD IS A MEMBER OF OTIS, IN FACT, CHAIRS

SEVERAL OF THE COMMITTEES. WHEN OTIS LOOKED AT THE

SPECIFIC -- ZOLOFT-SPECIFIC DATA AND PREGNANCY, THE

ORGANIZATION TELLS US THAT OVERALL THE AVAILABLE

INFORMATION DOES NOT SUGGEST THAT ZOLOFT INCREASES THE

RISK FOR BIRTH DEFECTS ABOVE THE 3 TO 5 PERCENT

BACKGROUND RISKS THAT IS SEEN IN THE GENERAL POPULATION.

THAT IS FROM 2010.

THEN THE LORENZO PAPER, ALSO LOOKING

SPECIFICALLY AT ZOLOFT DATA, SAYS, DOES IT CAUSE BIRTH


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DEFECTS? NO. IN SUMMARY, THERE IS NO EVIDENCE THAT

ZOLOFT INCREASES THE OVERALL RISK FOR MAJOR

MALFORMATIONS.

MYLEY WHICH IS A META-ANALYSIS FROM 2013,

AGAIN DEALING WITH ZOLOFT DATA, TELLS US THAT ZOLOFT IS

NOT STATISTICALLY ASSOCIATED WITH CONGENITAL

MALFORMATIONS.

NOW, IS THERE SOMETHING THAT WE ARE

MISSING HERE? ARE THERE AGENCIES, PROFESSIONAL

ORGANIZATIONS, PEER REVIEWED TREATISES OR PUBLISHED

STUDIES THAT STATE THAT ZOLOFT CAUSES MAJOR

MALFORMATIONS? DR. BERARD, UNDER OATH, TOLD US NO. SO

IN ADDITION TO THE ZOLOFT-SPECIFIC DATA, ALL OF THESE

OTHER DATA END POINTS, DR. BERARD HAS TOLD US THAT NONE

OF THEM HAVE DETERMINED THAT ZOLOFT CAUSES MAJOR

MALFORMATIONS. AGAIN, IT'S PART OF THIS LUMPING

CONCEPT. DR. BERARD, I THINK, WOULD HAVE THE COURT

BELIEVE THAT, WELL, IF YOU LOOK AT ALL OF THE DATA, IF

YOU LOOK AT THE SSRI DATA GENERALLY, YOU WILL SEE

SOMETHING DIFFERENT THAT MIGHT BE INSTRUCTIVE IN TERMS

OF TERATOGENICITY AND ZOLOFT.

BUT LET'S LOOK AT WHAT THE WORLD'S

SCIENTISTS HAVE TOLD US WITH RESPECT TO SSRI DATA

GENERALLY. THIS IS AGAIN -- THESE ARE ALL VERY RECENT

DATA POINTS. THIS IS FROM THE AMERICAN PSYCHIATRIC


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ASSOCIATION, THE AMERICAN COLLEGE OF OBSTETRICIANS AND

GYNECOLOGISTS. CURRENT DATA ON SSRI EXPOSURE SHOW NO

CONSISTENT INFORMATION TO SUPPORT SPECIFIC MORPHOLOGICAL

TERATOGENIC RISKS.

THE GENTILE PAPER: THE HYPOTHESIZED

TERATOGENICITY OF SSRIS REMAINS UNDEMONSTRATED, 2011.

THE CANADIAN PEDIATRIC SOCIETY: SSRI USE

DURING THE FIRST TRIMESTER OF PREGNANCY IS NOT FOUND TO

INCREASE RISK OF MAJOR CONGENITAL MALFORMATIONS. THAT

IS FULLY CONSISTENT WITH WHAT DR. BERARD PREVIOUSLY

PUBLISHED.

THE DIAV-CITRIN PAPER OF 2012: THE

OVERALL CURRENT SCIENTIFIC EVIDENCE HAS NOT FULFILLED

THE CRITERIA -- HAS NOT FULFILLED THE CRITERIA FOR PROOF

OF HUMAN TERATOGENICITY OF SSRIS.

MARGULIS, 2013. THE AUTHORS OF THE

MARGULIS PAPER, INCLUDING MARGULIS, WERE ALL EMPLOYED BY

THE FDA AT THE TIME THEY DID THE UNDERLYING WORK FOR

THIS PAPER. DID THEY FIND THAT SSRIS ARE BROAD-BASED

TERATOGENS? NO. THEY SAID THERE IS NO ASSOCIATION

BETWEEN MATERNAL USE OF SSRIS IN EARLY PREGNANCY AND

CARDIAC MALFORMATIONS OR SEPTAL DEFECTS IN THE

OFFSPRING.

AND THEN FINALLY, IN THE KOREN 2013

PAPER: SSRIS CAN PROBABLY BE ADDED TO THE INFAMOUS LIST


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OF DRUGS WRONGLY INCRIMINATED AS HUMAN TERATOGENS, ONLY

TO BE ACQUITTED FROM BEING MAJOR TERATOGENIC AGENTS

AFTER MUCH SUFFERING BY EXPECTING MOTHERS AND THEIR

FAMILIES.

THAT IS WHAT THE ZOLOFT-SPECIFIC DATA

SAYS. THAT IS WHAT THE RECENT CURRENT SSRI DATA SAYS

WITH RESPECT TO BIRTH DEFECTS. IT REALLY IS DR. BERARD

VERSUS THE WORLD.

THE REASON WHY DR. BERARD STANDS ALONE,

YOUR HONORS, IS THAT TERATOGENS SIMPLY DON'T ACT IN THE

WAY THAT DR. BERARD HAS SUGGESTED. THEY DON'T HAVE A

SHOTGUN EVERYBODY SYSTEM, HEAD TO TOE APPROACH. THAT IS

NOT THE WAY THE TERATOGENS WORK. TERATOGENS DO NOT

UNIFORMLY INCREASE THE RATES OF ALL BIRTH DEFECTS, BUT

RATHER, INCREASE RATES OF SELECTED DEFECTS. THIS IS DR.

MITCHELL'S CHAPTER IN DR. KIMMEL'S BOOK. SO WE KNOW.

WE HAVE EXPERIENCE WITH ACCUTANE AND VALPROIC ACID. AND

THEY DON'T ACT THE WAY THAT DR. BERARD HAS SUGGESTED.

IN ORDER TO BE CONSIDERED A TERATOGEN, A

DRUG SHOULD BE SHOWN TO CAUSE A SPECIFIC PATTERN OF

BIRTH DEFECTS THAT IS CONSISTENTLY DEMONSTRATED IN THE

EPIDEMIOLOGICAL STUDIES. AS REFLECTED IN THE TERATOLOGY

SOCIETY'S POSITION PAPER ON CAUSATION-RELATED

LITIGATION, ONE CRITERIA FOR ASSESSING CAUSATION IS THAT

EPIDEMIOLOGY STUDIES THAT CONSISTENTLY DEMONSTRATE AN


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INCREASE IN THE FREQUENCY OF CONGENITAL MALFORMATIONS

AND ESPECIALLY A RECOGNIZABLE SYNDROME IN THE EXPOSED

POPULATION. SO YOU NEED TO HAVE SPECIFICITY. THAT IS A

HALLMARK OF TERATOGENICITY.

THE NINTH CIRCUIT TOLD US IN THE LUST

CASE VERSUS MERRILL-DOW: THE NOTION THAT AN AGENT

SUBSTANTIALLY INCREASES THE PROBABILITY OF ALL BIRTH

DEFECTS, ALL TYPES OF BIRTH DEFECTS, AS OPPOSED TO A

SPECIFIC PATTERN OF BIRTH DEFECTS, IS NOT ACCEPTED BY

EVEN A MINORITY OF TERATOLOGISTS.

ANOTHER HALLMARK, IN ADDITION TO

SPECIFICITY OF A TERATOGEN, IS CONSISTENCY. WE KNOW

THAT BECAUSE THE WADE-GREAUX CASE WHICH WAS AFFIRMED BY

THE 3RD CIRCUIT AND IT IS THE LAW IN THE 3RD CIRCUIT

TELL US THAT: ABSENT CONSISTENT REPEATED HUMAN

EPIDEMIOLOGICAL STUDIES SHOWING A STATISTICALLY

SIGNIFICANT INCREASED RISK OF PARTICULAR BIRTH DEFECTS

ASSOCIATED WITH EXPOSURE TO A SPECIFIC AGENT, THE

COMMUNITY OF TERATOLOGISTS DOES NOT CONCLUDE THAT THE

AGENT IS A HUMAN TERATOGEN. SO WE NEED BOTH SPECIFICITY

AND WE ALSO NEED CONSISTENCY.

AND THERE IS SOME IRONY HERE IN THAT WE

HAVE CONSISTENCY. AND THE MANUAL, OUR REFERENCE MANUAL

TALKS ABOUT THE NEED FOR CONSISTENCY. THE TERATOLOGY

PAPER SAYS THAT YOU -- THE CRITERION IS THAT YOU HAVE


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EPIDEMIOLOGY STUDIES THAT CONSISTENTLY DEMONSTRATE AN

INCREASE IN THE FREQUENCY OF CONGENITAL MALFORMATIONS.

AGAIN, THE IRONY HERE IS THAT WE HAVE CONSISTENCY. THE

DATA, ALL OF THE DATA AND END POINTS SHOW THAT THERE IS

NO ASSOCIATION, MUCH LESS A CAUSAL CONNECTION, BETWEEN

ZOLOFT AND BIRTH DEFECTS.

AND SINCE 2009 WHEN DR. BERARD SUBMITTED

HER REPORT WHEN SHE WAS A RETAINED PAXIL EXPERT AND SHE

DISTINGUISHED BETWEEN SSRIS AND PAXIL, THE OVERALL DATA

HAVE ONLY GOTTEN STRONGER IN DEMONSTRATING A LACK OF

CAUSATION BETWEEN ZOLOFT AND BIRTH DEFECTS.

AGAIN, THE OTIS STUDY TELLS US THAT

ZOLOFT IS ONE OF THE BETTER STUDIED ANTIDEPRESSANTS

DURING PREGNANCY: MOST STUDIES HAVE NOT FOUND THAT

WOMEN TAKING ZOLOFT DURING PREGNANCY ARE MORE LIKELY TO

HAVE A BABY WITH A BIRTH DEFECT THAN WOMEN NOT TAKING

ZOLOFT. YOU HAVE TO LOOK AT ALL OF THE DATA. WHAT IS

THE TAKEAWAY? AGAIN, IT DOES NOT SUGGEST THAT ZOLOFT

INCREASES THE RISK FOR BIRTH DEFECTS ABOVE THE

BACKGROUND RATE.

IN MYLES, AGAIN, A ZOLOFT-SPECIFIC

META-ANALYSIS. ZOLOFT WAS NOT SIGNIFICANTLY ASSOCIATED

WITH CONGENITAL MALFORMATIONS. THIS IS 2013: ZOLOFT

SHOULD BE CONSIDERED AS A FIRST LINE SSRI TREATMENT IN

PREGNANCY. NOW AGAIN DR. BERARD REALLY SHOULD NOT TAKE


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ISSUE WITH THAT BECAUSE THAT IS WHAT SHE HAS WRITTEN,

AND THAT IS STILL WHAT STANDS IN THE LITERATURE BASED ON

HER OWN PUBLICATIONS.

NOW, APOLOGIES IN ADVANCE AGAIN, THIS IS

ANOTHER SOMEWHAT BUSY SLIDE, BUT IT'S BUSY ONLY BECAUSE

WE HAVE TRIED TO CAPTURE THE VAST ARRAY OF BIRTH DEFECTS

THAT DR. BERARD ATTRIBUTES TO ZOLOFT. WHAT WE HAVE

ATTEMPTED TO DO HERE IN THESE THREE CATEGORIES -- AND I

SHOULD ADD, THERE IS KIND OF A FOURTH CATEGORY THAT IS

NOT EVEN INCLUDED. THOSE ARE ALL THE BIRTH DEFECTS OF

WHICH THERE ARE NO OUTCOMES. HERE WHAT WE HAVE ARE

OUTCOMES WHERE STUDIES REPORT NO POSITIVE ASSOCIATION

WITH A CONFIDENCE INTERVAL GREATER THAN 1. WE'VE TALKED

ABOUT CONSISTENCY AND SPECIFICITY. AND HERE, THERE ARE

NO OUTCOMES IN ANY OF THOSE -- THOSE STUDIES WITH A

CONFIDENCE INTERVAL GREATER THAN 1. AS YOU CAN SEE,

THEY ARE BROKEN DOWN. CARDIACS ARE NOT NECESSARILY

LUMPED TOGETHER.

THE MIDDLE COLUMN IS OUTCOMES WHERE THERE

IS ONLY ONE INDEPENDENT STUDY REPORTS A POSITIVE

ASSOCIATION WITH A CONFIDENCE INTERVAL GREATER THAN 1.

AND AS A CONTEXT, OF COURSE, YOUR HONOR, THE BACKGROUND

HERE IS THAT YOU HAVE OVER A DOZEN ZOLOFT RELATED

STUDIES TO BEGIN WITH. AND WHEN YOU TALK ABOUT THINGS

LIKE CONSISTENCY AND SPECIFICITY, OF COURSE, THOSE ARE


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IMPORTANT FACTORS WHEN YOU EVEN LOOK AT THIS

INFORMATION.

AND ON THE RIGHT, YOU HAVE HEARD AND YOU

WILL HEAR, I'M SURE, A LOT ABOUT SEPTAL DEFECTS. AND

THAT REALLY SHOULD JUST SAY OUTCOME, AS OPPOSED TO

OUTCOMES, BECAUSE THERE IS ONLY ONE. AND THAT'S WHERE

ONLY TWO INDEPENDENT STUDIES REPORTED POSITIVE

ASSOCIATION WITH A CONFIDENCE INTERVAL GREATER THAN 1.

SO -- AND WE WILL TALK ABOUT, YOUR HONOR,

IN A MINUTE OR TWO AS TO WHY BOTH -- IT'S IMPORTANT TO

LOOK AT WHETHER THERE IS CONSISTENCY AND SPECIFICITY

WITH RESPECT TO THE PUBLISHED LITERATURE, BUT ALSO WHY

YOU MUST EVALUATE THINGS LIKE FALSE ASSOCIATIONS AND

CHANCE AND BIAS AND CONFOUNDING AS THEY MIGHT AFFECT

SOME OR ALL OF THESE DATA POINTS.

SO AT THIS POINT, I SUSPECT THE COURT MAY

BE ASKING, AND I CERTAINLY DON'T WANT TO BE

PRESUMPTUOUS, WELL, IF THIS IS ALL TRUE, THEN HOW IS IT

THAT DR. BERARD CAN REACH THE CONCLUSIONS AND OPINIONS

THAT SHE HAS? AND I THINK THE ANSWER TO THAT IS SIMPLE.

SHE HAS DONE IT BY CHERRY-PICKING, CLASS EFFECT FALLACY.

SHE'S IGNORED THE STATISTICAL SIGNIFICANCE. SHE HAS NOT

LOOKED FOR FALSE ASSOCIATIONS, MUCH LESS DISTINGUISHED

BETWEEN TRUE AND FALSE ASSOCIATIONS. SHE HAS LUMPED

BIRTH DEFECTS AND SHE HAS EXCEEDED THE BOUNDS OF THE


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STUDIES.

SO CHERRY-PICKING. DESPITE WHAT THE

ACTUAL DATA SHOWS, DR. BERARD CLAIMS THAT THERE IS

CONSISTENCY IN THE DATA WITH RESPECT TO BIRTH DEFECTS,

BUT SHE HAS CREATED ONLY AN ILLUSION OF CONSISTENCY

BECAUSE SHE SELECTIVELY CITES ONLY FINDINGS THAT SHE

SAYS SUPPORT HER THEORIES. NOW, WHEN ASKED THE QUESTION

DO YOU THINK CHERRY PICKING IS GOOD OR BAD, OF COURSE,

DR. BERARD SAYS, WELL, SURE, NO, IT'S NOT. IT'S NOT A

GOOD THING. IT'S INCONSISTENT WITH THE VALID SCIENTIFIC

METHOD. BUT IN WHAT I BELIEVE IS A STUNNING ADMISSION,

WHAT DR. BERARD TELLS US IS THAT I ONLY PUT IN THE

REPORT THE STUDIES THAT WERE SUPPORTING MY OPINION.

THERE ARE MANY, MANY EXAMPLES. I'M JUST

GOING TO COVER A FEW, YOUR HONOR. BUT DR. BERARD WAS

ASKED: IN THE SECTION OF YOUR REPORT OR ANYWHERE ELSE

IN YOUR REPORT DO YOU DESCRIBE, ANALYZE OR EXPLAIN THIS

FINDING THAT IS INCONSISTENT WITH YOUR DISCUSSION OF

ZOLOFT AS INCREASING THE RISK OF MALFORMATIONS, YOU

DON'T DO THAT?

IN THE REPORT, NO, I DON'T DO THAT.

DO YOU LOOK AT THIS PARTICULAR OTHER

DATA?

NO, I DON'T.

DO YOU EXPLAIN THE FINDINGS THAT WE JUST


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DISCUSSED FOR MALM OR JIMINEZ-SOLEM?

I DON'T PRESENT THEM IN MY REPORT.

DO YOU DESCRIBE OR ANALYZE OR EXPLAIN THE

FINDINGS, THE CONTRARY FINDINGS THAT WERE JUST DISCUSSED

BETWEEN MALM, COLVIN, JIMINEZ-SOLEM?

EACH SECTION I'M PRESENTING THE STUDIES

AND THE FINDINGS THAT SUPPORT MY OPINION.

THERE ARE OTHER EXAMPLES, YOUR HONOR. I

JUST DON'T HAVE TIME TO GO INTO IT TODAY.

NOW, I'M NOT GOING TO READ THIS BECAUSE

YOUR HONOR WROTE IT. BUT I WOULD HIGHLIGHT THE

DISTINCTION HERE. YOUR HONOR HAD AN APPROPRIATELY HIGH

STANDARD IN TERMS OF REQUIRING EXPERTS TO ADDRESS

INFORMATION AND DATA THAT WAS INCONSISTENT WITH THEIR

OPINIONS. AND AGAIN, YOUR HONOR, YOUR HONOR HAS NOT

ONLY ENDORSED BUT REQUIRED A VERY, VERY CLEAR PROCESS IN

TERMS OF HOW WE GOT HERE TODAY. REPORTS WERE SUPPOSED

TO BE WRITTEN, THEN DEPOSITIONS. AND THERE WAS EVEN A

TIME AT PLAINTIFFS' INSISTENCE THAT THERE COULD HAVE

BEEN REBUTTAL REPORTS. IF THERE WAS SOMETHING THAT WAS

NOT IN THE REPORT, THEY COULD HAVE DONE IT. PLAINTIFFS

HAVE NOT SUBMITTED ANY REBUTTAL REPORTS IN THIS

LITIGATION.

SO IN AVANDIA, YOUR HONOR SAID THAT THE

DOCTOR THERE GAVE A DETAILED SPECIFIC -- UNIQUE,


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SPECIFIC CRITIQUE OF THE STUDIES WITH OUTCOMES CONTRARY

TO HIS OPINION. HE DID NOT SIMPLY IGNORE THESE STUDIES,

BUT INSTEAD ANALYZES THEIR STRENGTHS AND WEAKNESSES

BEFORE CONCLUDING THAT THEY NEITHER CONTRADICT NOR

UNDERMINE HIS OPINION. THAT IS PRECISELY THE OPPOSITE

OF WHAT DR. BERARD HERE DID IN THIS LITIGATION.

NOW CLASS EFFECT. MS. BIRNBAUM TALKED A

LITTLE BIT ABOUT THAT. THE NOTION OF CLASS EFFECT AS TO

TERATOGENICITY IS A FALLACY AND IT'S NOT SCIENTIFICALLY

VALID. GENERALLY ACCEPTED TERATOLOGY PRINCIPLES AS

ESPOUSED BY THE TERATOLOGY SOCIETY, WHICH, AGAIN, DR.

BERARD IS A MEMBER OF THE TERATOLOGY SOCIETY, PROVIDE

THAT: DETERMINATION OF A CAUSAL RELATIONSHIP BETWEEN A

CHEMICAL AND AN OUTCOME IS SPECIFIC TO THE CHEMICAL AT

ISSUE. SO IN OTHER WORDS, IF YOU WANT TO FIND OUT IF

ZOLOFT OR SOME OTHER CHEMICAL CAUSES BIRTH DEFECTS, YOU

LOOK AT ZOLOFT OR THAT OTHER CHEMICAL.

AND IN THE TERATOLOGY SOCIETY'S 2010

PRIMER, WRITTEN IN PART BY DR. ALWAN -- AND DR. ALWAN

WAS THE PRIMARY AUTHOR IN THE 2007 ALWAN PAPER THAT YOU

WILL BE HEARING ABOUT. DR. ALWAN SAID THAT WHILE ALL

SSRIS SHARE A SIMILAR MECHANISM OF ACTION, THEIR

CHEMICAL STRUCTURES AND PHARMACOKINETIC PROPERTIES VARY

AND DIFFERENT SSRIS MAY ACTUALLY AFFECT THE DEVELOPING

FETUS DIFFERENTLY. SHOULD WE LOOK AT A CLASS EFFECT?


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DR. ALWAN SAYS, NO, WE SHOULD NOT.

DR. BERARD INVOKED A CHAPTER BY DR.

MITCHELL IN THE PHARMACOEPIDEMIOLOGY BOOK BY DR. STROM.

WHAT DR. BERARD DOES NOT FOCUS ON IS WHAT DR. MITCHELL

HAS INDICATED IS THE FALLACY OF CLASS ACTION

TERATOGENESIS: CLASS-BASED PHARMACOLOGIC EFFECTS CANNOT

BE ASSUMED TO HOLD WHEN THE ADVERSITY AT ISSUE IS

TERATOGENESIS. WHAT DOES DR. BERARD TELL US? SHE SAYS

THAT YOU CAN LOOK AT THE ENTIRE CLASS OF SSRIS. IT'S

INHERENTLY UNRELIABLE.

AND WE KNOW THAT THE FDA AGREES AT LEAST

IN TERMS OF CLASS EFFECT, AS MS. BIRNBAUM SPENT SOME

TIME TALKING ABOUT, THAT PAXIL IS A CATEGORY D MEDICINE.

ZOLOFT AND ALL OF THE OTHER SSRIS, ALL OF THE OTHERS UP

UNTIL TODAY ARE CATEGORY C MEDICINES.

IN THE 3RD CIRCUIT WE KNOW THIS FROM THE

SOLDO CASE. THE 3RD CIRCUIT AND ITS DISTRICT COURTS

HAVE HELD THAT: EVIDENCE CONCERNING THE EFFECT OF

ALLEGEDLY SIMILAR CHEMICALS ON THE BODY CANNOT

SUBSTITUTE FOR DIRECT EVIDENCE ABOUT THE DRUG IN

QUESTION.

LET'S TURN FOR A MINUTE TO STATISTICAL

SIGNIFICANCE. DR. BERARD RELIES ON FINDINGS THAT ARE

NOT STATISTICALLY SIGNIFICANT. THE SOLDO CASE SAYS THAT

COURTS HAVE EMPHASIZED THAT EPIDEMIOLOGIC PROOF MUST BE


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STATISTICALLY SIGNIFICANT. DR. BERARD TELLS US UNDER

OATH: I DIDN'T LOOK AT STATISTICAL SIGNIFICANCE.

ANOTHER REASON WHY DR. BERARD IS ABLE TO

REACH THE CONCLUSIONS THAT SHE DOES, WHICH ARE CONTRARY

TO THE REST OF THE WORLD'S SCIENTIFIC COMMUNITY, IS BY

FAILING TO LOOK FOR OR ASSESS TRUE OR FALSE

ASSOCIATIONS. A STUDY MAY FIND A POSITIVE ASSOCIATION

EVEN IF THERE IS NO TRUE ASSOCIATION. THE REFERENCE

MANUAL ON SCIENTIFIC EVIDENCE TELLS US THAT WHEN WE ARE

LOOKING AT STUDIES AND DATA POINTS, PARTICULARLY WHEN WE

HAVE A LOT, YOU KNOW, KIND OF CONSTELLATION OF STUDIES,

AND YOU SEE WHAT MIGHT APPEAR TO BE ABERRATIONAL IN ONE

STUDY, YOU HAVE TO TAKE A CRITICAL EYE. THIS IS WHAT

SCIENTISTS DO OUTSIDE THE COURTROOM. YOU HAVE TO TAKE A

CRITICAL EYE AND SAY, WELL, IS IT AS A RESULT OF CHANCE

OR BIAS OR CONFOUNDING? IS THAT WHAT IS CAUSING THIS

BLIP, THIS ANOMALOUS FINDING?

I THINK THE CONCEPT OF CHANCE IS BEST

REALLY ARTICULATED BY THIS SLIDE. SO IN STUDIES

CONDUCTING ONE TEST, A POSITIVE FINDING IS DEEMED

STATISTICALLY SIGNIFICANT IF THE PROBABILITY DUE TO

CHANCE IS LESS THAN FIVE PERCENT. NOW WHAT HAPPENS IF

WE CONDUCT 13 TESTS? AND JUST TAKING A STEP BACK, WHEN

WE ARE TALKING ABOUT TESTS HERE, THESE ARE NOT BENCH

SCIENCE TESTS. WE'RE TALKING ABOUT TAKING THE DATA AND


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CRUNCHING THE NUMBERS AND DOING -- REVIEW A COMPARISON

OF THE SIMILAR DATA. SO CONDUCTING 13 TESTS INCREASES

THE PROBABILITY OF A POSITIVE FINDING DUE TO CHANCE TO

50 PERCENT. THE MORE YOU SLICE AND DICE AND LOOK AT

THIS DATA, THE MORE LIKELY YOU ARE GOING TO HAVE A

RESULT AS A RESULT OF CHANCE. THEN IF YOU CONDUCT 60

TESTS, IT MAKES THE PROBABILITY OF A POSITIVE FINDING

DUE TO CHANCE GREATER THAN 95 PERCENT. WELL, SOME OF

THE STUDY AUTHORS AND STUDIES THAT DR. BERARD HAS RELIED

ON HAVE CONDUCTED 265 AND 108 TESTS.

AND DR. BERARD HAS RECOGNIZED HERSELF

THAT THIS CONCEPT IS VALID. THE MORE COMPARISONS YOU

STUDY, THE MORE LIKELY THAT YOU ARE GOING TO GET -- A

STATISTICALLY SIGNIFICANT FINDING WILL BE SPURIOUS

BECAUSE OF CHANCE ALONE.

SHE HAS ALSO TOLD US IN HER PEER REVIEWED

LITERATURE THAT IDEALLY ADJUSTMENT FOR MULTIPLE TESTINGS

SHOULD BE MADE. YET THE STUDIES THAT SHE RELIES ON

RECOGNIZE THE VERY SIGNIFICANT LIMITATIONS OF TESTS OF

CHANCE DUE TO THE NUMBER OF COMPARISONS OR TESTS THAT

THEY HAVE DONE.

ALWAN. BECAUSE OF THE LARGE NUMBER OF

COMPARISONS EVALUATED IN OUR ANALYSIS, IT IS LIKELY THAT

SOME OF THE OBSERVED ASSOCIATION REFLECT CHANCE

VARIATION.


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LOUIK. THE POSSIBILITY THAT CHANCE

ACCOUNTS FOR SOME OR ALL OF THESE RESULTS CANNOT BE

RULED OUT, ESPECIALLY IN VIEW OF THE MANY COMPARISONS

THAT WERE MADE IN THESE ANALYSES.

PEDERSEN: THE STUDY WAS DESIGNED WITH NO

ADJUSTMENT FOR MULTI-HYPOTHESIS TESTING AND THE FINDINGS

COULD POTENTIALLY HAVE OCCURRED BY CHANCE.

DR. BERARD, IN HER WRITINGS, RECOGNIZES

CHANCE.

THE REIS AND KALLEN PAPER. AS IN SIMILAR

STUDIES, THE PROBLEMS ENCOUNTERED IN MULTIPLE TESTING

ARE IMPORTANT.

MALM. BECAUSE OF THE LARGE NUMBER OF

COMPARISONS PERFORMED IN OUR ANALYSES, IT'S POSSIBLE

THAT SOME OF THE OBSERVED ASSOCIATIONS REFLECT

VARIATIONS BY CHANCE.

DR. ALWAN SAYS IN THE TERATOLOGY PRIMER,

WRITTEN THAT: MANY OF THE ASSOCIATIONS FOUND IN THE

STUDIES ON SSRIS MAY BE ATTRIBUTED TO CHANCE DESPITE

THEIR NOMINAL STATISTICAL SIGNIFICANCE BECAUSE OF

MULTIPLE COMPARISONS MADE WITHIN THE STUDIES.

BIAS IS THE NEXT OF THE THREE-PRONG

FACTORS IN DETERMINING WHETHER SOMETHING IS A TRUE OR

FALSE ASSOCIATION. BIAS IS ANYTHING THAT RESULTS IN A

SYSTEMATIC NONRANDOM ERROR IN A STUDY RESULT, AND


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THEREBY COMPROMISES ITS VALIDITY.

DR. BERARD DOES NOT TAKE INTO ACCOUNT THE

POTENTIAL THAT DETECTION BIAS CAN EXPLAIN THE FINDING

THAT SHE RELIES ON. WHAT IS DETECTION BIAS? BASICALLY

WE KNOW THAT IN INFANTS OF WOMEN WHO WERE TAKING SSRIS,

WOMEN WHO HAVE SERIOUS PSYCHOLOGICAL AND DEPRESSIVE

HEALTH EFFECTS, THOSE CHILDREN ARE TESTED TWICE AS MANY

TIMES AS CHILDREN OF MOMS WHO ARE NOT TAKING SSRIS. SO

THE MORE YOU ARE LOOKING, THE MORE YOU WILL FIND. AND

THAT IS PARTICULARLY IMPORTANT IF YOU THINK ABOUT

SOMETHING LIKE SEPTAL DEFECTS, FOR EXAMPLE, USING THAT

AS ONE EXAMPLE. SEPTAL DEFECTS ARE OFTEN ASYMPTOMATIC.

IN OTHER WORDS, ANY OF US COULD HAVE BEEN BORN WITH A

SEPTAL DEFECT. AND FOR THE VAST MAJORITY OF THEM, THEY

DON'T CAUSE ANY PROBLEMS. THEY RESOLVE THEMSELVES.

YOU'D NEVER KNOW THAT YOU OR ANYONE HAD THEM. THERE ARE

EXCEPTIONS, BUT THAT IS THE GENERAL MAJORITY OF PEOPLE.

SO IF YOU ARE LOOKING TWICE AS MUCH IN THE POPULATION OF

CHILDREN WHO WERE BORN TO MOTHERS ON SSRIS, OF COURSE

YOU ARE GOING TO FIND TWICE AS MANY.

NOW CONFOUNDING IS THE THIRD AND FINAL

FACTOR WITH RESPECT TO FALSE ASSOCIATION. CONFOUNDING

IS BASICALLY, YOU KNOW, WHAT MAY APPEAR TO BE A

RELATIONSHIP BETWEEN A AND B IS ACTUALLY DUE TO THE FACT

THAT BOTH A AND B ARE RELATED TO ANOTHER VARIABLE THAT


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WAS OVERLOOKED IN THE POPULATION BEING STUDIED. AND

THIS IS ALSO RECOGNIZED IN THE REFERENCE MANUAL.

I THINK THE WAY I THOUGHT ABOUT

CONFOUNDING IS IF YOU WERE GOING TO DO AN ASSOCIATION

BETWEEN SOMEONE WHO HAD YELLOW FINGERTIPS AND LUNG

CANCER, WELL, THE FACT THAT THEY WERE ALSO -- YOU MIGHT

FIND AN ASSOCIATION, BUT OF COURSE THERE ARE ALSO

SMOKERS AS TO WHY THEY WOULD HAVE YELLOW FINGERTIPS.

AND THAT -- THAT YELLOWFINGER TIPS IS A CONFOUNDING

FACTOR. THIS IS A VERY WELL ACCEPTED AND UNDERSTOOD AND

FRANKLY DIFFICULT ISSUE WITH RESPECT TO ANALYZING BIRTH

DEFECTS AND WOMEN WHO ARE ON SSRIS BECAUSE OF THE FACT

THAT THEY ARE ON SSRIS BECAUSE THEY HAVE DEPRESSION.

AND THAT UNDERLYING DEPRESSION CAN PLAY A SIGNIFICANT

IMPACT -- HAVE A SIGNIFICANT IMPACT ON HOW WE UNDERSTAND

AND EVALUATE THE STUDY DATA.

DR. BERARD HAS TOLD US AT HER DEPOSITION,

IN STUDIES OF DEPRESSED WOMEN, CONFOUNDING BY INDICATION

IS THE WORST CONFOUNDER THAT WE HAVE TO DEAL WITH IN

PHARMACOEPIDEMIOLOGY.

AGAIN, THERE ARE A NUMBER OF THESE, YOUR

HONOR. I APOLOGIZE BUT I THINK IT'S REALLY IMPORTANT

HERE BECAUSE WHAT THE AUTHORS HAVE TOLD US IS, THIS IS

WHAT THEY HAVE UNDERSTOOD AND THEY HAVE LOOKED AT IN

TERMS OF CONFOUNDING. AND THIS IS WHY THE WORLD


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SCIENTIFIC COMMUNITY WHEN THEY READ THESE STUDIES DOES

NOT COME TO THE SAME CONCLUSION THAT DR. BERARD HAS COME

TO. WE CANNOT RULE OUT INCREASED RISK OF CONGENITAL

MALFORMATIONS CAUSED BY THE DISEASE ITSELF OR BY RELATED

FACTORS, RATHER THAN BY SSRI USE.

ALWAN TOLD US THAT AN IMPORTANT

LIMITATION OF THIS STUDY IS OUR INABILITY TO SEPARATE

THE EFFECT OF MATERNAL SSRI USE FROM THE UNDERLYING

DEPRESSION. IT'S IMPORTANT TO UNDERSTAND WHY THESE

WOMEN ARE TAKING THESE MEDICINES. WE HAVE NO

INFORMATION ON THE SEVERITY OF THE DEPRESSION AND

POTENTIAL CONFOUNDING BY INDICATION IS IMPOSSIBLE TO

RULE OUT IN A NONRANDOMIZED DESIGN.

KORNUM. WE CANNOT EXCLUDE THE

POSSIBILITY THAT INCREASED RISK OF CONGENITAL

MALFORMATIONS IS CAUSED BY THE DISEASE UNDERLYING SSRI

USE OR BY OTHER DISEASE-RELATED FACTORS RATHER THAN BY

THE SSRI USE ITSELF.

MALM. ONE OF THE MAJOR PROBLEMS IN

PHARMACOEPIDEMIOLOGIC STUDIES IS CONFOUNDING BY

INDICATION. UNTREATED MATERNAL DEPRESSION HAS A

NEGATIVE IMPACT ON SEVERAL PREGNANCY OUTCOME MEASURES

AND IS DIFFICULT TO CONTROL FOR IN EPIDEMIOLOGICAL STUDY

SETTINGS.

JIMINEZ-SOLEM. THE APPARENT ASSOCIATION


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BETWEEN SSRI USE AND CONGENITAL MALFORMATIONS OF THE

HEART MAY BE CONFOUNDED BY INDICATIONS.

SO YOUR HONOR, THIS CONFOUNDING CONCEPT,

OF WHICH DR. BERARD HAS RECOGNIZED AS IMPORTANT, IS

EXTREMELY, EXTREMELY IMPORTANT WHEN YOU LOOK AT WHY

THERE MAY BE CERTAIN CHERRY PICKED OR ANOMALOUS DATA.

I HAVE TOUCHED A LITTLE BIT ABOUT THEM.

JUST BRIEFLY COME BACK TO LUMPING OF BIRTH DEFECTS. YOU

ONLY LUMP BIRTH DEFECTS WHEN YOU DON'T HAVE DATA

SPECIFIC. SO TO THE EXTENT THAT THERE WERE SPECIFIC

KIND OF BIRTH DEFECT OUTCOMES, THERE WOULD BE NO NEED TO

LUMP ALL OF THESE THINGS TOGETHER. BUT SHE OPINES THAT

ZOLOFT CAUSES A VAST ARRAY OF BIRTH DEFECTS THAT SPAN A

NUMBER OF BODY SYSTEMS.

BUT MANY OF THE DEFECTS ARE DISTINCT. WE

KNOW THEY ARE DISTINCT BECAUSE BAKER IS AN AUTHOR, A

DOCTOR THAT DR. BERARD HAS RELIED ON. AND WHAT THE

BAKER PAPER SAYS IS THAT HEART DEFECTS AS A GROUP ARE

HETEROGENEOUS. THE DEVELOPMENT OF THE HEART IS A

COMPLEX PROCESS AND A WIDE VARIETY OF HEART DEFECTS CAN

OCCUR. SO JUST SINGLE THIS ONE OUT, BECAUSE WHEN WE ARE

TALKING ABOUT LUMPING EVERYTHING TOGETHER, EVEN WITHIN

CARDIAC DEFECTS, THE EXPERTS WHEN THEY ARE WRITING IN

THEIR PEER REVIEWED LITERATURE TELL US YOU CAN'T LUMP

ALL OF THESE HEART DEFECTS WITH RESPECT TO MAKING CAUSAL


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DETERMINATIONS OF WHETHER SOMETHING IS OR IS NOT A BIRTH

DEFECT.

AND IN THE TERATOLOGY SOCIETY'S PRIMER,

TELLS US THAT TYPICALLY TERATOGENIC EXPOSURES DO NOT

INCREASE RISKS OF ALL BIRTH DEFECTS, EVEN SPECIFIC

GROUPS OF DEFECTS, FOR EXAMPLE, HEART DEFECTS ARE

HETEROGENOUS IN ANATOMY, DEVELOPMENT AND EPIDEMIOLOGIC

FACTORS.

DR. BERARD EXCEEDS THE BOUNDS -- I'M

SORRY. EXCUSE ME. SHE EXCEEDS THE BOUNDS OF THE

STUDIES AND WHAT THE STUDY AUTHORS TELL US. NOW, AGAIN

IN A CASE THAT IS AFFIRMED BY THE 3RD CIRCUIT, THE LAW

WARNS AGAINST USE OF MEDICAL LITERATURE TO DRAW

CONCLUSIONS NOT DRAWN IN THE LITERATURE ITSELF.

RELIANCE UPON MEDICAL LITERATURE FOR CONCLUSIONS NOT

DRAWN THEREIN IS NOT ACCEPTED SCIENTIFIC METHODOLOGY.

YET DR. BERARD REPEATEDLY TRIES TO RELY

ON THE FINDINGS OF SELECTED STUDIES IN MULTIPLE

CONCLUSIONS -- FOR MULTIPLE CONCLUSIONS THAT THE AUTHORS

THEMSELVES DO NOT REACH. THIS IS JUST ONE EXAMPLE. SHE

WAS ASKED THAT DESPITE THE STATEMENT FROM THE LOUIK

INVESTIGATORS THAT THEIR ESTIMATES SHOULD NOT BE

INTERPRETED AS STRONG EVIDENCE OF INCREASED RISK, HERE

YOU ARE ADVANCING THIS ESTIMATE FROM LOUIK AS EVIDENCE

SHOWING THAT ZOLOFT IS CAUSALLY RELATED WITH


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OMPHALOCELE. YES, THAT'S CORRECT. SAME QUESTION WITH

RESPECT TO ANAL ATRESIA.

NOW DR. BERARD ALSO DEPARTS FROM KEY

CAUSATION PRINCIPLES. AND FROM A LEGAL FRAMEWORK,

PERSPECTIVE, AGAIN, GOING BACK TO THE WADE-GREAUX CASE

WHICH WAS AFFIRMED BY THE 3RD CIRCUIT, BECAUSE DR.

BERARD, AND THIS IS A QUOTE, IS OFFERING AN OPINION WITH

RESPECT TO HUMAN BIRTH DEFECTS AND THEIR CAUSES, I.E.

THE FIELD OF TERATOLOGY, HER METHODOLOGY MUST BE

COMPARED WITH THE METHODOLOGY GENERALLY ACCEPTED BY THE

COMMUNITY OF TERATOLOGISTS.

NOW THE GOOD NEWS IS, WE ARE NOT ALONE ON

AN ISLAND WITH RESPECT TO -- FROM A JUDGE'S PERSPECTIVE,

OR -- JUDGE'S PERSPECTIVE OR ATTORNEY'S PERSPECTIVE. WE

HAVE SOME GUIDANCE FROM ORGANIZATIONS LIKE THE

TERATOLOGY SOCIETY ABOUT WHAT THE ACCEPTED CRITERIA FOR

DETERMINING TERATOGENICITY IS. SO WHAT THE SOCIETY DID

WAS THEY REVIEWED ACCEPTED AND COMPLEMENTARY LISTS OF

TERATOLOGY CAUSATION CRITERIA AND THEY DISTILLED ALL OF

THOSE KEY PRINCIPLES THAT UNDERLIE ALL SCIENTIFIC

DETERMINATIONS. AND THEY STATED THAT THE CONCLUSIONS

THAT VIOLATE THESE PRINCIPLES ARE NOT CONSIDERED

SCIENTIFICALLY VALID.

THEY GAVE US EIGHT PRINCIPLES. THEY ARE

ALL IN OUR BRIEF. I'M GOING TO HIGHLIGHT THREE FOR JUST


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A MINUTE. CAUSATION DETERMINATIONS ARE MADE USING ALL

THE SCIENTIFIC EVIDENCE. THAT IS WHAT WE HAVE BEEN

TALKING ABOUT, NO CHERRY-PICKING AND NOT JUST

SUGGESTING, WELL, I CONSIDERED THAT AND NOT TALKING

ABOUT IT. THAT IS NOT WHAT THE CRITERIA HERE IS. YOU

HAVE TO ACTUALLY USE IT. YOU HAVE TO LOOK AT ALL OF THE

DATA, AND TO THE EXTENT THAT THERE ARE THINGS THAT ARE

INCONSISTENT, YOU HAVE TO TALK ABOUT THEM AND TELL US

AND YOUR HONOR WHY.

NUMBER THREE. DETERMINATION OF A CAUSAL

RELATIONSHIP BETWEEN A CHEMICAL AND AN OUTCOME IS

SPECIFIC TO THE CHEMICAL AT ISSUE, RIGHT, THE

SPECIFICITY FACTOR. IF YOU WANT TO KNOW IF ZOLOFT

CAUSES A PROBLEM, YOU LOOK AT ZOLOFT.

FOUR. DETERMINATION OF A CAUSAL

RELATIONSHIP BETWEEN A CHEMICAL AND AN OUTCOME IS

SPECIFIC TO THE OUTCOME AT ISSUE. IF YOU WANT TO KNOW

WHETHER ZOLOFT CAUSES A SPECIFIC BIRTH DEFECT, DO YOU

LUMP? NO. YOU LOOK AT THE DATA SPECIFIC TO THAT

OUTCOME.

THE TERATOLOGY SOCIETY, OF WHICH DR.

BERARD IS A MEMBER, STATES THAT THESE ARE NOT GENERAL

GUIDEPOSTS. THESE ARE CONSIDERED MINIMUM REQUIREMENTS.

HOW DOES DR. BERARD ADDRESS THOSE? I DO NOT AGREE WITH

THIS, BUT THAT IS WHAT IS WRITTEN. THAT IS NOT ACCEPTED


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METHODOLOGY UNDER 702 OR DAUBERT, YOUR HONOR.

NOW, BRADFORD HILL. BRADFORD HILL

FRANKLY IS A RED HERRING IN THIS CONTEXT. THE REASON

WHY IT IS INAPPLICABLE IS BECAUSE ESSENTIALLY YOU DON'T

PASS GO TO NUMBER THREE, TO BOX NUMBER THREE, UNLESS YOU

HAVE A TRUE ASSOCIATION. THERE IS NO TRUE ASSOCIATION

HERE BETWEEN ANY OF THE BIRTH DEFECTS AND ZOLOFT.

THEREFORE THE BRADFORD HILL CRITERIA ARE NOT APPLICABLE.

I'M GOING TO VERY BRIEFLY JUST TURN TO

THE MECHANISM EXPERTS. DR. SADLER. HE BASES HIS

OPINIONS UPON TEST TUBE, WHOLE EMBRYO CULTURE STUDIES

THAT HE CONDUCTED BACK IN THE '90S. BUT THE TEST TUBE

STUDIES DO NOT DEMONSTRATE THAT ZOLOFT CAUSES BIRTH

DEFECTS. IN FACT, DR. SADLER FOUND NO ADVERSE EFFECTS

ON THE EMBRYO EVEN AT DOSES THAT WOULD HAVE BEEN LETHAL

TO THE MOTHER. DR. SADLER AGREES THAT HE HAS NO

EVIDENCE THAT EXPOSURE OF ZOLOFT AT A CONCENTRATION THAT

IS EQUIVALENT TO THE HUMAN THERAPEUTIC DOSE HAS ANY

EFFECT ON THE EMBRYO. THAT IS WHAT HE TESTIFIED TO.

DR. SADLER'S OPINIONS WERE CREATED FOR

LITIGATION. PRIOR TO WORKING AS A LITIGATION EXPERT

HERE, DR. SADLER WAS INVOLVED -- I THINK HE WAS THE ONLY

AUTHOR OF THIS TEXTBOOK. AND PRIOR TO BEING ENGAGED, HE

HAD NEVER OPINED THAT SEROTONIN PLAYS AN IMPORTANT ROLE

IN EMBRYONIC DEVELOPMENT. HE NEVER SUGGESTED THAT


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ZOLOFT OR OTHER SSRIS MIGHT BE IMPLICATED AS CAUSAL

AGENTS FOR BIRTH DEFECTS. THUS WHILE HIS 11TH EDITION,

WHICH WAS PUBLISHED IN 2010, INCLUDES A CHAPTER

REGARDING DRUGS THAT CAN CAUSE BIRTH DEFECTS, THERE IS

NO MENTION OF SSRIS OR ZOLOFT. SO PRESUMABLY WHEN

WRITING THE CHAPTER, DR. BERARD -- I'M SORRY, DR. SADLER

LOOKED AND DID THE RESEARCH. YET HE DID NOT MENTION

ZOLOFT AT ALL. HOWEVER, WHEN HE WAS ASKED ABOUT WHAT

CHANGED BETWEEN HIS 12TH EDITION, WHICH WAS COPYRIGHTED

IN 2012, WHERE THE TEXTBOOK NOW SAYS THAT SSRIS

INCLUDING ZOLOFT CAUSE BIRTH DEFECTS, HE VOLUNTEERED NO,

BUT THIS WAS WRITTEN BEFORE I HAD SIGNED ON WITH COUNSEL

OR DONE ANYTHING. WELL, HE CERTAINLY HAD AN OPPORTUNITY

TO DO IT AND IT'S INSTRUCTIVE THAT HIS OPINIONS CHANGED

ABOUT THE SAME TIME THAT HE WAS RETAINED AS AN EXPERT IN

THIS LITIGATION.

DR. CABRERA. HE IS IN THE PROFESSION OF

TESTING DRUGS FOR POTENTIAL TO CAUSE BIRTH DEFECTS.

HOWEVER, HE HAS NOT PERFORMED ANY STUDIES ON ZOLOFT, HAS

NOT TESTED ZOLOFT AT ALL OR ANY SSRI TO TEST HIS

HYPOTHESIS THAT ZOLOFT IS CAPABLE OF CAUSING BIRTH

DEFECTS. HIS HYPOTHESIS IS ONLY PRESENTED IN THIS

LITIGATION. HE HAS PUBLISHED NOTHING IN THE PEER

REVIEWED LITERATURE, NOT MADE ANY ORAL PRESENTATION TO

SCIENTIFIC AUDIENCES, HE HAS NOT EXPRESSED ANY OPINIONS


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OR THEORIES THAT ZOLOFT OR ANY SSRI CAUSES BIRTH DEFECTS

BY ANY MECHANISM. HE CANNOT IDENTIFY ANY STUDY IN WHICH

ANY ANIMAL EXPOSED TO ZOLOFT WAS REPORTED TO HAVE A

HEART MALFORMATION, DESPITE THE FACT THAT HE

HYPOTHESIZES THAT ZOLOFT CAUSES HEART DEFECT. HIS

FAILURE TO TEST, BEING A PERSON WHO IS IN THE BUSINESS

OF TESTING, AND HIS INABILITY TO IDENTIFY ANY ANIMAL

STUDY, IS COMPELLING UNDER DAUBERT.

DR. LEVIN. DR. LEVIN. HE OPINES THAT

ZOLOFT DISTURBS THE EMBRYONIC SIGNALING PROCESSES AND

THAT SUCH DISTURBANCES CAUSE BIRTH DEFECTS. DR. LEVIN

BASES HIS OPINIONS ON RESEARCH ON FROGS, CHICKS AND

ZEBRA FISH. BUT OF COURSE FROGS, CHICKS AND ZEBRA FISH

ARE NOT MAMMALS. THEY ARE CERTAINLY NOT HUMANS.

DR. LEVIN ACKNOWLEDGES, PERHAPS MOST IMPORTANTLY IN HIS

PUBLISHED, PEER REVIEWED ARTICLES, THAT THERE IS NO

EVIDENCE THAT THE SIGNALING PATHWAYS HE HAS ELUCIDATED

IN LOWER LIFE FORMS, FROGS, WORMS, CHICKS, ZEBRA FISH,

ARE PRESENT IN MAMMALS, MUCH LESS HUMANS. SO LIKE THE

OTHER EXPERTS THERE IS FAR TOO MUCH OF A DISCONNECT AND

A DIVIDE BETWEEN THEIR CONCLUSORY LITIGATION OPINIONS

AND DAUBERT.

NOW IN CONCLUSION, YOUR HONOR, I'M GOING

TO COME BACK REALLY TO WHERE I STARTED. DR. BERARD AND

THE OTHER EXPERTS HAVE OPINED THAT ZOLOFT CAUSES THIS


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WIDE CONSTELLATION OF BIRTH DEFECTS. IF DR. BERARD AND

THESE THREE MECHANISM EXPERTS ARE PERMITTED TO OPINE

THAT ZOLOFT CAN CAUSE ALL OF THESE BIRTH DEFECTS, IT

WILL ALMOST CERTAINLY LIMIT WOMEN'S ACCESS TO SSRIS AND

ZOLOFT. BUT BECAUSE THE DATA AND THE SCIENTIFIC

INFORMATION AND COMMUNITY DO NOT SUPPORT THAT, THAT

WOULD BE A PUBLIC HEALTH TRAGEDY. IF THERE WAS EVER A

CASE, YOUR HONORS, FOR THE COURT TO EXERCISE ITS

GATEKEEPING FUNCTION UNDER DAUBERT, THIS IS THAT CASE.

THANK YOU, YOUR HONOR.

THE COURT: THANK YOU, MR. CHEFFO. WOULD

YOU LIKE A RECESS?

MR. CHEFFO: I WOULD, YOUR HONOR.

THE COURT: YES, WE ALL WOULD.

MS. NAST: YOUR HONOR, OUR OPENING WILL

BE ABOUT THE SAME LENGTH AS THE DEFENDANTS', ABOUT AN

HOUR AND 15 MINUTES. SO I DON'T KNOW IF THAT -- I DON'T

KNOW IF IT'S MONDAY, IF YOU HAVE A LUNCH MEETING.

THE COURT: ACTUALLY, I DO HAVE SOMETHING

BUT NOT THE SAME TIME. SO I WAS GOING TO ASK YOU IF YOU

WANTED TO BREAK NOW FOR AN HOUR AND 15 MINUTES OR AN

HOUR AND-A-HALF SO THAT --

MS. NAST: CONSENSUS ON THIS TABLE IS

YES.

MR. TRACEY: YOUR HONOR, WE WOULD RATHER


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NOT BREAK. WE WOULD LIKE TO TAKE A BRIEF BREAK, GET SET

UP AND MOTOR ON THROUGH.

THE COURT: MOTOR ON THROUGH TILL

2 O'CLOCK TO GET TO LUNCH?

MR. NAST: WE COULD DO THAT.

MR. AYLSTOCK: WHAT WE COULD DO, YOUR

HONOR, IS MR. TRACEY AND I HAVE DIVIDED IT. MR. TRACEY

CAN GO AND THEN LUNCH. I'M HAPPY TO TAKE MINE AFTER

LUNCH.

THE COURT: WELL, WE ARE TAKING TEN

MINUTES NOW. LET ME THINK ABOUT IT AND I WILL CHECK TO

SEE HOW MUCH THEY NEED ME ON THE OTHER END OF THE

COURTHOUSE. WE ARE IN BRIEF RECESS.

(RECESS TAKEN.)

THE CLERK: PLEASE REMAIN SEATED. COURT

IS IN SESSION.

THE COURT: PLEASE BE SEATED. MR.

TRACEY, WE WILL TRY TO COMPLETE YOUR PRESENTATION AND

OPENING BEFORE WE TAKE A SHORTER LUNCH BREAK.

MR. TRACEY: YES. GREAT. THANK YOU,

YOUR HONOR.

MAY IT PLEASE THE COURT. PFIZER SPENT A

LOT OF TIME TALKING ABOUT ANICK BERARD AND THEY HAVE

PORTRAYED ANICK, DR. BERARD, AS BEING SOMEBODY WHO IS

OUT ON AN ISLAND AND WHOSE OPINIONS ARE SUCH RADICAL


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DEPARTURES FROM THE ACCEPTED SCIENTIFIC METHODOLOGY THAT

THIS COURT SHOULD REJECT THEM AND FORBID A JURY FROM

HEARING THEM. AND THE FIRST THING I WANT TO SAY IS NOT

ONLY IS SHE NOT ON AN ISLAND GENERALLY, SHE IS NOT OUT

ON AN ISLAND IN THIS COURTROOM. WE HAVE NOT ONE, NOT

TWO, NOT THREE, BUT FOUR DIFFERENT EXPERTS ALL FULLY

QUALIFIED TO RENDER OPINIONS ON THE ISSUES IN THIS CASE

INDEPENDENTLY OF EACH OTHER.

AND YOU ASKED THE QUESTION, YOUR HONOR,

BEFORE WE GOT STARTED AND THE QUESTION WAS THIS IS, IS

ANYBODY CHALLENGING THE CREDENTIALS OF ANY OF OUR

EXPERTS AND THE QUESTION WAS NO. AND I THINK THAT IS A

VERY GOOD QUESTION AND THERE IS A VERY GOOD REASON WHY

THE CREDENTIALS OF OUR EXPERTS HAVE NOT BEEN CHALLENGED.

THERE IS A DISTRICT COURT HERE IN THE

EASTERN DISTRICT OF PENNSYLVANIA WHO LOOKED AT AN ISSUE

LIKE THIS AND SAID, YOU KNOW WHAT, BEFORE I LOOK AT THE

METHODOLOGY, THE SCIENTIFIC PRINCIPLES THAT HAVE BEEN

EMPLOYED IN THIS CASE, THE FIRST THING I'M GOING TO DO

IS I'M GOING TO LOOK AT THE QUALIFICATIONS, BECAUSE THE

QUALIFICATIONS OF AN EXPERT HELP INFORM ME ON WHETHER OR

NOT THE SCIENTIFIC METHODOLOGY AND PRINCIPLES THAT HAVE

BEEN EMPLOYED ARE VALID.

AND SO I'M GOING TO INVITE THE COURT AND

I'M GOING TO TALK A LITTLE BIT AT LEAST ABOUT THE


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QUALIFICATIONS OF THE EXPERTS AND THEN I'M GOING TO

LAUNCH INTO THE METHODOLOGY. AND THE METHODOLOGY IN

THIS CASE, I WILL POINT OUT, NOT IN THE PAPERS OR THIS

MORNING, HAS NOT BEEN ATTACKED. NOBODY HAS ATTACKED THE

METHODOLOGIES THAT I'M GOING TO TALK ABOUT THAT THREE

OUT OF THE FOUR EXPERTS HAVE USED. AND WHAT THEY HAVE

DONE ULTIMATELY IS CHALLENGE THE CONCLUSIONS OF EACH AND

EVERY EXPERT.

SO WHO ARE THESE GUYS, WHO ARE THESE

EXPERTS? AS YOU HEARD, THERE IS ANICK BERARD, DR.

CABRERA, DR. SADLER AND DR. LEVIN. EACH AND EVERY ONE

OF THESE EXPERTS, YOUR HONOR, HAS DEDICATED -- YOUR

HONORS, HAVE DEDICATED THEIR PROFESSIONAL LIFE TO TRYING

TO FIND THE CAUSE OF AND THE CURE FOR BIRTH DEFECTS.

THAT IS WHAT THEY HAVE BEEN ENGAGED IN, DR. CABRERA

SINCE HE WAS 17 YEARS OLD, DR. BERARD FOR THE PAST

20 YEARS, TOM SADLER FOR 40, AND DR. LEVIN FOR THE PAST

20 YEARS. THAT IS WHAT THEY DO WHEN THEY GET UP IN THE

MORNING.

AND SO I'M A LITTLE TAKEN ABACK, ALTHOUGH

THEY DID IT TWICE, THEY DID IT IN THEIR PAPERS AND THEY

DID IT IN -- ALL DAY TODAY, THIS MORNING, IS THEY HAVE

ACCUSED OUR EXPERTS, EACH AND EVERY ONE OF THEM, OF

COMING INTO COURT WITH LITIGATION OPINIONS, WHATEVER

THAT MEANS.


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THE WAY I ESSENTIALLY TAKE LITIGATION

OPINIONS IS THEY ARE GETTING PAID TO SAY SOMETHING. AND

WHAT I'M GOING TO DEMONSTRATE FOR YOU TODAY IS EACH AND

EVERY ONE OF THESE EXPERTS, DR. BERARD, CABRERA, SADLER

AND LEVIN, HAVE EMPLOYED THE SAME METHODOLOGY IN THIS

CASE THAT THEY DO WHEN THEY GO TO WORK EVERY DAY TRYING

TO FIND THE CAUSE OF AND THE CURE FOR BIRTH DEFECTS.

AND DR. BERARD IS A PERINATAL

EPIDEMIOLOGIST. SO THIS IS VERY IMPORTANT. A PERINATAL

EPIDEMIOLOGIST IS A SCIENTIST CONCERNED SOLELY WITH THE

STUDY OF ADVERSE PREGNANCY OUTCOMES, THEIR CAUSE AND

THEIR CURE. DR. BERARD IS THE ONLY PERINATAL

EPIDEMIOLOGIST IN THIS LITIGATION. AND I WAS A LITTLE

SHOCKED THAT PFIZER WITH ALL THEIR -- ALL THEIR

INFLUENCE, ALL THEIR MONEY, ALL THE, PEOPLE THEY KNOW,

ALL THE EXPERTS THEY ISSUE GRANTS TO EACH AND EVERY

YEAR, ONE OF WHOM IS DR. BERARD, YOU ARE GOING TO HEAR

IN A MINUTE THAT THEY WERE UNABLE TO FIND A PERINATAL

EPIDEMIOLOGIST TO COME IN HERE AND DEFEND THEIR CONDUCT.

AND IN LISTENING TO THEIR ARGUMENT, IF THIS IS SUCH AN

EASY CASE, IF DR. BERARD IS OUT ON SUCH AN ISLAND AND

THESE EXPERTS ARE ENGAGING IN SCIENTIFIC, ESSENTIALLY

SCIENTIFIC MISCONDUCT IN COMING TO THE CONCLUSIONS THEY

HAVE COME TO, WHY COULD THEY NOT FIND AN EXPERT WHO IS A

PERINATAL EPIDEMIOLOGIST TO COME IN AND DEFEND THEIR


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CONDUCT AND EXPLAIN THE LITERATURE TO YOU.

NOW, DIANE NAST, MISS NAST TALKED A

LITTLE BIT ABOUT THIS. SHE SAID THAT DR. BERARD HAS A

POST DOCTORATE IN PHARMACOEPIDEMIOLOGY FROM HARVARD

MEDICAL SCHOOL. SHE IS AN EPIDEMIOLOGIST. SHE RECEIVED

THAT DEGREE FROM MCGILL UNIVERSITY AND SHE WENT TO --

HAS A STATISTICS DEGREE IN CLINICAL SCIENCE, MASTERS.

SHE IS A FULL PROFESSOR AT THE UNIVERSITY OF MONTREAL,

ONE OF THE LEADING TEACHING UNIVERSITIES IN CANADA. SHE

HOLDS THE RESEARCH CHAIR ON MEDICATIONS, PREGNANCY AND

LACTATION. SHE IS THE CHAIR OF THE SPECIAL INTEREST

GROUP FOR MEDICATIONS AND PREGNANCY FOR THE

INTERNATIONAL SOCIETY OF PHARMACOEPIDEMIOLOGY. SHE HAS

OVER 104 ORIGINAL ARTICLES PUBLISHED ON THE ISSUES THAT

WILL BE DECIDED IN THIS CASE. SHE HAS BEEN CALLED UPON

AND GIVEN GRANTS TO DO RESEARCH ON THE ISSUES PRESENTED

IN THIS CASE, SPECIFICALLY, DO ANTIDEPRESSANTS, ALL OF

THEM, ARE THEY CAPABLE OF CAUSING BIRTH DEFECTS AND, IF

SO, WHEN AND HOW. THAT IS SOMETHING SHE HAS ACTIVELY

DONE FOR THE PAST EIGHT YEARS NOW AND SOMETHING THAT THE

CANADIAN GOVERNMENT IS CONTINUING TO ASK FOR HER

ASSISTANCE IN.

SHE HAS RECEIVED, AS I SAID, GRANT MONEY

FROM THE DEFENDANT IN THIS CASE. PFIZER CANADA HAS

GIVEN HER MONEY TO DO RESEARCH AND STUDIES, AND THEY


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WANTED HER OPINION ON ISSUES RELATED TO BIRTH DEFECTS

AND THE CAUSES OF THEM.

GLAXOSMITHKLINE, THE MAKER OF PAXIL, HAS

DONE THE SAME THING. SHE IS ONE OF THE TOP TEN MOST

CITED RESEARCHERS AT THE UNIVERSITY OF MONTREAL FOR TWO

YEARS. THIS IS IMPORTANT BECAUSE THESE EXPERTS, EACH

AND EVERY ONE OF THEM, HAVE PUBLISHED TOGETHER HUNDREDS

OF PEER-REVIEWED PAPERS, WHERE THEY HAVE EMPLOYED THE

SCIENTIFIC METHODOLOGY THAT HAS -- THAT HAS GUIDED THEIR

CAREER, HAD IT REVIEWED, HAD THEIR PAPERS LITERATELY

GRADED, AND THEN THEY HAVE BEEN ACCEPTED FOR

PUBLICATION. THESE FOUR EXPERTS ARE PUBLISHING ARTICLES

ON THE ISSUES IN THIS CASE IN SOME OF THE HIGHEST IMPACT

JOURNALS IN THE WORLD.

AND THE TERATOLOGY SOCIETY HAS BEEN

MENTIONED MANY TIMES THIS MORNING, MANY TIMES BY MR.

CHEFFO AND MISS BIRNBAUM, AND I'M SORT OF GLAD THEY DID

THIS. ONE OF THEIR EXPERTS, DR. HOOD, HE CATEGORIZED

THE TERATOLOGY SOCIETY AS THE LEADING SCIENTIFIC

ORGANIZATION CONCERNED WITH THE CAUSES OF AND PREVENTION

OF BIRTH DEFECTS. THAT IS RONALD HOOD, ONE OF THEIR

EXPERTS.

NOW, I DON'T KNOW IF DR. HOOD KNEW THIS

AT THE TIME, BUT AS IT TURNS OUT, LAST WEEK, ON

APRIL 1ST, THE SOCIETY THAT HE SAYS IS THE MOST


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IMPORTANT ONE IN THE WORLD ON THE ISSUE OF BIRTH DEFECTS

GAVE DR. ANICK BERARD THEIR MOST PRESTIGIOUS AWARD FOR,

FOR HER RESEARCH INTO ANTIDEPRESSANTS AND THE CAUSE OF

BIRTH DEFECTS.

SHE IS GOING TO BE GIVEN THIS AWARD AT

THE MEETING. IT SAYS THIS AWARD RECOGNIZES HER RESEARCH

INVESTIGATING THE POTENTIAL ADVERSE IMPACTS OF

ANTI-DEPRESSANT USE DURING PREGNANCY, REFERENCING HER

PAPER WITH PAXIL AND BIRTH DEFECTS.

NOW, DR. CABRERA IS A TERATOLOGIST. NOW

A TERATOLOGIST OR TERATOLOGY IS THE SCIENCE THAT CAUSES

STUDIES MECHANISMS IN PATTERNS OF ABNORMAL DEVELOPMENT.

HE IS THE GUY THAT WHEN HE GETS UP IN THE MORNING HE

GOES TO A LAB. THE LAB, IT'S CALLED THE FINNELL LAB FOR

BIRTH DEFECT RESEARCH IN AUSTIN, TEXAS. AND WHAT HE

DOES EACH AND EVERY DAY IS HE TRIES TO FIND OUT HOW

BIRTH DEFECTS ARE BEING CAUSED BY COMPOUNDS IN THE

ENVIRONMENT, INCLUDING PHARMACEUTICAL COMPANIES. HE HAS

BEEN -- OR HE HAS A PH.D. FROM THE CENTER FOR

ENVIRONMENTAL AND GENETIC MEDICINE AT TEXAS A&M IN

HOUSTON. HE HAS BEEN EMPLOYED, OH, FOR THE PAST TEN

YEARS OR SO AT DELL PEDIATRIC RESEARCH INSTITUTE AND THE

TEXAS A&M INSTITUTE FOR GENOMIC MEDICINE. HE HAS, I

THINK, NOW ABOUT 20 PEER-REVIEWED PAPERS. HE'S

RELATIVELY YOUNG. BUT EACH AND EVERY ONE OF HIS


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PEER-REVIEWED PAPERS IS ON ONE TOPIC: HOW DO BIRTH

DEFECTS GET CAUSED AND WHAT CAN WE DO TO PREVENT THEM.

HE HAS TRAINED UNDER DR. RICK FINNELL,

WHO I THINK ALL PARTIES IN THE COURTROOM WILL AGREE IS

ONE OF THE MOST FAMOUS TERATOLOGISTS IN THE WORLD. HE

CO-AUTHORED THE REPORT WITH DR. FINNELL. DR. FINNELL

HAS RECEIVED THE PFIZER AWARD FOR RESEARCH EXCELLENCE,

WHICH IS ATTACHED TO HIS RESUME AND IN THE RECORD.

AND SO WHAT DR. CABRERA IS GOING TO

EXPLAIN TO YOU HE DOES, YOUR HONORS, IS HE DEVELOPS WHAT

ARE CALLED ADVERSE OUTCOME PATHWAYS. I'M GOING TO TALK

ABOUT THE METHODOLOGY IN A SECOND. BUT ESSENTIALLY WHAT

HE DOES AND REALLY WHAT ALL THREE OF THE -- WHAT WE ARE

CALLING THE MECHANISM EXPERTS DO, IS THEY LOOK AT THE --

AT THE -- FROM THE VERY BEGINNING TO THE VERY END. WE

LOOK AT THE MOLECULE, WE LOOK AT THE MOLECULE INTRODUCED

INTO THE BODY, WE LOOK AT THE CELLULAR AND THE MOLECULAR

REACTION, AND THEN WE GO TO THE TISSUE, THE ORGAN, AND

THEN THE HUMAN BEING.

DR. CABRERA IS ONE OF THESE EXPERTS WHO

DOES SORT OF STEM-TO-STERN RESEARCH. THE EPA MAY

APPROACH HIM, THE DEPARTMENT OF DEFENSE. DRUG COMPANIES

COME IN AND THEY SAY, WE WANT YOU TO TELL US WHETHER OR

NOT THIS COMPOUND IS A TERATOGEN. HE DOES THE BENCH

RESEARCH IN THE LABORATORY. HE HELPS DESIGN PERINATAL


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EPIDEMIOLOGY STUDIES WITH DOCTORS LIKE DR. BERARD, AND

HE DOES THE WHOLE PANOPLY OF TERATOLOGY FROM BEGINNING

TO END, FROM THE CELL TO THE HUMAN POPULATION.

TOM SADLER, AS YOU'VE HEARD, IS AN

EMBRYOLOGIST. HE HAS WRITTEN A VERY IMPORTANT BOOK ON

EMBRYOLOGY THAT MOST EXPERTS IN THIS CASE WILL HAVE

SOMEWHERE IN THEIR REFERENCE LIST. HE GOT HIS PH.D. AT

THE UNIVERSITY OF VIRGINIA AND HIS POST-DOC FELLOWSHIP

FROM THE NATIONAL INSTITUTES OF HEALTH, ALSO AT

UNIVERSITY OF VIRGINIA SCHOOL OF MEDICINE.

HE, FOR TEN YEARS, WAS THE DIRECTOR OF A

BIRTH DEFECT PREVENTION CENTER IN NORTH CAROLINA, CHAPEL

HILL. HE HAS BEEN THE EDITOR AND ASSOCIATE EDITOR OF

THE JOURNAL TERATOLOGY. HE HAS WRITTEN, ONE, TWO,

THREE, FOUR, FIVE, SIX OR SEVEN PAPERS ON THE VERY

PRECISE ISSUES IN THIS CASE. HE WAS ONE OF THE EARLY

RESEARCHERS WHO WAS LOOKING AT THE CELLULAR BIOLOGY AND

HOW SEROTONIN AFFECTS HUMAN DEVELOPMENT. DR. SADLER

WILL SPEAK ABOUT HIS RESEARCH, WHAT HE KNEW, WHEN HE

KNEW IT, AND WHAT HE COMMUNICATED TO THE WORLD AT LARGE

ABOUT WHAT HE KNEW. AND AS RECENTLY AS 2011, IN A

PEER-REVIEWED PAPER, HE PUBLISHED AN ARTICLE ON SSRIS,

PLURAL, AND HEART DEFECTS, AND HE PUT FORTH HIS THEORY,

HIS BELIEF ABOUT WHY ALL SSRIS ARE CAPABLE OF CAUSING

HEART DEFECTS. AND HE IS WORKING ON THE REST OF HIS


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OPINION. THAT HAS BEEN PEER REVIEWED AND APPROPRIATELY

CITED BY OTHER RESEARCHERS. I FOUND NO CRITICISM OF

THIS JOURNAL BY ANY RESEARCHER IN THE PEER-REVIEWED

PUBLISHED LITERATURE.

FINALLY, HE HAS RECEIVED TWO AWARDS I

THINK THAT ARE IMPORTANT. ONE, PFIZER ACTUALLY AWARDED

HIM A GRANT AND A PROFESSORSHIP IN DIABETES AT YALE IN

1990, AND HE RECEIVED THE GODFREY P. OAKLEY AWARD FROM

THE NATIONAL BIRTH DEFECTS PREVENTION NETWORK. THIS IS

GENERALLY CONSIDERED ONE OF THE MOST, IF NOT THE MOST

PRESTIGIOUS TERATOLOGICAL AWARD, FOR HIS CONTRIBUTIONS

TO THE FIELD OF BIRTH DEFECTS.

DR. LEVIN, AS YOU HEARD, IS A MOLECULAR

DEVELOPMENTAL BIOLOGIST. HIS TRAINING IS MOSTLY AT

HARVARD, BUT HE ALSO WENT TO TUFTS. HE IS AN

INSTRUCTOR -- HAS BEEN AN INSTRUCTOR AT HARVARD IN

DEVELOPMENTAL BIOLOGY. HE HAS ALSO BEEN AN INSTRUCTOR,

IS CURRENTLY, OR WAS UNTIL LAST YEAR, AN ASSOCIATE

PROFESSOR OF DEVELOPMENTAL BIOLOGY AT HARVARD

UNIVERSITY, AND, MOST IMPORTANTLY, DR. LEVIN'S RESEARCH

HAS BEEN SOME OF THE MOST IMPACTFUL RESEARCH IN THE

HISTORY OF MEDICINE ON THE SUBJECT OF BIOLOGY. AND

CELLULAR BIOLOGY NATURE, WHICH IS, I WOULD THINK MOST

WOULD AGREE, ONE OF THE LEADING SCIENTIFIC JOURNALS IN

THE YEAR, TOP TWO OR THREE AT LEAST, CREDIT HIM WITH


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BEING THE FIRST RESEARCHER THAT EXPLAINED THE MOLECULAR

DROP MECHANISMS DRIVING THE LEFT RIGHT ASYMMETRY IN THE

PLACEMENT OF THE HEART AND OTHER ORGANS, AND CALLED THIS

ONE OF THE MILESTONES IN DEVELOPMENTAL BIOLOGY OF THE

LAST CENTURY.

SO THIS IS WHO IS BEFORE THE COURT AND

I'M PLEASED TO SAY THAT -- THE GOD'S HONEST TRUTH THIS

IS THE BEST GROUP OF EXPERTS I HAVE EVER SEEN IN ONE

PLACE ON ONE SUBJECT IN A COURTROOM IN MY ENTIRE CAREER.

THESE FOUR EXPERTS, EACH AND EVERY ONE OF

THEM, ARE UNIQUELY INDEPENDENTLY QUALIFIED TO SPEAK

ABOUT THE ISSUES IN THIS CASE AND WHETHER OR NOT SSRIS

AND ZOLOFT CAUSE BIRTH DEFECTS.

AND SO SINCE THIS IS A HEARING NOT ABOUT

CONCLUSIONS, OR AT LEAST IT'S NOT SUPPOSED TO BE ABOUT

CONCLUSIONS, IT'S SUPPOSED TO BE ABOUT METHODOLOGY. I'M

GOING TO DO JUST THAT, WHICH IS TALK ABOUT THEIR

METHODOLOGY.

AND THE METHODOLOGY THAT OUR EXPERTS HAVE

EMPLOYED, AND THAT REALLY GO UNCHALLENGED IS -- THE

FIRST ONE IS CALLED WILSON'S PRINCIPLES, WILSON'S SIX

PRINCIPLES OF METHODOLOGY WERE WRITTEN ORIGINALLY IN

1959 BY THE VERY FAMOUS TERATOLOGIST NAMED JAMES G.

WILSON. EVERYBODY IN THE COURTROOM, PFIZER INCLUDED,

AGREES THIS IS THE STANDARD METHODOLOGY TO APPLY IN


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TRYING TO FIGURE OUT WHETHER A DRUG IS A TERATOGEN.

NOW, THESE SIX PRINCIPLES ARE, TO THIS

DAY, THE MOST IMPORTANT UNDERPINNINGS OF TRYING TO

FIGURE OUT WHETHER OR NOT A DRUG IS A TERATOGEN. THEY

ARE USED TO DRAW CONCLUSIONS FROM THESE SIX PRINCIPLES.

AND PFIZER PUT UP SOMETHING SIMILAR, BUT NOT QUITE,

WILSON'S PRINCIPLES. WHAT PFIZER PUT BEFORE YOU, AND

WHAT THEY ARE GOING TO ARGUE, WHAT THEY HAVE BEGUN TO

ARGUE, AND WHAT THEY ARE GOING TO CONTINUE TO ARGUE IS

WILSON'S PRINCIPLES ARE TRUE, BUT WE HAVE SORT OF

REFINED THEM FOR THE COURT. AND WHAT I MEAN BY THAT IS

THIS. THERE IS A RESEARCHER OUT THERE, REALLY MORE OF

AN EXPERT WITNESS, NAMED ANTHONY SHIALI. ANTHONY SHIALI

IS THE AUTHOR OF THE TERATOLOGY SOCIETY PAPER THAT

PFIZER PUT UP ON THE SCREEN AND SAID, IT'S THESE EIGHT

OR NINE DIFFERENT CRITERIA THAT ARE MINIMUM CRITERIA.

AND THE REASON I BRING THIS TO YOUR ATTENTION, IS NOBODY

REALLY USES THOSE CRITERIA EXCEPT FOR DEFENDANTS IN

LITIGATION. DR. SHIALI'S PAPER, WHICH HE GOT INTO THE

LITERATURE THROUGH HIS CONNECTIONS WITH THE TERATOLOGY

SOCIETY SAYS IT'S WRITTEN FOR LITIGATION, THAT HE

BELIEVES THERE IS A DIFFERENT STANDARD BETWEEN

LITIGATION OPINIONS AND TERATOLOGICAL OPINIONS, AND WHAT

WE ARE GOING TO SUGGEST IS THAT NOTHING COULD BE FURTHER

FROM THE TRUTH, THAT THERE IS NO DISTINCTION. THERE IS


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SCIENCE OR THERE IS NOT SCIENCE. AND DR. SHIALI, I'M

INTIMATELY FAMILIAR WITH, HE HAS TESTIFIED ON BEHALF OF

THE DEFENDANTS IN EVERY BIRTH DEFECT CASE FOR THE PAST

DECADE IN THIS COUNTRY. HE WORKS FOR EVERY DRUG COMPANY

UNDER THE SUN. HE HAS A COMPANY DEDICATED TO SUPPORTING

DRUG COMPANIES IN LITIGATION.

AND SO I'M GOING TO SUGGEST TO THE COURT

THAT THE PROPER METHODOLOGY TO EMPLOY IS WILSON'S

PRINCIPLES. AND DR. CABRERA IS GOING TO BE OUR FIRST

WITNESS AND HE IS GOING TO EXPLAIN HOW THESE GET

APPLIED.

AND WHAT HE IS GOING TO TELL YOU, AND

DR. LEVIN AND DR. SADLER ALL TRAVEL ESSENTIALLY DOWN THE

SAME ROAD TO GET TO THE SAME PLACE. BUT WHAT THEY DO IS

THEY GET THERE FROM THEIR DIFFERENT AREAS OF EXPERTISE.

THEY WILL TRAVEL DOWN THE SAME ROAD AND COME TO THE SAME

CONCLUSIONS, BUT FROM THE VIEWPOINT OF A TERATOLOGIST OR

A MOLECULAR BIOLOGIST OR AN EMBRYOLOGIST OR AN

EPIDEMIOLOGIST BUT THEY ALL CONVERGE AT THE SAME PLACE.

AND WHAT DR. CABRERA IS GOING TO EXPLAIN

TO YOU IS THAT ADVERSE OUTCOME PATHWAYS ARE THE STATE OF

THE ART. THIS IS HOW THE WORLD DETERMINES HOW BIRTH

DEFECTS OCCUR. THIS IS HOW THE WORLD USES WILSON'S

PRINCIPLES OF TERATOLOGY AND APPLIES THEM IN THE REAL

WORLD. AND DR. CABRERA IS GOING TO EXPLAIN -- WOW, THAT


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IS A LOT SMALLER THAN I THOUGHT.

THE COURT: YES. THERE WAS A TIME WHEN

THAT WORKED. I'M VERY GRATEFUL THAT COUNSEL HAVE

BROUGHT THE BIG SCREEN.

MR. TRACEY: SO WHAT DR. CABRERA IS GOING

TO EXPLAIN IS THE STATE OF THE ART THAT IS APPLIED BY

THE EPA, BY THE WORLD HEALTH ORGANIZATION, BY EVERY

REGULATORY BODY THAT IS CONCERNED WITH TOXIC

INTERACTIONS IS THIS FLOW CHART, THIS FLOW SHEET. THIS

IS ACTUALLY COPIED FROM THE EPA. THIS IS WHAT DR.

CABRERA DOES DAY-TO-DAY, AS DOES DR. LEVIN AND DR.

SADLER.

WHAT HE IS GOING TO TELL YOU IS THAT WHAT

WE DO NOW IS WE LOOK AT THE DRUG OR THE TOXICANT, THEN

WE LOOK AT ITS MOLECULAR INTERACTION, AND THEN WE GO TO

THE CELLULAR INTERACTION, AND THEN WE LOOK AT THE

TISSUE, AND THEN WE GO TO THE ORGAN, FOR EXAMPLE, THE

HEART, AND THEN WE LOOK AT THE EPIDEMIOLOGY. IT'S THIS

STEM-TO-STERN SCIENTIFIC ANALYSIS OF THE EVIDENCE THAT

IS BEFORE US.

ONE THING IS VERY IMPORTANT, AND

DR. LEVIN HAS BEEN INCREDIBLY INFLUENTIAL IN THIS

REGARD. BUT WE KNOW SO MUCH MORE THAN WE DID 10 OR

15 YEARS AGO. THE ABILITY TO PUT TRACER CHEMICALS ON

CELLS AND WATCH WHAT HAPPENS TO THEM AT A MOLECULAR AND


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CELLULAR LEVEL IS SO MUCH BETTER THAN IT WAS TEN YEARS

AGO.

AND WHAT THEY ARE GOING TO TELL YOU IS

EPIDEMIOLOGY IS HELPFUL, AND WE NEED EPIDEMIOLOGY. BUT

WHAT THEY ARE GOING TO EXPLAIN TO YOU IS THIS IS JUST AS

IMPORTANT. BECAUSE IF WE HAVE AN EPIDEMIOLOGY STUDY

THAT WE DON'T UNDERSTAND, IF IT SHOWS A POSITIVE EFFECT,

BUT WE DON'T HAVE BIOLOGIC PLAUSIBILITY OR WE DON'T

UNDERSTAND, OR IT'S NOT SENSIBLE THAT IT CAN DO WHAT --

WHAT EPIDEMIOLOGY SEEMS TO BE SUGGESTING, THEN WE

QUESTION IT. BUT IN THIS CASE, DR. CABRERA IS GOING TO

TAKE YOU THROUGH EACH ONE OF THOSE STEPS. AND HE IS

GOING TO DEMONSTRATE TO YOU, BECAUSE THE SCIENCE IS

THERE, THAT EACH AND EVERY STEP OF THE WAY, FROM THE

CHEMICAL INTRODUCTION OF SSRIS, ZOLOFT INCLUDED, TO THE

MOLECULAR, FROM THE CELLULAR TO THE TISSUE TO THE ORGAN

TO THE PEOPLE, TO THE EPIDEMIOLOGY, EVERY STEP OF THE

WAY, THAT METHODOLOGY, THOSE FACTS THAT HE NEEDS TO

REACH HIS CONCLUSIONS ARE IN THE MEDICAL SCIENCE, SOME

OF IT IS TOM SADLER'S.

AND CLASS EFFECT IS AN ISSUE, AND CLASS

EFFECT, IT SOUNDS LIKE IT'S HOTLY CONTESTED. I'M GOING

TO SUGGEST THAT DR. BERARD AND THE OTHER EXPERTS ARE NOT

ONLY OUT ON AN ISLAND HERE, THEY ARE CONSISTENT WITH

OTHER RESEARCHERS, AND THEY ARE CONSISTENT WITH PFIZER


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THEMSELVES. PFIZER ACTUALLY OUTSIDE OF THE COURTROOM

BELIEVES THERE IS A CLASS EFFECT. PFIZER OUTSIDE OF

THIS COURTROOM HAS ARGUED THAT THERE IS A CLASS EFFECT.

AND THE REASON IS BECAUSE IT'S TRUE.

WHAT I HAVE ON THE SCREEN, AGAIN WAY

SMALLER THAN I EXPECTED, IS ALL OF THE DIFFERENT SSRIS.

AND THESE ARE VERY TINY EXCERPTS FROM THE LABEL. WHAT

EACH AND EVERY ONE OF THEM SAY IS, THE WAY THESE DRUGS

WORK IS THEY ALL INHIBIT THE UPTAKE OF SEROTONIN. AND

SO THE REASON IT'S PROPER, ALL OF OUR EXPERTS ARE GOING

TO SAY TO PUT THEM TOGETHER AS A CLASS, IS REALLY NOT

BECAUSE THEY ARE ANTIDEPRESSANTS, OR EVEN THAT THEY ARE

SSRIS, ALTHOUGH THAT IS HELPFUL. THE REASON WE CLASSIFY

THEM TOGETHER, AS A TERATOLOGIST, IS BECAUSE THEY ALL

HAVE THE SAME MECHANISM. THERE ARE DRUGS IN A CLASS

THAT DON'T HAVE THE SAME MECHANISM. THERE ARE

ANTIDEPRESSANTS THAT ARE NOT SSRIS, BUT THEY ARE IN THE

SAME CLASS. THAT IS NOT THE CASE HERE. EVERY SSRI THAT

WE ARE LOOKING AT DOES THE SAME THING. AND DR. CABRERA

AND SADLER AND DR. LEVIN WILL EXPLAIN HOW THAT IS TRUE.

AND QUITE FRANKLY, I DON'T THINK ANY

LEGITIMATE SCIENTIST ON THEIR SIDE WHO TAKES THE STAND

WILL ARGUE OTHERWISE.

NOW, I CAN'T REMEMBER, I APOLOGIZE, I

THINK IT WAS MISS BIRNBAUM, BUT I WROTE DOWN, AND HAD A


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SLIDE MADE THAT THEY SAID THERE IS NO TERATOGENIC EFFECT

AT ANY DOSE LEVEL. AND WHAT THEY WERE DOING, THEY WERE

INVOKING THE SANCTITY OF THE FDA. THE FDA, THEY SAID,

OR THEY SAY SAYS, THAT THERE IS NO TERATOGENIC EFFECT AT

ANY DOSE LEVEL.

THE PROBLEM WITH THAT IS IT'S NOT TRUE.

NOW, IT IS TRUE THAT THEIR LABEL SAYS THAT, AND THEIR

LABEL AT A DIFFERENT TIME AND PLACE WILL PROVE TO YOU

AND THE JURY HOPEFULLY THAT THEIR LABEL IS FALSE. BUT

IN 1995, WHAT THE FDA REALLY TOLD THEM IN A LETTER TO

MARGARET LONGSHORE, PFIZER'S DIRECTOR OF REGULATORY

AFFAIRS, IS THAT, AS WITH OTHER SEROTONIN REUPTAKE

INHIBITORS, WE FIND IT NECESSARY TO CHANGE THE PREGNANCY

CATEGORY FROM B TO C.

YOU SEE, BELIEVE IT OR NOT, THE FDA GETS

THINGS WRONG SOMETIMES. THE FDA LET EVERY ONE OF THESE

DRUGS GET MARKETED FOR YEARS WRONGFULLY AS A CATEGORY B.

AND AS YOU KNOW, YOUR HONORS, THE LABEL

IS THEIR RESPONSIBILITY, NOT THE FDA'S. AND IN 1995

THEY TOLD PFIZER BECAUSE OF THE FINDINGS OF DECREASED

FERTILITY, DECREASED PUP BIRTH WEIGHTS, INCREASED NUMBER

OF STILLBIRTHS AND INCREASED PUP DEATHS IN RATS, ZOLOFT

MUST BE LABELED PREGNANCY CATEGORY C.

SO THE FDA TREATED THIS DRUG LIKE A

CLASS. THE FDA LOOKED AT INDEPENDENTLY ALL OF THE


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ANIMAL STUDIES INCLUDING PFIZER'S AND CAME TO THE

CONCLUSION THAT THIS DRUG IS A TERATOGEN IN ANIMALS.

NOW, WHY THEY WERE ALLOWED TO HAVE THEIR

LABEL REMAIN THE WAY IT DOES ACTUALLY TO THIS DAY, I

DON'T KNOW. THIS IS NOT A REGULATORY HEARING. I THINK

WE WILL HEAR EVIDENCE ABOUT HOW THAT WAS ALLOWED TO

HAPPEN AT THE TRIAL. BUT THE REALITY IS THE FDA HAS

TREATED THIS DRUG WITH RESPECT TO ANIMAL TERATOGENICITY

AS A CLASS.

ONE OTHER THING, SINCE THEY BROUGHT THIS

TO YOUR ATTENTION, THIS IDEA THAT THE FDA -- SINCE THE

FDA -- FIRST OF ALL, THE FDA -- THERE IS NO EVIDENCE

THAT THE FDA HAS EVER DONE WHAT THEY SUGGEST THEY DID IN

THE COURT, WHICH IS ANALYZE ALL THE STUDIES AND COME TO

A CONCLUSION THAT ZOLOFT DOES NOT CAUSE BIRTH DEFECTS.

NOTHING COULD BE FURTHER FROM THE TRUTH. THEY HAVE NOT

DONE THAT.

BUT THEIR SILENCE, THOUGH, SHOULD NOT BE

TAKEN AS -- IN MY OPINION, IT SHOULD NOT BE TAKEN AS A

STAMP OF APPROVAL ON THE SAFETY OF ZOLOFT. BECAUSE WE

KNOW VERY RECENTLY THE FDA ALLOWED TOPAMAX, A KNOWN

ANTIEPILEPTIC TERATOGEN, TO BE MARKETED FOR 12 YEARS AS

A CATEGORY C DRUG, WHEN EVERY OTHER DRUG IN THE CLASS

WAS A D OR AN X. AND JUST RECENTLY THE FDA CAUGHT THEIR

SNAP AND SAID, YOU KNOW WHAT, IT'S A CATEGORY D. IT'S


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THE REASON WHY THE BURDEN IS ON THE DRUG COMPANY TO

ALTER THE LABEL. WE DON'T RELY ON THE FDA.

WYETH VERSUS LEVINE SAYS, AT ALL TIMES

IT'S THEIR RESPONSIBILITY, NOT THE FDA. THE FDA DOES

NOT HAVE RESEARCH SCIENTISTS LOOKING AT THESE ISSUES.

THE FDA IS UNDERFUNDED. THEY, BY THEIR OWN ADMISSION,

ARE NOT CAPABLE OF CARRYING OUT THE CHARTER THAT

CONGRESS HAS GIVEN TO THEM.

AND SO I JUST I WANT TO BE CLEAR AT LEAST

AS I CAN THAT THE FDA'S SILENCE IS NOT APPROVAL.

AND THEN FINALLY, THIS IS THE DOCUMENT

THAT CAUSES THEM I THINK SOME HEARTBURN, THE MOST

HEARTBURN.

THERE WE GO. SO IT'S NOT JUST ANICK

BERARD, IT'S NOT JUST TOM SADLER, IT'S NOT JUST ROBERT

CABRERA, IT'S NOT MIKE LEVIN. IT'S ACTUALLY PFIZER THAT

AGREES THIS IS A CLASS EFFECT. INTERNALLY, OUTSIDE OF

THE COURTROOM, OUTSIDE OF HEARINGS LIKE THIS, THEIR

DIRECTOR OF EPIDEMIOLOGY WAS ASKED TO LOOK AT

LITERATURE. AND THE REASON SHE WAS ASKED TO LOOK AT

LITERATURE ON SSRIS AND BIRTH DEFECTS, BECAUSE THE NEW

ZEALAND GOVERNMENT SAID, WAIT A SECOND, WE ARE LOOKING

AT THE LITERATURE AND IT LOOKS LIKE SSRIS MAY BE CAUSING

BIRTH DEFECTS. SO INTERNALLY THEY WENT UP THE

APPROPRIATE CHANNELS AND THEY ENDED UP WITH CYNTHIA


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DELUISE, WHO WAS THE EPIDEMIOLOGIST WHO HAD BEEN

ASSIGNED TO SERTRALINE. AND AFTER A BUNCH OF BACK AND

FORTH, HERE IS WHAT SHE TOLD THEM. SHE SAID, MY OPINION

IS THAT THE TOTALITY OF THE LITERATURE HAS IMPLICATED

BOTH THE SSRI AND SNRI CLASSES. IT'S NOT JUST THE

SHALEEN STUDY ALONE; RATHER ON THE ENTIRE BODY OF THE

LITERATURE.

NOW, THAT IS EXACTLY WHAT ANICK BERARD

TESTIFIED TO IN THIS CASE. WE DID NOT HAVE THIS

DOCUMENT BACK THEN, WHEN SHE WAS WRITING A REPORT, AND

IT REALLY WOULDN'T HAVE BEEN -- I DON'T THINK SHE WOULD

HAVE RELIED ON IT. BUT I THINK THE FACT THAT PFIZER,

OUTSIDE OF THE COURTROOM, BELIEVES THIS CLASS EFFECT IS

TRUE IS EXTRAORDINARILY IMPORTANT.

AND PFIZER HAS ACKNOWLEDGED -- WHEN IT

MEETS THEIR OWN REGULATORY AND MARKETING AND BUSINESS

ENDS, THEY HAVE ALSO AGREED, PRIOR TO THIS TIME, THAT

THERE IS A CLASS EFFECT. AND I THINK IT WAS TEN YEARS

AGO. I APOLOGIZE, NOT HAVING THE DATE ON THIS. BUT

THEY WERE TRYING TO GET THE DRUG OF ZOLOFT APPROVED --

THEY WERE TRYING TO EXPAND THE INDICATION TO THE

JUVENILE -- TO JUVENILES. THEY WERE NOT APPROVED FOR --

TO GET IT APPROVED FOR JUVENILES, AND THEY WERE TRYING

TO GET IT APPROVED IN EUROPE. AND THE REGULATORY

AUTHORITIES IN EUROPE CAME BACK AND SAID, YOU NEED TO DO


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JUVENILE TOXICITY STUDIES, YOU NEED TO DO ALL THIS WORK

TO FIND OUT WHETHER OR NOT WE ARE GOING TO HAVE A

PROBLEM WITH ZOLOFT. PFIZER'S RESPONSE WAS, WAIT A

MINUTE. WE DON'T HAVE TO DO ALL THAT. IT'S ALREADY

BEEN DONE. IT'S BEEN DONE BY ELI LILLY.

AND IT SAYS, BECAUSE ALL OF THE FINDINGS ARE

MECHANISM-RELATED, WE EXPECT ZOLOFT TO PRODUCE SIMILAR

FINDINGS. AND THEY'RE RIGHT. THEY'RE RIGHT. EVERY

EXPERT IN THIS CASE IS GOING TO TELL YOU THEY ARE RIGHT.

SO WHEN WE SEE ONE SSRI IN A

MECHANISM-RELATED FORUM ACTING ONE WAY AND WE SEE IT IN

EVERY ANIMAL STUDY ACTING THE SAME WAY, IT IS

APPROPRIATE AND SCIENTIFICALLY VALID AND, QUITE FRANKLY,

SCIENTIFICALLY IT IS THE BEST SCIENTIFIC WAY TO LOOK AT

THE LITERATURE. WE WILL ASSUME THAT A DRUG ACTING BY

THE SAME MECHANISM WILL ACT THE SAME WAY IN TERATOLOGY.

AND THEN I HEARD TODAY, AND I READ IN

THEIR BRIEFS TIME AND TIME AND TIME AGAIN, DR. BERARD,

DR. SADLER, DR. CABRERA, YOU CAN'T DO THIS. YOU CAN'T

ASSUME WITH BIRTH DEFECTS -- THEY SAID IT TODAY -- YOU

CAN'T ASSUME WITH BIRTH DEFECTS THAT ONE MEMBER OF THE

CLASS WILL CAUSE BIRTH DEFECTS IF ANOTHER ONE DOES.

THEY SAID IT TODAY. THEY SAID, NO, NO, NO. THERE IS A

DIFFERENT SET OF RULES FOR TERATOLOGY.

WELL, THIS IS THEIR 2013 LABEL FOR A DRUG


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PFIZER MAKES CALLED XANAX. AND WHAT THEY TELL THE WORLD

ABOUT THIS DRUG IS, BECAUSE OF OUR EXPERIENCE WITH OTHER

MEMBERS OF THE BENZODIAZEPINE CLASS, XANAX IS ASSUMED TO

BE CAPABLE OF CAUSING AN INCREASED RISK OF CONGENITAL

ABNORMALITIES WHEN ADMINISTERED TO PREGNANT WOMEN DURING

THE FIRST TRIMESTER. BECAUSE USE OF THESE DRUGS IS

RARELY A MATTER OF URGENCY, THEIR USE DURING THE FIRST

TRIMESTER SHOULD ALWAYS BE AVOIDED.

SO THIS IDEA THAT DR. BERARD AND CABRERA

AND SADLER AND LEVIN ARE OUT ON THIS CRAZY INTELLECTUAL

ISLAND IS UNTRUE. THEY, THEMSELVES, PARTICIPATE IN THE

EXACT SAME TYPE OF SCIENTIFIC EXERCISE. AND THEY DID IT

IN 2013 WITH XANAX.

AND IN MY CONTINUING EFFORT TO SHOW YOU

WITH SMALL PRINT THAT DR. BERARD IS NOT ALONE, THIS IS A

TABLE OUT OF A TEXTBOOK BY ONE OF THE MOST FAMOUS

GENETICISTS IN OUR COUNTRY AND PROBABLY THE WORLD, IS

NAMED AUBREY MILUNSKY. HE HAS PEER REVIEWED OVER 400

PAPERS ON THE SUBJECT OF BIRTH DEFECTS. HE HAS WRITTEN

I THINK 25 TEXTBOOKS. HE RUNS THE GENETIC CENTER AT

BOSTON UNIVERSITY. PRIOR TO THAT, HE WAS AT HARVARD.

IN HIS BOOK, YOUR GENES, YOUR HEALTH, HE HAS A TABLE

THAT SAYS: MEDICATIONS CONCLUSIVELY SHOWN TO CAUSE

BIRTH DEFECTS.

REMEMBER THE SLIDE WITH EVERYBODY THAT


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DISAGREED WITH DR. BERARD. WELL, DR. MILUNSKY IS

APPARENTLY NOT ONE OF THEM. HE LISTS ANTIDEPRESSANTS

AND HE GIVES US THREE EXAMPLES, LITHIUM, SERTRALINE AND

PAROXETINE UNDER MEDICATIONS CONCLUSIVELY SHOWN TO CAUSE

BIRTH DEFECTS. WHAT BIRTH DEFECTS? HE SAYS HEART AND

OTHER BIRTH DEFECTS.

THERE HAVE ALSO BEEN A NUMBER OF

RESEARCHERS THAT HAVE STUDIED THE VERY ISSUES IN THIS

CASE THAT THESE COURTS ARE GOING TO BE CONFRONTED WITH.

AND THEY HAVE REPEATEDLY SAID, WE BELIEVE THERE IS A

CLASS EFFECT. ANICK BERARD IS NOT THE ONLY ONE. THE

PEDERSON STUDY SAYS THE RESULTS SUGGEST A CLASS EFFECT

ON SSRIS AND HEART DEFECTS. THE NIKFAR STUDY, ALTHOUGH

THE RISK OF SPONTANEOUS ABORTIONS WAS HIGHER WITH THE

USE OF SSRIS DURING PREGNANCY THAN WITH USE OF OTHER

ANTIDEPRESSANT CLASSES, WE DID NOT OBSERVE SIGNIFICANTLY

DIFFERENT RISKS BETWEEN SSRIS. THESE RESULTS WOULD

SUGGEST AN OVERALL CLASS EFFECT ON SSRIS ARE HIGHLY

ROBUST, GIVEN THE LARGE NUMBER OF USERS STUDIED.

NOW, THEY SAID -- ANICK BERARD WAS IN

HERE AND AFTER SHE STARTED GETTING MONEY FROM PFIZER'S

LAWYERS, SHE CHANGED HER OPINION. BUT THE REALITY IS,

THIS IS 2010. THIS IS ANICK BERARD. THIS IS HER PAPER.

SHE STARTED RECOGNIZING IN 2010 THAT IT WAS NOT JUST

PAXIL. THAT IT WAS A -- THAT THERE WAS POTENTIALLY A


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CLASS EFFECT HERE. AND BRIAN IS GOING TO TALK ABOUT DR.

BERARD SPECIFICALLY, SO I PROBABLY SHOULD SHUT UP ABOUT

IT. BUT THERE IS SOME VERY LEGITIMATE ACADEMIC RESEARCH

REASONS WHY SHE STAYED HER HAND AND DID NOT JUMP TO

CONCLUSIONS ABOUT CLASS EFFECT ON CONGENITAL

ABNORMALITIES.

DR. CABRERA, I PROBABLY SHOULD HAVE SAID

THIS, THE REASON WE ARE SO CONCERNED ABOUT SPONTANEOUS

ABORTIONS IS WE KNOW THAT IF A DRUG CAUSES SPONTANEOUS

ABORTIONS, THAT IS ONE OF WILSON'S PRINCIPLES, THAT THE

ULTIMATE BIRTH DEFECT IS DEATH. AND IF WE START SEEING

THAT, WE KNOW IT'S A TERATOGEN. IT'S ONE OF THE FACTORS

THAT WILSON LISTS TO DETERMINE WHETHER A DRUG IS

TERATOGEN. AND THAT IS WHY DR. BERARD'S PAPER IS SO

IMPORTANT WITH RESPECT TO TERATOLOGY.

WE KNOW THAT WITH RESPECT TO PPHN,

PRIMARY PULMONARY HYPERTENSION OF THE NEWBORN, THAT

EVERY LABEL SAYS THAT IT CAUSES IT. KIELER, ANOTHER

RESEARCHER, AGREES WITH THIS. IT SEEMS TO BE A CLASS

EFFECT.

TUCCORI, ANOTHER VERY WELL KNOWN

RESEARCHER. HE ACTUALLY -- HE WENT A LITTLE BIT

FURTHER. HE SAID, YOU KNOW WHAT, I'M GOING TO LOOK AT

THE EPIDEMIOLOGY AND THEN I'M GOING TO LOOK AT THE

ANIMAL STUDIES. I'M GOING DO WHAT CABRERA DOES. AND HE


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SAID, THE OVERALL CURRENT FINDINGS SUGGEST A TREND

TOWARDS A MAJOR TERATOGENIC EFFECT OF PAROXETINE.

HOWEVER, BASED ON THIS INFORMATION, IT CANNOT BE STATED

THAT ANY OF THE OTHER SSRIS SHOULD BE RECOMMENDED DURING

PREGNANCY IN PLACE OF PAROXETINE, SINCE A TERATOGENIC

POTENTIAL HAS BEEN SHOWN FOR EACH DRUG BELONGING TO THIS

CLASS.

WELL, THERE WAS ANOTHER SLIDE THERE

SOMEWHERE THAT SAID WHAT HE DID -- WHAT HE DID -- AND

DR. CABRERA OR DR. BERARD WILL TALK ABOUT THIS. HE SAID

THIS IS CONSISTENT WITH THE ANIMAL STUDIES, THAT THE

ANIMAL FINDINGS ON EACH AND EVERY SSRI IS THAT THEY ARE

TERATOGENS, THEY'RE CAUSING BIRTH DEFECTS, PUPS ARE

DYING. AND HE SAID THAT IS CONSISTENT WITH WHAT WE SEE.

AND THEN FINALLY, IT IS THE CONCLUSION OF

EACH AND EVERY ONE OF THESE EXPERTS THAT WITHIN A

REASONABLE DEGREE OF SCIENTIFIC CERTAINTY, SSRIS, AS A

CLASS, ARE TERATOGENS BOTH IN ANIMALS AND IN HUMANS WHEN

INGESTED DURING PREGNANCY.

AND AS YOU CAN TELL, I DID NOT MENTION

MUCH ABOUT THE LAW. THAT IS BECAUSE BRIAN IS GOING TO

HANDLE THE LAW ON DR. BERARD SPECIFICALLY.

AND I DON'T THINK I FORGOT ANYTHING, DID

I, MARK?

MR. ROBINSON: YOU DID GREAT.


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83

MR. TRACEY: YOUR HONOR, THANK YOU FOR

THE TIME.

THE COURT: THANK YOU, MR. TRACEY.

HOW LONG DO YOU EXPECT TO BE, MR.

ALYSTOCK?

MR. ALYSTOCK: PROBABLY ABOUT 40 MINUTES

OR 45.

THE COURT: THEN WE WILL POSTPONE, AND WE

WILL NOW TAKE ONE HOUR FOR LUNCH. IT'S ABOUT 1 O'CLOCK,

I BELIEVE, 12:48. SO LET'S BE BACK HERE AT 2 O'CLOCK,

PLEASE.

MR. HEIM: YOUR HONOR, MAY I BE EXCUSED

AFTER LUNCH? I HAVE ANOTHER TRIAL THAT I HAVE TO MOVE

ON TO.

THE COURT: YES. THANK YOU. NICE TO SEE

YOU ANYWAY.

MR. HEIM: THANK YOU, YOUR HONOR.

WE ARE IN RECESS.

(LUNCHEON RECESS TAKEN.)


IS IN SESSION.

THE COURT: GOOD AFTERNOON. PLEASE BE

SEATED, EVERYONE.

MR. AYLSTOCK: GOOD AFTERNOON. MAY IT

PLEASE THE COURT, IT'S AN HONOR TO BE BEFORE BOTH OF


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84

YOUR HONORS TODAY TO GIVE A LITTLE PRESENTATION ON

DAUBERT AND IN PARTICULAR MY FOCUS IS GOING TO BE ON DR.

BERARD, BECAUSE, IN CASE YOU DID NOT NOTICE, THE

DEFENDANT HAS CHOSEN TO SPEND A LOT OF BRIEFING TIME AND

ARGUMENT TIME ATTACKING IN PARTICULAR DR. ANICK BERARD.

BUT BEFORE I GO TO HER SPECIFICALLY, I

WANTED TO TALK A LITTLE BIT ABOUT SOME OF THE LEGAL

PRINCIPLES. I KNOW THE COURT IS WELL AWARE OF THEM, BUT

THERE ARE A COUPLE OF THINGS THAT SEEMED A LITTLE BIT

INCONSISTENT IN THE PRESENTATIONS THAT WE HEARD THIS

MORNING.

FIRST OF ALL, I THINK I WROTE DOWN FROM

THE PRESENTATION OF PFIZER THAT WE HAVE TO PROVE GENERAL

ACCEPTANCE OF THE ULTIMATE OPINION OF DR. BERARD AND

THESE OTHER EXPERTS THAT ARE IN THE COURTROOM. WELL,

THAT IS NOT THE LAW. IN FACT, DAUBERT STANDS FOR THE

PROPOSITION THAT YOU DON'T JUST LOOK AT THAT. YOU LOOK

AT A MULTIFACTORIAL TEST. AND THE 3RD CIRCUIT HAS

SPECIFICALLY FOUND THAT EXPERT TESTIMONY DOES NOT HAVE

TO OBTAIN GENERAL ACCEPTANCE OR EVEN BE SUBJECT TO PEER

REVIEW TO BE ADMITTED UNDER 702.

I'M NOT GOING TO READ ALL THESE SLIDES.

YOUR HONORS KNOW THE LAW. BUT IN PARTICULAR, AS THE

PINEDA DECISION, SEMINAL DECISION FROM JUDGE BECKER FROM

THE 3RD CIRCUIT MADE CLEAR, THAT THE FOCUS OF THIS COURT


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85

IN THIS HEARING SHOULD BE ON THE METHODOLOGY THAT THE

EXPERTS USE AND IN PARTICULAR DR. BERARD, BUT ALSO DR.

CABRERA, DR. SADLER, DR. LEVIN. IT'S THE METHODOLOGY

THAT IS IMPORTANT. THE METHODOLOGY, IS THAT A RELIABLE

METHODOLOGY THAT DR. BERARD AND THE OTHER EXPERTS USE.

I THINK I ALSO WROTE DOWN DAUBERT IS A

HIGH STANDARD, IT'S A WEIGHTY STANDARD. WELL, IN FACT,

DAUBERT IS THE EXCEPTION RATHER THAN THE RULE. THIS IS

FROM THE ADVISORY COMMITTEE NOTES. AND I DID HEAR A LOT

OF CROSS EXAMINATION MATERIAL FROM MR. CHEFFO TODAY, AND

I LOOK FORWARD TO HEARING IT IN TRIAL, BUT VIGOROUS

CROSS EXAMINATION AND THE PRESENTATION OF CONTRARY

EVIDENCE, THAT IS FOR TRIAL. THE METHODOLOGY IS WHAT

THE COURT, ACCORDING TO THIRD CIRCUIT PRECEDENT, NEEDS

TO BE FOCUSED ON HERE TODAY.

AGAIN, THE PINEDA CASE, LIBERAL POLICY,

ADMISSIBILITY AND A STRONG PREFERENCE FOR ADMITTING

EVIDENCE THAT MAY ASSIST THE TRIER OF FACT.

WE WENT THROUGH IN GREAT DETAIL AND I'M

SURE WE WILL GO IN EVEN GREATER DETAIL, THE FACT THAT

SOME OF THE STUDIES THAT DR. BERARD RELIES UPON AND

THESE OTHER EXPERTS RELY UPON HAVE FLAWS. THERE IS

NOTHING SURPRISING ABOUT THAT. IN FACT, THIS IS FROM

THE REFERENCE GUIDE ON EPIDEMIOLOGY FROM THE REFERENCE

MANUAL ON SCIENTIFIC EVIDENCE, SECOND EDITION. I THINK


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THERE WAS A QUOTE PUT UP THIS MORNING FROM THE SAME

MANUAL. WELL, MOST STUDIES HAVE FLAWS. IN FACT, FLAWS

ARE INEVITABLE. THEY ARE DONE BY HUMANS. HUMANS ARE

FLAWED.

IN EVALUATING EPIDEMIOLOGIC EVIDENCE, THE

KEY QUESTION THEN IS TO WHAT EXTENT DO A STUDY'S FLAWS

COMPROMISE ITS FINDINGS AND WHETHER THE EFFECT OF THOSE

FLAWS CAN BE ASSESSED AND TAKEN INTO ACCOUNT IN MAKING

REFERENCES. YOU ARE GOING TO HEAR FROM DR. BERARD ON

THE EPIDEMIOLOGICAL STUDIES AND YOU ARE GOING TO SEE

THAT SHE RECOGNIZES THESE FLAWS. IN FACT, HER OWN

STUDIES HAVE LIMITATIONS. THEY LOOKED AT DIFFERENT

THINGS. BUT THE QUESTION IS, ARE THEY CONSIDERED? ARE

THEY TAKEN INTO ACCOUNT? AND ARE THEY PROPERLY

EVALUATED UNDER A RELIABLE METHODOLOGY. NOT WHETHER THE

STUDY ITSELF HAS SOME FLAW OR LIMITATION OR SOME

CONFOUNDER. INDEED, EPIDEMIOLOGIC STUDIES ARE NOT EVEN

REQUIRED FOR US TO PROVE GENERAL CAUSATION IN THIS

COURT.

NOW, WE HAVE A GREAT DEAL OF

EPIDEMIOLOGICAL EVIDENCE TO SUPPORT OUR CASE AND DR.

BERARD HAS EVALUATED THE ENTIRE BODY OF LITERATURE WHEN

IT COMES TO THE ABILITY OR THE PROPENSITY OF SSRIS IN

GENERAL AND SERTRALINE OR ZOLOFT IN PARTICULAR TO CAUSE

BIRTH DEFECTS AND CERTAIN BIRTH DEFECTS.


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87

THIS IS FROM THE NEURONTIN OPINION, YOUR

HONOR. AND NEURONTIN WAS A PFIZER DRUG. I THINK MR.

CHEFFO REPRESENTED PFIZER IN THAT CASE AS WELL. IT'S AN

MDL. THE SAME ARGUMENTS THAT ARE BEING FOISTED UPON

THIS COURT TODAY WERE ASSERTED IN THAT BRIEFING, THE

SAME EXACT ARGUMENTS. WE'VE LOOKED AT THE BRIEFING.

IT'S ALMOST A CUT AND PASTE JOB. AND WHAT WE HAVE IS

THAT COURT PROPERLY FINDING THAT EPIDEMIOLOGIC STUDIES

ARE NOT REQUIRED TO PROVE CAUSATION. WE HAVE IT AND WE

WILL GO THROUGH IT.

STATISTICAL SIGNIFICANCE OF THE

EPIDEMIOLOGY IS NOT REQUIRED. THE MATRIXX CASE, SUPREME

COURT CASE, YOU'VE HEARD ABOUT THAT. BUT IT'S ALL BASED

UPON CRITERIA THIS COURT KNOWS VERY WELL. IT'S FROM SIR

AUSTIN BRADFORD HILL. THIS COURT HAS APPLIED THIS

CRITERIA IN THE AVANDIA DECISION. I'M SURE IT HAS

APPLIED IT IN OTHER CONTEXTS IN DAUBERT. WHAT SIR

AUSTIN BRADFORD HILL SAID IN HIS PAPER, WHICH WE'LL GET

TO IN A LITTLE BIT, IS THAT NO FORMAL SIGNIFICANCE CAN

ANSWER THESE QUESTIONS OF CAUSATION -- NO FORMAL TESTS

OF SIGNIFICANCE. SUCH TESTS CAN AND SHOULD REMIND US OF

THE EFFECTS AND THAT THE PLAY OF CHANCE CAN CREATE, AND

CERTAINLY DR. BERARD WILL TALK ABOUT THAT. AND THEY

WILL INSTRUCT US ON THE LIKELY MAGNITUDE OF THOSE

EFFECTS. BEYOND THAT, THEY CONTRIBUTE NOTHING TO THE


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PROOF OF OUR HYPOTHESIS. THAT IS SIR BRADFORD HILL.

SO THIS IDEA THAT I HEARD THIS MORNING

AND WAS PRESENTED IN THE BRIEFS THAT WITHOUT

STATISTICALLY SIGNIFICANT DATA WE'RE OUT ON OUR EARS IS

SIMPLY NOT THE LAW, AND FRANKLY IT'S NOT GOOD SCIENCE.

IT'S NOT CONSISTENT WITH BRADFORD HILL.

JUDGE BARTLE MADE THIS EXACT FINDING IN

THE DIET DRUG LITIGATION JUST A YEAR AND-A-HALF AGO.

DAUBERT DOES NOT REQUIRE THAT AN EXPERT OPINION

REGARDING CAUSATION BE BASED ON STATISTICAL EVIDENCE IN

ORDER TO BE RELIABLE.

YOUR HONOR FOUND THAT IN AVANDIA. I

WON'T BELABOR THIS POINT. BUT EXPERTS CAN RELY ON

NONSIGNIFICANT DATA TO BOLSTER THEIR INFERENCE, NOT AS

THEIR SOLE SORT OF SUPPORT, AND THAT IS NOT WHAT

HAPPENED HERE. THERE ARE TRENDS. THERE ARE THINGS THAT

EPIDEMIOLOGISTS LOOK AT IN THEIR PRACTICE. THEY LOOK AT

ELEVATED RISK. THEY LOOK AT ODDS RATIOS. THEY LOOK AT

THE ENTIRE BODY OF THE LITERATURE. THAT IS WHAT DR.

BERARD DID AND YOU WILL SEE THAT. YOU WILL HEAR FROM

HER PERSONALLY.

NOW, EVEN BRADFORD HILL ITSELF IN THIS

SSRI CASE, THE CELEXA, LEXAPRO LITIGATION, BRADFORD HILL

ITSELF IS NOT EVEN REQUIRED. IT'S CERTAINLY A GENERALLY

ACCEPTED METHODOLOGY. BUT IT'S NOT REQUIRED CERTAINLY


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89

TO EVEN BE USED. IN FACT THIS COURT HAS RECOGNIZED THAT

EXPERTS WHEN THEY ARE EVALUATING CAUSATION, THEY DON'T

EVEN NECESSARILY GO THROUGH EVERY CRITERIA IN THEIR HEAD

BECAUSE IT'S SO INGRAINED IN WHAT THEY LEARN IN MEDICAL

SCHOOL, IN PH.D., WHEN THEY ARE GETTING THEIR DOCTORATE

DEGREES AT HARVARD. THEY LEARN THESE PRINCIPLES AND

THEY BECOME INGRAINED, SIMILAR TO THE WAY A LAWYER JUST

KIND OF UNDERSTANDS SOME PRINCIPLE OF LAW. DOES NOT

NEED TO CITE CHAPTER AND VERSE. IT'S JUST INGRAINED

WITH THEM. WELL, THERE'S PALSGRAF. WE KIND OF KNOW

WHAT THAT IS WITHOUT NEEDING TO CITE THAT OPINION.

MUCH WAS MADE HERE IN THIS COURTROOM THIS

MORNING ABOUT THE FDA HAS CONCLUDED THAT THESE DRUGS

DON'T CAUSE -- THAT SSRIS IN GENERAL AND ZOLOFT

SPECIFICALLY. DOES NOT CAUSE BIRTH DEFECTS. WELL, MR.

TRACEY POINTED OUT, WELL, THAT IS NOT EVEN TRUE. IN

FACT, PFIZER, UNLIKE GSK, CHOSE NOT TO DO A REGISTRY

LIKE GSK DID. WHEN GSK DID THEIR REGISTRY ON PAXIL,

THEY SAW MUCH EARLIER THAN DR. BERARD SAW AND SOME OF

THE OTHER EXPERTS, BUT THEY WERE ABLE TO SEE THE EFFECT

AND THEY VOLUNTARILY CHOSE TO CHANGE THEIR LABEL FROM A

C TO A D. THAT WAS GSK. PFIZER DID NOT DO THAT, BUT

THAT DOES NOT MEAN THE FDA MADE SOME DETERMINATION AFTER

REVIEWING EVERYTHING THAT IN FACT IT DOES NOT CAUSE --

ZOLOFT DOES NOT CAUSE BIRTH DEFECTS. BUT EVEN IF THEY


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90

DID, THAT IS IRRELEVANT TO THIS PROCEEDING BECAUSE THE

FOCUS IS THE METHODOLOGY, NOT THE CONCLUSION, DOES ONE

EXPERT DISAGREE WITH ANOTHER EXPERT.

AGAIN, THIS IS AN SSRI DECISION, CELEXA,

AND LEXAPRO. THAT PARTICULAR COURT FOUND, I CANNOT AND

WILL NOT EXCLUDE ONE EXPERT'S OPINION SIMPLY BECAUSE IT

DISAGREES WITH ANOTHER. AND EVEN IF THE OTHER EXPERT IS

THE FDA. IF THAT WERE THE LAW, THEN THE SUPREME COURT

IN THE WYETH CASE WOULD HAVE COME OUT DIFFERENTLY AND WE

WILL NOT BE HERE IN ANY PHARMACEUTICAL LITIGATION. BUT

THEY DID NOT SAY THAT. THAT IS NOT WHAT HAPPENED AND

THAT IS NOT WHAT THE LAW IS.

NO REQUIREMENT THAT AN EXPERT REACH THE

SAME CONCLUSION USING DATA OF OTHERS. WE SAW A LOT

ABOUT THAT THIS MORNING. WELL, AN EXPERT IS PROHIBITED

UNDER THIRD CIRCUIT LAW, THEY SAY, FROM LOOKING AT THE

DATA, MAKING AN INDEPENDENT JUDGMENT ABOUT THE DATA.

RATHER THE EXPERT SIMPLY HAS TO TAKE WHATEVER THAT

EXPERT HAS WRITTEN ABOUT HIS OR HER OWN DATA AS GOSPEL,

THE GOSPEL TRUTH. THERE CAN BE NO SCIENTIFIC DEBATE

ABOUT THE DATA IF AN AUTHOR HAS SAID SOMETHING ABOUT IT.

WELL, THAT IS NOT THE LAW EITHER.

AGAIN, AN SSRI CASE, CITING JOINER:

TRAINED EXPERTS COMMONLY EXTRAPOLATE FROM EXISTING DATA.

AND THEY CAN AND THEY DO MAKE DIFFERENT CONCLUSIONS FROM


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THE DATA. THERE'S NOTHING UNUSUAL ABOUT THAT. THERE'S

NO REQUIREMENT THAT DR. HEALY REACH THE SAME CONCLUSION

AS THE DEFENSE EXPERT, DR. KAHN, JUST BECAUSE HE RELIED

ON DR. KAHN'S DATA. THAT IS NOT THE LAW. THAT IS NOT

THE WAY SCIENCE OPERATES. IF IT DID, THERE WOULD BE NO

REASON FOR ANY EXPERT TO EVER LOOK AT THE DATA AGAIN.

AGAIN, THE HORMONE REPLACEMENT MDL.

JUDGE WILSON FOUND THE DEFENDANTS REFER TO MANY STUDIES

THAT HAVE A DIFFERENT CONCLUSION, JUST AS WE HEARD THIS

MORNING. THAT GOES TO THE WEIGHT OF THE EVIDENCE. THAT

IS CROSS EXAMINATION. THAT IS CREDIBILITY. THAT IS NOT

DAUBERT.

CHANTIX, AGAIN ANOTHER PFIZER. PFIZER

HAS GIVEN US THE OPPORTUNITY TO HAVE A LOT OF LAW BEEN

CREATED ON THESE SAME ISSUES BECAUSE THESE SAME

ARGUMENTS HAVE BEEN ADVANCED AND REJECTED BY OTHER

COURTS. WHY DID DR. KRAMER CHOOSE TO EXCLUDE OR INCLUDE

DATA FROM SPECIFIC CLINICAL TRIALS? IS THAT A

METHODOLOGICAL FLAW THAT MEANS HE CAN'T TESTIFY? NO.

THAT IS A MATTER FOR CROSS EXAMINATION, NOT EXCLUSION.

HERE -- THEY ALSO -- PFIZER AGAIN,

CHALLENGING DR. OLMSTEN. WELL, HE COMBINED DATA FROM

CONTROLLED AND UNCONTROLLED STUDIES AND THIS TAINTED THE

DATA AND THEREFORE HE CAN'T GIVE AN OPINION. WELL, NO.

THE COURT FOUND, EVEN THOUGH NO OTHER RESEARCHER


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COMBINED THE DATA IN THE MANNER DR. OLMSTEN DID, THAT

DOES NOT MAKE HIS DATA NECESSARILY FLAWED. THEY ARE

MATTERS OF CREDIBILITY, NOT RELIABILITY, AND THEY ARE

STRICTLY WITHIN THE PROVINCE OF THE JURY. JUDGE INGA

JOHNSON, NORTHERN DISTRICT OF ALABAMA IN THE PFIZER

CASE, ADDRESSING THESE SAME TYPES OF ARGUMENTS.

NOW I APOLOGIZE FOR THE WORDINESS OF THIS

SLIDE. I MADE IT BECAUSE OF SOMETHING THAT HAPPENED

THIS MORNING. IT RELATED TO THIS CONCEPT -- YOU SAW A

SLIDE, YOUR HONORS, RELATED TO THE PRINCIPLES OF

TERATOLOGY. AND ON THE RIGHT ARE WILSON'S PRINCIPLES

THAT HAVE BEEN USED BY DR. SADLER --

MR. TRACEY: LEFT. THAT IS A PATTERNING

DEFECT.

MR. ALYSTOCK: IT MAY BE.

WILSON PUT OUT HIS PRINCIPLES IN 1977,

GENERALLY ACCEPTED. THERE IS NO -- THEIR OWN EXPERTS

RELY ON THESE PRINCIPLES. DR. CABRERA DOES, DR. LEVIN

DOES, DR. SADLER DOES, IN A WAY DR. BERARD DOES, BECAUSE

IT'S REALLY SAYING THE SAME THING THAT THE BRADFORD HILL

CRITERIA DO. IT'S A METHODOLOGY, A WAY TO GO ABOUT

EVALUATING EVIDENCE OF TERATOLOGY. WELL, ON THE RIGHT,

IT WAS VERY INTERESTING IN MR. CHEFFO'S SLIDE HE DID NOT

GIVE YOU THE TITLE OF WHAT HE WAS REFERRING TO. THIS IS

DR. SHIALI, HIS CREATION. HE WAS CHAIR OF THE COMMITTEE


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AT THE TIME THIS WAS CREATED, THE GSK EXPERT IN PAXIL

BIRTH DEFECT RELATED LITIGATION. HE CAME UP WITH

PRINCIPLES IN CAUSATION DETERMINATIONS IN

TERATOLOGY-RELATED LITIGATION. WELL, THAT'S THE

OPPOSITE OF DAUBERT.

DAUBERT SAYS LET'S TAKE SCIENCE FOR WHAT

IT IS. LET'S APPLY SCIENCE LIKE SCIENTISTS APPLY IT

EVERY DAY. IT MATTERS WHAT THEY TEACH THEIR STUDENTS.

AND THE LAW SAYS IF AN EXPERT DEVELOPS SOME SORT OF

STANDARD FOR LITIGATION THAT IS DIFFERENT FROM HOW THEY

OPERATE IN THEIR DAY-TO-DAY LIVES AS SCIENTISTS AND

MEDICAL DOCTORS AND EPIDEMIOLOGISTS, THAT IS BAD

SCIENCE. THAT IS THE OPPOSITE OF DAUBERT. THAT IS

LITIGATION-DRIVEN EXPERTISE. THAT IS A NEGATIVE FACTOR

IN ADMISSIBILITY.

SO THE ONE ON THE RIGHT WHEN YOU ARE -- I

GOT IT RIGHT THIS TIME -- THE ONE ON THE RIGHT WHEN YOU

ARE LOOKING AT THIS, THIS IS THE ONE THAT MR. CHEFFO

SHOWS, WELL, IT HAS SOME ADDITIONAL THINGS AND DR.

BERARD RIGHTLY SAID, WELL, I DON'T NECESSARILY ASCRIBE

TO THEM ALL. I KNOW WILSON'S PRINCIPLES. I CERTAINLY

APPLY THE BRADFORD HILL CRITERIA, BUT I'M NOT GOING TO

CHANGE MY OPINION WHETHER THIS IS LITIGATION OR NOT.

THAT IS NOT GOOD SCIENCE, AND IT'S NOT THE LAW.

SO DR. SHIALI HAS SOME PRINCIPLES FOR


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CAUSATION LITIGATION, BUT THEY ARE NOT GENERALLY

ACCEPTED.

COURT IS FAMILIAR WITH BRADFORD HILL.

HEARD THIS -- HEARD IT IN OTHER SIMILAR HEARINGS:

STRENGTH OF ASSOCIATION, TEMPORALITY, CONSISTENCY,

COHERENCE. NO ONE FACTOR IS NECESSARY, BUT SCIENTISTS

APPLY THESE FACTORS IN A FLEXIBLE WAY, SIMILAR TO THE

WAY DAUBERT FACTORS ARE APPLIED, IN FACT, TO COME UP

WITH CAUSATION OPINIONS. THAT IS WHAT DR. BERARD DID IN

THIS VERY CASE.

THE DEFENDANTS DID ME A FAVOR BECAUSE I

HAD NEVER ACTUALLY READ THE BRADFORD HILL PAPER. THEY

ATTACHED IT TO THEIR REPLY BRIEF, I THINK IT'S

EXHIBIT 60. I HAVE SEEN THESE FACTORS. I WENT AND I

SAID, WELL, THAT IS INTERESTING, LET ME READ IT. WELL,

LET'S LOOK AT THIS. HERE IS THIS PAPER. THIS IDEA THAT

ALL OF A SUDDEN YOU DON'T PROVE YOUR ASSOCIATION BY SOME

MASSIVELY HIGH STANDARD, YOU CAN'T EVEN GET TO THE

BRADFORD HILL CRITERIA? YOU REMEMBER THE DIAGRAM WHERE

YOU HAVE AN ASSOCIATION. IF YOU CAN'T ADJUST AND FIGURE

OUT EVERYTHING AND PROVE YOUR CASE, YOU HAVE TO STOP AND

YOU CAN'T APPLY THE BRADFORD HILL CRITERIA AT ALL? THAT

IS NOT WHAT SIR ARTHUR BRADFORD HILL SAID. HE SAID IN

HIS VERY FAMOUS PAPER: WE MUST NOT BE TOO READY TO

DISMISS A CAUSE AND EFFECT HYPOTHESIS MERELY ON THE


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GROUNDS THAT THE OBSERVED ASSOCIATION APPEARS TO BE

SLIGHT. WE -- JUST AS IN DAUBERT WHERE WE DON'T HAVE TO

PROVE OUR CASE TO YOU AND THEN PROVE OUR CASE TO THE

JURY, YOU DON'T HAVE TO PROVE CAUSATION BEFORE YOU

EVALUATE CAUSATION. THAT IS IN EFFECT WHAT IS BEING

ASKED THIS COURT TO APPLY THAT STANDARD.

INDEED, AN ASSOCIATION CAN EVEN BE ODD.

IT CANNOT MAKE A WHOLE LOT OF SENSE. IT MIGHT BE NEW TO

SCIENCE AND MEDICINE UNDER BRADFORD HILL, BUT IT SHOULD

NOT BE JUST DISMISSED. IF WE LOOK AND WE SEE, WELL,

THERE MAY BE SOMETHING GOING ON HERE, LET'S APPLY THE

BRADFORD HILL CRITERIA. WE DON'T HAVE SOME HIGH BURDEN

OF PROVING A QUOTE, UNQUOTE, TRUE ASSOCIATION. THAT IS

NOT IN BRADFORD HILL, IT'S NOT IN THE LAW, AND IT'S NOT

IN SCIENCE. AND IT'S NOT GOOD SCIENCE.

INDEED, STATISTICIANS AND CERTAINLY

EPIDEMIOLOGISTS, THEY DO FOCUS ON STATISTICAL

SIGNIFICANCE, BUT THAT IS NOT WHAT BRADFORD HILL SAYS.

I WONDER IF THE PENDULUM HAS NOT SWUNG TOO FAR. NOT

ONLY WITH ATTENTIVE PUPILS, BUT WITH EVEN THE

STATISTICIANS THEMSELVES, TO DECLINE TO DRAW CONCLUSIONS

WITHOUT STANDARD ERRORS CAN SURELY BE JUST AS SILLY.

SO WE ARE GOING TO HAVE FLAWED STUDIES.

WE'RE GOING TO HAVE METHODOLOGICAL ISSUES. WE ARE GOING

HAVE TO LOOK AT BIAS AND CONFOUNDERS. WE ARE GOING TO


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96

HAVE TO LOOK AT EVERYTHING WHEN WE ARE A SCIENTIST.

WE'RE GOING TO HAVE TO APPLY THE CRITERIA. SO THAT IS

THE METHODOLOGY THAT WAS USED IN THIS CASE.

THE QUESTION FOR THE COURT AND AFTER

HEARING PFIZER'S OPENING, YOU KNOW, WHO IS ANICK BERARD?

WHO IS THIS FRENCH-SPEAKING CANADIAN, WHO I HAVE COME TO

SPEND MANY, MANY HOURS WITH. WHO IS SHE? WHO IS THIS

EXPERT THAT PFIZER SAYS ABANDONED HER SCIENTIFIC

PRINCIPLES, WHO COMES IN THIS COURT -- EVEN THOUGH THIS

IS HER REPUTATION, THIS IS WHAT SHE DOES, THIS IS WHAT

SHE DOES FOR A LIVING DAY IN AND DAY OUT, THIS IS HOW

SHE TEACHES HER STUDENTS -- WHO IS THIS PERSON WHO CAME

TO TAKE THE MONEY FROM ME AND THE OTHER PLAINTIFFS'

LAWYERS TO CHANGE HER OPINION ONLY FOR THIS COURT? WHO

IS THIS PERSON WHO CHERRY-PICKED THE DATA, WHICH IS NOT

TRUE BY THE WAY? IN FACT, REPEATEDLY IN HER DEPOSITION

SHE WILL TELL YOU AGAIN TODAY OR TOMORROW, WHENEVER SHE

TESTIFIES, SHE LOOKED AT EVERYTHING. THIS IS -- SHE

COULD NOT HELP BUT LOOK AT EVERYTHING BECAUSE SHE DOES

THIS. THIS WHAT IS SHE DOES. WHO IS THIS PERSON WHO

HAD THE COURAGE TO COME INTO THIS COURTROOM AND LISTEN

TO THE ATTACKS ON HER ALL MORNING LONG TO SAY THAT SHE

HAS ABANDONED HER SCIENTIFIC PRINCIPLES?

SHE IS A WOMAN OF COURAGE BECAUSE SHE

BELIEVES IT. IT'S IN HER CORE. YOU ARE GOING TO SEE


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THAT WHEN YOU SEE HER TESTIFY. THIS IS WHAT SHE DOES,

AND THIS IS WHAT SHE BELIEVES. SHE IS ALSO THE OTHER

PRENATAL EPIDEMIOLOGIST FOR EITHER SIDE. SHE'S THE ONLY

PH.D. FOR EITHER SIDE IN EPIDEMIOLOGY, AND SHE IS ONE OF

THE MOST QUALIFIED EXPERTS IN ALL THE WORLD ON THIS.

YOU ARE GOING TO GET TO HEAR FROM HER.

SO AFTER APPLYING THESE BRADFORD HILL

CRITERIA, WHAT IS HER OPINION? FIRST OF ALL, WHAT IS

HER OPINION, AND I WILL GET TO HOW SHE ARRIVED ON IT.

HER OPINION IS THAT THERE IS EXTENSIVE PEER-REVIEWED

SCIENTIFIC EVIDENCE DEMONSTRATING A STRONG AND

REPLICATED CAUSAL ASSOCIATION BETWEEN EXPOSURE TO SSRIS

IN GENERAL AND ZOLOFT SPECIFICALLY, AND CONGENITAL

MALFORMATIONS OF MULTIPLE ORGAN SYSTEMS, AND PPHN. SHE

DOES NOT APOLOGIZE FOR THE FACT THAT SHE FOUND MORE THAN

ONE INJURY, MORE THAN ONE BIRTH DEFECT, BECAUSE THAT IS

WHAT THE DATA SHOWS.

BRADFORD HILL CRITERIA IN SUPPORT OF THIS

CAUSAL ASSOCIATION INCLUDES THE STRENGTH OF ASSOCIATION,

CONSISTENTLY ELEVATED ODDS RATIOS. WE WILL LOOK AT THAT

IN A MINUTE, AND YOU WILL SEE IT WHEN SHE TESTIFIES.

TEMPORALITY. THE EXPOSURE PRECEDES THE

CONGENITAL MALFORMATION AND IT'S IN THE CORRECT TIME

FRAME FOR WHEN THE ORGANS ARE BEING FORMED.

CONSISTENCY. EXPOSURE TO ZOLOFT AND


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SSRIS INCREASE THE RISK OF CONGENITAL MALFORMATION IN

MANY STUDIES DESPITE VARYING DESIGNS AND POPULATIONS.

ALL THESE STUDIES ARE DESIGNED DIFFERENTLY, THEY HAVE

DIFFERENT COHORTS, THEY ARE FROM DIFFERENT DATABASES,

BUT THERE IS A CONSISTENCY OF RESULTS. AND WE WILL LOOK

AT THAT IN A MINUTE.

COHERENCE. THE CAUSAL ASSOCIATION IS

CONSISTENT WITH KNOWN TERATOGENS AND HOW THEY IMPACT

FETAL DEVELOPMENT. YOU ARE GOING TO HEAR A LOT ABOUT

THAT FROM DR. SADLER, DR. CABRERA, DR. LEVIN. THIS IS

CONSISTENT WITH HOW KNOWN TERATOGENS OPERATE AND HOW

THEY IMPACT FETAL DEVELOPMENT. IN PARTICULAR, THIS

MECHANISM OF ACTION, OF HOW IT AFFECTS THE SEROTONIN.

AND CERTAINLY THERE IS BIOLOGIC PLAUSIBILITY. THERE ARE

PUBLISHED MECHANISMS WHERE ALTERATION IN SEROTONIN CAN

ADVERSELY AFFECT FETAL DEVELOPMENT. IN FACT WE KNOW

THAT THAT HAPPENS. IT'S NOT EVEN A THEORY. WE KNOW

THAT IT HAPPENS.

SO, DID ANICK BERARD -- DID DR. BERARD

LOOK AT SSRIS AS A CLASS? WELL, SHE DID. WAS THAT

SOMEHOW AN OPINION THAT IS OFF ON AN ISLAND? IS THAT

JUST CRAZY TALK? WELL, NO. THAT IS -- IN FACT, STUDY

AFTER STUDY AFTER STUDY ANALYZES THE SSRIS AS A GROUP.

THEY ANALYZE THEM AS A CLASS. THERE IS A REASON FOR

THAT. THEY ALL AFFECT SEROTONIN THE SAME WAY. IT'S THE


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SEROTONIN SIGNALING WHICH IS WHAT YOU WILL HEAR FROM THE

MECHANISM EXPERTS THAT LEAD TO THE BIRTH DEFECTS AND THE

VARIETY OF THE BIRTH DEFECTS, AND THEY ALL AFFECT IT IN

THE SAME WAY. AND THE PUBLISHED LITERATURE LOOKS AT

THIS.

NEW ENGLAND JOURNAL OF MEDICINE, ALWAN,

USE OF ANY SSRI IN MAJOR BIRTH DEFECTS. IS THAT SOMEHOW

BAD SCIENCE IN THE NEW ENGLAND JOURNAL OF MEDICINE?

WELL, AGAIN, TABLES WHERE THEY LOOK AT

SSRIS IN GENERAL, DO THEY BREAK THEM OUT BY SSRI TO MAKE

SOME OTHER COMPARISONS? OF COURSE THEY DO. BUT THEY

LOOK AT THEM ALL TOGETHER. INDEED, THE FDA HAS TREATED

ALL SSRIS TOGETHER IN THE SAME PHARMACOLOGIC CLASS.

HERE IS THE GUIDANCE FOR INDUSTRY FROM

THE FDA. AND FOR PURPOSES OF THIS GUIDANCE, THE

PHARMACOLOGIC CLASS IS A GROUP OF DRUGS THAT SHARE

SCIENTIFICALLY DOCUMENTED PROPERTIES. SPECIFICALLY FOR

PURPOSES OF THIS GUIDANCE, PHARMACOLOGIC CLASS IS

DEFINED AS ANY ONE OF THE FOLLOWING ATTRIBUTES OF THE

DRUG: MECHANISM OF ACTION, SAME; PHYSIOLOGIC EFFECT,

SAME. WE HAVE TWO. THIS IS NOT JUNK SCIENCE. THIS IS

HOW SCIENTISTS AND IN PARTICULAR PERINATAL

EPIDEMIOLOGISTS AROUND THE WORLD IN PUBLISHED PEER

REVIEW LITERATURE LOOK AT THE GROUP OF SSRIS.

NOW, I HAVE BEEN ACCUSED BY MR. CHEFFO OF


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100

BEING A LUMPER. SO THIS IS LUMPY RUTHERFORD FROM LEAVE

IT TO BEAVER. I HAVE NEVER BEEN ACCUSED OF BEING A

LUMPER BEFORE, BUT I TAKE IT AS A COMPLIMENT BECAUSE

THAT IS IN FACT GOOD SCIENCE. THERE IS NOTHING ODD OR

LUMPY ABOUT LUMPING BY ORGANOGENESIS. WHY IS THAT?

WELL, YOU ARE GOING TO HEAR ABOUT THAT FROM OUR

EMBRYOLOGIST, DR. SADLER. THE WAY ORGANS FORM, EARLY IN

UTERO THESE CELLS DIVIDE AND WHEN THEY DIVIDE IF THERE

ARE SIGNALING PROBLEMS, IT'S NOT JUST A SPECIFIC DEFECT,

IT'S A SPECTRUM OF DEFECTS. WHY IS THAT? BECAUSE

MULTIPLE ORGAN SYSTEMS ARE FORMING AT THE SAME TIME IN

THE DEVELOPMENT OF THE FETUS. THAT IS MITCHELL FROM THE

FDA.

AGAIN, THE FDA: IT HAS BEEN -- HERE,

INTERFERENCE WITH NEURAL CREST CELLS LEAD TO A SPECTRUM

OF BIRTH DEFECTS, HEART, NEURAL TUBE, PARTS OF THE FACE

AND EARS. WHEN THOSE NEURAL CREST CELLS ARE AFFECTED

ADVERSELY, IT'S GOING TO LEAD TO A CLUSTERING OF

DEFECTS. IT'S GOING TO LEAD TO LUMPING OR GROUPING BY

ORGANOGENESIS. DOES IT NEED TO BE IN THE RIGHT TIME

FRAME IN FETAL DEVELOPMENT? OF COURSE. BUT IT IS GOOD

SCIENCE, NOT BAD SCIENCE.

AGAIN, JELLINEK. GROUPING DEFECTS THAT

SHARE EMBRYOLOGY AND PATHOGENESIS INCREASES THE

LIKELIHOOD THAT A TERATOGENIC EFFECT WILL BE APPARENT.


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SO GROUPING HELPS PERINATAL

EPIDEMIOLOGISTS LOOK FOR CAUSE AND EFFECT. THERE IS

NOTHING UNUSUAL ABOUT THAT. IT IS GOOD SCIENCE, AND

IT'S A STANDARD RELIABLE METHODOLOGY.

AGAIN, THE SHAW PAPER. GROUPING SPECIFIC

MALFORMATIONS MAY HAVE BIOLOGIC VALIDITY. IF SEVERAL

MALFORMATIONS SUSPECTED TO HAVE A SIMILAR ETIOLOGY OR

EMBRYOLOGY ARE CONSIDERED AS A SINGLE GROUP, OR IF

EXPOSURE OCCURS WHEN A NUMBER OF ORGAN SYSTEMS ARE

DEVELOPING. DOES THE TIME OF EXPOSURE MATTER? OF

COURSE IT DOES AND YOU ARE GOING TO HEAR THAT. BUT IT'S

NOT BAD SCIENCE TO GROUP BY ORGANOGENESIS. IT'S GOOD

SCIENCE.

SO WHAT IS IT THAT DR. BERARD DID IN THIS

CASE? HOW DID SHE APPLY THE BRADFORD HILL CRITERIA?

WHAT DID SHE DO? WELL, YOU SAW SHE LOOKED AT

EVERYTHING. SHE USED -- SHE LOOKED AT EVERY STUDY. IN

FACT SHE CONDUCTED SOME OF THE STUDIES HERSELF. AND A

LOT OF THEM DID NOT REALLY -- THEY WERE NOT MEANT TO

ANSWER THE QUESTION BEING ASKED IN THIS COURT TODAY.

FOR EXAMPLE, HER EARLY STUDY, 2007, IT

HAD -- THERE WAS NOT AN INACTIVE COMPARATOR IN THAT

STUDY. IT WAS COMPARING PAXIL TO OTHER SSRIS AND OTHER

TRICYCLIC ANTIDEPRESSANTS. THERE WAS NOT AN INACTIVE

COMPARATOR. SHE WILL TALK ABOUT WHY. WELL, THAT STUDY


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REALLY WAS NOT IMPORTANT. IT WAS NOT ROBUST. IT DID

NOT HELP ME ANSWER THE QUESTION THAT I NEED TO ANSWER

HERE TODAY: DO SSRIS AS A CLASS AND SEROTONIN IN

PARTICULAR CAUSE BIRTH DEFECTS AND IF SO WHICH ONES?

SHE LOOKED AT THE MEDICAL LITERATURE.

ALWAN, WELL, YOU SAW SOME SLIDES. ALWAN

WAS IN NEW ENGLAND JOURNAL OF MEDICINE. MR. CHEFFO WENT

THROUGH AND SAID, WELL, LOOK, BECAUSE THERE ARE SO MANY

DIFFERENT THINGS BEING LOOKED AT, THE CHANCE -- THE RISK

OF CHANCE HAS NOT BEEN RULED OUT WITH SCIENTIFIC

CERTAINTY. SO THIS BASICALLY REJECTS THE ENTIRE PAPER

BECAUSE DR. BERARD WAS NOT ABLE TO RULE OUT CHANCE.

WELL, DOES SHE KNOW THE EPIDEMIOLOGIC PRINCIPLES OF

THAT? OF COURSE, SHE DOES. DID SHE LOOK AT THAT? OF

COURSE SHE DID. BUT THE NEW ENGLAND JOURNAL OF MEDICINE

THOUGHT THERE WAS SOME IMPORTANT INFORMATION HERE THAT

SHOULD BE SHARED. WHAT THEY FOUND WAS THAT MATERNAL

SSRI USE WAS ASSOCIATED WITH ANENCEPHALI,

CRANIOSYNOSTOSIS, AND OMPHALOCELE, AGAIN, GROUPING BY

SSRIS, LOOKING AT ORGAN SYSTEMS, AND THEY FIND INCREASED

RISK.

LOUIK, SHE LOOKED AT LOUIK. SHE

DESCRIBED IT IN HER REPORT. AND BY THE WAY, SHE LOOKS

AT THESE STUDIES. SHE PUTS THE MOST SIGNIFICANT AND

ROBUST ONES, THE ONES SHE RELIES UPON, WHICH IS REQUIRED


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103

UNDER RULE 26, YOU ARE SUPPOSED TO SET FORTH THE

OPINIONS AND WHAT YOU RELY UPON FOR YOUR OPINIONS, SHE

DOES THAT. SHE ALSO GOES THROUGH AND SAYS, WELL, THERE

ARE SOME LIMITATIONS FOR SOME OF THESE STUDIES, IN HER

REPORT. THERE IS NO CHERRY-PICKING OR IGNORING OF

CONFOUNDERS.

BUT LOUIK, ALSO NEW ENGLAND JOURNAL OF

MEDICINE, ANALYSIS OF ASSOCIATIONS BETWEEN INDIVIDUAL

SSRIS AND SPECIFIC DEFECTS SHOWED SIGNIFICANT

ASSOCIATIONS BETWEEN THE USE OF SERTRALINE AND

OMPHALOCELE AND SEPTAL DEFECTS, AND BETWEEN THE

PAROXETINE AND RIGHT VENTRICULAR OUTFLOW TRACT

OBSTRUCTIONS, ALSO LIMB REDUCTIONS, LIMB REDUCTION

DEFECTS, CLUB FOOT, ANAL ATRESIA.

MARGOLISA, AGAIN, LOOKING AT SSRIS IN

GENERAL. THEY FOUND AN ASSOCIATION IN EARLY PREGNANCY

AND THEY FOUND A STATISTICALLY SIGNIFICANT INCREASED

RISK AND IN FACT, AGAIN, STRONGER ASSOCIATIONS IN THE

DEFINED PERIOD WHEN ORGANOGENESIS OCCURS, AS WOULD BE

EXPECTED IF THE ASSOCIATION WERE CAUSAL.

SO SHE LOOKED AT PEDERSON 2009, AGAIN,

SAME THING. THERE ARE STUDY AFTER STUDY THAT SHE LOOKED

AT. SHE LOOKED AT EVERYTHING. AND THESE ARE THE ONES

THAT SHE PICKED OUT AS THE ONES THAT WERE MOST RELIABLE

WITH THE MOST ROBUST DATA AND WERE CONSISTENT WITH THE


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OPINION TO A REASONABLE DEGREE OF EPIDEMIOLOGICAL

CERTAINTY THAT THE SSRIS IN GENERAL AND ZOLOFT IN

PARTICULAR CAUSED BIRTH DEFECTS.

KORNUM, AGAIN: SERTRALINE, ASSOCIATED

WITH THREE-FOLD RISK OF CARDIAC MALFORMATIONS. OH,

WELL, THAT GROUP, THAT CARDIAC MALFORMATIONS, THAT

INCLUDES NUMEROUS CARDIAC DEFECTS. THEY GROUP. DR.

KORNUM DECIDED THAT WAS SIGNIFICANT TO SAY. HE GROUPED

THEM TOGETHER AND THE ODDS RATIO WAS THREE. IN FACT,

SSRI USE IN GENERAL WAS ALSO STATISTICALLY SIGNIFICANT

IN FINDING AN ASSOCIATION.

SAME WITH JIMENEZ. JIMENEZ FOUND

NUMEROUS FINDINGS OF STATISTICALLY SIGNIFICANT INCREASED

RISK.

SO ALL OF THESE STUDIES WERE ONES THAT

DR. BERARD LOOKED AT AND SHE LOOKED AT THE ENTIRE BODY

OF LITERATURE. AND SHE LOOKED AT HOW THEY COMPARED.

SHE STACKED THEM UP. THIS IS A FOREST BLOCK. YOU HAVE

SEEN THESE BEFORE. THE RIGHT IS ONE ODDS RATIO. AND

SHE LOOKED TO SEE, WELL, HOW ARE THESE TRENDING? THIS

IS MAJOR CONGENITAL MALFORMATIONS. DID SHE DO EVERY

SINGLE STUDY UNDER THE SUN? NO. NOT ALL OF THEM ARE

MEANT TO ANSWER THE QUESTION. NOT ALL OF THEM HAVE

ROBUST DATA. SOME HAVE METHODOLOGIC FLAWS THAT MAKE

THEM NOT INSTRUCTIVE. BUT WHEN YOU LOOK, YOU SEE


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105

CONSISTENT RESULTS ELEVATED RISK. ARE THEY ALL

STATISTICALLY SIGNIFICANT? NO. A LOT OF THEM ARE. BUT

IT'S CONSISTENCY OF RESULTS AND STATISTICAL SIGNIFICANCE

IS NOT THE END ALL, BE ALL OF DAUBERT AND IT'S NOT THE

END ALL BE ALL OF GOOD SCIENCE. SO SAYS SIR ARTHUR

BRADFORD HILL.

SO THEN SHE LOOKED AND SAID, LET'S LOOK

AT SPECIFIC DEFECTS. LET'S SEE WHAT I CAN FIND ABOUT

WHETHER ZOLOFT IN PARTICULAR AND SSRIS AS A CLASS

INCREASE SPECIFIC CARDIAC DEFECTS. SHE LOOKED AT ALWAN,

SHE LOOKED AT KORNUM. SHE LOOKED AT COLVIN. SHE LOOKED

AT PETERSON. SHE LOOKED AT LOUIK. SHE LOOKED AT

JIMENEZ. AND AGAIN, TIME AND TIME AND TIME AGAIN ON THE

STUDIES WITH THE MOST ROBUST DATA WITH THE MOST

RELIABLE, TAKING INTO ACCOUNT THE CONFOUNDERS, TAKING

INTO ACCOUNT THE POSSIBILITY OF DETECTION BIAS, TAKING

INTO ACCOUNT ALL OF THE METHODOLOGICAL FLAWS OR

LIMITATIONS THAT EXIST IN VIRTUALLY EVERY STUDY EVER

PERFORMED. SHE LOOKS AND SEES CONSISTENT RESULTS OF

CARDIAC DEFECTS IN GENERAL WITH SSRIS AND IN ZOLOFT IN

PARTICULAR.

NEURAL TUBE DEFECTS, SAME THING. WE HAVE

CONSISTENCIES, THERE'S MULTIPLE RESULTS. SHE IS LOOKING

AT IT. SHE ALSO UNDERSTANDS THE ORGANOGENESIS AND THE

MECHANISM AND WHEN AND HOW THE SEROTONIN AFFECTS THE


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SIGNALING OF THE CELLS AS THEY ARE DIVIDING AND BECOMING

ORGANS. AND SHE IS FINDING CONSISTENT INCREASED RISK.

SAME WITH GASTROINTESTINAL DEFECTS.

AGAIN, ALWAN, JIMENEZ, COLVIN, LOUIK.

CRANIOSYNOSTOSIS, AGAIN, THERE ARE

MULTIPLE RESULTS.

AND SHE IS GOING TO GO THROUGH WHY THESE

STUDIES MEAN WHAT SHE SAYS THAT THEY MEAN AND HOW SHE

REACHED HER CONCLUSION.

CLEFT LIP WITHOUT PALATE. ZOLOFT IS ON

THERE, BUT ALSO ALL SSRIS. THERE IS TRENDING. THERE IS

CONSISTENCY. THERE IS ORGANOGENESIS.

MR. CHEFFO MAKES A BIG DEAL ABOUT IN

FEBRUARY OF 2009 DR. BERARD WROTE AN OPINION IN PAXIL

AND SHE SAID, WELL, EXISTING DATA, EXISTING DATA DOES

NOT YET SUGGEST AN SSRI EFFECT. NOW, THAT WAS A PAXIL

REPORT. SHE WAS NOT ASKED TO LOOK AT THE DATA FOR SSRIS

IN GENERAL OR ZOLOFT IN PARTICULAR. BUT THE IDEA THAT

AN EXPERT CANNOT CHANGE HIS OR HER OPINION BASED UPON

EVOLVING SCIENCE IS ITSELF BAD SCIENCE.

ON THE LEFT IS THE FLAT EARTH SOCIETY

LOGO. I LOOKED IT UP LAST NIGHT AND WIKIPEDIA SAID

THERE IS STILL A FLAT EARTH SOCIETY. IT DID NOT HAVE

THE MEMBERSHIP BECAUSE I THOUGHT MAYBE I WOULD SEE IF

SOME OF MY COLLEAGUES WERE THERE. BUT INDEED WE KNOW


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THE EARTH IS ROUND NOW. AND THE SCIENCE EVOLVED FOR DR.

BERARD. AT THE TIME SHE HELD HER HAND AND SAID, WELL,

I'M GOING TO WAIT AND SEE WHAT ELSE COMES OUT. AND

INDEED MORE CAME.

AND THIS IS BRADFORD HILL, AGAIN, HIS

PAPER, EXHIBIT 60 FROM THE REPLY: ALL SCIENTIFIC WORK IS

INCOMPLETE, WHETHER IT BE OBSERVATIONAL OR EXPERIMENTAL.

ALL SCIENTIFIC WORK IS LIABLE TO BE UPSET OR MODIFIED BY

ADVANCING KNOWLEDGE. THAT DOES NOT CONFER UPON US A

FREEDOM TO IGNORE THE KNOWLEDGE WE ALREADY HAVE OR TO

POSTPONE THE ACTION THAT IT APPEARS TO DEMAND AT A GIVEN

TIME.

SO IF INDEED DR. BERARD OR ANY EXPERT

WERE TO SIMPLY IGNORE THE NEW EVIDENCE THAT HAS COME OUT

AND NOT BE OPEN TO CHANGE HER OPINION, THEN THAT ITSELF

WOULD BE BAD SCIENCE. THAT ITSELF WOULD BE CONTRARY TO

DAUBERT.

SO, WHAT HAPPENED? MR. CHEFFO SAID,

WELL, NOTHING HAPPENED. NOTHING CHANGED. THE EARTH

REMAINED FLAT FROM 2009 UNTIL TODAY WHEN THIS COURTROOM

AND THERE WERE NO OTHER RESULTS THAT COULD POSSIBLY

CAUSE DR. BERARD TO CHANGE HER MIND. IT MUST BE THE

MONEY. IT MUST BE A LITIGATION OPINION. SHE IS PUTTING

HER REPUTATION ON THE LINE. SHE'S COMING HERE IN THIS

COURTROOM TO TAKE ALL OF THE STATEMENTS ABOUT HER


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BECAUSE THERE IS NOTHING TO CHANGE. THERE IS NOTHING

CHANGED SINCE FEBRUARY OF 2009. WELL, THAT IS NOT TRUE.

THIS IS PEDERSON. THIS IS PEDERSON, FALL

OF 2009, LATER THE SAME YEAR. OUR RESULTS SUGGEST A

CLASS EFFECT ON SSRI AND HEART DEFECT. PEER-REVIEWED

PUBLISHED LITERATURE.

THIS IS KORNUM, 2010, SERTRALINE

ASSOCIATED WITH A THREE-FOLD INCREASE RISK OF CARDIAC

MALFORMATIONS. I GUESS DR. BERARD SHOULD IGNORE THAT.

AGAIN, WE'VE GOT JIMENEZ, 2012. RISKS OF

CONGENITAL MALFORMATIONS OF THE HEART ARE INCREASED FOR

INFANTS WHOSE MOTHERS WERE EXPOSED TO AN SSRI IN THE

FIRST TRIMESTER. IGNORE THAT, SAYS PFIZER.

SHE DID NOT IGNORE THAT, AND THESE

OPINIONS THAT SHE HAS ARRIVED AT ARE NOT LITIGATION

OPINIONS. THIS IS HER OPINION ARRIVED AT INDEPENDENT OF

ANY LITIGATION.

THIS IS ANICK BERARD IN JULY 13TH, 2010,

MY BIRTHDAY. AGAIN, MR. TRACEY POINTED THIS OUT BUT SHE

FOUND THE RESULTS OF HER STUDY SUGGESTS AN OVERALL CLASS

EFFECT OF SSRIS AND THE DATA ARE HIGHLY ROBUST GIVEN THE

NUMBER OF USERS STUDIED. SO HER OPINION BEGAN TO

EVOLVE.

THIS -- THIS IS A SLIDE. SHE WAS ASKED

TO GIVE A PRESENTATION TO HER PEERS IN OTTAWA IN THE


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SUMMER OF 2012. THE PRESENTATION WAS GIVEN IN OCTOBER

OF 2012 TO THE CANADIAN CONGENITAL AND ANOMALY

SURVEILLANCE NETWORK. THIS IS WELL BEFORE HER REPORT IN

THIS CASE. AND SHE WAS ASKED -- DR. BERARD, CAN YOU

COME AND TALK TO THE SCIENTISTS IN CANADA WHO ARE

LOOKING AT THE ISSUE OF PREGNANCY AND BIRTH DEFECTS AND

ANTIDEPRESSANTS AND TELL US WHAT YOU THINK ABOUT THAT

ISSUE. CAN YOU LOOK AT THE LITERATURE? CAN YOU APPLY

THE BRADFORD HILL CRITERIA? CAN YOU TELL US WHAT YOU

THINK, DR. BERARD? WELL, SHE DID EXACTLY THAT. SHE

MADE A SLIDE, INDEPENDENT OF ANY LITIGATION. IT'S A

FOREST PLOT. THAT IS WHAT PHARMACOEPIDEMIOLGISTS DO.

THAT'S WHAT PERINATAL EPIDEMIOLOGISTS DO. AND YOU LOOK,

AND THE ELEVATED ODDS RATIO, AGAIN, YOU HAVE GOT ONE

HERE, STUDY AFTER STUDY, EVERY SINGLE STUDY, NO, BUT YOU

SEE A CONSISTENCY OF RESULTS. DR. BERARD SAW A

CONSISTENCY OF RESULTS IN 2012. AND HER OPINION TO HER

PEERS, IN OTTOWA, AT THE CANADIAN SOCIETY, WAS THE DATA

ARE SHOWING SSRIS ARE INCREASING THE RISK OF SPONTANEOUS

ABORTIONS, MAJOR CONGENITAL MALFORMATIONS, LOWER BIRTH

WEIGHT, LOWER COGNITIVE FUNCTION, HENCE MEETING ALL

PRINCIPLES OF TERATOGENICITY. THIS IS NOT A SLIDE I

MADE FOR THIS COURT TODAY. THIS IS A SLIDE THAT DR.

BERARD MADE IN 2012. AND SHE PRESENTED TO HER PEERS.

SO I'M NOT GOING TO BELABOR THE POINT.


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SHE IS NOT ON AN ISLAND. SHE IS NOT OUT THERE IN SOME

FLAT EARTH SOCIETY AT THE LAUGHING STOCK OF SCIENCE. IN

FACT SHE AGREES WITH PFIZER'S OWN CHIEF OF EPIDEMIOLOGY

CYNTHIA DELUISE. SHE DID THE SAME THING THAT DR.

DELUISE APPARENTLY DID IN REACHING HER OPINIONS, THAT

BOTH THE SSRI AND THE SNRI, WHICH EFEXOR IS ONE ARE

IMPLICATED IN THE DEVELOPMENT OF BIRTH DEFECTS. SHE DID

EXACTLY DR. DELUISE DID. SHE LOOKED AT THE STUDIES AND

SHE CAME -- THE ONLY DIFFERENCE REALLY, IS DR. DELUISE

AND PFIZER DID NOT HIDE THEIR OPINION. DR. BERARD PUT

HERSELF OUT THERE. THIS IS FROM DECEMBER OF LAST YEAR.

AND SHE PUTS HERSELF OUT THERE AND SHE SAYS HER

OPINION -- SHE MAKES NO BONES ABOUT HER OPINION. SHE

TALKS ABOUT HOW THE DATA SHOWED THAT THESE DRUGS CARRY

AN INCREASED RISK OF BIRTH DEFECTS AND PROBLEMS. AND

YOU KNOW, THERE HAS BEEN A LOT MADE, WELL, THIS IS A

DRUG THAT IS SAVING WOMEN'S LIVES, PREGNANT WOMEN GET

DEPRESSED, AND THEY NEED THIS DRUG.

NOBODY IN THIS COURTROOM IS ASKING FOR

THIS DRUG TO BE PULLED OFF THE MARKET. WHAT WE ARE

SAYING IS THAT, FIRST OF ALL, WHY DON'T WE TELL WOMEN

THE TRUTH ABOUT THE RISKS OF ZOLOFT AND SSRIS WHEN THEY

ARE TAKING THIS DRUG DURING PREGNANCY. MAYBE WE SHOULD

DO WHAT THE UK DID, AND WHAT WE DID IN THE UK, AND

WARNED WOMEN TO TAKE CONTRACEPTION IF THEY ARE GOING TO


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BE USING THIS DRUG. BUT LET'S NOT MAKE THIS ZOLOFT THE

END-ALL BE-ALL IN HELPING PREGNANT WOMEN, BECAUSE THERE

ARE SERIOUS RISKS ASSOCIATED WITH THIS DRUG IN THE

DEVELOPMENT OF BIRTH DEFECTS. THERE ARE OTHER

TREATMENTS FOR DEPRESSION. THE FDA NEVER SAID -- NO

SOCIETY EVER SAID ZOLOFT -- ZOLOFT, I THINK I HEARD THAT

THIS MORNING -- ZOLOFT IS NECESSARY FOR THESE WOMEN,

OTHERWISE THEY ARE GOING TO RUN OFF IN PREGNANCY AND DO

GOD KNOWS WHAT. THERE ARE A LOT OF OTHER THINGS THAT

CAN BE USED FOR WOMEN DURING PREGNANCY. IT'S NOT JUST

ZOLOFT.

SO WE TALKED ABOUT THE SOCIETY FOR

TERATOLOGY AND DR. BERARD HAS PUT HERSELF OUT TO HER

PEERS TO THE WORLD WITH HER OPINION, SHE'S A MEMBER OF

THE SOCIETY, DID THEY RUN HER OUT ON A RAIL AND SAY THAT

IS BAD SCIENCE, THIS IS HORRIBLE METHODOLOGY, YOU ARE

MISLEADING THE AMERICAN PUBLIC, YOU ARE MISLEADING THE

CANADIAN PUBLIC, YOU ARE HURTING PREGNANT WOMEN WHO NEED

THIS DRUG? THEY DID NOT DO THAT. THEY DID NOT RUN HER

OUT ON A RAIL, THEY GAVE HER AN AWARD, THE MOST

DISTINGUISHED AWARD THEY HAVE FOR HER WORK ANALYZING

THESE VERY ISSUES.

NOW, WE ARE NOT ASKING THIS COURT OR

ANYBODY ELSE TO GIVE HER AN AWARD. SHE DOES NOT NEED

ANY MORE AWARDS, BUT WHAT SHE DOES NOT DESERVE, AND WHAT


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THE LAW DOES NOT DEMAND -- IN FACT, THE LAW DEMANDS THE

OPPOSITE, IS THAT THIS COURT PERMIT DR. BERARD AND ALL

OF THESE HIGHLY QUALIFIED EXPERTS TO GIVE THEIR OPINIONS

TO A JURY, TO STAND UP TO THE CROSS EXAMINATION OF MR.

CHEFFO OR WHOEVER DECIDES TO CROSS EXAMINE DR. BERARD.

AND SHE WILL STAND HERE AND SHE WILL DEFEND HER OPINION,

SHE WILL DEFEND IT TO YOUR HONOR HERE IN THAT CHAIR.

SHE WILL DEFEND IT TO A JURY. THAT IS ALL WE ARE

ASKING. GIVE HER THE OPPORTUNITY TO DEFEND THE

METHODOLOGY, WHICH IS RELIABLE, WHICH THIS COURT HAS

ALREADY PASSED UPON, WHICH SHE APPLIES TO HER STUDENTS

EVERY DAY WHAT SHE WAS TAUGHT AT HARVARD, AND WHAT SHE

HAS PUT OUT TO HER PEERS AND INDEED BEEN GIVEN AN AWARD

FOR HER WORK IN THIS VERY FIELD.

AND WITH THAT, I THANK YOU.

THE COURT: THANK YOU, MR. ALYSTOCK.

MR. TRACEY: WE WOULD LIKE TO CALL OUR

FIRST WITNESS, YOUR HONOR.

THE COURT: YOU MAY.

MR. TRACEY: THE PLAINTIFFS CALL DR.

ROBERT CABRERA.

ROBERT MATTHEW CABRERA, PLAINTIFF'S

WITNESS, SWORN.

THE CLERK: STATE AND SPELL YOUR FULL


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NAME FOR THE RECORD, PLEASE.

MR. TRACEY: MAY I PROCEED, YOUR HONOR?

THE COURT: YOU MAY.

DIRECT EXAMINATION

BY MR. TRACEY:

Q. PLEASE INTRODUCE YOURSELF.

A. MY NAME IS ROBERT MATTHEW CABRERA.

Q. WHAT DO YOU DO FOR A LIVING?

A. I'M A TERATOLOGIST.

Q. WHERE ARE YOU A TERATOLOGIST?

A. I WORK AT THE DELL PEDIATRIC INSTITUTES AND PART

OF THE UNIVERSITY OF TEXAS IN AUSTIN.

Q. WHO DO YOU WORK WITH THERE AT THE DELL PEDIATRIC

INSTITUTE?

A. I WORK FOR THE DIRECTOR OF THE GENOMICS FACILITY

THERE, WHO IS ALSO -- RICHARD FINNELL, WHO IS MY

LONG-TIME MENTOR AND A TRAINED CLINICAL GENETICIST AND

TERATOLOGIST.

Q. HOW DID YOU GET TO MEET DR. FINNELL?

A. I MET DR. FINNELL AS AN UNDERGRADUATE AT TEXAS

A&M UNIVERSITY. HE WAS THEN A PROFESSOR AND STUDYING

THE IMPACTS OF FAMODISIN (SIC) ON BIRTH DEFECTS RESEARCH

AND THROUGH THE HONORS PROGRAM, WHICH HIS WIFE ACTUALLY

HEADED THE UNIVERSITY, SHE HAD PLACED ME IN HIS

LABORATORY.


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Q. AND DID YOU INTERVIEW WITH DR. FINNELL?

A. YES, I DID.

Q. HAVE YOU WORKED IN AND AROUND TERATOLOGY SINCE

YOU WERE 17 YEARS OLD?

A. YES, I HAVE.

Q. HAVE YOU WORKED MOST OF THAT TIME WITH OR AROUND

DR. FINNELL?

A. YES, I HAVE.

Q. DID DR. FINNELL COAUTHOR THE REPORT THAT WAS

FILED IN THIS CASE?

A. YES, HE HAS.

Q. GIVE THE COURT AN IDEA OF WHAT YOU DO AT THE

FINNELL LAB DAY-TO-DAY. WHAT IS YOUR GOAL OR ROLE

THERE?

A. SO WE GENERALLY REFER TO OUR GOAL AS PREVENTING

PREVENTABLE BIRTH DEFECTS, AND THAT IS LOOKING AT THE

INTERACTIONS OF THE ENVIRONMENT AND CHEMICALS ON THE

DEVELOPING EMBRYO OR FETUS, AND THEN ULTIMATELY ALSO

LOOKING AT NUTRITIONAL MODIFIERS OF DEVELOPMENT THAT CAN

POTENTIALLY REDUCE THE INCIDENCE OF BIRTH DEFECTS.

Q. I WANT TO BREAK THAT DOWN. THE FIRST PART, I

THINK I UNDERSTOOD, IS YOU ARE LOOKING AT THE CAUSES OF

BIRTH DEFECTS?

A. YES.

Q. THE SECOND PART OF THAT IS NUTRITIONAL


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MODIFIERS. DOES THAT MEAN YOU ARE LOOKING AT WAYS TO

PREVENT BIRTH DEFECTS THROUGH NUTRITION?

A. ABSOLUTELY. WE HAVE THE GENETIC MODELS FOR

FOLATE, WHICH IS THE LARGEST NUTRITIONAL MODIFIER OF

BIRTH DEFECT RISK. AND THE MAJORITY OF MY GRADUATE WORK

WAS DONE ON THOSE MOUSE MODELS, AND ALSO VALPROIC ACIDS

AND ANTIEPILEPTIC DRUGS, AND LOOKING AT BASICALLY THOSE

CHEMICALS THAT CAN BE BENEFICIAL TO THEIR PREGNANCY AND

THOSE CHEMICALS THAT CAN BE DETRIMENTAL.

Q. WAS DR. FINNELL AND HIS LAB INSTRUMENTAL IN

HELPING ERADICATE NEURAL TUBE DEFECTS DUE TO FOLATE

PROBLEMS IN THE AMERICAN DIET?

A. YES. HE PUBLISHED I THINK ONE OF THE SEMINAL

PAPERS IN REGARD TO THE GENETIC MODELS DEMONSTRATING THE

EFFECTS OF FOLATES AND REDUCING BIRTH DEFECT RISKS.

Q. AND DR. FINNELL IS A GENETICIST?

A. YES, CLINICAL GENETICIST, YES.

Q. ARE YOU A GENETICIST?

A. I HAVE GENETIC TRAINING, BUT I'M NOT A BOARD

CERTIFIED CLINICAL GENETICIST AS DR. FINNELL IS.

Q. I PROBABLY SHOULD HAVE DONE THIS FIRST. BUT CAN

YOU TELL US FOR THE RECORD WHAT EXACTLY IS TERATOLOGY?

A. SO TERATOLOGY, AS IT SAYS HERE ON THE BOARD, IS

THE STUDY OF THE CAUSES, MECHANISMS AND PATTERNS OF

ABNORMAL DEVELOPMENTS. AND THAT IS, WE EXAMINE THE


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CAUSES OF BIRTH DEFECTS.

Q. OKAY. AND DO YOU AT THE FINNELL LAB -- --

INCIDENTALLY, IS IT CALLED THE FINNELL LAB FOR, IS IT

BIRTH DEFECT RESEARCH?

A. YES, IT IS.

Q. WOULD IT BE FAIR TO SAY THAT EACH AND EVERY DAY

THAT YOU GO TO WORK AT THE FINNELL LAB, YOUR GOAL, YOUR

PROFESSIONAL GOAL, YOUR DUTY, IS TO TRY TO FIGURE OUT

WHAT CAUSES BIRTH DEFECTS?

A. YES, IT IS.

Q. AND IN YOUR LABORATORY SETTING, GIVE THE COURT

AN IDEA OF WHAT KIND OF RESEARCH YOU DO TO MEET THAT

GOAL?

A. WE USE PREDOMINANTLY ANIMAL MODELS IN TESTING.

THAT IS, WE HAVE MOUSE MODELS, WE HAVE GENETIC MOUSE

MODELS. WE ALSO TEST ENVIRONMENTAL AND PHARMACEUTICAL

CHEMICALS ON MOUSE MODELS.

ADDITIONALLY, I HEAD THE PROGRAM FOR

DOING EMBRYONIC STEM CELL AND STEM CELL RESEARCH, AND

THAT IS USING HUMAN OR ANIMAL CELLS IN ORDER TO TEST

TOXICITY ON POTENTIAL TERATOGENICITY ON CHEMICALS AS

WELL.

Q. AND WHO DO YOU DO THIS FOR? WHO HIRES YOUR LAB,

AND YOU AND DR. FINNELL?

A. CURRENTLY, MY WORK IS FUNDED THROUGH NATIONAL


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INSTITUTES OF HEALTH AND THEN ALSO PROTECTION AGENCY,

AND IN THE PAST WE HAVE ALSO DONE SOME WORK FOR DTRA,

THROUGH THE DEPARTMENT OF DEFENSE, WHICH IS THE DEFENSE

THREAT REDUCTION AGENCY.

Q. HAVE YOU ALSO DONE WORK AT THE FINNELL LAB FOR

PRIVATE COMPANIES?

A. YES, WE HAVE DONE SOME FOR NONPROFIT

ORGANIZATIONS.

Q. AND ARE THERE OCCASIONS WHEN PEOPLE WILL COME TO

YOU AND SAY WE HAVE THIS COMPOUND, DR. CABRERA, DR.

FINNELL, WE WANT TO KNOW WHETHER OR NOT THIS IS A

TERATOGEN, CAN YOU GIVE US THE ANSWER TO THAT QUESTION?

A. YES, WE HAVE ONGOING WORK WITH ANTIEPILEPTIC

DRUGS, SCREENING THEM, PRE-SCREENING, AND LOOKING FOR

TERATOGENICITY IN ANIMAL MODELS. ADDITIONALLY, PEOPLE

WILL APPROACH US IN DEVELOPING NUTRACEUTICALS,

INTERESTED IN POTENTIAL FOR USING THEM IN PREGNANT

ANIMALS TO SHOW SAFETY OF THOSE CHEMICALS AS WELL.

Q. INCIDENTALLY, IF SOMEBODY WERE TO SAY THAT

TERATOGENS ARE SPECIFIC, MEANING IT WOULD BE UNLIKELY OR

UNUSUAL OR SCIENTIFICALLY SORT OF CRAZY TO SUGGEST THAT

ONE DRUG CAN CAUSE MULTIPLE DEFECTS, WHAT WOULD YOU SAY

TO THAT?

A. I WOULD SAY IT DEPENDS ON THE MECHANISM OF

ACTION, AND THAT IS THOSE CHEMICALS THAT INTERACT WITH


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EARLY MECHANISMS AND PARTICULAR CELL POPULATIONS THAT

ARE DIVERSE DURING DEVELOPMENT WOULD BE EXPECTED TO ALSO

HAVE A DIVERSE PRESENTATION OF OUTCOMES OR CONGENITAL

MALFORMATIONS.

Q. HAVE YOU SEEN THAT TIME AND TIME AGAIN IN YOUR

RESEARCH?

A. I HAVE SEEN THAT ACTUALLY IN THE MAJORITY OF THE

CHEMICALS WE HAVE TESTED.

Q. SO IN THE MAJORITY OF THE CHEMICALS THAT YOU

TEST, THE EXPECTED OUTCOME IS NOT ONE DEFECT, IT'S

MULTIPLE DEFECTS ACROSS DIFFERENT ORGAN SYSTEMS?

A. YES. THAT IS WHY WE EXAMINE ALL THE ORGAN

SYSTEMS IN OUR ANALYSIS.

Q. IN YOUR LAB?

A. YES.

Q. DID YOU ALSO PARTICIPATE IN THE NATIONAL BIRTH

DEFECT PREVENTION STUDY?

A. YES. WE HAVE CONDUCTED WORK WITH THE NATIONAL

BIRTH DEFECTS PREVENTION STUDY, ONGOING WORK WHERE WE DO

GENETIC ANALYSIS FOR PATIENT POPULATIONS AND LOOKING FOR

GENETIC RISK FACTORS IN BIRTH DEFECTS.

Q. WHAT'S THE NATIONAL BIRTH DEFECTS PREVENTION

STUDY?

A. SO THIS IS PART OF A PROGRAM, IT'S A MONITORING

PROGRAM. CURRENTLY WE ARCHIVE TEXAS, CALIFORNIA AND


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MASSACHUSETTS SAMPLES, BLOOD SAMPLES. WE DO GENETIC

ANALYSES ON THESE PATIENTS, AND WE LOOK TO SEE WHETHER

THERE ARE GENETIC RISK FACTORS AND WE CAN ALSO LOOK TO

SOME EXTENT BASED ON QUESTIONNAIRES, WHAT KIND OF

ENVIRONMENTAL OR BEHAVIORAL RISK FACTORS ARE PRESENT IN

THE POPULATION.

Q. AND WHO ARE YOU REPORTING YOUR FINDINGS TO?

A. I MEAN, WE PUBLISH THOSE AS WE ARRIVE AT THEM.

ADDITIONALLY, THEY ARE PRESENTED BACK TO THE NATIONAL

BIRTH DEFECTS MONITORING PROGRAM AND TO THE NIH AS PART

OF GRANTS.

Q. IS THIS A FEDERAL, U.S. FEDERAL GOVERNMENT

PROGRAM?

A. YES. IT'S FUNDED THROUGH THE NIH.

Q. HOW LONG HAVE YOU BEEN RESPONSIBLE FOR

CALIFORNIA, TEXAS AND MASSACHUSETTS WAS IT?

A. SO THAT PROGRAM HAS BEEN ONGOING. I'M NOT SURE

WHEN ITS INCEPTION WAS, BUT IT HAS BEEN ONGOING IN THE

LAB SINCE I HAVE BEEN A MEMBER.

Q. HOW LONG HAVE YOU HAD A PH.D., DR. CABRERA?

A. I RECEIVED MY PH.D. IN 2006.

Q. WHAT IS YOUR PH.D. IN?

A. MEDICAL SCIENCES.

Q. WHAT DOES THAT MEAN? WHAT IS A MEDICAL SCIENCE

PH.D.?


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A. SO MY TRAINING WAS AT THE UNIVERSITY OF TEXAS IN

HOUSTON, UNIVERSITY OF TEXAS MEDICAL SCHOOL. I DID MY

DIDACTIC WORK AT THE MEDICAL SCHOOL, THEN WHEN -- THE

MD'S THEN GO TO CLINICAL PRACTICE, I WENT TO THE

LABORATORY AND BEGAN DOING SCIENTIFIC RESEARCH BASED ON

CLINICAL ANALYSIS OF BIRTH DEFECTS AND THEN ALSO LOOKING

AT THE ANIMAL MODELS FOR MODELS FOR THE BIRTH DEFECTS.

Q. IT SAYS HERE ON THE SCREEN YOU DID POST DOCTORAL

RESEARCH LOOKING AT BIRTH DEFECTS USING THE NORWEGIAN

AND DANISH BIRTH REGISTRIES?

A. YES.

Q. WHAT ARE THE NORWEGIAN AND DANISH BIRTH

REGISTRIES?

A. WE HAVE A COLLABORATION WHEN I WAS DOING MY POST

DOCTORAL RESEARCH AND WE HAD AN INTEREST IN LOOKING AT

IMMUNOLOGICAL RISK FACTORS FOR BIRTH DEFECTS. AND SO

THESE ARE NATIONAL REGISTRIES THAT HAVE ENROLLED IN THEM

HUNDREDS OF THOUSANDS OF WOMEN THAT ARE USED TO ANALYZE

THE INCIDENCE AND THE RISK FACTORS FOR BIRTH DEFECTS.

AND SO THEY PROVIDED US WITH BLOOD SAMPLES IN

COLLABORATION FOR US DOING ANALYSIS ASSISTING BASICALLY,

AND BEING ABLE TO ANALYZE THEIR DATA.

Q. AND AT THE FINNELL LAB, I'VE GOT THIS SCREEN

SHOT FROM THE LAB. IT SAYS -- AT THE TOP IT SAYS:

RESEARCH IN DR. FINNELL'S LABORATORY FOCUSES ON GENETIC


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SUSCEPTIBILITY TO ENVIRONMENTALLY-INDUCED COMPLEX

CONGENITAL ANOMALITIES. BOTH GENETICALLY MODIFIED MOUSE

MODELS AND POPULATION BASED HUMAN STUDIES ARE UTILIZED.

I THINK YOU EXPLAINED THE MOUSE MODELS.

ARE THE POPULATION BASED HUMAN STUDIES, ARE THEY

EPIDEMIOLOGY STUDIES?

A. YES, THOSE ARE EPIDEMIOLOGY STUDIES.

Q. DO YOU PARTICIPATE IN THE DESIGN OF EPIDEMIOLOGY

STUDIES?

A. I PARTICIPATE IN THEIR CONDUCT, I GUESS, IS THE

-- GENERALLY WE HAVE EPIDEMIOLOGISTS THAT SUPERVISE

THEIR DESIGN IMPLEMENTATION, AND THEN WHEN THEY ACTUALLY

GO IN AND DO THE ANALYSIS, I'M ONE OF THE PEOPLE THAT

HELPS WITH THE ANALYSIS AND THEN ALSO WITH ACTUALLY

PROCESSING THE SAMPLES, GENERATING THE DATA.

Q. DO YOU HAVE EPIDEMIOLOGISTS THAT YOU WORK WITH

WHEN YOU ARE UNDERTAKING THESE STUDIES AT THE LAB?

A. ABSOLUTELY. ACTUALLY MY COLLEAGUE THERE ON THE

FAR LEFT IS OUR EPIDEMIOLOGIST THAT WAS IN THE FINNELL

LABORATORY.

Q. AND SHE WORKS FOR THE FINNELL LAB OR SHE DID?

A. SHE IS IN INDUSTRY NOW, BUT SHE WAS WORKING FOR

THE FINNELL LABORATORY FOR A NUMBER OF YEARS AS WELL.

Q. AND WHEN YOU AND DR. FINNELL -- BY THE WAY, DR

FINNELL IS THE GUY IN THE MIDDLE WITH THE BEARD HERE AND


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THE GLASSES?

A. YES.

Q. YOU ARE SOMEWHERE?

A. ME, WITHOUT THE BEARD, ON THE RIGHT.

Q. AND WHEN YOU ARE AT THE LAB, AT THE FINNELL LAB,

WHEN YOU GUYS ARE PARTICIPATING IN EPIDEMIOLOGY STUDIES,

DO YOU DEAL WITH PERINATAL EPIDEMIOLOGISTS?

A. YES, WE DO.

Q. WHAT ARE PERINATAL EPIDEMIOLOGISTS?

A. SO THOSE ARE YOUR EPIDEMIOLOGISTS THAT FOCUS

SPECIFICALLY ON BIRTH DEFECTS, AND USUALLY EARLY

DEVELOPMENTS AS FAR AS HUMAN DEVELOPMENT GOES FOR DOING

STUDIES ON A LOT OF TIMES ENVIRONMENTAL EFFECTS OR

PHARMACEUTICAL EFFECTS ON DEVELOPMENT.

Q. IS THE FINNELL LAB DEVOTED SOLELY AND

EXCLUSIVELY TO BIRTH DEFECT RESEARCH?

A. YES, WE ARE.

Q. NOW, I MET WITH YOU A COUPLE OF TIMES, AND DR.

FINNELL AND I ASKED YOU TO REVIEW A VARIETY OF THINGS IN

THIS CASE, DIDN'T I?

A. YES, YOU DID.

Q. THEN I ASKED YOU AND DR. FINNELL TO ARRIVE AT

WHATEVER OPINIONS YOU WERE GOING TO ARRIVE AT?

A. YES.

Q. AND SO WE ARE GOING TO TALK ABOUT HOW YOU GOT


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THERE. BUT THE FIRST THING I WANT TO ASK YOU ABOUT IS,

WHEN YOU GIVE OPINIONS TODAY TO THE COURT, I WOULD ASK

WHETHER OR NOT ALL OF YOUR OPINIONS WILL BE BASED ON

REASONABLE SCIENTIFIC CERTAINTY?

A. YES, THEY ARE.

Q. AND THE THINGS YOU UNDERTOOK TO DO FOR ME IN

THIS CASE ON BEHALF OF THE MDL, DID YOU GO ABOUT THEM

THE SAME WAY YOU WOULD TRY TO FIGURE OUT WHETHER A DRUG

WAS A TERATOGEN IN YOUR PROFESSIONAL LIFE?

A. ABSOLUTELY.

Q. WAS THE METHODOLOGY YOU EMPLOYED IN THIS CASE

THE EXACT SAME METHODOLOGY YOU WOULD HAVE DONE IF PFIZER

HAD COME TO YOU AND SAID I WANT TO KNOW WHETHER OR NOT

ZOLOFT IS A TERATOGEN?

A. YES.

Q. AND YOU WOULD HAVE TOLD THEM THE SAME THING HAD

THEY DONE THAT, THAT YOU ARE GOING TO TELL THESE JUDGES

TODAY?

A. ABSOLUTELY.

Q. USING THE SAME METHODOLOGY THAT YOU USED IN THIS

CASE?

A. YES.

Q. ALL RIGHT. SO JUST TO START OFF WITH A SUMMARY

OF YOUR OPINIONS, DR. CABRERA, THIS IS ACTUALLY OUT OF

YOUR REPORT. IT SAYS IT IS OUR OPINION WITHIN A


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REASONABLE DEGREE OF SCIENTIFIC CERTAINTY THAT

ALTERATION OF SEROTONIN SIGNALING BY SSRIS INCLUDING

SERTRALINE, CAN IMPACT EMBRYONIC DEVELOPMENT RESULTING

IN SEVERAL DIFFERENT CONGENITAL MALFORMATIONS INVOLVING

VARIOUS ORGAN AND BODY SYSTEMS INCLUDING BUT NOT LIMITED

TO THE FOLLOWING.

AND THEN WE HAVE A LIST OF WHAT THEY ARE.

IS THAT A SUMMARY OF YOUR OPINION WHAT I JUST READ?

A. YES, IT IS.

Q. AND ON THIS SLIDE WE HAVE, INTRAUTERINE DEATH,

CRANIOFACIAL DEFECTS, SKELETAL/LIMB DEFECTS,

CARDIOVASCULAR DEFECTS, ABDOMINAL WALL DEFECTS, AND

CENTRAL NERVOUS SYSTEM DEFECTS. THESE ARE ALL YOUR

OPINIONS WITH RESPECT TO SERTRALINE AND SSRIS GENERALLY?

A. YES, THEY ARE.

Q. WE HAVE TALKED A LOT ABOUT MR. WILSON OR DR.

WILSON. I WANT YOU TO TELL THE COURT WHO JAMES WILSON

IS AND WHY WE CARE ABOUT HIM.

A. JAMES WILSON, AS IT SAYS HERE, IS THE CO-FOUNDER

OF THE TERATOLOGY SOCIETY. HE DEVELOPED WHAT IS

COMMONLY REFERRED TO AS WILSON'S PRINCIPLES, OR THE SIX

PRINCIPLES OF TERATOLOGY. AND THESE ARE PRINCIPLES THAT

ARE APPLIED IN ORDER TO CONDUCT TERATOLOGY RESEARCH AND

DETERMINE WHETHER CHEMICALS HAVE THE POTENTIAL TO BE

TERATOGENS IN HUMANS.


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Q. HOW LONG HAVE THESE PRINCIPLES BEEN USED IN THE

FIELD OF TERATOLOGY?

A. I BELIEVE THEY WERE DEVELOPED IN THE '50S AND

WIDELY ACCEPTED DURING THE '60S AND '70S.

Q. AND THESE ARE THE PRINCIPLES UPON WHICH YOU BASE

YOUR RESEARCH IN YOUR LAB THERE IN AUSTIN?

A. YES, THEY ARE.

Q. SO LET'S TALK ABOUT WILSON'S PRINCIPLES. ARE

THERE SIX?

A. YES, THERE ARE.

Q. THERE ARE NOT EIGHT OR NINE?

A. THERE ARE NOT.

Q. ARE YOU AWARE OF DR. SHIALI'S LITIGATION

PRINCIPLES OF TERATOLOGY?

A. I HAVE READ THE PAPER, YES.

Q. BEFORE YOU HAD READ THE PAPER, WERE YOU AWARE OF

SHIALI'S LITIGATION PRINCIPLES OF TERATOLOGY?

A. THEY ARE NOT PRACTICALLY TAUGHT IN TERATOLOGY,

NO.

Q. HAVE YOU EVER SEEN ANYBODY APPLY SHIALI'S

LITIGATION PRINCIPLES OF TERATOLOGY IN THE REAL WORLD

PRACTICE OF TERATOLOGY?

A. I HAVE NOT.

Q. HAVE YOU EVER SEEN ANY PAPERS IN THE PEER

REVIEWED SCIENCE EMPLOYING SHIALI'S LITIGATION


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PRINCIPLES OF TERATOLOGY?

A. I HAVE NOT.

Q. SO LET'S TALK ABOUT THEM. WE HAVE THEM UP HERE.

WHAT ARE THE SIX PRINCIPLES OF TERATOLOGY?

A. SO IN BRIEF, THEY ARE SUSCEPTIBILITY. AND THAT

IS, USUALLY WE CONSIDER IT GENETIC, AS GENETIC

SUSCEPTIBILITY. THAT IS EVERYONE HAS UNIQUE GENETIC

MAKEUP AND SO A LOT OF TIMES THEY ARE UNIQUELY

SUSCEPTIBLE TO CHEMICALS.

THE SECOND ONE IS DEVELOPMENTAL STAGE,

AND THAT IS THE TIMING. I THINK THE MOST ESSENTIAL

ELEMENT OF THAT IS THAT YOU ARE NOT GOING TO CREATE

DEFECT AFTER A PARTICULAR ORGAN SYSTEM HAS DEVELOPED.

MECHANISMS, AND THIS IS THE ACTION AND

HOW THE CHEMICALS INTERACT SPECIFICALLY WITH MOLECULES,

SO WE ARE LOOKING AT MECHANISTIC INTERACTIONS.

ACCESS, AND THAT IS ACTUALLY THE ABILITY

FOR THE COMPOUND OR CHEMICAL TO INTERACT WITH THE

DEVELOPING SYSTEM.

THE LAST POINT, WHICH I THINK IS OF

CRITICAL IMPORTANCE IS THE ENDPOINTS. I THINK IT WILL

-- A LOT OF TIMES PEOPLE GET CONFUSED. AND THEY THINK

AN ENDPOINT CAN ONLY BE CONGENITAL MALFORMATIONS IN

TERATOLOGY. BUT IN TRUTH, AND AS ESPOUSED BY WILSON,

OTHER ENDPOINTS SUCH AS DEATH, IN ADDITION TO CHANGES IN


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GROWTH, AND IN ADDITION TO CHANGES IN THE

FUNCTIONAL ABILITY OF THE ANIMAL ARE ALL SUGGESTED AS

ENDPOINTS FOR TERATOLOGY.

AND THEN THE LAST ONE IS DOSE RESPONSE.

AND THAT IS LOOKING FOR DOSE EFFECT.

Q. SO LET'S TAKE THOSE ONE AT A TIME.

THE FIRST PRINCIPLE IS SUSCEPTIBILITY TO

TERATOGENESIS DEPENDS UPON THE GENOTYPE OF THE CONCEPTUS

AND THE MANNER IN WHICH IT INTERACTS WITH THE

ENVIRONMENT?

IS THIS THE FIRST PRINCIPLE?

A. YES, IT IS.

Q. AND SO LET'S MAYBE MAKE THAT A LITTLE MORE

SIMPLE FOR US. TELL US WHAT THAT MEANS?

A. SO IN GENERAL TERMS, IT SIMPLY MEANS THAT WE ARE

EACH UNIQUE INDIVIDUALS AND THAT OUR GENETIC MAKEUP IS

ACTUALLY WHAT GIVES US SUSCEPTIBILITY TO DIFFERENT --

WHETHER THEY ARE INFECTIOUS CHEMICALS OR INFECTIOUS

DISEASES OR CHEMICALS IN THE ENVIRONMENT THAT COULD

POTENTIATE BIRTH DEFECTS.

Q. SO THIS IS THE IDEA THAT WHILE MANY PEOPLE MAY

BE EXPOSED TO A DIFFERENT TERATOGEN OR TOXIN, MOST OF

THEM WON'T GET SICK?

A. YES.

Q. FOR EXAMPLE, WE KNOW THAT PEOPLE, MANY THOUSANDS


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OR MILLIONS OF PEOPLE, CAN BE EXPOSED TO ASBESTOS AND

NOT GET SICK FROM IT?

A. YES.

Q. BUT SOME PEOPLE DO GET SICK FROM TOXIC

EXPOSURES?

A. YES, AND IT'S GENERALLY REFERRED TO AS GENETIC

SUSCEPTIBILITY.

Q. OKAY. SO ALL CHILDREN THAT GET EXPOSED TO SSRIS

DON'T GET BIRTH DEFECTS?

A. TRUE.

Q. AND THAT IS BECAUSE OF GENETIC SUSCEPTIBILITY?

A. PRESUMABLY.

Q. WHAT IS THE SECOND PRINCIPLE?

A. SO THE SECOND PRINCIPLE DESCRIBED HERE IS THE

TIMING, AND THAT IS SUSCEPTIBILITY TO TERATOGENIC AGENTS

VARIES WITH THE DEVELOPMENTAL STAGE AND AT THE TIME OF

EXPOSURE TO AN ADVERSE INFLUENCE. AND DESCRIBES HERE

WHAT ARE REFERRED TO AS CRITICAL PERIODS OF

SUSCEPTIBILITY OF AGENTS TO ORGAN SYSTEMS AFFECTED BY

THESE AGENTS.

Q. SO THAT MEANS -- THAT MEANS YOU HAVE TO GET

EXPOSED AT THE RIGHT TIME TO THE RIGHT AGENT FOR THE

BIRTH DEFECT TO OCCUR?

A. YES.

Q. AND I THINK DR. SADLER IS GOING TO TALK IN SOME


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DETAIL ABOUT THE EMBRYOLOGICAL ASPECTS OF EXPOSURE. BY

THE WAY, ARE YOU FAMILIAR WITH DR. SADLER'S BOOK ON

EMBRYOLOGY?

A. YES, I AM.

Q. DO YOU HAVE IT?

A. YES, I DO.

Q. THE THIRD PRINCIPLE OF TERATOLOGY IS WHAT?

A. SO THE THIRD PRINCIPLE HAS TO DO WITH MECHANISM

AND AS IT IS DESCRIBED HERE, IS THAT TERATOGENIC AGENTS

ACT IN SPECIFIC WAYS, WHICH WE USUALLY REFER TO AS

MECHANISMS OF ACTION OR MODES OF ACTION AND THAT THEY

IMPACT DEVELOPING CELLS AND TISSUES AND THAT THEY

INITIATE A SEQUENCE OF EVENTS THAT ULTIMATELY PRODUCE

ABNORMAL OUTCOMES IN DEVELOPMENT.

Q. THIS THIRD PRINCIPLE OF TERATOLOGY, IS THIS, AT

LEAST IN PART, WHAT YOU DO IN YOUR LAB THERE IN AUSTIN?

A. YES, IT IS.

Q. WE HAVE A SECOND SLIDE HERE ON THIS. IT'S THE

FIRST BULLET POINT, IT'S A CHEMICAL INTERACTS WITH A

SPECIFIC CELL TYPE. WHAT DOES THAT MEAN?

A. SO CHEMICALS, IN PARTICULAR, WHEN WE ARE LOOKING

AT CHEMICALS FOR TERATOGENIC EFFECT, WE WANT TO KNOW

WHAT CELLS EXPRESS THE TARGET OF THE CHEMICAL. SO A LOT

OF TIMES THE CHEMICAL INTERACTS WITH A SPECIFIC PROTEIN

AND THIS PROTEIN IS USUALLY EXPRESSED IN A SPECIFIC CELL


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TYPE. SO IN REGARDS TO SERTRALINE, WE ARE LOOKING AT

CELLS THAT WILL BE POSITIVELY EXPRESSING SERT

TRANSPORTER OR RECEPTORS FOR SEROTONIN.

Q. AND WHY DO WE CARE ABOUT THAT?

A. BECAUSE THAT IS WHAT IS GOING TO INITIATE THE

CASCADE AT THE CELLULAR LEVEL FOR THE CHEMICAL.

Q. THIS NEXT BULLET POINT: THE CELL TYPE WILL

ULTIMATELY PRODUCE SPECIFIC ORGAN/TISSUES WHICH IS

ADVERSELY AFFECTED BY THE CHEMICAL.

WHAT DOES THAT MEAN?

A. SO BASICALLY THIS IS -- YOU KNOW, DEVELOPMENT IS

A CONTINUOUS PROCESS, AND THOSE CELLS THAT ARE AFFECTED

EARLY ON WILL ULTIMATELY GIVE RISE TO TISSUES AND ORGANS

AND ORGANISM AND IT'S THESE EARLY CELLS THAT IF YOU

AFFECT THEM YOU CAN ULTIMATELY PRODUCE THE MALFORMATIONS

THAT WE WILL LOOK FOR LATER.

Q. WHAT IS THE FOURTH PRINCIPLE OF TERATOLOGY?

A. SO THE FOURTH PRINCIPLE WE REFERRED TO AS

ACCESS. HERE IT IS DESCRIBED AS THE ACCESS OF AN

ADVERSE INFLUENCE TO DEVELOPING TISSUES DEPENDS ON THE

NATURE OF THE INFLUENCE.

AND I THINK THIS COULD BE SPECIFIC IN

THAT THERE ARE BOTH PHYSICAL OR INFECTIOUS OR EVEN

CHEMICAL INTERACTIONS, AND THEY WILL AFFECT THE ORGANISM

DIFFERENTLY.


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Q. OKAY.

AND WE HAVE A SECOND SLIDE ON THIS. DOES

THIS HELP EXPLAIN THAT ANY BETTER?

A. YES. I WOULD LIKE TO -- ONE OF THE THINGS THAT

WE LIKE TO CONSIDER IS THAT IF THERE IS A SPECIFIC

FUNCTION ON THE EMBRYO OR FETUS OR THE MOTHER JUST THAT

THE CHEMICAL SHOULD BE CAPABLE OF REACHING THE EMBRYO OR

FETUS OR IT SHOULD ADVERSELY AFFECT THE MOTHER'S

PHYSIOLOGY THAT WOULD ADVERSELY AFFECT THE EMBRYO OR

FETUS DURING DEVELOPMENT.

AND IT IS DESCRIBED HERE, THE NATURE OF

THE AGENTS AND THE ROUTES AND DEGREE OF MATERNAL

EXPOSURE. AND THEN ADDITIONALLY, WE LIKE TO LOOK AT

PLACENTAL TRANSFER OR EVEN EARLIER THAN THAT,

SYNCYTIOTROPHOBLAST WHICH IS THE CELL THAT MAKES UP THE

PLACENTA, AND THE TRANSPORT OF THE CHEMICAL TO THE

EMBRYO OR FETUS. AND THEN ULTIMATELY WE ALSO HAVE AN

INTERACTION WITH THE FIRST PRINCIPLE, WHICH IS THE

IMPACT OF THE GENETICS OF THE CONCEPTUS AND THE MOTHER.

Q. SO WOULD IT BE FAIR TO SAY WHAT THIS MEANS IS

THE DRUG HAS GOT TO GET TO WHERE IT NEEDS TO GET TO

CAUSE THE PROBLEM?

A. YES, THAT WOULD BE CORRECT.

Q. AND THEN THE PRINCIPLE OF TERATOLOGY YOU

MENTIONED EARLIER IS VERY IMPORTANT. AND LET'S TALK


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ABOUT THIS. THIS SAYS THERE ARE FOUR MANIFESTATIONS OF

DEVIANT DEVELOPMENT, DEATH, MALFORMATION, GROWTH

RETARDATION AND FUNCTIONAL DEFICIT. WHY IS THIS SO

IMPORTANT?

A. SO THIS IS IMPORTANT BECAUSE LARGELY I THINK

PEOPLE THAT ARE UNFAMILIAR WITH TERATOLOGY ASSUME THAT

TERATOLOGY IS SPECIFIC TO CONGENITAL MALFORMATIONS AND

GROSS MALFORMATIONS. IN ACTUALITY, WE LOOK AT A VARIETY

OF DEVIANT DEVELOPMENTAL OUTCOMES, WHICH INCLUDE DEATH,

GROWTH RETARDATION, AND FUNCTIONAL DEFECT. SO IT'S NOT

LIMITED TO ONLY THE PRODUCTION OF GROSS MALFORMATIONS.

WE ALSO LOOK AT OTHER POTENTIALLY, EVEN MORE

CATASTROPHIC OUTCOMES, SUCH AS DEATH.

Q. SP WOULD IT BE FAIR TO SAY THAT IF YOU WERE

TESTING A COMPOUND AND ANY ONE OF THOSE FOUR OUTCOMES

WERE PRESENT, IT WOULD BE APPROPRIATE SCIENTIFICALLY TO

CONCLUDE THAT A DRUG WAS A TERATOGEN?

A. YES, I WOULD REFER TO THAT HAS A TERATOGENIC

EFFECT, YES.

Q. AND TELL US WHY WE CONSIDER DEATH TO BE

TERATOGENIC?

A. THERE ARE MULTIPLE REASONS, SOME OF WHICH ARE

DESCRIBED HERE, AND THAT I THINK IT'S IMPORTANT TO

EMPHASIZE AGAIN THAT IT'S NOT JUST STRUCTURAL

MALFORMATIONS WE ARE LOOKING AT, THAT THERE ARE OTHER


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PROBLEMS AND THAT DEATH ULTIMATELY HAS A CAUSE, AND THAT

THESE CAUSES OF DEATH, ALTHOUGH WE MAY NOT IDENTIFY

THEM, DIRECTLY THROUGH PATHOLOGY, WE SHOULD LOOK FOR

THEM. AND ULTIMATELY WHATEVER THE PATHOLOGICAL

EXPLANATION IS, A LOT OF TIMES IT WILL BE RELATED TO A

CONGENITAL MALFORMATION. IT'S JUST SIMPLY OUR ABILITY

TO DELVE INTO THE BIOLOGICAL SYSTEM AND IDENTIFY WHAT

ULTIMATELY IS DEVIANT DURING THE DEVELOPMENT THAT WILL

PRODUCE THE DEATH.

Q. DO WE KNOW AND UNDERSTAND OR DO YOU, I SHOULD

SAY, DO TERATOLOGISTS KNOW AND UNDERSTAND THAT DEATH

MANY TIMES IN UTERO IS DUE TO STRUCTURAL MALFORMATIONS?

A. YES, EITHER A PHYSIOLOGIC CHANGE THAT IS

INCOMPATIBLE WITH LIFE OR A STRUCTURAL CHANGE THAT IS

INCOMPATIBLE.

Q. AND THEN THE SIXTH PRINCIPLE OF TERATOLOGY IS

MANIFESTATIONS OF DEVIANT DEVELOPMENT INCREASE IN

FREQUENCY AND DEGREE AS DOSAGE INCREASES FROM THE NO

OBSERVABLE ADVERSE EFFECT LEVEL TO A DOSE PRODUCING

100 PERCENT LETHALITY.


A. SO TYPICALLY IF WE SEE A MANIFESTATION OF

DEVIANT DEVELOPMENT, BASED ON THE FIFTH PRINCIPLE, WE

THEN WOULD GO IN AND WE WOULD LOOK TO SEE WHAT IS THE

LOWEST DOSE THAT CAN PRODUCE THESE DEVIANT EFFECTS.


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THIS IS REFERRED TO COMMONLY AS THE NOAEL, WHICH IS THE

NO OBSERVABLE ADVERSE EFFECT LEVEL, SO IT'S JUST

BASICALLY LOWERING THE DOSE UNTIL THE ADVERSE EFFECT

GOES AWAY. AND THIS IS USED TO CALCULATE SAFETY

MARGINS.

ADDITIONALLY, TYPICALLY NOT PRACTICE, BUT

YOU CAN ALSO DO INCREASING DOSE RESPONSES UNTIL YOU

PRODUCE 100 PERCENT LETHALITY IN EITHER THE DAM OR THE

EMBRYO OR FETUS.

Q. NOW, ARE THESE TESTS USING THE SIXTH PRINCIPLE

OF TERATOLOGY, ARE THESE TESTS THAT ARE DONE IN THE

LABORATORY THERE AT THE FINNELL LAB?

A. YES, THEY ARE.

Q. ARE THESE TESTS THAT ARE DONE IN ANIMALS THEN?

A. YES, THEY ARE.

Q. AND BY THE WAY, AT THE FINNELL LAB, DO YOU DO

BOTH IN VITRO TESTING AND IN VIVO TESTING?

A. YES, WE DO.

Q. SO DO YOU LOOK AT THE MOLECULAR AND CELLULAR AT

THE FINNELL LAB?

A. YES, I DO.

Q. YOU DO, OKAY.

WHAT IS ADVERSE OUTCOME PATHWAYS?

A. SO ADVERSE OUTCOME PATHWAYS ARE A METHOD THAT IS

IMPLEMENTED, THAT IS CONSISTENT WITH BRADFORD HILL BUT


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IS ORGANIZED IN A FRAMEWORK SO WE CAN ANALYZE EACH LEVEL

OF BIOLOGICAL ORGANIZATION FOR CAUSALITY OF A CHAIN OF

EVENTS BIOLOGICALLY.

Q. WOULD IT BE FAIR TO SAY -- I HOPE SO BECAUSE I

SAID IT THIS MORNING -- WOULD IT BE FAIR TO SAY THAT THE

ADVERSE OUTCOME PATHWAYS ARE THE WAY WHERE SCIENTISTS,

SUCH AS YOURSELF, PRACTICALLY IMPLEMENT WILSON'S

PRINCIPLES AND BRADFORD HILL IN THE REAL WORLD?

A. YES, THEY ARE.

Q. IS THAT WHERE -- IS IT THE ADVERSE OUTCOME

PATHWAYS THAT SCIENTISTS USE TO TRY TO GET THE ANSWERS

TO THE QUESTIONS IN WILSON'S PRINCIPLES?

A. YES, THEY ARE.

Q. AND I ACTUALLY -- OR YOU, I SHOULD SAY, PUT

TOGETHER THIS FLOW SHEET, THIS FLOW CHART. CAN YOU TELL

THE COURT WHAT THIS IS AND WHY IT IS IMPORTANT?

A. SO THIS IS THE GENERAL FRAMEWORK THAT IS USED TO

ORGANIZE AN ADVERSE OUTCOME PATHWAY. AS DESCRIBED HERE,

FROM LEFT TO RIGHT, WE LOOK AT THE MOLECULE OR THE

CHEMICAL ITSELF, WHICH IS DESCRIBED HERE AS POTENTIAL

TOXICANT THAT WE ARE GOING TO TEST AN ADVERSE OUTCOME

PATHWAY. WE WANT TO -- WE LOOK AT THE LITERATURE OR

DETERMINE EXPERIMENTALLY THE INTERACTION IT HAS AT THE

MOLECULAR LEVEL. AND THAT IS HOW THE CHEMICAL INTERACTS

WITH SPECIFIC RECEPTORS OR LIGANDS. DOES IT INTERACT


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WITH THE DNA, POTENTIALLY CREATE MUTATIONS OR ALTER THE

CHANGES IN CELLS, OR DOES IT IMPACT PROTEINS, THAT IS

BIND TO A PARTICULAR PROTEIN AND CAUSE PROTEIN

DEGRADATION.

SO BASICALLY WE ARE LOOKING AT BIOLOGICAL

ORGANIZATION AND ANALYZING THIS IN A HIERARCHICAL

STRUCTURE. AND ULTIMATELY, AS WE BUILD UPON THIS, WE

BUILD COMPLEXITY. AND THE NEXT LEVEL WOULD BE LOOKING

AT THE IMPACTS ON THE CELL, WITH THE CHEMICAL AT A

MOLECULAR LEVEL. THEN FROM THE CELL WE WANT TO KNOW HOW

THE CELL -- THESE CELLS WILL FORM TISSUES, AND ALSO

THESE TISSUES ULTIMATELY WILL CREATE ORGANS. AND THEN

THIS IS WHAT IS COMPOSED OF, BODY OF ORGANS, AND THEN

ULTIMATELY THE IMPACT THIS HAS ON THE ORGANISM. AND AS

THE POPULATION OF ORGANISMS, WE LOOK AT ALSO THE

POPULATION EFFECTS, AND THAT IS THE EPIDEMIOLOGICAL

LEVEL OF THESE STUDIES.

Q. SO THIS PATHWAY FOLLOWS LOGICALLY AND

SCIENTIFICALLY FROM THE INTRODUCTION OF THE CHEMICAL

EARLY ON IN EMBRYOGENESIS THROUGH TO EPIDEMIOLOGY

STUDIES?

A. YES, IT DOES.

Q. IS THIS WHAT YOU AND DR. FINNELL DO IN YOUR LAB

EACH AND EVERY DAY?

A. YES, IT IS.


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Q. IN SOME FORM OR FASHION, IS THIS WHAT YOUR

RESEARCH IS AT THE FINNELL LAB?

A. YES, IT IS.

Q. IS THIS THE GENERALLY ACCEPTED METHODOLOGY FOR

DETERMINING TERATOGENS IN THE WORLD?

A. YES. THIS IS CURRENTLY WHAT IS EXPECTED BY

REGULATORY BODIES FOR DETERMINING ADVERSE OUTCOME

PATHWAYS, BE THOSE EPA OR THE WORLD HEALTH ORGANIZATION.

Q. NOW, ARE THERE TIMES WHEN SOMEBODY COMES TO YOU

AND SAYS I WENT AN ADVERSE OUTCOME PATHWAY FOR A

PARTICULAR DRUG OR COMPOUND AND YOU CAN'T FILL IN ALL

THE CHARTS BECAUSE THE RESEARCH HAS NOT BEEN DONE?

A. THAT IS CORRECT.

Q. AND THEN DOES YOUR LAB SOMETIMES GET TO DO THE

RESEARCH TO FILL IN THE GAPS AND SCIENCE?

A. YES.

Q. AND DO YOU ALL DO THAT?

A. YES, WE HAVE.

Q. AND WOULD THE RESEARCH AT YOUR LAB INCLUDE

EVERYTHING FROM THE VERY BEGINNING OF THE FLOW CHART TO

THE VERY END WITH HELPING -- WITH THE INTERPRETATION OF


A. YES, WE ARE CAPABLE OF DOING EACH LEVEL OF

ORGANIZATION.

Q. DO YOU GUYS MAP THE HUMAN GENOME AT THE FINNELL


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LAB?

A. WE DO WHAT IS REFERRED TO AS RESEQUENCING. WHEN

I WAS IN INDUSTRY, IT WAS STILL PART OF THE HUMAN GENOME

PROJECT. SO I DID CONTRIBUTE TO HUMAN GENOME PROJECT

BUT CURRENTLY WE ARE WHAT IS REFERRED TO AS

RESEQUENCING, WE GO BACK IN AND WE WILL RESEQUENCE

PATIENT POPULATIONS TO LOOK AT GENETIC VARIABILITIES.

Q. AND WHY ARE YOU DOING THAT, WHY IS THAT

IMPORTANT FOR BIRTH DEFECTS?

A. IT KIND OF GOES BACK TO THE FIRST PRINCIPLE, AS

FAR AS WILSON'S PRINCIPLE. AND THERE ARE GENETIC

MODIFIERS FOR BIRTH DEFECT RISKS. AND SO WE GO IN AND

WE LOOK AT THE DIFFERENT GENE VARIANTS AND LOOK FOR

INTERACTIONS WITH ENVIRONMENTAL CHEMICALS OR BEHAVIORS

IN GENETIC POPULATION, GENETICALLY DIVERSE POPULATIONS.

Q. AND SO THAT IS NOT TO SUGGEST, THOUGH, THAT

PEOPLE THAT ARE GETTING AFFECTED BY CHEMICALS HAVE

SOMETHING GENETICALLY WRONG WITH THEM, IS IT?

A. NO, THESE ARE NOT GENETIC DEFECTS. THESE ARE

JUST GENETIC SUSCEPTIBILITIES. SO IN THE ABSENCE OF A

CHEMICAL EXPOSURE, THESE PATIENTS WOULD BE OTHERWISE

EXPECTED TO DEVELOP NORMALLY.

Q. AND WHY ARE YOU TRYING TO IDENTIFY AN EXPOSED

POPULATION CERTAIN TYPES OF GENES, WHERE PEOPLE HAVE

CERTAIN TYPES OF GENES, WHAT IS THE END GAME THERE?


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A. SO THE END GAME, AS I REFERRED TO EARLIER, IS

PREVENTING PREVENTABLE BIRTH DEFECTS. AND IF WE CAN

LOOK AT THE GENETIC CAUSES OF BIRTH DEFECTS, WE CAN

UNDERSTAND SOMETHING ABOUT THE MOLECULAR CASCADES, AND

ULTIMATELY THIS HELPS US DESIGN POTENTIAL INTERVENTION

STRATEGIES, AND WHETHER THOSE WOULD BE NUTRACEUTICALS OR

PROVIDING ANTIOXIDANTS OR INSULIN TO ANIMALS THAT ARE

EXPOSED TO CERTAIN CHEMICALS. IT'S ULTIMATELY TRYING TO

FIND REMEDIES FOR EXPOSURES.

Q. SO FOR EXAMPLE, IF YOU WERE ABLE TO IDENTIFY A

GENE THAT A PARTICULAR -- THAT WOMEN HAVE THAT PUT THEM

AT INCREASED SUSCEPTIBILITY FOR AN EXPOSURE, AND YOU

IDENTIFIED THEM, THEN YOU COULD INFORM THOSE WOMEN THAT

THEY ARE GENETICALLY SUSCEPTIBLE FOR A PARTICULAR

COMPOUND OR DRUG AND THEY COULD AVOID IT?

A. YES. WE ARE CURRENTLY DOING SIMILAR RESEARCH OF

THAT WITH THE ANTIEPILEPTIC DRUGS AND THAT WE'VE

IDENTIFIED VARIANTS IN THE METABOLISM OF THE

ANTIEPILEPTIC DRUGS AND ULTIMATELY ARE TRYING TO TEST

NUTRITIONAL STRATEGIES IN ORDER TO OVERCOME THAT OR

POTENTIALLY JUST IDENTIFY THE GENETIC POPULATION THAT IS

AT RISK, AND THEN SUGGEST THAT THEY MAY WANT TO AVOID

THE MEDICATION DURING THEIR PREGNANCY OR THE GENERAL

POPULATION MAY NOT BE AT SUCH AN INCREASED RISK.

Q. ARE ANTIEPILEPTICS, ARE THEY TERATOGENIC?


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A. AS A CLASS, THEY ARE GENERALLY REFERRED TO AS

TERATOGENIC COMPOUNDS, YES.

Q. NOW, WHEN I ASKED YOU A QUESTION, BEFORE WE GOT

HERE, AND DID ALL THIS, I SAID IS THIS ADVERSE OUTCOME

PATHWAY, ARE THERE OTHER PEOPLE DOING IT AND YOUR

RESPONSE WAS TO SEND ME THIS PAPER, WASN'T IT?

A. YES, IT WAS.

Q. AND THIS WAS A 2013 PAPER BY MEEK. AND WHAT IS

THE IMPORTANCE OF THIS PAPER?

A. SO THIS PAPER IS IN REFERENCE -- IT GIVES

INTERNATIONAL PRECEDENTS TO THIS MEMBERS OF THE -- OF

OUR OWN U.S. ENVIRONMENTAL PROTECTION AGENCY IN ADDITION

TO THE WHO, THE WORLD HEALTH ORGANIZATION, AND ALSO SOME

MEMBERS OF THE CONSORTIUM, LOOKING AT POTENTIAL ADVERSE

OUTCOMES, ARE BASICALLY PUTTING FORTH THE ADVERSE

OUTCOME PATHWAY AS THE ESTABLISHED METHOD, THAT IS GOING

TO BE EXPECTED METHOD FOR LOOKING AT ADVERSE EVENTS OR

ADVERSE OUTCOMES DUE TO CHEMICAL EXPOSURE.

Q. AND THE UNDERLINED PORTION YOU HAVE SAYS, THIS

ALLOWS FOR THE DEVELOPMENT AND USE OF ALTERNATIVE IN

VITRO ASSAYS TO TARGET PARTICULAR CELLULAR OR

PHYSIOLOGICAL KEY EVENTS ALONG A SPECIFIC PATHWAY.

WHAT DOES THAT MEAN AND WHY IS IT

IMPORTANT?

A. SO THE IMPORTANCE OF THIS IS, WE DON'T JUST RELY


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ON EPIDEMIOLOGY DATA. WE DON'T JUST RELY ON ANIMAL

STUDIES. WE DO CONSIDER ALL OF THOSE. BUT

ADDITIONALLY, WE CAN DESIGN SPECIFIC AND MECHANISTIC

STUDIES USING TISSUES OR CELLS, AND THESE ARE GENERALLY

REFERRED TO AS IN VITRO ASSAYS, AND ULTIMATELY DESIGN

THESE ASSAYS IN ORDER TO TEST MODES OF ACTION OR

MECHANISMS OF ACTION AND USE THE ENTIRETY OF THE DATA

BOTH -- THAT IS AVAILABLE FOR MOLECULAR, CELLULAR,

TISSUE, ORGAN AND WHOLE ANIMAL STUDIES IN ADDITION TO

THE HUMAN STUDIES AS WELL.

Q. AND THEN IT GOES ON TO SAY: ONCE THE MODE OF

ACTION HAS BEEN ESTABLISHED, THE KEY EVENT DATA CAN BE

USED FOR READ-ACROSS FROM OTHER CHEMICALS.


A. SO ONCE WE HAVE ESTABLISHED A PARTICULAR

MECHANISM OF ACTION THAT PRODUCES AN ADVERSE OUTCOME, WE

HAVE AN ASSAY THAT IS DESIGNED FOR THAT. WE CAN TEST

HOW ROBUST THAT ASSAY IS USUALLY WITH TRAINING SETS OF

CHEMICALS, AND THEN WE CAN SCREEN ADDITIONAL CHEMICALS,

BE THOSE ENVIRONMENT CHEMICALS OR PHARMACEUTICAL

CHEMICALS AND HAVE A PREDICTIVE OUTCOME ON WHICH ONES

WOULD BE EXPECTED TO HAVE SIMILAR ADVERSE OUTCOME.

Q. SO I'M GOING TO TRY TO BREAK THAT DOWN.

DOES THAT MEAN IF YOU TEST ONE CHEMICAL

AND FIND OUT IT'S A TERATOGEN AND YOU HAVE GOT OTHER


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CHEMICALS IN THE SAME CLASS WITH THE SAME MECHANISM OF

ACTION, WE CAN ASSUME THEY WILL BE TERATOGENS ALSO?

A. YES, IT DOES.

Q. OKAY.

IS THAT SCIENTIFICALLY ACCEPTED?

A. GENERALLY, IF YOU HAVE A COMMON MECHANISM OF

ACTION, AND THAT MECHANISM OF ACTION IS PRODUCING A

COMMON ENDPOINT THEN THAT -- I MEAN, THAT IS JUST HOW

THE DATA WORKS OUT, THAT WOULD BE RELATIVELY ACCEPTED

SCIENTIFICALLY.

Q. ANYTHING ELSE ON THIS PAPER YOU WANT TO POINT

OUT?

A. I THINK YOU HAVE ALLUDED TO IN YOUR OPENING

STATEMENT THE BOTTOM RIGHT HERE, AND THAT A LOT -- KIND

OF SCIENTISTS ARE A SKEPTICAL BUNCH AND THAT WHEN THERE

IS ONLY EPI DATA WE GENERALLY WANT TO KNOW HOW THE

MECHANISM WORKS. AND THIS DESCRIBES HERE WITH AMBIENT

PARTICLE MATTER, AND THAT WHEN THEY INITIALLY FOUND IN

EPI STUDIES THAT THERE WAS AN INCREASED RISK FOR

CARDIOVASCULAR MORTALITY, IT WAS ONLY AFTER THE SCIENCE

STUDY WAS DONE. AND WE ACTUALLY LOOKED AT THE IMPACT ON

THE CELLS AND THE TISSUES AND THE ANIMALS DID THE

SCIENTIFIC COMMUNITY READILY ACCEPT USING ADVERSE

OUTCOME PATHWAYS, THAT THESE PARTICULATES COULD

ADVERSELY AFFECT THE CARDIOVASCULAR HEALTH OF THE


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PEOPLE.

Q. SO WHAT YOU ARE SAYING IS, WHEN EPI STUDIES WERE

DONE IN THIS PARTICULAR MATTER, THEY SHOWED A POSITIVE

OUTCOME MEANING IT LOOKED LIKE THERE WAS A CAUSE AND

EFFECT RELATIONSHIP, BUT UNTIL THE MECHANISTIC RESEARCH

WAS DONE TO SUPPORT THE CAUSAL CHAIN, PEOPLE WERE A

LITTLE SKEPTICAL?

A. ABSOLUTELY.

Q. AND THEN THE KIND OF RESEARCH YOU DID IS THE

KIND OF RESEARCH THAT CONFIRMED THE EPIDEMIOLOGY?

A. YES, IT IS.

Q. SO LET'S TALK ABOUT SSRIS AND GENERALLY AT FIRST

AND THEN SPECIFICALLY. WHAT IS THE PURPOSE OF THIS

SLIDE?

BY THE WAY, YOU HELPED ME, DR. CABRERA,

PUT THIS POWERPOINT TOGETHER TO HELP EXPLAIN YOUR

TESTIMONY TO THE COURT?

A. YES.

Q. AND TELL THE COURT THE IMPORTANCE OF THIS SLIDE

AND WHY IT MATTERS TO YOU?

A. SO THIS SLIDE SHOWS A NUMBER OF THINGS. AT THE

TOP YOU WILL SEE THE DIFFERENT COMPOUNDS THAT ARE

REFERRED TO AS THE SSRIS OR THE SELECTIVE SEROTONIN

REUPTAKE INHIBITORS. AND YOU CAN SEE THERE ARE

DIFFERENCES IN THEIR CHEMICAL STRUCTURES, WHICH HAS


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ALREADY BEEN POINTED OUT. THEY ARE DIFFERENT CHEMICALS

AND THEY HAVE DIFFERENT CHEMICAL PROPERTIES, THEY HAVE

DIFFERENT METABOLIC PROPERTIES AND THAT IS DESCRIBED

HERE. AS FAR AS THE TIMING THAT IS SHOWN, FOUR ROWS

DOWN AND FIVE ROWS DOWN IS THE METABOLISM OF THEM. WE

ARE NOT ARGUING THAT THEY DON'T HAVE DIFFERENT CHEMICAL

PROPERTIES OR DIFFERENT PROPERTIES AS FAR AS THEIR

METABOLISM GOES. WHAT WE'RE IDENTIFYING IS AT THE

BOTTOM OF EACH ONE OF THESE, WHICH HAS BEEN HIGHLIGHTED,

IS THAT THEIR COMMON -- WHAT IS PRESENTED AS THERAPEUTIC

MECHANISM OF ACTION HAS TO DO WITH THE IMPACT OF EACH

ONE OF THESE CHEMICALS ON THE SEROTONIN TRANSPORTER,

WHICH IS GENERALLY REFERRED TO AS SERT, S-E-R-T. AND

ULTIMATELY, THE ALTERATIONS THAT THIS HAS ON SEROTONIN

CONCENTRATIONS, BOTH NEUROLOGICALLY AND SYSTEMICALLY, IT

IDENTIFIES IT HERE NEURONAL IMPACTS, BUT THERE'S ALSO AN

IMPACT ON THE BLOOD AND THE CHANGES IN THE SEROTONIN IN

THE BLOOD AS WELL.

Q. AND FOR TERATOLOGISTS IS THIS THE APPROPRIATE

WAY TO LOOK AT CLASSES OF DRUGS?

A. IF THE MECHANISM OF ACTION OF THE CHEMICALS IS

ALSO THE MECHANISM OF ACTION THAT IS EXPECTED FOR THE

TERATOGENICITY THEN YES, THAT WOULD BE THE CORRECT

PROCEDURE.

Q. ALL RIGHT. DO YOU BELIEVE, DR. CABRERA, THAT


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SSRIS ARE A CLASS OF TERATOGENS?

A. YES, THEY ARE.

Q. DO YOU BELIEVE THAT SSRIS ARE A CLASS THAT ARE

CAPABLE OF CAUSING A VARIETY OF DIFFERENT BIRTH DEFECTS?

A. YES, THEY DO.

Q. WHEN YOU UNDERTOOK TO REVIEW THE LITERATURE IN

THIS CASE, DID YOU FIND THAT THERE WAS ENOUGH LITERATURE

TO ANSWER THE QUESTIONS THAT YOU HAD WITH RESPECT TO

WHETHER SSRIS WERE TERATOGENS?

A. YES, THERE IS.

Q. GIVE THE COURT AN IDEA OF THE ROBUSTNESS OF THE

LITERATURE THAT IS AVAILABLE FOR SOMEBODY LIKE YOURSELF.

A. IN REGARDS TO PUBLICATIONS AT EACH LEVEL FOR THE

ADVERSE OUTCOME PATHWAY, THERE IS, AS WE WOULD BE

EXPECTED, IN ORDER TO FULFILL BRADFORD HILL CRITERIA AT

EACH LEVEL, THERE ARE MULTIPLE STUDIES CONFIRMING THE

IMPACTS OF ALTERING SEROTONIN, WHICH EACH ONE OF THESE

COMPOUNDS DOES BY THE LABEL AND ULTIMATELY HOW THAT CAN

INEVITABLY IMPACT THE DEVELOPING EMBRYO OR FETUS.

Q. AND THE NEXT SLIDE YOU HAVE UP HERE IS

SEROTONIN, WHAT IS SEROTONIN?

A. SO SEROTONIN, AS DESCRIBED HERE, IS A MOLECULE

THAT IS USED FOR SELF SIGNALING AND THAT IS IT ALLOWS

CELLS TO COMMUNICATE WITH EACH OTHER. AND IT REGULATES

A VARIETY OF CELLULAR PROCESSES DESCRIBED HERE, WHICH


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INCLUDE CELL PROLIFERATION, MIGRATION, WHICH IS THE

MOVEMENT OF CELLS FROM ONE AREA TO ANOTHER. ALSO THE

DIFFERENTIATION, AND DEVELOPMENTALLY THAT MEANS THE

CHANGING OF A CELL. SO AS I REFERRED TO EARLIER, STEM

CELLS, THESE ARE EARLY CELLS IN DEVELOPMENT THAT CAN

ULTIMATELY GIVE RISE TO DIFFERENT TYPES OF CELLS. SO

THEY MAY DEVELOP INTO HEART TISSUE, IF THEY ARE A TYPE

OF CARDIAC STEM CELL OR ANOTHER TYPE OF TISSUE. THEN

ALSO CHANGES IN GENE EXPRESSION, AND THAT IS HOW THE

CELL ACTUALLY PERFORMS DIFFERENT TASKS. IT USES ITS DNA

TO CREATE THE EXPRESSION OF GENES AND ULTIMATELY THESE

GET TRANSLATED INTO PROTEINS. AND PROTEINS ARE KIND OF

THE ENGINES OF THE CELL TO PERFORM DIFFERENT TASKS.

Q. THIS IS NOT EVEN CONTROVERSIAL UP HERE ON THE

SCREEN, IS IT, FOR SCIENTISTS?

A. THIS IS READILY ACCEPTED.

Q. EVERYBODY AGREES WITH WHAT YOU HAVE ON HERE WITH

RESPECT TO CELLULAR SIGNALING AND SEROTONIN, DON'T THEY?

A. YES.

Q. ARE YOU FAMILIAR WITH DR. SADLER'S LITERATURE ON

SEROTONIN?

A. YES, I AM.

Q. ARE YOU FAMILIAR WITH DR. LEVIN'S RESEARCH IN

THE AREA OF BIRTH DEFECTS IN SEROTONIN?

A. YES, I AM.


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Q. AND I'M ASSUMING YOU ARE AWARE OF DR. BERARD'S

RESEARCH IN EPIDEMIOLOGY AND BIRTH DEFECTS?

A. YES, I AM.

Q. HAVE YOU USED IN FORMING YOUR OPINION EACH AND

EVERY -- SOME OF THEIR ARTICLES OF EACH AND EVERY ONE OF

THOSE THREE EXPERTS IN ARRIVING AT YOUR CONCLUSIONS?

A. YES, I HAVE.

Q. TELL US WHAT THIS SLIDE IS AND WHY IT IS

IMPORTANT? WELL, THERE IS SADLER AND LEVIN. I GUESS

THAT IS WHY. GO AHEAD AND EXPLAIN THIS TO ME, DR.

CABRERA.

A. SO THIS DESCRIBES THE IMPORTANCE OF SEROTONIN

DEVELOPMENTALLY. AND I THINK THAT IS WHAT THE RELEVANCE

HERE IS, IS WE WANT TO KNOW HOW SEROTONIN AND THAT IS

HOW SSRIS, WHICH ALTER SEROTONIN CONCENTRATIONS, AND HOW

THIS WILL IMPACT THE DEVELOPING EMBRYO OR FETUS. AND AS

WE SEE HERE, SEROTONIN HAS BEEN SHOWN TO BE AN IMPORTANT

SIGNALING MOLECULE IN GASTRULATION. GASTRULATION IS A

DEVELOPMENTAL EVENT IN YOUR LIFE, WHICH DEVELOPMENTAL

BIOLOGISTS WILL OFTEN REFER TO AS THE MOST IMPORTANT

EVENT IN YOUR LIFE, AND THAT IS, WHEN YOU TURN FROM A

BALL OF CELLS INTO A THREE-LAYERED STRUCTURE OF AN EARLY

EMBRYO, AND THIS IS DEPENDENT UPON SEROTONIN SIGNALING.

ADDITIONALLY, THE ESTABLISHMENT OF

LATERALITY, WHICH IS A LEFT AND RIGHT AXIS FORMATION.


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SO WE ARE BI-SYMMETRICAL, BUT A LOT OF OUR SYSTEMS ARE

ASYMMETRICAL. AND SO THE ESTABLISHMENT OF THIS LEFT AND

RIGHT ASYMMETRY HAS ALSO BEEN IMPLICATED BY SEROTONIN

AND ULTIMATELY PROCESSES SUCH AS CRANIOFACIAL

DEVELOPMENT, CARDIAC MORPHOGENESIS, EVEN BONE

DEVELOPMENT HAVE ALL BEEN IMPLICATED BY SEROTONIN.

Q. SO EXPLAIN GENERALLY HOW IT WORKS, HOW DOES

SEROTONIN OR DISRUPTING OR ALTERING LEVELS OF SEROTONIN

CAUSE BIRTH DEFECTS?

A. SO SEROTONIN, IN AND OF ITSELF, AND THAT IS KIND

OF REFERENCED HERE AT THE BOTTOM, AND THAT IS

PERTURBATIONS, WHETHER THERE IS TOO MUCH SEROTONIN OR

TOO LITTLE SEROTONIN, IN TERMS OF ITS SIGNALING ABILITY.

IF YOU ARE IN A CROWDED ROOM AND EVERYONE IS SPEAKING AT

A HIGH VOLUME OR PITCH, IT WOULD BE DIFFICULT TO CONVEY

MESSAGES TO EACH OTHER, AND THE PRESENCE OF EXCESS

SEROTONIN, THE CELLS INEFFECTIVELY COMMUNICATE WITH EACH

OTHER. IN THE ABSENCE OF SEROTONIN, THEY ALSO HAVE

AN INABILITY TO COMMUNICATE PROPERLY. AND IT'S

ULTIMATELY THIS INABILITY TO COMMUNICATE THAT PRODUCES

CONGENITAL MALFORMATIONS WHICH INCLUDE DISRUPTING THINGS

LIKE CELL PROLIFERATION OR MIGRATION OF CELLS TO SITES

WHERE THE CELL SHOULD BE MIGRATING TO.

Q. SO WOULD IT BE FAIR TO SAY THAT THE INTRODUCTION

OF AN SSRI LIKE ZOLOFT INTO A PREGNANT MOTHER WOULD


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INTERFERE WITH THIS CELL SIGNALING?

A. ABSOLUTELY. THE PRESENCE OF AN SSRI, HAS

CLEARLY ACTUALLY SHOWN IN THE LABEL IS TO ALTER

SEROTONIN LEVELS IN THE BRAIN, PARTICULARLY IN THE

SYNAPSIS BY INHIBITING SEROTONIN TRANSPORTER. THIS ALSO

HAS AN EFFECT ON THE BLOOD LEVELS AND ULTIMATELY

DECREASES PLATELET CONCENTRATIONS OF SEROTONIN. AND AS

YOU SEE HERE, WHETHER IT'S A DECREASE OR AN INCREASE, AS

YOU SEE A DECREASE IN THE BRAIN OR A DECREASE IN THE

BLOOD, THIS IS PARTICULARLY IMPORTANT FOR THE MATERNAL

SYSTEM, WHERE DECREASED AMOUNTS OF SEROTONIN HAD BEEN

SHOWN IN THE GENETIC MODEL, THAT IS THE COTE PAPER IN

2006 AND WHEN THEY HAVE LOW SEROTONIN LEVELS DUE TO

GENETIC DEFICIENCY IN THE PRODUCTION OF SEROTONIN, THEIR

OFFSPRING PRESENT WITH CONGENITAL MALFORMATIONS. AND

IT'S NOT THE OFFSPRING'S GENETIC PROBLEM, IT'S ACTUALLY

TE MATERNAL SYSTEMS HAVING LOW SEROTONIN LEVELS THAT

CREATES THE PROBLEM.

Q. WHY ARE THEY LOW SEROTONIN LEVELS IF WE SUPPOSED

TO INCREASE IT FROM THE DRUG?

A. THE INCREASE IS DOCUMENTED IN THE BRAIN.

ULTIMATELY THE PLATELETS ALSO USE THE SEROTONIN

TRANSPORTER TO ACCUMULATE SEROTONIN AS WELL. THE SUPER

DOMINANCE RESERVOIR FOR SEROTONIN IN THE BLOOD AND

ULTIMATELY CAUSES A DECREASE OF BLOOD SEROTONIN IN THE


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MATERNAL SYSTEM.

Q. BEFORE YOUR REPORT, YOU REVIEWED THIS DOCUMENT,

AND I WANT YOU TO EXPLAIN TO THE COURT WHY THIS IS

IMPORTANT. LET ME READ IT INTO RECORD.

IT SAYS: THE MOST DEFINITIVE STUDY

AVAILABLE IS WITH FLUOXETINE, THAT IS AN SSRI, THAT IS

PROZAC MADE BY ELI LILLY. IS THAT RIGHT, DR. CABRERA?

A. YES.

Q. IT SAYS: WHICH SHOWED EFFECTS ON GROWTH, CNS,

AND FUNCTION, AND REPRODUCTIVE DEVELOPMENT AND FUNCTION.

BECAUSE ALL OF THESE FINDINGS ARE BELIEVED TO BE

MECHANISM RELATED, WE EXPECT SERTRALINE TO PRODUCE

SIMILAR FINDINGS. THEREFORE, AN ADDITIONAL STUDY WITH

SERTRALINE WOULD NOT BE EXPECTED TO ADD TO THIS BODY OF

WORK.

DO YOU AGREE WITH WHAT PFIZER IS SAYING

HERE?

A. YES, I DO.

Q. WAS THIS ANOTHER WAY OF SAYING THAT IF WE HAVE

SOME STUDIES THAT PROVE THAT PROZAC OR PAXIL ARE

TERATOGENIC IN INDUCING BIRTH DEFECTS, BECAUSE IT'S THE

SAME MECHANISM OF ACTION IN SERTRALINE, WE CAN EXPECT

THE SAME RESULTS?

A. YES, THAT IS WHAT IT SAYS.

Q. DO YOU AGREE WITH THAT, DR. CABRERA?


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151

A. I DO.

Q. IS THAT BORNE OUT IN ALL OF THE LITERATURE THAT

YOU HAVE REVIEWED?

A. FOR COMMON MECHANISMS OF ACTION, PARTICULARLY

FOR THE DEVELOPMENT OF TERATOGENESIS, YOU WOULD EXPECT

COMMON EFFECTS AS WELL.

Q. NOW, WHAT IF THEY SAY, BUT WAIT A SECOND, DR.

CABRERA, THIS IS A JUVENILE TOXICITY STUDY. THIS IS

SOMEBODY ALREADY BORN, THIS IS DIFFERENT. WHAT DO YOU

SAY TO THAT?

A. WELL, DEVELOPMENT IS A CONTINUUM. I ASSUME

EVERYONE HERE, AS YOU GROW UP, WHEN YOU ARE BORN YOU ARE

NOT FULLY DEVELOPED. YOUR BRAIN CERTAINLY IS NOT FULLY

DEVELOPED, AND THE RISKS OF EXPOSURE IN THE JUVENILE

SYSTEM IS JUST AS SEVERE. THAT IS, THE RISK FOR

BEHAVIOR. IF YOU LOOK AT THE SERT MUTANT, THAT IS THE

SERT MOLMOL (SIC) WHICH ACTUALLY HAS A KNOCKOUT GENETIC

CONDITION. IN A PARTICULAR BACKGROUND THIS ANIMAL

PRESENTS WITH AUTISM-TYPE BEHAVIOR, OBESITY AND OTHER

DEVELOPMENTAL PROBLEMS. THE SERT MUTANT ALSO HAS BONE

GROWTH MORPHOLOGY PROBLEMS. IT HAS BEEN DOCUMENTED IN

THE LITERATURE. SO BASICALLY WHAT THEY ARE SUGGESTING

IS THAT BECAUSE OF THE IMPACT OF FLUOXETINE. AND I

WOULD ARGUE ALSO -- I HAVE LOOKED AT SOME OF THE OTHER

SSRIS AS WELL, PAROXETINE, AS WELL, THAT YOU SEE THESE


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IMPACTS ON THE JUVENILE SYSTEM, YOU WOULD EXPECT IT FOR

THE OTHER SSRIS AS WELL.

Q. WOULD YOU ALSO IT IN A DEVELOPING FETUS?

A. YES.

Q. YOU SAW THIS IN THE OPENING STATEMENT. YOU

REVIEWED THIS PFIZER LABEL?

A. YES.

Q. DO YOU AGREE WITH WHAT PFIZER SAYS HERE, THAT

XANAX BECAUSE OF OTHER MEMBERS OF THE BENZODIAZEPINE

CLASS, XANAX IS ALSO ASSUMED TO BE CAPABLE OF CAUSING AN

INCREASED RISK OF CONGENITAL ABNORMALITIES WHEN

ADMINISTERED TO A PREGNANT WOMAN DURING THE FIRST

TRIMESTER.

DO YOU AGREE WITH PFIZER'S LABEL HERE?

A. I WOULD ACTUALLY SUGGEST THAT, YOU KNOW,

PROBABLY WOULD HAVE BEEN MORE TESTING, BUT -- AND THEY

GROUPED THE CLASS BENZODIAZEPINE AND XANAX BEING A

MEMBER OF THAT CLASS, AND IT SEEMS THAT THEY ARE WILLING

TO ACCEPT THAT IT WAS THE CLASS EFFECT AND THEY ALSO

EXPECTED CONGENITAL ABNORMALITIES DUE TO XANAX EXPOSURE.

Q. AND DO TERATOLOGISTS DO THIS, DO THEY SOMETIMES

LOOK IF THE MECHANISM OF ACTION IS APPROPRIATE, IT'S THE

SAME, DO THEY SOMETIMES DRAW CONCLUSIONS, LIKE PFIZER

DID HERE, ABOUT THE RISKS OF CONGENITAL ABNORMALITIES

FOR OTHER DRUGS IN THE CLASS?


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A. YES. YOU CAN FORM CLASSES USING DIFFERENT

METHODS. I THINK IT WAS TALKED ABOUT EARLIER. AND ONE

YOU CAN DO IT BASED ON STRUCTURE AND SOMETIMES THIS IS

APPROPRIATE TO DO, IF YOU HAVE COMMON STRUCTURES THAT

ARE PRODUCING CONGENITAL MALFORMATIONS. LIKEWISE, YOU

CAN DO IT ON MECHANISM OF ACTION, THAT IS, EVEN IF YOU

HAVE DIVERSE STRUCTURES AND THEY ARE ALL TARGETING THE

SAME MOLECULE AND YOU GET A COMMON OUTCOME AS WELL. SO

IN THIS CASE, THEY FOUND IT ACCEPTABLE THAT THE

BENZODIAZEPINE CLASS AND AS A STRUCTURAL CLASS WAS

PRODUCING COMMON CONGENITAL MALFORMATIONS.

Q. YOU KNOW THAT PFIZER HAS AN EXPERT NAMED DR.

STEVEN KIMMEL?

A. YES.

Q. YOU ARE FAMILIAR WITH SOME OF HIS LITERATURE?

A. YES, I AM.

Q. HE IS, I BELIEVE, A CARDIOLOGIST AND AN

EPIDEMIOLOGIST?

A. YES.

Q. AND YOU ARE FAMILIAR WITH THIS PIECE OF

LITERATURE THAT HE WROTE IN 2008?

A. YES, I AM.

Q. AND DR. KIMMEL SAID HE WAS ACTUALLY LOOKING AT

ANTIDEPRESSANTS, WASN'T HE?

A. YES, HE WAS.


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Q. HE SAID: WE DID NOT RELY ON CATEGORIZATION OF

ANTIDEPRESSANT MEDICATIONS ACCORDING TO THE CHEMICAL

STRUCTURE, BUT RATHER CATEGORIZED ANTIDEPRESSANTS

ACCORDING TO THEIR AFFINITY FOR THE SEROTONIN UPTAKE

RECEPTOR.

IS THAT WHAT YOU DID IN THIS CASE?

A. YES. I GROUPED BASED ON THEIR COMMON MECHANISM

OF ACTION, WHICH IS THEIR INTERACTION WITH THE SEROTONIN

UPTAKE RECEPTOR.

Q. AND IS THAT APPROPRIATE TO DO FOR A

TERATOLOGIST?

A. YES.

Q. SO LET'S TALK ABOUT THE ADVERSE OUTCOME PATHWAYS

IN THIS CASE AND HOW YOU APPLIED THEM, AND BRIEFLY TELL

US WHAT TYPES OF STUDIES THAT YOU YOURSELF USED OR

EMPLOYED IN THIS CASE TO REACH THE CONCLUSIONS THAT YOU

DID.

A. SO I LOOK AT THE BODY OF EVIDENCE, WHICH I

BASICALLY QUERIED THE LITERATURE, THE PUBLICLY AVAILABLE

LITERATURE AND I'M INTERESTED IN EACH LEVEL OF

ORGANIZATION BIOLOGICALLY, AND THAT INCLUDES CELLULAR

ORGANIZATION, MOLECULAR ORGANIZATION, COMMONLY REFERRED

TO AND ANALYZED BY IN VITRO STUDIES, AND THESE ARE

GENERALLY DONE IN CELL CULTURE DISHES OR FLASKS. AND

THEN ALSO IN VIVO STUDIES, THAT IS LOOKING AT WHOLE


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ANIMAL STUDIES OR EXPLANT STUDIES LOOKING AT TISSUES OR

EMBRYOS AND THEN ALSO LOOKING AT THE EPIDEMIOLOGY DATA

AND WHETHER THE DEFECTS THAT WOULD BE EXPECTED DUE TO

ADVERSE OUTCOME PATHWAYS ARE PRESENT IN THE HUMAN

POPULATION. AND THEN WE ALSO CONSIDER CONSERVED

BIOLOGICAL MECHANISMS. AND SO WE MAY OFTEN LOOK AT

OTHER SPECIES, INCLUDING CHICKS, FROGS OR FISH, TO SEE

IF THEIR COMMON MECHANISMS ARE CONSERVED THROUGHOUT THE

ANIMAL KINGDOM.

Q. LET ME ASK YOU ABOUT THAT LAST ONE FOR A SECOND.

YOU KNOW DR. LEVIN, THAT IS HIS AREA OF SPECIALTY?

A. YES, IT IS.

Q. THE MODEL ORGANISMS. DID YOU CONSIDER THE MODEL

ORGANISMS IN YOUR ADVERSE OUTCOME PATHWAY?

A. YES, I DID.

Q. AND YOU CONSIDERED IN VITRO STUDIES?

A. YES.

Q. THAT'S LIKE A TEST TUBE?

A. CULTURE DISHES, YES.

Q. AND THEN IN VIVO STUDIES, THAT IS WHOLE ANIMALS

THAT GET PREGNANT?

A. YES, IT IS.

Q. AND THEN YOU CONSIDERED THE EPIDEMIOLOGY?

A. YES.

Q. ALL RIGHT.


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AND AGAIN, WHEN YOU REVIEWED THE EXISTING

LITERATURE, WAS THERE ENOUGH OUT THERE THAT HAD ALREADY

BEEN DONE IN THE LAST TWO OR THREE DECADES THAT ENABLED

YOU TO REACH THE CONCLUSIONS THAT YOU DID?

A. YES.

Q. SO WHAT I ASKED YOU TO DO FOR TODAY WAS TO PLUG

IN, IF THAT IS THE RIGHT TERM, THE ACTUAL LITERATURE AND

EVIDENCE THAT WAS BEFORE YOU INTO YOUR ADVERSE OUTCOME

PATHWAY WITH YOUR VARIOUS DEFECT OR BODY SYSTEM DEFECTS.

RIGHT?

A. YES.

MR. TRACEY: AND WE'RE GOING TO START

WITH HEART DEFECTS. AND WHAT WE MAY DO, IN THE INTEREST

OF TIME AND TEDIOUSNESS, YOUR HONOR, IF IT IS ALL RIGHT

WITH YOU, ALTHOUGH I'M GLAD TO GO THROUGH ALL OF THEM,

WE ARE GOING TO DO HIS HEART DEFECTS AND HIS METHODOLOGY

THAT HE USED TO REACH HIS CONCLUSIONS IN HEART DEFECTS.

AND I THINK DR. CABRERA IS GOING TO TELL YOU HE USED THE

SAME METHODOLOGY FOR ALL OF THEM. BUT RIGHT NOW I THINK

WE ARE JUST GOING TO FOCUS ON HEARTS, IF THAT IS OKAY?

THE COURT: THAT IS FINE.

BY MR. TRACEY:

Q. ALL RIGHT. DR. CABRERA, TAKE US THROUGH THE

ADVERSE OUTCOME PATHWAY WITH RESPECT TO SSRIS OR ZOLOFT

IN BIRTH DEFECTS.


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A. SO WE START WITH LOOKING AT THE CHEMICAL. THAT

IS SERTRALINE OR ZOLOFT AS THE CHEMICAL ITSELF. WE WILL

CONSIDER THINGS HERE SUCH AS THE SOLUBILITY OR ABILITY

OF THE CHEMICAL TO BE ABSORBED AS A PHARMACEUTICAL THAT

WAS DESIGNED TO BE TAKEN ORALLY. IT HAS HIGH

ABSORBANCE. AND THEN WE KIND OF MOVE ONTO THE NEXT STEP

AND SAY IT HAS ACCESS NOW TO LOOKING AT MOLECULAR

INTERACTIONS.

THE MOLECULAR INTERACTIONS FOR ZOLOFT AND

ADDITIONALLY FOR SSRIS AS A CLASS IS THAT THEY INTERACT

WITH SEROTONIN. IT'S DESCRIBED HERE AS ANTAGONIST

FUNCTION THAT IS, IT INHIBITS THE ACTIVITY OF SERT. AND

SERT IS ULTIMATELY USED TO MOVE SEROTONIN AROUND, AROUND

THE CELLS, AND IN THE NEURONS IT WOULD BE USED IN THE

PRE-SYNAPTIC CLEFT IN ORDER TO PULL THE SEROTONIN OUT

AFTER IT IS RELEASED. AND BY INHIBITING THAT, IT

BASICALLY KEEPS THE SEROTONIN CONCENTRATIONS HIGHER

AROUND THE NEURON.

AS I MENTIONED EARLIER, PHYSIOLOGICALLY

IN THE PLATELETS AND IN THE BLOOD, IT ACTUALLY KEEPS THE

PLATELETS FROM TAKING OUT THE SEROTONIN. AND SO IT

DECREASES THE SEROTONIN IN THE BLOOD. ULTIMATELY, WE

SEE THIS, AS THE INTERACTIONS HERE, IT SHOWS THAT THERE

ARE HIGH AFFINITIES FOR EACH ONE OF THE SSRIS.

DEPENDING ON WHICH ONES THEY ARE, THEY HAVE SUBNANOMOLAR


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OR A NANOMOLAR AFFINITIES AND THE ABILITY TO INHIBIT

CERTAIN ACTIVITY, ULTIMATELY ALTER SEROTONIN

CONCENTRATIONS. AND THIS HAS DOWN STREAM IMPACTS AS FAR

AS SIGNALING GOES.

Q. SO THE FIRST BOX WE LOOKED AT WAS THE ABILITY TO

ALTER SEROTONIN CONCENTRATIONS AND THEREFORE SIGNALING?

A. YES.

Q. WHAT IS THE NEXT BOOK ON THE CELLULAR?

A. AND THEN IT HAS AN IMPACT ON THE CELLS AND THE

PARTICULAR CELL POPULATION THAT WE ARE INTERESTED IN, OR

THE CELL POPULATIONS WE ARE INTERESTED IN WITH HEART

DEVELOPMENT. AND THIS INSTANCE IS THAT THE ALTERATIONS

IN SEROTONIN CONCENTRATION HAS BEEN SHOWN ON CELLS,

PARTICULARLY NEURAL CREST CELLS, WHICH WILL CONTRIBUTE

TO THE SECONDARY HEART FIELD AND ALSO THE OUTFLOW TRACTS

OF THE HEART, AND THEN ALSO THE CARDIOMYOCYTE WHICH THAT

IS THE HEART CELLS THEMSELVES ARE ALSO INFLUENCED BY THE

CONCENTRATIONS OF SEROTONIN. AND ULTIMATELY THIS WILL

IMPACT THE PROLIFERATION AND THE MIGRATION OF THESE

CELLS DURING THE HEART DEVELOPMENT, WHICH IS OUR NEXT

LEVEL OF ORGANIZATION.

Q. AND THAT IS THE ORGAN RESPONSE?

A. YES.

Q. WHAT DID YOU FIND THERE?

A. SO AS FAR AS THE ORGAN RESPONSE GOES, WE FIND


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THAT SERT, THAT IS THE SEROTONIN TRANSPORTER AND THE

RECEPTORS FOR DOWNSTREAM SEROTONIN SIGNALING. WHAT WE

REFER TO AT THE RIGHT PLACE AT THE RIGHT TIME. THAT IS,

THEIR EXPRESSION OF THESE TRANSPORTERS AND RECEPTORS,

AND THE EMBRYONIC HEART, TOO. AND ALSO THE AORTIC WALLS

OF THE DEVELOPING HEART. AND SO THIS IS BASICALLY THE

IMPACT OF SEROTONIN OR THESE SSRIS HAS THE INTERACTION

AND THE CORRECT TARGETS FOR THE CELL TYPE AND THE TISSUE

TYPE THAT WE ARE INTERESTED IN ANALYZING.

Q. SO RIGHT NOW WE HAVE GONE FROM THE INTRODUCTION

OF THE ZOLOFT TO WHAT IT IS DOING TO THE MOLECULAR, TO

WHAT IT'S DOING ON THE CELLULAR RESPONSE AND NOW IT'S

NOW CAUSING PROBLEMS IN SPECIFIC CARDIAC TISSUE.

A. YES.

Q. OR CELLS THAT MAY BECOME, ARE SUPPOSED TO BECOME

CARDIAC TISSUE?

A. YES. EITHER THE CARDIOMYOCYTES OR THEIR

PREDECESSORS OR THE MESODERMAL CELLS OR EVEN EARLIER

THAN THAT, BUT ULTIMATELY IT'S THOSE CELLS THAT ARE

RESPONSIVE TO SEROTONIN, EITHER THROUGH THE TRANSPORTS

OR THE RECEPTORS OF SEROTONIN.

Q. IS IT TOO SIMPLISTIC TO SAY THAT WHAT THE

PROBLEM WITH SSRIS ARE IS THAT THEY INTERRUPT CELLULAR

SIGNALING, SO THAT THE CELL THAT IS SUPPOSED TO BE TOLD

TO GO AND FORM A VENTRICULAR SEPTUM GET WRONG SIGNALS


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AND INSTEAD OF GOING THERE AND POPULATING THE SEPTUM

THEY GET THE WRONG SIGNAL AND THEY DIE, LEAVING A HOLE

IF THE HEART? IS THAT TOO SIMPLISTIC?

A. I MEAN, IN A PARTICULAR INSTANCE THAT MAY BE THE

CASE, BUT ULTIMATELY IT'S SEROTONIN SIGNALING, NOT JUST

SIMPLY CELL SIGNALING, IN AND OF ITSELF. AS LONG AS THE

CELL IS SERT POSITIVE OR RECEPTOR POSITIVE, YOU WOULD

EXPECT IT TO HAVE AN IMPACT SO YES THAT WOULD BE MAYBE

ALMOST TOO SIMPLE.

Q. BUT IS THE NET EFFECT -- IS THE NET EFFECT THE

HOLE IN THE HEART?

A. YES. THE NET EFFECT IS THE SAME, YES.

Q. AND NEXT ON THE LIST WE HAVE THE ORGANISM

RESPONSE. WHAT IS THAT?

A. SO THE ORGANISM RESPONSE IS LOOKING AT THE

IMPACTS OF ALTERED SEROTONIN ON THE ORGANISM. AND WE

SEE THAT ELEVATED SEROTONIN PRODUCES HEART VALVE DEFECTS

AND ALSO LOSS OF CARDIAC NEURAL CREST CELLS LEADS TO

DEFECTS INCLUDING OUTFLOW TRACT DEFECTS AND SEPTAL

DEFECTS. AND ALSO I THINK IN THIS GROUPING WOULD BE THE

COTE PAPER AND THAT IS IN EXCESS -- IN THE ABSENCE OF

SEROTONIN, WHICH IS THE LOW MATERNAL SEROTONIN, AND THAT

IS THE IN VIVO MODEL FOR THIS, THAT LOW SEROTONIN

PRODUCES ALSO CONGENITAL MALFORMATIONS INCLUDING HEART

DEFECTS.


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Q. AND THEN WE END UP WITH DR. BERARD,

EPIDEMIOLOGIST, TO FIGURE OUT WHETHER THIS ALL

CULMINATES IN EPIDEMIOLOGY THAT IS CONSISTENT WITH WHAT

WE KNOW TO BE HAPPENING MOLECULARLY, CELLULARLY, TISSUE

ON A TISSUE AND THEN ON AN ORGAN?

A. YES. SO BASED ON THIS PATHWAY, WE WOULD HAVE

THE EXPECTATION, IF WE ARE GOING FROM THE MOLECULAR TO

THE POPULATION EFFECT, WE HAVE THE EXPECTATION FOR THE

PRESENTATION OF A VARIETY OF HEART DEFECTS DUE TO THE

SSRI EXPOSURE.

Q. SO LET'S DRILL DOWN A LITTLE BIT WITH RESPECT TO

HEART DEFECTS.

MR. TRACEY: AND YOUR HONOR, THIS IS

DENSE, SO I'M GOING TO TRY TO MAKE IT -- I DON'T KNOW

THAT I CAN, BUT I'M GOING TO TRY TO GET DR. CABRERA TO

MAKE THIS AS UNDERSTANDABLE AS POSSIBLE.

BY MR. TRACEY:

Q. ON THE MOLECULAR PART OF THIS, DID YOU FIND

EXISTING LITERATURE TO SUPPORT WHAT YOU WERE LOOKING FOR

WITH RESPECT TO SSRIS AND THEIR EFFECT ON THE MOLECULES?

A. YES, WE DID.

Q. TELL ME WHAT YOU FOUND.

A. SO WHEN I LOOKED -- AND, YOU KNOW, IT'S RIGHT

THERE ON THE LABEL. ALL THE SSRIS AS A CLASS ALTER

SEROTONIN TRANSPORT. THAT IS, THEY TARGET THE SEROTONIN


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TRANSPORTER SERT, AND THAT ULTIMATELY THIS CHANGES

CONCENTRATIONS OF SEROTONIN. AND IT'S BY INHIBITION OF

THIS TRANSPORTER THAT IS THE PROPOSED THERAPEUTIC

MECHANISM ACTION AND NEURONS. BUT THIS ALSO HAS

SYSTEMATIC EFFECTS AS I MENTIONED EARLIER IN THE BLOOD.

ADDITIONALLY, IT HAS BEEN DEMONSTRATED BY

BENMANSOUR, THE CHRONIC EXPOSURE TO SEROTONIN ALSO HAS

IMPACTS IN THAT THE CELLS RESPOND BY INTERNALIZING THEIR

SEROTONIN TRANSPORTER, SO THAT IT'S NOT PRESENT ON THEIR

OUTSIDE, SO THEY ACTUALLY DISRUPT THEIR OWN SEROTONIN

SIGNALING AFTER CHRONIC EXPOSURE TO SSRIS AND ULTIMATELY

THERE'S CHANGES ALSO AT THE GENE EXPRESSION OR PROTEIN

EXPRESSION OR A LETTER ASSOCIATED WITH THAT.

Q. THAT WAS A?

A. THAT WAS A.

Q. WHAT DO WE SEE IN B?

A. SO B, WE ARE LOOKING AT HERE THE CHANGES IN

SEROTONIN SIGNALING AND SPECIFIC THEIR DOWNSTREAM

RECEPTORS SO THE TRANSPORTER ITSELF IS USED TO TRANSPORT

SEROTONIN, BUT THERE IS ALSO RECEPTORS WHICH INITIATE

DOWNSTREAM SIGNALLING WITH SEROTONIN. AND WE FIND THAT

THE SEROTONIN RECEPTOR 5HT2B, WHICH IS REQUIRED FOR THE

LONG-TERM EFFECTS OF SSRIS APPEARS TO BE A TARGET FOR

ALL THE CONVENTIONAL SSRIS AS A CLASS AS WELL.

Q. THE CONVENTIONAL SSRIS, IS THAT PAXIL, ZOLOFT,


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CELEXA, LEXAPRO AND PROZAC?

A. YES.

Q. SO THAT TOOK CARE OF THE MOLECULAR PART OF THE

ADVERSE OUTCOME PATHWAY. AND THAT BRINGS US TO THE

CELLULAR.

A. YES.

Q. WHAT DID YOU FIND WITH RESPECT TO THE CELLULAR?

A. SO THE CELLULAR LEVEL WE ACCEPT THAT THERE IS AN

ALTERATION IN SEROTONIN CONCENTRATIONS AND THEN WE WANT

TO SEE WHAT EFFECTS THIS ALTERED SEROTONIN CONCENTRATION

WILL HAVE ON CELL POPULATIONS THAT ARE RESPONSIVE TO

SEROTONIN. AND HERE ARE INCLUDED WHAT'S ABBREVIATED

HERE AS THE NCC, WHICH IS THE NEURAL CREST CELLS. THESE

ARE GOING TO BE CARDIAC NEURAL CREST CELLS, AND THEN

ALSO THE CARDIOMYOCYTE PROLIFERATION. THAT IS THE HEART

ITSELF AND THE CELLS THAT WILL PRODUCE THE HEART, BOTH

OF WHICH ARE SHOWN HERE IN THESE REFERENCES TO BE

RESPONSIVE FOR -- AND TO HAVE THE RIGHT TARGETS FOR

SEROTONIN, AND ULTIMATELY BE RESPONSIVE TO SSRIS.

Q. OKAY. AND YOU KNOW DR. SADLER IS GOING TO

EXPLAIN THE PRIMARY AND SECONDARY HEART FIELD TOMORROW,

I BELIEVE, WITH SOME FAIRLY GOOD EXHIBITS. CAN YOU

EXPLAIN WHAT THE PRIMARY AND SECONDARY HEART FIELD ARE?

A. YES. SO DURING DEVELOPMENT OF THE HEART,

UNDERGOES LOOPING, WHICH IS THE HEART TUBE IN AND OF


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ITSELF, AND THEN THERE IS ALSO WHAT IS REFERRED TO AS

THE PRIMARY AND SECONDARY HEART FIELD, AND THERE IS

MIGRATION OF CELLS, WHICH I IDENTIFIED HERE AS NEURAL

CREST CELLS INTO THIS FIELD AND THEY INFLUENCE THE

OUTFLOW TRACT AND THE VASCULAR DEVELOPMENT OF THE HEART.

OUTSIDE OF THE CARDIOMYOCYTES IN AND OF THEMSELVES, YOU

HAVE CONTRIBUTIONS FROM THE NEURAL CREST CELL IN THE

HEART FIELDS.

Q. AND SO IF A COMPOUND -- IF ZOLOFT, IF SSRIS

INTERRUPT EITHER THE PRIMARY OR THE SECONDARY -- THE

FORMATION OF THE PRIMARY OR SECONDARY HEART FIELD, DOES

THAT EXPLAIN VIRTUALLY EVERY CARDIAC DEFECT WE SEE?

A. COLLECTIVELY, YES.

Q. YES. COLLECTIVELY. ALL RIGHT. ANYTHING ELSE

UNDER THE CELLULAR?

A. I THINK THAT IS -- MOST OF THAT IS COVERED, BUT

IT'S SIMPLY DESCRIBING THE DIFFERENT CELLS THAT EXPRESS

EITHER THE TRANSPORT OR THE RECEPTORS AND THAT THEY

WOULD BE RESPONSIVE TO ALTERATIONS IN SEROTONIN

CONCENTRATIONS.

Q. SO LET'S MOVE TO THE ISSUE. MOLECULAR CELLULAR.

NOW, WE ARE ON THE TISSUE. WHAT DID YOU FIND IN THE

RESEARCH WHEN YOU LOOKED AT THE TISSUE?

A. SO THE IMPACTS THAT WE SEE ON THE CELLS, THAT IS

ON THE CARDIAC CELLS, AND ON THE NEURAL CREST CELLS, WE


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SEE SOME DATA THAT SHOWS THAT THESE CHEMICALS ARE ABLE

TO INHIBIT THE CELL PROLIFERATION OF CARDIAC TISSUES.

THAT IS THE FIRST -- IDENTIFIED THERE AS A.

ADDITIONALLY, IN THE CARDIAC NEURAL CREST

CELLS, WE SEE THAT THESE CELLS WHICH I SHOWED EARLIER

HAVE RECEPTORS FOR SEROTONIN AND THEY ARE ALTERED BY

LEVELS OF SEROTONIN THAT THESE WILL ULTIMATELY MIGRATE

INTO THE AORTIC ARCHES, AORTICOPULMONARY SEPTUM AND

TRUNCUS OF THE HEART. AND SO DEFECTS ARE A DISRUPTION

OF THE CREST CELLS WHICH WE WILL SEE LATER CAN DISRUPT

ALSO DEVELOPING TISSUES AND ORGANS, AND ULTIMATELY THE

DOWNSTREAM RECEPTORS FOR SEROTONIN ARE EXPRESSED

THROUGHOUT DIFFERENT SYSTEMS. HERE I'VE DESCRIBED THEM

IN THE GUT, THE HEART AND THE BRAIN, SO WE CAN ALSO

EXPECT OTHER DEFECTS DUE TO CHANGES IN SEROTONIN

CONCENTRATIONS, AND ULTIMATELY THE RECEPTOR ITSELF IS

EXPRESSED DURING THE HEART DEVELOPMENT. AND YOU SEE

HERE IT'S IN THE VALVES WHERE WE SAW THE VALVE DEFECTS,

AND ULTIMATELY THE SERT MUTANTS AS FAR AS THE EXPRESSION

OR THE SERT'S EXPRESSION IS ALSO EXPRESSED. THAT IS

TRANSPORTER FOR SEROTONIN IS ALSO EXPRESSED IN THE

HEART, OF THE DEVELOPING HEART. AND I GUESS THE LAST

PART THERE IS INJECTIONS WITH SEROTONIN PRODUCES

DISEASES OF THE HEART VALVE IN RATS. AND ADDITIONALLY,

WE KNOW, BASED ON THE NAME SEROTONIN, THAT IT ACTUALLY


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HAS AN IMPACT ON THE VASCULATURE. AND THAT IS IT'S A

SEROTONIN -- THE NAME ITSELF TONIN AND THE FACT THAT

IT'S FOUND IN SERUM IS WHERE THE NAME DERIVED FROM AND

THAT IT HAS AN IMPACT ON THE VASCULATURE AND THE

SIGNALING OF ITS CELLS.

Q. SO YOU HAVE MENTIONED MUTANT A COUPLE OF TIMES,

AND EXPLAIN TO THE COURT WHAT YOU MEAN BY MUTANT?

A. SO WE OFTEN IMPLEMENT GENETIC MODELS WHERE WE

MUTATE GENES DEVELOPMENTALLY, KIND OF GARNERED A NOBEL

PRIZE FOR THE INDIVIDUAL THAT DEVELOPED THIS TECHNIQUE.

YOU CAN ACTUALLY TAKE EARLY EMBRYONIC STEM CELLS, MUTATE

SPECIFIC GENES AND ULTIMATELY TEST THE IMPACT OF

SPECIFIC GENES, HOW THEY INTERACT WITH DEVELOPMENT. AND

THE ONES THAT ARE RELEVANT I THINK FOR THIS PARTICULAR

CASE WOULD BE THE SERT MUTANT, THAT IS THE KNOCKOUT OF

THE SEROTONIN TRANSPORTER AND THEN ALSO THE TPH1, WHICH

WOULD BE THE ACTUALLY KNOCKOUT OF THE PRODUCTION OF

SEROTONIN WHICH CAUSES LOW MATERNAL SEROTONIN.

Q. OKAY.

THEN WE END UP HERE AT THE PHENOTYPE.

WHAT DOES THE PHENOTYPE MEAN?

A. SO THE PHENOTYPE IS, QUITE LITERALLY, MEANS WHAT

DOES IT LOOK LIKE, PHENOTYPICALLY WE ARE GOING TO

DESCRIBE WHAT IS THE OUTCOME PHYSICALLY. AND SO HERE IN

THIS FIRST STUDY, I INCLUDED A STUDY IN OVO. AND THAT


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IS IN THE EGG. AND SO THIS IS NOT NECESSARILY A

MAMMILLARY STUDY. I DID CONSIDER, AS I MENTIONED

EARLIER, THAT I'M LOOKING AT -- I ACCEPT CONSERVED

MECHANISMS, IF THEY EXIST THROUGHOUT THE ANIMAL KINGDOM.

AND IN THIS CASE, EXPOSURE TO SEROTONIN IS SHOWN TO

INDUCE A VARIETY OF HEART DEFECTS, INCLUDING DEFECTS OF

ARTRIAL VALVES AND VENTRAL SEPTAL DEFECTS AND OUTFLOW

TRACT DEFECTS, WHICH WOULD BE CONSISTENT WITH A LOT OF

THE LATERALITY DEFECTS WHICH WOULD BE EXPECTED BY

DISRUPTION OF SEROTONIN.

ALSO REMOVAL OF THE NEURAL CREST CELL AND

THAT IS SEROTONIN ITSELF CAN IMPACT THE CREST CELL

PROLIFERATION AND MIGRATION AND THEIR REMOVAL. IT HAS

ALSO BEEN CLEARLY SHOWN TO PRODUCE OUTFLOW TRACT

MALFORMATIONS AND LIKEWISE THE ABLATION THAT IS USING

GENETIC MODELS OR CHEMICAL MODELS HAS ALSO BEEN SHOWN TO

PRODUCE DEFECTS SUCH AS PERSISTENT TRUNCUS OR VENTRAL

SEPTAL DEFECTS OR DEXTRACARDIO, AND ALSO A VARIETY OF

OTHER OUTFLOW TRACT DEFECTS. AND ULTIMATELY, IT'S THE

INHIBITION OF THE SERT AND THE IMPACT THIS HAS ON THE

RECEPTORS DOWNSTREAM SEROTONIN THAT IS ABLE TO PRODUCE A

VARIETY OF CONGENITAL MALFORMATIONS BASED ON THIS

ADVERSE OUTCOME PATHWAY.

Q. AND THIS WAS THE EXISTING LITERATURE THAT YOU

WERE ABLE TO FIND?


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A. YES.

Q. AND THIS IS AT THE ORGAN LEVEL, THE LEVEL OF THE

HEART, THE DEVELOPED HEART?

A. THIS IS THE LEVEL OF THE ANIMAL.

Q. SO THIS IS -- THIS IS A WHOLE ANIMAL?

A. YES, THESE STUDIES ARE BASICALLY THE

PRESENTATION OF THE WHOLE ANIMAL STRUCTURES.

Q. BY THE WAY, WHY DO TERATOLOGISTS LOOK AT MICE

AND RATS?

A. WELL, WE ARE ETHICALLY NOT ABLE TO TEST

CHEMICALS ON HUMANS AND SO WE HAVE TYPICALLY A RODENT

AND NONRODENT SPECIES THAT ARE USED IN ORDER FOR

TESTING.

Q. AND HAS SCIENCE DEMONSTRATED THAT TERATOLOGISTS

OR IN TERATOLOGY THAT ANIMAL MODELS CAN BE VERY GOOD

PREDICTORS OF WHAT HAPPENS IN HUMANS?

A. YES. I WOULD ADD THAT USING A VARIETY OF ANIMAL

MODELS GENERALLY STRENGTHENS YOUR ABILITY TO DRAW

CONCLUSIONS, IF YOU SEE CONSERVATION THROUGHOUT VARIOUS

SPECIES AND LIKEWISE WE CAN DO IN VITRO TESTING NOW AND

TEST OUT HOW WELL THESE IN VITRO TESTS WORK BASED ON

EXISTING LITERATURE ON CHEMICALS.

Q. WHEN YOU USE THE TERM CONSERVATION IN THIS

CONTEXT, WHAT ARE YOU TALKING ABOUT?

A. SO AS FAR AS MECHANISMS GO, WE WOULD EXPECT IF A


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PARTICULAR PROTEIN AND -- HAS -- THE SAME PROTEIN IS

ALSO FOUND IN OTHER LOWER ORGANISMS. FOR INSTANCE,

SEROTONIN IS USED AS A SIGNALING MOLECULE AND ITS BASIC

USE IS INCLUDED IN SIMPLE ORGANISMS LIKE FLIES OR FISH

OR FROGS. SEROTONIN HAS A SIGNALLING MODEL THAT HAS

BEEN CONSERVED IN NATURE, SUCH THAT WE EXPECT TO HAVE A

SIMILAR IMPACT ON MAN AND VERTEBRAE TO MAMMALS AS WE SEE

THROUGHOUT THE REST OF THE ANIMAL KINGDOM.

Q. HAVE ALL OF THOSE THINGS YOU JUST SAID ABOUT

SEROTONIN BEEN DEMONSTRATED IN SCIENCE?

A. YES, THEY HAVE.

Q. AND SO THAT BRINGS US TO EPIDEMIOLOGY.

IS THIS SOME OF THE EPIDEMIOLOGY STUDIES

THAT YOU HAVE REVIEWED THAT ARE CONSISTENT WITH SSRIS

AND ZOLOFT INDUCING CARDIOVASCULAR DEFECTS?

A. YES, THEY ARE.

Q. TELL US THE IMPORTANCE OF THESE STUDIES? WHY

ARE THESE IMPORTANT TO YOU IN YOUR OPINION?

A. FOR FORMING MY OPINION, I LOOKED AT -- RELIED

UPON THE ENTIRE BODY OF EVIDENCE. AND THERE ARE SOME

EXCEPTIONS BUT ULTIMATELY, WHAT I'M LOOKING FOR IS

WHETHER MULTIPLE STUDIES HAVE BEEN PUBLISHED SHOWING

THAT SSRIS, EITHER AS A CLASS OR THAT SPECIFIC SSRIS ARE

INCREASING THE RISK FOR CARDIOVASCULAR MALFORMATIONS AND

BOTH AS A GROUP AND FOR SPECIFIC TYPES OF CARDIOVASCULAR


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MALFORMATIONS.

Q. AND SO WHAT ABOUT THE ARGUMENT -- THEY ARE GOING

TO STAND UP AND SAY WELL, DR. CABRERA, THEY ALL DON'T DO

IT. HOW COME EVERY SINGLE EPIDEMIOLOGY STUDY DOES NOT

PROVE WHAT YOU SAY IS TRUE?

A. I THINK, YOU KNOW, GO BACK TO WILSON'S FIRST

PRINCIPLES. THERE ARE DIFFERENCES IN GENETICS.

LIKEWISE, AS FAR AS THE -- HOW THE EPIDEMIOLOGY STUDIES

THEMSELVES ARE CONDUCTED. THEY DIFFER IN POWER, THEY

DIFFER IN POPULATION, AND THEY DIFFER IN STUDY DESIGNS.

SO THEY MIGHT NOT ALWAYS DRAW THE SAME CONCLUSIONS.

Q. WHAT ABOUT THE FACT THAT SOME STUDIES DID NOT

SHOW INCREASED RISK OF CARDIAC DEFECTS IN ALL SSRIS?

A. THERE'S EXPECTED AMOUNT OF VARIABILITY. AND I

THINK THE MOST IMPORTANT FACTOR THAT I CONSIDER, I DO

TRY TO CONSIDER ALL OF THE LITERATURE, AND IF THERE WAS

OVERWHELMING -- THERE IS ONLY ONE OR TWO OF THESE THAT

WERE POSITIVE THAT WOULD BE A MATTER OF CONSIDERATION.

BUT THE FACT THAT THERE ARE SO MANY OF THEM THAT PRESENT

WITH POSITIVE DATA IS WHAT STEERS ME TO MY CONCLUSIONS.

Q. AND IS THE EPI DATA THAT YOU SEE HERE -- I

ACTUALLY THINK THERE IS PROBABLY A COUPLE OF PAGES OF

IT, TWO OR THREE PAGES OF IT, IS THIS EXACTLY WHAT A

TERATOLOGIST WOULD EXPECT TO SEE BASED ON YOUR REVIEW OF

THE ANIMAL STUDIES?


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A. YES. SO BASED ON THE ADVERSE OUTCOME PATHWAY

THAT I JUST WENT OVER, YOU'LL SEE A VARIETY OF

CARDIOVASCULAR DEFECTS. AND ADDITIONALLY, YOU WILL SEE

THE OUTFLOW TRACT DEFECT THAT WOULD BE EXPECTED, THE

SEPTAL DEFECTS, THE VENTRICLE DEFECTS, AND SO ALL OF THE

DEFECTS THAT I DESCRIBED WOULD BE AS EXPECTED BASED ON

THESE ADVERSE OUTCOME PATHWAY.

Q. YOU HAVE SEEN THIS MORNING THIS MEMO FROM

CYNTHIA DELUISE AT PFIZER AND HER OPINION WITH RESPECT

TO THE CLASS EFFECT OF SSRIS ON BIRTH DEFECTS AND I JUST

HAVE A QUESTION. DO YOU AGREE WITH HER?

A. YES, I DO.

Q. DO YOU BELIEVE THERE IS A CLASS EFFECT WITH

RESPECT TO THE INDUCTION OF CARDIAC DEFECTS IN SSRIS?

A. YES, I DO.

Q. ARE THERE OTHER --

MR. TRACEY: AND JUST TO CLOSE THE LOOP

HERE, YOUR HONOR, I HAVE THE EXACT SAME ADVERSE OUTCOME

PATHWAY STRUCTURE THAT I THINK AT THE END OF THE WEEK, I

HAVE TALKED TO MR. CHEFFO, WE ARE GOING TO SORT OF

EXCHANGE EVERYBODY'S POWERPOINTS AND MAYBE MARK THEM AS

EXHIBITS AND PUT THEM IN THE RECORD SO THAT YOU CAN

FOLLOW THE SAME METHODOLOGY FOR THE OTHER DEFECTS WITH

DR. CABRERA. AT LEAST IT WILL BE IN THE RECORD,

ALTHOUGH IT IS IN HIS REPORT ALSO.


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BY MR. TRACEY:

Q. SO DID YOU, DR. CABRERA, FOLLOW THE SAME

METHODOLOGY WITH RESPECT TO THE OTHER TYPES OF BIRTH

DEFECTS THAT YOU EXPLAINED TO THE COURT WITH YOUR

CARDIAC OPINIONS?

A. YES, I HAVE.

Q. NOW, YOU AND I TALKED A LITTLE BIT ABOUT THIS,

BUT THERE ARE SOME FAIRLY WELL-KNOWN TERATOGENS IN THE

WORLD THAT CAUSE MULTIPLE DEFECTS THAT ARE VERY SIMILAR

TO WHAT SSRIS DO, IN YOUR OPINION, ISN'T THAT TRUE?

A. THAT IS TRUE.

Q. AND ON THE SCREEN WE HAVE GOT THALIDOMIDE AND

RETINOIDS. WHAT ARE THALIDOMIDE AND RETINOIDS?

A. THALIDOMIDE, I THINK, WAS FAIRLY WELL-KNOWN AS

AN ESTABLISHED HUMAN TERATOGEN THAT IS PREDOMINANTLY AND

GENERALLY REFERRED TO AS PRESENTING WITH PHOCOMELIA, AND

THAT IS THE LIMB DEFECTS. BUT IF YOU ACTUALLY LOOK AT

THE LITERATURE, YOU WILL FIND THAT THERE IS A VARIETY OF

OTHER DEFECTS THAT PRESENT WITH THALIDOMIDE. LIKEWISE,

RETINOIDS, SUCH AS RETINOIC ACID OR ALL TRANS RETINOIC

ACID OR ACCUTANE, PRODUCE A VARIETY OF DIFFERENT

CONGENITAL MALFORMATIONS. SOME TERATOGENS, IF THEY HAVE

VERY SPECIFIC MECHANISMS OR MECHANISMS THAT ARE NOT

WIDELY USED THROUGHOUT CELLULAR AND DEVELOPMENTAL

BIOLOGY, MAY PRODUCE VERY SPECIFIC MALFORMATIONS. BUT


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OTHER TERATOGENS IF THEY AFFECT A VARIETY OF CELLS,

EARLY DEVELOPMENTALLY THEY WILL PRODUCE A VARIETY OF

DIFFERENT MALFORMATIONS.

Q. AND SO THIS LIST HERE, STARTING WITH MICROTIA

AND ENDING WITH CENTRAL NERVOUS SYSTEM MALFORMATIONS, IS

THIS A THALIDOMIDE ANALYSIS?

A. YES. THESE ARE DIFFERENT PRESENTATIONS FOR

EXPOSED POPULATIONS.

Q. AND IS IT GENERALLY ACCEPTED IN THE MEDICAL

LITERATURE IN TERATOLOGY THAT, FOR EXAMPLE, THALIDOMIDE

IN ADDITION TO THE LIMB DEFECTS CAN CAUSE CLEFT PALATE?

A. ACTUALLY IT SAYS UP THERE THIS IS ACTUALLY ONE

OF THE RETINOIDS.

Q. I SEE. SO THIS IS THE RETINOID WHICH IS

COMMERCIALLY -- WHAT WOULD THE NAME BE, ACCUTANE, IS

THAT A RETINOID?

A. THAT WOULD BE ONE OF THE RETINOIDS, YES.

Q. AND SO IS IT GENERALLY ACCEPTED THAT ACCUTANE

AND RETINOIDS AS A CLASS INDUCE A VARIETY OF BIRTH

DEFECTS?

A. YES, IT IS.

Q. DO THEY INDUCE CARDIAC DEFECTS?

A. YES, THEY DO.

Q. DIFFERENT TYPES OF CARDIO DEFECTS?

A. YES.


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Q. DO THEY INDUCE CRANIOFACIAL ABNORMALITIES?

A. YES, THEY DO.

Q. DO THEY INDUCE CENTRAL NERVOUS SYSTEM

MALFORMATIONS LIKE SPINA BIFIDA?

A. YES, THEY DO.

Q. IS THIS AN EXAMPLE OF A TERATOGEN THAT IS

SIMILAR TO AN SSRI WITH ONE DRUG INDUCTING A VARIETY OF

DIFFERENT DEFECTS?

A. IT IS SIMILAR IN THAT REGARD, YES.

MR. TRACEY: YOUR HONOR, I'M ABOUT TO

SWITCH TOPICS. WOULD THIS BE A GOOD TIME FOR A BREAK OR

DO YOU WANT TO --

THE COURT: LET'S TALK ABOUT HOW LONG

EVERYONE EXPECTS TO BE ABLE TO GO TODAY. AND WE DON'T

KNOW HOW FAR YOU ARE FROM HANDING HIM OVER TO MR. CHEFFO

FOR CROSS. SO CAN YOU GIVE ME AN IDEA.

MR. TRACEY: I THINK, I WOULD PROBABLY --

IF WE'RE GOING TO GO TO FIVE, I THINK I'M PROBABLY GOING

TO GO TO FIVE OR PRETTY CLOSE TO IT.

THE COURT: TO FINISH YOUR DIRECT?

MR. TRACEY: I HOPE SO, YES.

THE COURT: BUT YOU MIGHT NOT.

MR. TRACEY: I MIGHT NOT, DEPENDING ON

WHAT THE PEANUT GALLERY OVER HERE SAYS TO ME.

MR. ALYSTOCK: WE THINK HE WILL, YOUR


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HONOR.

MR. TRACEY: I WILL FINISH TODAY.

MR. ROBINSON: I DON'T THINK HE WILL.


THE COURT: HOW ABOUT IF I ASK YOU TO

FINISH TODAY SO WE CAN --


THE COURT: LET'S TAKE A FIVE-MINUTE

RECESS AND WE CAN FINISH TODAY.

(RECESS TAKEN.)


IS IN SESSION.

THE COURT: PLEASE BE SEATED.

MR. TRACEY: MAY I PROCEED?

THE COURT: PLEASE DO.

MR. TRACEY: YOUR HONOR, I TALKED ON THE

BREAK WITH MR. CHEFFO. AND I'M GOING TO TONIGHT, THIS

AFTERNOON, GIVE PFIZER A COPY OF THE POWERPOINT OR

PRESENTATION SLIDES THAT HAS THE ADVERSE OUTCOME

PATHWAYS FOR EACH DISCRETE, SORT OF DEFECT OR BODY CLASS

SYSTEM. HE IS GOING TO HAVE IT OVERNIGHT AND MAKE

SURE -- I DON'T HAVE TO -- I'M NOT FORCED TO DO IT ON

THE RECORD SLIDE BY SLIDE, AND THEN WE WILL KNOW IN THE

MORNING.

THE COURT: WELL, THAT IS A REASONABLE


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WAY TO PROCEED.

MR. CHEFFO: WE WANT TO BE EFFICIENT. I

HAVEN'T SEEN THEM YET, SO I WILL TAKE A LOOK AT THEM

TONIGHT AND I WILL FIND OUT IF I CAN AGREE WITH

MR. TRACEY AND LET HIM KNOW TOMORROW.

THE COURT: OKAY. AND I THINK THAT AFTER

EVERYONE -- OR EVEN DURING THE INTERIM OF YOUR

TESTIMONY, YOU COULD CONSIDER PROVIDING A HARD COPY OR

LATER IDENTIFYING THE POWERPOINTS. THEY'RE

DEMONSTRATIVE, OF COURSE, BUT IT'S HELPFUL. IT SAVES MY

HAND FROM WRITING NOTES.

BUT OTHER THAN THAT SELFISH REASON, I

THINK IT'S VERY HELPFUL, BECAUSE THAT IS THE FLOW OF

YOUR ARGUMENT. THAT IS THE FLOW OF YOUR POSITION. AND

IT'S A GUIDE TO HOW WE ANALYZE THIS.

MR. TRACEY: YES, YOUR HONOR. I THINK WE

HAVE A COPY.

THE COURT: I DON'T NEED IT RIGHT NOW.

I'M FOLLOWING ON THREE SCREENS. THANK YOU.

MR. TRACEY: OKAY.

MAY I PROCEED, YOUR HONOR?

THE COURT: PLEASE DO.

BY MR. TRACEY:

Q. DR. CABRERA, IN ADDITION TO THE PUBLISHED

LITERATURE THAT YOU HAVE TOLD US ABOUT, HAVE YOU ALSO


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REVIEWED PFIZER'S INTERNAL ANIMAL STUDIES?

A. YES, I HAVE.

Q. NOW, TELL THE COURT WHAT THESE ANIMAL STUDIES

WERE OR ARE?

A. THESE ARE THE PRECLINICAL STUDIES. THESE ARE

REPRODUCTIVE AND DEVELOPMENTAL TOXICITY STUDIES

PERFORMED ON ANIMALS, WHICH INCLUDE PREDOMINANTLY RATS

AND RABBIT MODELS, AND THEY'RE SUMMARIZED HERE IN REGARD

TO THE EFFECTS THAT ZOLOFT HAS IN THESE STUDIES.

Q. ALL RIGHT. AND SO JUST TO SORT OF BREAK IT

DOWN. THESE ARE WHOLE ANIMAL STUDIES THAT PFIZER WAS

REQUIRED TO DO BY THE FDA PRIOR TO GETTING APPROVAL TO

MARKET ZOLOFT?

A. YES.

Q. NOW, THESE STUDIES ARE NOT JUST -- WELL, ARE

THESE CALLED REPRODUCTIVE TOXICITY STUDIES?

A. THEY ARE REPRODUCTIVE AND DEVELOPMENTAL TOXICITY

STUDIES, YES.

Q. AND EXPLAIN THE IMPORTANCE OR THE PURPOSE OF

REPRODUCTIVE TOXICITY STUDIES?

A. SO WE WANT TO SEE A NUMBER OF THINGS, WHICH

INCLUDE WHETHER THERE IS AN IMPACT ON THE REPRODUCTIVE

FUNCTION OF ANIMALS, AND THAT IS BOTH THE MALES AND THE

FEMALES THAT ARE EXPOSED TO THE PHARMACEUTICALS OR THE

CHEMICALS OF INTEREST.


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ADDITIONALLY, WE WANT TO KNOW IF THERE IS

AN IMPACT GESTATIONALLY, THAT IS DURING DEVELOPMENT ON

PREGNANT ANIMALS, AND ULTIMATELY WE WANT TO ANALYZE

THESE DATA AND WE ALSO DO GENERATIONAL STUDIES, WHERE WE

LOOK AT MULTIGENERATION EFFECTS, POTENTIAL EFFECTS OF A

COMPOUND ON THE DEVELOPMENT OF MULTIGENERATIONAL

STUDIES.

Q. AND SO THESE REPRODUCTIVE TOXICOLOGY STUDIES,

ARE THEY, STRICTLY SPEAKING, TERATOLOGICAL STUDIES?

A. NOT STRICTLY SPEAKING. THEY ARE REPRODUCTIVE

AND DEVELOPMENTAL TOXICITY STUDIES, BUT THEY DO HAVE A

SEGMENT THAT INCLUDES ORGANOGENESIS, WHICH IS USUALLY

REFERRED TO AS A TERATOLOGY PART OF A STUDY.

Q. AND IF YOU WERE GOING TO DO TERATOLOGICAL

STUDIES ON MICE OR RATS OR RABBITS, WOULD YOU DO STUDIES

SEPARATE AND DISTINCT OR DIFFERENT OR IN ADDITION TO

THESE REPRODUCTIVE TOXICITY STUDIES?

A. YES, WE WOULD.

Q. AND WHY IS THAT?

A. THE STUDIES ARE ACKNOWLEDGED, EVEN WITHIN THE

GUIDELINES PROVIDED TO INDUSTRY, THROUGH THE

HARMONIZATION GUIDELINES, AND THE FDA GUIDELINES, THAT

THEY ARE UNDERPOWERED IN ORDER TO IDENTIFY CONGENITAL

MALFORMATIONS OR RARE CONDITIONS THAT MAY PRESENT DUE TO

EXPOSURE TO THE COMPOUNDS.


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Q. WHAT DOES UNDERPOWERED MEAN IN A STUDY?

A. THERE ARE TOO FEW DAMS AND THE ANALYSIS THAT IS

DONE ON THEM IS TYPICALLY NOT REFINED ENOUGH IN ORDER TO

IDENTIFY THE NECESSARY -- THE NECESSARY PATHOLOGY THAT

MAY PRESENT THERE. SO THEY ARE KIND OF A VOLUME STUDY

AND SO YOU DON'T REALLY GET THE DETAILS THAT ARE

REQUIRED FOR TERATOLOGY A LOT OF THE TIMES.

Q. AND SO THESE STUDIES THAT ARE DONE FOR

REPRODUCTIVE TOXICITY, THEN, ARE NOT POWERED, DO NOT

HAVE ENOUGH NUMBERS THEN TO SEE RARE OUTCOMES LIKE

CONGENITAL MALFORMATIONS?

A. THAT'S CORRECT.

Q. AND SPONTANEOUS ABORTIONS?

A. YES.

Q. TELL THE COURT WHAT YOU SAW WHEN YOU ANALYZED

THE PFIZER STUDIES?

A. SO I CAN JUST WALK THROUGH THE VARIOUS STUDIES

THAT I REVIEWED. THEY'RE GENERALLY REFERRED TO AS

SEGMENT STUDIES. AND AT THE TOP HERE WE SEE THE SEGMENT

ONE STUDY. AND RESULTS FROM THIS INITIAL STUDIES, WE

SEE THAT ALL OF THE ZOLOFT GROUPS EXPERIENCED DECREASED

PREGNANCY RATES. THAT IS, THEY FAILED TO GET PREGNANT,

AND THEN ALSO INCREASED POSTIMPLANTATION LOSS. AND THAT

IS, EMBRYOS THAT IMPLANTED IN THE UTERUS ULTIMATELY CAME

TO A DEMISE AND DIED.


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Q. IS THAT EVIDENCE OF TERATOGENICITY?

A. ABSOLUTELY. THAT IS CONSISTENT WITH TERATOGENIC

EFFECTS, ACCORDING TO WILSON.

Q. THAT WOULD BE WILSON'S PRINCIPLE OF -- ONE OF

HIS FOUR DEVIANT OUTCOMES?

A. YES, ABSOLUTELY.

Q. ALL RIGHT. AND THAT IS THE SEGMENT I STUDY.

WHAT IS THE SEGMENT I STUDY?

A. SO SEGMENT I STUDY IS DESIGNED TO LOOK AT

BASICALLY PREGNANCY, AND THEN ALSO PRESENTATION OF

GIVING THE DRUG DURING PREGNANT AND LOOKING FOR OUTCOMES

IN THE RESULTING PUPS.

Q. IT SAYS, ALL ZOLOFT GROUPS EXPERIENCED DECREASED

PREGNANCY RATES AND INCREASED POSTIMPLANTATION LOSS.

HOW MANY GROUPS WAS THIS, IF YOU RECALL?

A. THREE WERE, I BELIEVE, THREE TREATED GROUPS, AND

-- IN EACH ONE OF THESE STUDIES. AND THERE IS LIKE A

LOW, MEDIUM AND HIGH DOSE, WHICH IS BASED ON HOW ALL OF

THESE STUDIES GENERALLY ARE DESIGNED.

Q. OKAY. AND THE NEXT BOX DOWN, SEGMENT I PROTOCOL

80142, DONE IN 1982, I'M ASSUMING. IS THAT WHAT THAT

DATE IS?

A. YES.

Q. TELL US WHAT YOU FOUND THERE.

A. AGAIN, WE SEE A DRUG RELATED DECREASE IN


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SURVIVAL OF PUPS, AND THAT IS GENERALLY REFERRED TO AS

POSTNATAL LOSS OR LOSS AFTER THE ANIMALS WERE BORN, AND

THERE WAS ALSO A VARIETY OF PROBLEMS IN THESE ANIMALS,

THAT ULTIMATELY RESULTED IN DEATH. AND THIS PARTICULAR

CASE, YOU SEE 36 CASES OF BLOOD IN THE PERITONEUM, WHICH

IS BLOOD IN THE ABDOMINAL CAVITY VERSUS ONE IN THE

CONTROLLED. AND THERE'S ALSO A VARIETY OF

MALFORMATIONS, ALTHOUGH I BELIEVE AS YOU SEE HERE,

MICROTHALMIA, WHICH I WILL SAY WAS NOT STATISTICALLY

SIGNIFICANT, BUT IT'S CLEARLY A CONGENITAL MALFORMATION

PRESENT IN A TREATED ANIMAL. AND THEN ALSO A NUMBER OF

TREATED PUPS DIED DURING LACTATION.

THIS IS ALSO TO BE EXPECTED IN THAT SERT

MUTANTS THAT HAVE NOT GOT -- ADMINISTRATION OF THESE

CHEMICALS, EVEN IN HUMANS IS ASSOCIATED WITH PROBLEMS

AFTER DELIVERY, AND POTENTIALLY SUDDEN INFANT DEATH

SYNDROME. SO THAT YOU ALSO HAVE LOSS OF PUPS DURING

LACTATION, THAT IS EARLY DEVELOPMENT.

Q. NOW, ON THIS SEGMENT I STUDY, THE SECOND BOX

DOWN, IS THERE ANYTHING ON THERE WHERE YOU CAN LOOK AND

SAY, WELL, YOU KNOW, JUDGE, HERE IS A BIRTH DEFECT IN A

RAT PUP?

A. THE MICROTHALMIA IS A BIRTH DEFECT. AS I

MENTIONED, IT DID NOT ACHIEVE STATISTICAL SIGNIFICANCE,

BUT IT IS CLEARLY A CONGENITAL MALFORMATION, YES.


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Q. SO LET ME ASK YOU THIS. IF YOU GOT A STUDY --

AND THIS IS ONE OF THE STUDIES THAT IS NOT POWERED TO

FIND BIRTH DEFECTS, RIGHT?

A. YES.

Q. YOU ARE NOT SUPPOSED TO SEE BIRTH DEFECTS, AND

YOU ARE NOT SUPPOSED TO SEE DEAD RAT PUPS BECAUSE THERE

IS NOT ENOUGH TO DETERMINE WHETHER OR NOT THAT IS GOING

ON?

A. CORRECT.

Q. SO WHEN YOU SEE DEAD RAT PUPS AND BIRTH DEFECTS

IN A STUDY THAT IS NOT POWERED TO SEE IT, DOES THAT MEAN

ANYTHING TO A SCIENTIST?

A. TYPICALLY IF I WAS CONDUCTING THIS RESEARCH I

WOULD REQUEST THAT WE INCREASE NUMBER OF ANIMALS IN

ORDER TO INCREASE THE POWER OF THE STUDY TO SEE IF

ADDITIONAL DEFECTS PRESENT OR WHETHER THESE ARE JUST

SIMPLY BACKGROUND RATES OF MALFORMATIONS.

Q. WAS THAT DONE?

A. IT WAS NOT.

Q. THE NEXT BOX ON YOUR SLIDE SAYS SEGMENT II,

PROTOCOL NUMBER 80107, A 1981 RABBIT STUDY.

WHAT DID YOU FIND THERE?

A. SO THIS STUDY WE FIND INCREASED PERSISTENCE OF

THE LEFT CARDINAL VEIN. GENERALLY WOULD NOT BE CAUSE

FOR MAJOR CONCERN EXCEPT FOR THE FACT THAT THESE VEINS


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SHOULD GO AWAY. THE FACT THAT IT STAYED AROUND MAY

INDICATE THERE IS A PROBLEM IN THE DEVELOPMENT SYSTEM

SPECIFIC WITH LATERALITY AND DEVELOPING HEART AND

VASCULATURE.

ALSO, THERE WAS A PROBLEM IN THE STUDY,

EARLIER IT WAS MENTIONED THINGS LIKE CONFOUNDING. AND

IN PARTICULAR. THIS STUDY THERE WAS AN INFECTION WITH A

HIGHLY CONTAGIOUS BACTERIA THAT WAS A POTENTIAL

CONFOUNDER BECAUSE IT ALSO HAS BEEN KNOWN TO INFLUENCE

REPRODUCTIVE HEALTH OF THESE ANIMALS. BUT WE STILL FIND

A NUMBER OF OSSIFICATION AND BONE PROBLEMS SPECIFIC TO

TREATED ANIMALS, MOST NOTABLY THE IMPACT ON THE HYOID

BONE AND THE TALUS, WHICH ARE BONES OF THE FOOT AND

WOULD ULTIMATELY DESCRIBE SOME INDICATION FOR A SKELETAL

PROBLEM, POTENTIALLY CLUB FOOT OR FOOT DEVELOPMENT AND

BONE DEVELOPMENT PROBLEMS.

Q. NOW, THE INCREASED PERSISTENCE OF THE LEFT

CARDINAL VEIN, YOU HAVE 7.1 PERCENT CONTROL VERSUS 16.7

PERCENT IN THE HIGH DOSE GROUP. WHY DOES THAT MATTER?

A. WE GENERALLY COMPARE ANY ONE OF OUR EXPERIMENTAL

GROUPS TO A CONTROL GROUP THAT IS AN UNTREATED GROUP OR

A VEHICLE TREATED AND THAT IT DOES NOT GET THE

MEDICATION OR CHEMICAL THAT WE ARE TESTING. AND

ULTIMATELY WHEN WE SEE A CHANGE, WE WOULD TYPICALLY

MEASURE FOR STATISTICAL SIGNIFICANCE AND SEE IF THIS IS


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A SIGNIFICANT CHANGE. BUT ULTIMATELY THIS IS -- WHAT IS

DESCRIBED HERE AS ALMOST A DOUBLING, AND THE PERSISTENCE

OF THE CARDINAL VEIN WHICH WOULD BE CONSISTENT WITH THE

LATERALITY DEFECT.

Q. WELL, IT'S MORE THAN DOUBLING, ISN'T IT?

A. IT'S MORE THAN DOUBLING.

Q. SO THAT WOULD BE CONSISTENT WITH A LATERALITY

DEFECT?

A. YES.

Q. WOULD IT BE FAIR TO SAY BASED ON WHAT YOU HAVE

JUST SHOWN US SO FAR, THAT IF PFIZER PUT IN THEIR LABEL

THERE IS NO EVIDENCE OF TERATOGENICITY OF ANY DOSE LEVEL

IN OUR ANIMAL STUDIES, WOULD THAT BE AN ACCURATE

STATEMENT TO MAKE TO ANYBODY?

A. NO, I WOULD SAY THAT WOULD BE INACCURATE.

Q. IS THERE EVIDENCE OF TERATOGENICITY IN THESE

ANIMAL STUDIES?

A. THERE IS EVIDENCE OF TERATOGENIC EFFECT WHICH IS

ACTUALLY DESCRIBED WITHIN THE LABEL. IT'S IN THE SAME

PARAGRAPH AT THE END OF THE PARAGRAPH AS IN UTERO LOSS

AND THEN ALSO POST-NATAL LOSS. THAT WOULD BE A

TERATOGENIC EFFECT.

Q. THE NEXT SEGMENT TO PROTOCOL 85121/88516, 1986.

WHAT'S THE SIGNIFICANCE OF THIS STUDY?

A. SO IN THIS STUDY THERE WAS, I THINK A PROBLEM


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DESCRIBING THE DEFECT. I HAVE WORKED IN THIS FIELD FOR

A FEW DECADES AND I'VE WORKED WITH ANOTHER TERATOLOGIST,

AND A VETERINARIAN PATHOLOGIST AND WHEN I ASKED THEM

WHAT A PROTUBERANCE FROM THE HEAD MEANT, HE KIND OF

LAUGHED AND SAID, YOU KNOW, WHERE DID YOU GET THAT? AND

WE KIND OF TALKED ABOUT IT FOR A WHILE AND WE DECIDED IT

MAY BE AN NTD, POTENTIALLY AN ENCEPHALOCELE, BUT USING

THE LANGUAGE SUCH AS THE PROTUBERANCE WE HAVE NO ABILITY

TO ACTUALLY UNDERSTAND WHAT THEY MEANT PATHOLOGICALLY BY

THAT DESCRIPTION. SO EITHER THEY WERE TRYING TO BE

VAGUE OR THEY JUST WERE NOT VERY SKILLED IN

THEIR ABILITY TO DO PATHOLOGY.

Q. NTD IS A NEURAL TUBE DEFECT?

A. YES, THAT WOULD BE A NEURAL TUBE DEFECT,

PARTICULARLY OF THE CAUDAL REGION OF THE BRAIN, THE HEAD

REGION.

Q. SO A PROTUBERANCE OF THE LEFT PART OF THE HEAD,

IS THAT A SCIENTIFIC TERM THAT YOU ARE FAMILIAR WITH AS

A TERATOLOGIST?

A. NO, I HAVE NEVER DESCRIBED A NEURAL TUBE DEFECT

OR ANY KIND OF BUMP ON THE HEAD OR PROTUBERANCE FROM THE

HEAD AS A PROTUBERANCE FOR PATHOLOGY PURPOSES.

Q. THE NEXT THING YOU HAVE THERE IS REPORTED

SIGNIFICANT CHANGES IN OSSIFICATION. SO THAT IS THE

SECOND TIME NOW WE SEE CHANGES IN OSSIFICATION?


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A. YES.

Q. EXPLAIN TO THE COURT WHAT THAT MEANS AND WHY

THAT IS IMPORTANT.

A. SO AS I MENTIONED EARLIER, THE BONE ITSELF IS

ALSO DEPENDENT ON SERT SIGNALLING AND USES RECEPTORS FOR

SEROTONIN FOR BONE GROWTH AND OSSIFICATION, WHICH IS

BASICALLY THE GROWTH IN THE HARDENING OF THE BONES. AND

WE SEE THAT IN THE PRESENCE OF SERT OR MUTATION, THE

PRESENCE OF THESE COMPOUNDS OR MUTATION OF SERT OR THE

TRANSPORTERS WE SEE AN IMPACT ON BONE GROWTH AND BONE

DENSITY. AND IN THIS PARTICULAR ONE WE SEE CHANGES IN

OSSIFICATION THAT INCLUDES CHANGES IN THE METACARPALS.

Q. AND IF YOU SAW EPIDEMIOLOGY STUDIES THAT PROVED

THAT ZOLOFT AND SSRIS IN PEOPLE CAUSED CLUB FOOT AND YOU

LOOKED AT THESE STUDIES, WOULD YOU SAY THAT WAS

CONSISTENT OR INCONSISTENT?

A. I WOULD SAY THAT WAS EXPECTED BASED ON THESE

STUDIES?

Q. WHAT IS THE NEXT BOX?

A. THE NEXT ONE IS A SEGMENT III STUDY ON RATS,

83107.

Q. WE SEE THERE THAT WE HAVE DOSE RELATED INCREASES

IN STILLBIRTHS. DOSE RELATED INCREASES IN DEAD AND

CANNIBALIZED PUPS. AND THEN YOU HAVE THE NUMBERS DOWN

THERE. WHY ARE THESE IMPORTANT, THESE FINDINGS?


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A. SO ONCE AGAIN, WE SEE LOSS IN THESE STUDIES. I

THINK THE IMPORTANCE OF THESE DATA, AS YOU CAN SEE, HERE

THE INCREASE WITH LOW, MEDIUM AND HIGH DOSES, WITH AN

INCREASE IN STILLBIRTHS, THAT IS IN UTERO DEATHS, AND

THEN ALSO AN INCREASE IN ANIMALS THAT WERE ULTIMATELY

DEAD OR CANNIBALIZED. THE IMPORTANCE OF BEING

CANNIBALIZED IS THAT THESE ANIMALS, WHEN THEY HAVE A PUP

THAT IS MALFORMED OR A CONGENITAL MALFORMATION, THEY

WILL OFTEN CANNIBALIZE THEM, OR IF THE PUP IS BORN DEAD,

THEY WILL ALSO CANNIBALIZE THEM.

Q. A COUPLE OF QUESTIONS.

YOU HAVE GOT THE CONTROLS AT .9 PERCENT

GOING FROM THE LOW DOSE GROUP OF 7 PERCENT, THE MEDIUM

AT 26. AND THE HIGH OF 55 PERCENT. IS THAT A DOSE

RESPONSE?

A. YES, IT IS.

Q. IS THAT PART OF WILSON'S PRINCIPLES?

A. YES, IT IS.

Q. IS THAT WILSON'S PRINCIPLE NUMBER 6 WE PUT ON

THE SCREEN?

A. YES, IT IS.

Q. IS THAT WHY THAT IS IMPORTANT?

A. YES, IT IS.

Q. IT IS ALSO WILSON'S FIFTH PRINCIPLE WITH AN

ADVERSE OR DEVIANT OUTCOME OF EITHER CONGENITAL


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MALFORMATION OR DEATH?

A. WE DO EXPECT THAT BASED ON THE FOUR DEFINED

DEVIANT OUTCOMES, THAT DEATH IS ONE OF THOSE OUTCOMES,

YES.

Q. ALL RIGHT.

THE NEXT SECTION IS SEGMENT II, PROTOCOL

83112, A CROSS FOSTERING STUDY. TELL THE JUDGE WHAT A

CROSS FOSTERING STUDY IS?

THE COURT: YOU MEANT SEGMENT III FOR THE

RECORD.

MR. TRACEY: SORRY, SEGMENT III.

BY MR. TRACEY:

Q. TELL THE COURT WHAT A CROSS FOSTERING STUDY IS

AND WHY THEY ARE DONE?

A. SO THIS STUDY AND THE IMPORTANCE OF IT IS THAT

THERE WAS SOME DEBATE, I BELIEVE, AT THE TIME IN THAT

THE EFFECT OR THE LOSS OF THE PUPS EARLY ON THAT HAD

BEEN EXPOSED IN UTERO TO THE SERTRALINE THAT IT MAY BE

DUE TO CHANGES IN THE MOTHER'S BEHAVIOR AND SO

ULTIMATELY THEY DO CROSS FOSTERING. THAT IS, THE PUPS

THAT ARE BORN FROM DAMS THAT HAVE BEEN EXPOSED, THEY

ULTIMATELY GET NEW MOMS AND THESE MOMS HAVE NOT BEEN

EXPOSED, TO SEE HOW THEY REAR THE PUPS. AND ULTIMATELY,

THIS STUDY SHOWS THAT IT'S THE IN UTERO EXPOSURE IN AND

ITSELF THAT PRODUCES THE PROBLEM AND THE VIABILITY OF


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THE PUPS.

Q. IS THAT ANOTHER WAY OF SAYING THAT IS HOW THEY

PROVED IT WAS THE DRUG?

A. YES. WELL, NOT -- IT WAS THE EFFECT IN UTERO,

NOT THE CHANGES IN THE MOTHER'S BEHAVIOR.

Q. YES. IT WAS THE DRUG, NOT THE MOM?

A. RIGHT.

Q. OR THE DRUG EFFECT ON THE MOM?

A. YES.

Q. THE DRUG EFFECT ON THE EMBRYO?

A. ON THE FETUS.

Q. ON THE FETUS. OKAY.

LET ME ASK YOU THIS.

HAD PFIZER COME TO THE FINNELL LAB FOR

BIRTH DEFECT RESEARCH AND SAID, DR. CABRERA AND DR.

FINNELL, I WANT YOU TO REVIEW THESE FINDINGS BACK IN

1987 -- OF COURSE, YOU WERE PROBABLY A KID THEN, BUT

THEY COME TO YOU BEFORE THEY TOOK THIS DRUG TO MARKET

AND THEY HAD SAID, I WANT YOUR OPINION, DR. CABRERA, OF

WHETHER OR NOT YOU BELIEVE THIS DRUG IS LIKELY TO BE A

TERATOGEN? WHAT WOULD YOUR ANSWER HAVE BEEN TO THEM?

A. THERE IS EVIDENCE OF TERATOGENIC EFFECT. IT'S

NOT THE WORST I HAVE EVER SEEN, BUT THERE ARE POTENTIALS

FOR MALFORMATIONS IN EXPOSING THE POPULATION.

Q. WHAT WOULD YOU, IF YOU HAD -- IF IT WAS UP TO


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YOU, WHAT WOULD YOU HAVE DONE OR ADVISED THEM TO DO TO

TRY TO FIGURE OUT THAT ANSWER?

A. I WOULD INCREASE THE POWER OF THE STUDIES AND

THAT IS IN THOSE PARTS THAT WE SEE A SIGNIFICANT

INCREASE FROM THE CONTROL LEVELS WITHIN THE STUDY, TO

INCREASE THE NUMBERS TO LOOK FOR ADDITIONAL DEFECTS.

AND WHEN WE DO SEE DEFECTS TO INCREASE THE NUMBER OF

DOSE STUDIES TO MAKE SURE THAT THEY ARE NOT SIMPLY

BACKGROUND RATES, TO MAKE SURE -- TO SEE IF THEY ARE

DRUG RELATED.

Q. TELL THE COURT WHAT YOU THINK THE QUALITY OF

THESE STUDIES WAS.

A. IT'S POOR.

Q. WHY IS IT SO POOR?

A. THERE IS A LOT OF LOSS OF ANIMALS THROUGHOUT THE

STUDIES. I BELIEVE IT'S IDENTIFIED WITHIN THE STUDIES,

THAT THE BEHAVIOR OF THE DAMS CHANGED AND MADE IT

DIFFICULT FOR THEIR TREATMENT. AND ULTIMATELY MANY OF

THE DAMS DIED DURING THE TREATMENTS. AND AS I MENTIONED

EARLIER, THESE STUDIES BEGAN UNDERPOWERED AND THEN WHEN

YOU HAVE LOSS OF SOMETIMES ENTIRE GROUPS OF ANIMALS THAT

WERE GOING TO BE STUDIED FOR VISCERAL OR CONGENITAL

DEFECTS, SOMETIMES YOU LOSE ENTIRE GROUPS IN SOME OF

THESE STUDIES BECAUSE OF THAT EFFECT. AND THE LOSS OF

ANIMALS AND ALSO THE INFECTIONS THAT ARE ALSO PRESENT IS


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ALSO ANOTHER PROBLEM.

Q. SO BEFORE I GET TO THAT, HAD YOU REVIEWED ANIMAL

STUDIES ON OTHER SSRIS THAT DIDN'T HAVE THIS SORT OF

LOSS?

A. IT'S ACTUALLY A CONSISTENT FINDING THAT THEY

PRODUCE LOSS DURING UTERO, A LOSS, AND THEN ALSO

POSTNATAL LOSS IS A CONSISTENT FINDING WITH THESE

CHEMICALS.

Q. ACROSS ALL OF THE SSRIS?

A. YES.

Q. NOW, YOU -- I THINK IT WAS MAYBE IN RESPONSE TO

DR. HOOD OR THE CRITICISMS FROM PFIZER ABOUT SOME

CONCLUSIONS THAT YOU MADE, YOU DID THIS OR YOU CREATED

THIS EXHIBIT, DIDN'T YOU?

A. YES.

Q. SO TELL THE COURT WHY YOU CREATED THIS EXHIBIT

AND WHY IT IS IMPORTANT?

A. SO THIS IS A TABLE THAT IS DESCRIBED HERE THAT

WAS PREPARED BY DR. HOOD, AND THE PROTOCOL NUMBERS

LISTED AT THE TOP, 86-375-14. AND ULTIMATELY THIS STUDY

WAS CONDUCTED WITH INFORMATION THAT ULTIMATELY IS IN THE

LABEL FOR DIFFERENT EXPOSURE WINDOWS. AND THE GROUP A,

THEY BEGIN TREATMENT OF THE ANIMALS. ZERO, THAT IS THE

TIME OF COPULATION UP TO BIRTH. SO THEY FIND THE PLUGS

AND THEY START TREATMENT ON DAY ZERO, ULTIMATELY TREAT


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THE ANIMALS UNTIL THE DAY OF THEIR BIRTH.

WHAT THEY ARE INTERESTED IN HERE WHICH IS

DISPLAYED ON THE RIGHT IS POSTIMPLANTATION SURVIVAL TO

BIRTH. YOU CAN COUNT THE NUMBER OF IMPLANTATION SITES

IN THE UTERUS AND THEN ULTIMATELY YOU CAN LOOK AT THE

NUMBER OF LIVE BORN PUPS AND DETERMINE THE PERCENTAGE

THAT MAY BE LOST DUE TO EXPOSURE TO THE DRUG.

Q. LOSS MEANS DEAD?

A. YES.

Q. SO IN THE ZERO TO BIRTH HIGHLIGHTED AND ZERO TO

TEN HIGHLIGHTED, EXPLAIN THOSE FINDINGS.

A. SO THE LABEL INDICATES THAT ONLY EXPOSURES AFTER

15 WE WOULD GENERALLY CONSIDER THESE LATE-TERM EXPOSURES

OR POTENTIALLY THIRD-TRIMESTER EXPOSURES CREATED

POSTIMPLANTATION SURVIVAL LOSS. AND SO THAT IS

INDICATED THERE AS 76 PERCENT, POST IMPLANTATION

SURVIVAL TO BIRTH. AND THIS IS STATISTICALLY

SIGNIFICANT. THAT IS GROUP A.

THE IMPORTANCE IS IF YOU LOOK AT GROUP D,

AND THOSE ANIMALS ARE ONLY EXPOSED FROM ZERO TO TEN,

WHICH IS GENERALLY ACCEPTED AS THE PERIOD OF EARLY

EMBRYONIC DEVELOPMENT AND EMBRYONIC DEVELOPMENT, NEURAL

TUBE CLOSURE AND THEN SOME PARTS OF HEART DEVELOPMENT,

WE ALSO SEE A STATISTICALLY SIGNIFICANT EFFECT. FROM

THE SAME TABLE THAT IS PRESENTED FROM HOOD WE SEE THERE


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SIGNIFICANT POSTIMPLANTATION SURVIVAL TO BIRTH. THAT IS

THE LOSS OF THOSE ANIMALS THAT ACHIEVED STATISTICAL

SIGNIFICANCE.

Q. SO IN THIS ZERO TO TEN HIGHLIGHTED GROUP D, DOES

THAT ROUGHLY CORRESPOND TO FIRST-TRIMESTER EXPOSURE IN

HUMANS?

A. YES, IT WOULD.

Q. SO IF WE SEE STATISTICALLY SIGNIFICANT NUMBER

OF -- THIS WOULD BE SPONTANEOUS ABORTIONS ESSENTIALLY,

RIGHT?

A. BASED ON LOSS, WE WOULD EXPECT EITHER A

SPONTANEOUS ABORTION OR A POTENTIALLY IN UTERO DEATH MAY

RESULT IN SPONTANEOUS ABORTION, YES.

Q. NEITHER ONE IS A DEVIANT OUTCOME ACCORDING TO

WILSON, RIGHT?

A. YES.

Q. SO THAT IS NOT WHAT WE WOULD EXPECT TO SEE

UNLESS THE DRUG WAS A TERATOGEN, IS IT?

A. THAT IS DEFINITELY A TERATOGENIC EFFECT.

Q. THAT IS A TERATOGENIC EFFECT, ISN'T IT?

A. YES, IT IS.

Q. IS THERE ANY QUESTION ABOUT THAT IN YOUR MIND?

A. NO, IT IS NOT. I ALSO CONDUCTED ADDITIONAL

ANALYSIS JUST TO TEST POWER. I GROUPED AT THE BOTTOM

THERE, B, D AND E. GROUPS B, D AND E BEING EXPOSURE


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BEFORE 15 DAYS. AND WHEN YOU GROUP THESE GROUPS

TOGETHER, YOU ALSO SEE THAT THERE IS A STATISTICALLY

SIGNIFICANT EFFECT IN LOSS IN POSTIMPLANTATION OF

SURVIVAL TO BIRTH.

SO I DON'T THINK IT'S STRICTLY AN

ARTIFACT, AND YOU ALSO SEE VERY CLOSE .06, IF YOU ACCEPT

.05 PROBABILITY FOR THESE TESTS, THAT E ALMOST ACHIEVES

STATISTICALLY SIGNIFICANT RESULTS AS WELL.

Q. LET ME ASK YOU THIS.

DO SCIENTISTS SUCH AS YOURSELF, DO WE

KNOW, LOOK, IF WE DO TERATOLOGICAL TESTING AND WE SEE

CONGENITAL MALFORMATIONS IN MICE OR RATS, DO WE HAVE ANY

DATA TO KNOW WHAT THE ODDS OF IT HAPPENING IN HUMANS

ARE?

A. THERE ARE SOME DATA ON THAT, YES.

Q. WHAT IS THE DATA ON THAT?

A. SO TYPICALLY WE USE A RODENT AND A NONRODENT

SPECIES AND THEIR CO-RELATIONS BETWEEN THESE

POPULATIONS, SO MOUSES I THINK ARE 80 PERCENT

PREDICTABLE FOR THE PRESENCE OF CONGENITAL MALFORMATIONS

AND HUMANS IF IT PRESENTS WITH TERATOGENIC EFFECT.

Q. SO IF IN STUDIES LIKE THESE WE SEE TERATOGENIC

EFFECTS, WE KNOW WITH 80 PERCENT CERTAINTY WE SHOULD

EXPECT TO SEE THEM IN HUMANS?

A. YES.


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Q. IS THAT EVEN A CONTROVERSIAL TOPIC?

A. IT'S MATH. I MEAN, IT'S JUST HOW THE DATA WORKS

OUT.

Q. IT SEEMS CONTROVERSIAL TO ME.

SO MATHEMATICALLY, IS THAT WHY WE

TERATOLOGISTS DO THESE STUDIES IN MICE AND RATS?

A. THAT IS WHY ONE OF SPECIES IS A RODENT SPECIES

AND THEN WE ALSO USE ANOTHER SPECIES IN ORDER TO BUILD

SOME POWER ON THE OTHER SIDE SO THAT WE ARE NOT

NECESSARILY PRODUCING A LOT OF FALSE NEGATIVES.

Q. WHAT TYPE OF SPECIES DO YOU USE ON THE OTHER

SIDE?

A. GENERALLY A RABBIT.

Q. IS THIS WHAT YOU WERE TALKING ABOUT EARLIER, OR

IS THIS SOMETHING DIFFERENT?

A. SO THESE ARE JUST SOME CONCLUSIONS THAT WERE

PRESENTED, AND PARTICULARLY THESE ARE FOUND ON THE LABEL

AS I MENTIONED EARLIER, THAT THEY CONCLUDE THAT THERE IS

NO INCREASE OF DEATH FOR THE FIRST THREE GROUPS ONLY FOR

GROUP FOUR AND THAT IS THE GROUP THAT WAS EXPOSED

THROUGHOUT. THAT IS INCORRECT. WHETHER YOU GROUP THOSE

GROUPS OR IF YOU JUST LIKE AT GROUP D, YOU SEE THAT

THERE IS A STATISTICALLY SIGNIFICANT INCREASE IN

NEONATAL DEATH WITH EXPOSURE.

Q. OKAY. SO PFIZER WAS WRONG ACCORDING TO YOU ON


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TWO FRONTS. THEY CONCLUDED NO INCREASED DEATH FOR THE

FIRST THREE GROUPS AND THAT IS JUST WRONG?

A. YES.

Q. THEY CONCLUDED IN THEIR LABEL THAT THE

GESTATIONAL, DAY 16 THROUGH 21 WAS A PERIOD OF

VULNERABILITY, THEREFORE IT WAS NOT DURING THE TIME OF

ORGANOGENESIS WHEN MOST BIRTH DEFECTS ARE THOUGHT TO

OCCUR?

A. CORRECT. AND I THINK MOST IMPORTANTLY, WHEN

THEY IDENTIFY IT AS DAY 16 TO 21, IT WAS NOT JUST

EXPOSED DURING 16 TO 21, IT WAS EXPOSED THROUGHOUT

PREGNANCY, SO THEY ARE NOT AVOIDING THE EXPOSURE

THROUGHOUT. IT WAS A STUDY THAT WAS INCLUDING ALL THOSE

EARLIER EXPOSURES AS WELL.

Q. SO THOSE RATS, THEY JUST HAPPEN TO MAKE IT ALL

OF THE WAY TO 21 DAYS?

A. YES, ABSOLUTELY.

Q. BECAUSE THEY GOT THE DRUG THE WHOLE TIME?

A. YES.

Q. OKAY. WE HAVE SEEN THIS. THIS IS A LETTER FROM

PAUL LEBER, DR. CABRERA, TO MARGARET LONGSHORE OF PFIZER

WHERE THEY CONCLUDE THAT BECAUSE OF THE FINDINGS THAT

YOU HAVE JUST DESCRIBED I BELIEVE REGARDING DECREASED

FERTILITY, DECREASED PUP BIRTH WEIGHTS, AND INCREASED

NUMBERS OF STILLBIRTHS, INCREASED PUP DEATHS IN RATS


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ZOLOFT MUST BE LABELED CATEGORY C. AND SHE SAYS THIS IS

CONSISTENT WITH ALL THE OTHER SSRIS, ALL THE OTHER

SEROTONIN REUPTAKE INHIBITORS. AND MY QUESTION IS, DO

YOU AGREE WITH PAUL LEBER, THIS IS A CLASS EFFECT?

A. YES, I DO.

Q. DID YOU SEE IN YOUR STUDY ALL OF THE THINGS THAT

THE FDA TOLD PFIZER THERE IN 1995?

A. YES, I HAVE.

Q. COULD ANYBODY LOGICALLY OR SCIENTIFICALLY, WITH

ANY SCIENTIFIC DEGREE OF SCIENTIFIC CREDIBILITY SAY THAT

THESE FINDINGS WE SEE THAT THE FDA SENT TO PFIZER IN

1995 MEANS THERE IS NO TERATOGENIC EFFECT IN OUR ANIMAL

STUDIES?

A. IF YOU ARE FOLLOWING THE PRINCIPLES OF WILSON

YOU WOULD DRAW THE SAME CONCLUSION THAT I HAVE DRAWN

TODAY.

Q. ALL RIGHT.

INCIDENTALLY, MAYBE THIS IS A GOOD TIME

TO QUICKLY EXPLAIN THE DIFFERENT CATEGORIES, PREGNANCY

CATEGORIES. CAN YOU BRIEFLY GO THROUGH THESE, DOCTOR?

A. YES. SO THE CATEGORIES ARE LISTED HERE.

CATEGORY A, IN THAT WE WOULD CONDUCT OUR

PRECLINICAL STUDIES AND ULTIMATELY THESE STUDIES HAVE

FAILED TO DEMONSTRATE A RISK ON THE FETUS DURING THE

FIRST TRIMESTER OF PREGNANCY, THAT THERE WOULD BE NO


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INDICATION OF A TERATOGENIC EFFECT FOR CATEGORY A DRUGS.

CATEGORY B, WHICH I WOULD SAY WAS

MISAPPROPRIATELY GIVEN EARLY ON WOULD BE THAT ANIMAL

REPRODUCTION STUDIES HAVE FAILED TO DEMONSTRATE A RISK

TO THE FETUS AND THERE ARE NO ADEQUATE WELL CONTROLLED

STUDIES IN PREGNANT WOMEN.

IN REALITY, THERE WAS RISK TO THE FETUS

AND THE EMBRYO IN THOSE STUDIES. I THINK IT WAS WHY IT

WAS MOVED TO CATEGORY C. AND ULTIMATELY IN CATEGORY C

WE SEE ANIMAL REPRODUCTION STUDIES HAVE SHOWN ADVERSE

EFFECT ON THE FETUS AND THERE ARE NO ADEQUATE AND WELL

CONTROLLED STUDIES IN HUMANS AS WE WILL SEE IN, AS I

THINK I HAVE SHOWN, THERE ARE STUDIES IN HUMANS NOW AND

ULTIMATELY OTHER CONSIDERATION IS POTENTIAL BENEFITS MAY

WARRANT THE USE OF THESE DRUGS IN PREGNANT WOMEN DESPITE

THE POTENTIAL RISKS.

CATEGORY D THERE IS BOTH EVIDENCE OF RISK

IN THE HUMAN STUDIES AND ULTIMATELY YOU CONSIDER THE

POTENTIAL BENEFITS THAT MAY WARRANT CONTINUED USE OF THE

DRUG DESPITE THE POTENTIAL RISKS.

CATEGORY X, ABSOLUTELY THESE COMPOUNDS

SHOULD NOT BE USED BY PREGNANT WOMEN AND HAVE SHOWN

ADVERSE EFFECTS IN THESE POPULATIONS.

Q. LET ME ASK YOU THIS, DOCTOR.

AS WE SIT HERE NOW TODAY, ARE THERE


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ADEQUATE AND WELL-CONTROLLED STUDIES IN HUMANS?

A. YES, THERE ARE.

Q. HOW MANY ARE THERE, WOULD YOU ESTIMATE?

A. FOR LOOKING AT THE VARIOUS CONGENITAL

MALFORMATIONS, I HAVE LOOKED AT DOZENS OF STUDIES IN

THIS REGARD.

Q. WOULD IT BE A FAIR OR SCIENTIFICALLY CREDIBLE

STATEMENT TO PUT IN YOUR LABEL TODAY THAT THERE ARE NO

ADEQUATE AND WELL-CONTROLLED STUDIES IN HUMANS?

A. NO. THERE ARE STUDIES THAT HAVE BEEN CONDUCTED

OBSERVING IN THE POPULATIONS.

Q. OKAY.

NOW, YOU ALSO HAD REVIEWED OTHER SSRI

DRUGS. ONE OF THEM YOU REVIEWED WAS CELEXA, RIGHT?

A. YES.

Q. YOU HAVE ALSO REVIEWED PAXIL?

A. YES.

Q. HAVE YOU EVER REVIEWED ANY OTHER SSRI ANIMAL

STUDIES?

A. LEXAPRO.

Q. TELL US WHY YOU PUT THIS SLIDE TOGETHER?

A. AND PROZAC.

Q. AND PROZAC. OKAY. SO ALL THE BIG ONES.

TELL US WHAT THE IMPORTANCE OF THIS SLIDE

IS?


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A. SO AS SHOWN HERE IN REGARD TO THE PREGNANCY

CATEGORY, WE SEE HERE THAT CELEXA HAS BEEN SHOWN TO HAVE

ADVERSE EFFECTS ON EMBRYO AND FETAL AND POSTNATAL

DEVELOPMENT INCLUDING TERATOGENIC EFFECTS. I THINK THE

IMPORTANT PART OF THIS STUDY AND WHEN IT WAS CONDUCTED

IS THAT THEY INCREASED THE POWER OF THIS STUDY BY

ANALYZING THE ANIMALS THAT WERE PROPOSED FOR SIMPLY

SKELETAL ANALYSIS. THEY ALSO LOOKED AT THEIR VISCERA

BEFORE THEY MOVED THEM ON TO SKELETAL ANALYSIS, SO

INCREASED THE POWER OF THIS STUDY AND THEN THEY FOUND

ADDITIONAL DEFECTS IN THESE STUDIES.

Q. SO IN THE CELEXA ANIMAL STUDIES, THEY DID WHAT

YOU SAID YOU WOULD HAVE TOLD PFIZER TO DO, WHICH IS

INCREASE THE POWER?

A. YES.

Q. AND WHEN THEY INCREASED THE POWER, THEY ACTUALLY

FOUND DEFECTS, DIDN'T THEY?

A. YES, THEY DID.

ADDITIONALLY, THEY DID A MORE DETAILED

ANALYSIS OF THE CARDIOVASCULAR DOING SECTIONING, THAT IS

FINE SECTIONING OF THE HEART AS WELL.

Q. DOES THAT MEAN THEY LOOKED HARDER FOR STUFF?

A. YES, THEY LOOKED IN MORE DETAIL WHICH I WOULD

ALSO SUGGEST AS WELL.

Q. WHEN THEY INCREASED THE POWER OF THE STUDY AND


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LOOKED HARDER, WHAT DID THEY FIND IN TERMS OF CONGENITAL

ABNORMALITY?

A. THEY FIND A VARIETY OF CARDIOVASCULAR DEFECTS.

ADDITIONALLY, THEY FIND VARIOUS SKELETAL DEFECTS AND

OSSIFICATION PROBLEMS.

Q. THAT IS NOT A SURPRISE TO YOU, IS IT?

A. NO, IT'S NOT.

Q. HOW MUCH DID THEY INCREASE THE POWER? IS THIS A

COUPLE OF RATS? IS THIS DOUBLE? IS IT TRIPLE? HOW

MUCH IS IT?

A. THEY DOUBLED THE POWER. WELL, THEY DOUBLED THE

NUMBER OF ANIMALS THAT CHANGED THE POWER OF THIS STUDY.

Q. SO ONE CRITICISM I THINK OF YOU THAT I HEARD IS

THAT WAIT A SECOND, WAIT A SECOND, DR. CABRERA, IT'S NOT

THE DRUG CAUSING THE BIRTH DEFECTS, IT'S THE EFFECT ON

THE MOTHER. THE MOTHER IS GETTING SICK AND THEREFORE

SHE IS NOT TAKING CARE OF THE BABIES OR SHE IS NOT

EATING RIGHT WHEN THEY ARE STILL IN HER WOMB. AND THAT

IS THE PROBLEM. YOU HEARD THAT CRITICISM?

A. YES, I HAVE.

Q. TELL US WHAT THIS DOCUMENT IS HERE ON THE SCREEN

AND WHY IT IS IMPORTANT.

A. SO WHAT IS COMMONLY CITED, I GUESS, OR SUGGESTED

IS THAT THESE STUDIES THAT OFTEN YOU WILL SEE LOW

MATERNAL TOXICITY IN THESE STUDIES. IN ACTUALITY, THIS


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202

IS NOT AN ARGUMENT OR A DEFENSE. THIS IS ACTUALLY HOW

THE STUDY IS DESIGNED BY ITS VERY NATURE. THE HIGH DOSE

IS EXPECTED TO PRODUCE LOW MATERNAL TOXICITY WITHIN THE

GUIDELINES UP TO TEN PERCENT MATERNAL DEATH IS AN

ACCEPTABLE AMOUNT FOR THESE STUDIES. NONE OF THESE

STUDIES WERE ACTUALLY THAT HIGH. MATERNAL TOXICITY WAS

JUST INDICATED BY SOME WEIGHT LOSS. AND IN THESE

EVENTS, SUCH AS OCCURRED IN THESE STUDIES, IT SAYS HERE

THAT ANOTHER COMMON SITUATION IS WHEN ADVERSE

DEVELOPMENTAL EFFECTS OCCUR AT DOSES THAT CAUSE MINIMAL

MATERNAL TOXICITY, AS IN THE STUDIES WE REVIEWED. IN

THESE SITUATIONS, DEVELOPMENTAL EFFECTS SHOULD BE

ATTRIBUTED TO DEVELOPMENTAL TOXICITY. AND THAT IS, JUST

BECAUSE THE MOTHER LOST SOME WEIGHT, THAT DOES NOT GIVE

YOU AN OUT. THE EFFECTS, BASED ON THE GUIDELINES,

SHOULD STILL BE ATTRIBUTED TO DEVELOPMENTAL TOXICITY.

Q. SO IT'S NOT A DEFENSE TO SAY WE GAVE YOU THE

DRUG, IT MADE THE MOM SICK, THE BABIES DIED, IT'S

BECAUSE THE MOM GOT SICK. THAT IS NOT A DEFENSE?

A. NO, IT'S NOT.

Q. IN FACT THAT IS WHAT YOU EXPECT TO SEE ACCORDING

TO THE GUIDELINES?

A. ABSOLUTELY.

Q. YOU ARE REQUIRED ACTUALLY TO MAKE THE MOM SICK,

AREN'T YOU?


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203

A. YOU ARE EXPECTED TO, YES.

Q. SO WE HAVE BEEN TALKING ABOUT DEAD RAT PUPS.

WHAT IS THIS PAPER THAT IS ON THE SCREEN HERE?

A. SO THIS IS A 2010 NAKHAI-POUR PAPER, AND IT

SHOWS AN INCREASE IN THE RISK OF SPONTANEOUS ABORTION

WITH THE USE OF SSRIS AS A CLASS.

Q. SO WE HAVE SEEN THE ANIMAL STUDIES, WE HAVE SEEN

ALL THE DEAD RAT PUPS, WE HAVE SEEN THE EFFECTS OF

TERATOGENICITY. THIS IS THE END OF YOUR ADVERSE OUTCOME

PATHWAY, WHERE YOU LOOK AT THE EPIDEMIOLOGY TO LINK UP

THE DEAD ANIMALS WITH CHILDREN NOW THAT ARE DYING IN


A. THIS WOULD BE AN EXPECTED EFFECT BASED ON THE

ANIMAL DATA.

Q. AND THIS IS DR. BERARD'S STUDY IN 2010 WHERE SHE

CONCLUDES THIS IS A CLASS EFFECT THAT ALL OF THE SSRIS

ARE CAUSING THESE SPONTANEOUS ABORTIONS IN HUMANS?

A. YES.

Q. DO YOU AGREE WITH HER CONCLUSIONS?

A. YES, I DO.

Q. DOCTOR, YOU ARE AWARE THAT THERE ARE A NUMBER OF

RESEARCHERS THAT HAVE CONCLUDED AS YOU HAVE, AND DR.

BERARD AND DR. SADLER AND DR. LEVIN, THAT THIS IS A

CLASS EFFECT?

A. YES, I'M AWARE.


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12

13

14

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16

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19

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204

Q. AND DR. PEDERSON'S STUDY IS ONE OF THEM THAT

SUGGESTS, AT LEAST WITH RESPECT TO ALL SSRIS AND HEART

DEFECTS HE BELIEVES THERE IS A CLASS EFFECT?

A. YES.

Q. DO YOU AGREE WITH HIM?

A. YES.

Q. AND DR. BERARD'S STUDY IS THE ONE WE SEE JUST

BELOW THAT. AND THEN HAVE YOU REVIEWED THE BOOK BY

AUBREY MILUNSKY, A GENETICIST, WHERE HE SAYS -- HE HAS A

TABLE OF MEDICATIONS CONCLUSIVELY SHOWN TO CAUSE BIRTH

DEFECTS?

A. YES, I HAVE SEEN THE TABLE. I HAVE NOT READ THE

BOOK, BUT I'M FAMILIAR WITH THE TABLE AND YES --

Q. LET ME ASK YOU THIS. ARE ALL THE DRUGS ON HIS

TABLE, WE SEE SERTRALINE, PAROXETINE ON THE BOTTOM,

RIGHT?

A. YES.

Q. EVERY DRUG ON THAT TABLE KNOWN TO BE A HUMAN

TERATOGEN TO A SCIENTIST?

A. YES, THEY ARE.

Q. AND HE SAYS SERTRALINE AND PAROXETINE ARE HUMAN

TERATOGENS CONCLUSIVELY SHOWN, DOESN'T IT?

A. YES.

Q. AND HE SAYS JUST LIKE YOU, HEART AND OTHER

DEFECTS, DOESN'T HE?


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205

A. YES, HE DOES.

Q. DO YOU AGREE WITH HIM?

A. YES, I DO.

Q. TUCCORI IS ANOTHER RESEARCHER THAT HAS COME TO

THE SAME CONCLUSION, ISN'T HE?

A. YES.

Q. AND THAT WAS IN 2010?

A. YES.

Q. HE SAYS, AS POINTED OUT ABOVE, THE ONLY SSRI FOR

WHICH THE AVAILABLE EVIDENCE ON TERATOGENIC RISK IS TOO

SCARCE IS FLUVOXAMINE, A FACT THAT REFLECTS ITS LIMITED

CLINICAL USE COMPARED WITH OTHER SSRIS. THE OVERALL

CURRENT FINDINGS SUGGEST A TREND TOWARD A MAJOR

TERATOGENIC EFFECT OF PAROXETINE. HOWEVER, BASED ON

THIS INFORMATION, IT CANNOT BE STATED THAT ANY OF THE

OTHER SSRIS SHOULD BE RECOMMENDED DURING PREGNANCY IN

PLACE OF PAROXETINE, SINCE A TERATOGENIC POTENTIAL HAS

BEEN SHOWN FOR EACH DRUG BELONGING TO THIS CLASS.

DO YOU AGREE WITH HIM?

A. YES, I DO.

Q. AND THEN UP ABOVE THAT, HE SAYS, ALTHOUGH THERE

IS EVIDENCE TO SUPPORT THE ASSOCIATION BETWEEN BIRTH

DEFECTS AND FIRST-TRIMESTER EXPOSURE TO PAROXETINE,

FINDINGS FROM THE STUDIES REVIEWED SUGGEST A TERATOGENIC

POTENTIAL OF THE WHOLE SSRI CLASS, CONSISTENT WITH


1

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3

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10

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12

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PRECLINICAL EVIDENCE.

THAT IS EXACTLY WHAT YOU HAVE TESTIFIED

TO TODAY, ISN'T IT?

A. YES, THAT IS WHAT I REVIEWED AND TESTIFIED ON.

Q. YOU AGREE WITH DR. TUCCORI THAT THE PRECLINICAL

EVIDENCE IS CONSISTENT WITH THE EPIDEMIOLOGY?

A. YES, IT IS.

Q. AND IT IS YOUR OPINION, DR. CABRERA, IS IT NOT,

WITHIN A REASONABLE DEGREE OF SCIENTIFIC CERTAINTY, THAT

SSRIS AS A CLASS ARE TERATOGENS IN BOTH HUMANS AND

ANIMALS WHEN INGESTED DURING PREGNANCY?

A. YES, IT IS.

Q. ZOLOFT, OF COURSE, IS AN SSRI.

AND I DO WANT TO PUT THIS IN THE RECORD.

DR. CABRERA, WE PUT THIS SLIDE UP EARLIER. IS THIS A

LIST OF THE ADVERSE PREGNANCY OUTCOMES THAT YOU BELIEVE

TO BE ASSOCIATED WITH SSRIS AND ZOLOFT?

A. YES, THEY ARE.

Q. AND JUST TO GO THROUGH THEM, IS YOUR OPINION

BASED ON REASONABLE SCIENTIFIC CERTAINTY THAT ZOLOFT AND

SSRIS ARE CAPABLE OF CAUSING INTRAUTERINE DEATH?

A. YES.

Q. CRANIOFACIAL DEFECTS?

A. YES.

Q. SKELETAL AND LIMB DEFECTS?


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207

A. YES.

Q. THINGS LIKE CLUB FOOT?

A. YES.

Q. CARDIOVASCULAR DEFECTS?

A. YES.

Q. ABDOMINAL WALL DEFECTS?

A. YES.

Q. AND CENTRAL NERVOUS SYSTEM DEFECTS LIKE BRAIN

AND SPINAL CORD DEFECTS?

A. YES.

MR. TRACEY: THANK YOU, DR. CABRERA.

I WILL PASS THE WITNESS, YOUR HONOR.

THE COURT: THANK YOU. THAT IS WHERE WE

ARE GOING TO END FOR THIS EVENING. LET'S START AT TEN

TOMORROW.

YOU WILL BE ON THE STAND, SO THE RULES

ARE, YOU DON'T TALK TO ANYONE -- ANY MORE LAWYERS TODAY,

TONIGHT. WHILE HE IS ON THE STAND.

MR. TRACEY: CAN WE HAVE DINNER OR --

THE COURT: HE CAN TALK ABOUT ANYTHING

OTHER THAN THIS CASE.

MR. TRACEY: OKAY.

(COURT ADJOURNED AT 5:00 P.M.)

I CERTIFY THAT THE FOREGOING IS A CORRECT

TRANSCRIPT FROM THE RECORD OF PROCEEDINGS IN THE


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208

ABOVE-ENTITLED MATTER.

DATE SUZANNE R. WHITE

OFFICIAL COURT REPORTER


'

'50S [1] - 125:3

'60S [1] - 125:4

'70S [1] - 125:4

'90S [1] - 54:12

0

05 [1] - 194:7

06 [1] - 194:6

1

1 [5] - 38:13, 38:16,

38:21, 39:8, 83:9

10 [1] - 71:23

10(B)(5 [1] - 24:13

100 [2] - 133:20,

134:8

10010 [1] - 2:10

104 [1] - 62:14

108 [1] - 45:10

1101 [1] - 1:13

11TH [1] - 55:2

12 [1] - 75:22

12-A [1] - 1:7

12-MD-2342 [1] - 1:4

12:48 [1] - 83:10

12TH [1] - 55:9

13 [2] - 44:23, 45:2

13TH [1] - 108:18

15 [6] - 22:13, 57:17,

57:21, 71:24, 192:13,

194:1

16 [3] - 196:5,

196:10, 196:11

16.7 [1] - 183:18

16TH [1] - 2:6

17 [3] - 2:3, 60:16,

114:4

1700 [2] - 2:6, 2:15

1717 [1] - 2:19

19 [1] - 1:16

1900 [1] - 2:6

1901 [1] - 1:19

19103-7301 [1] -

2:19

19106 [2] - 1:7, 1:23

19107 [1] - 1:14

1959 [1] - 68:23

1977 [1] - 92:16

1981 [1] - 182:21

1982 [1] - 180:21

1986 [1] - 184:23

1987 [1] - 189:17

1990 [1] - 67:8

1991 [1] - 13:11

1992 [3] - 12:8, 12:9,

18:12

1995 [4] - 74:10,

74:19, 197:7, 197:12

1999 [1] - 2:15

1ST [1] - 63:25

2

2 [2] - 58:4, 83:10

20 [3] - 60:17, 60:18,

64:24

200 [1] - 2:3

2005 [3] - 18:12,

18:22, 27:13

2006 [2] - 119:21,

149:13

2007 [3] - 25:6,

42:20, 101:21

2008 [1] - 153:21

2009 [12] - 25:10,

25:16, 25:18, 25:20,

26:1, 26:10, 37:7,

103:21, 106:14,

107:20, 108:2, 108:4

2010 [16] - 16:21,

17:10, 20:19, 20:24,

26:5, 32:23, 42:18,

55:3, 80:23, 80:24,

108:7, 108:18, 203:4,

203:15, 205:7

2011 [2] - 34:6, 66:21

2012 [9] - 26:11,

26:12, 34:12, 55:10,

108:10, 109:1, 109:2,

109:17, 109:24

2013 [8] - 25:21,

33:4, 34:16, 34:24,

37:23, 78:25, 79:13,

140:8

21 [4] - 196:5,

196:10, 196:11,

196:16

215)627-1882 [1] -

1:24

22ND [1] - 2:9

2342 [1] - 1:3

25 [1] - 79:20

26 [2] - 103:1, 187:14

265 [1] - 45:10

2801 [1] - 1:13

3

3 [3] - 17:14, 18:2,

32:21

32502-5998 [1] - 2:3

36 [1] - 181:5

370 [1] - 2:12

3RD [8] - 36:14,

43:16, 43:17, 51:12,

52:6, 84:18, 84:25

4

4-7-14 [1] - 1:6

40 [3] - 7:18, 60:17,

83:6

400 [1] - 79:18

4000 [1] - 2:18

440 [1] - 1:19

45 [1] - 83:7

4500 [1] - 2:12

5

5 [3] - 17:14, 18:2,

32:21

50 [1] - 45:4

51 [1] - 2:9

55 [1] - 187:14

5:00 [1] - 207:23

5HT2B [1] - 162:22

6

6 [1] - 187:19

60 [3] - 45:6, 94:14,

107:6

601 [1] - 1:23

7

7 [1] - 187:13

7.1 [1] - 183:18

702 [4] - 24:1, 54:1,

84:21

76 [1] - 192:16

77003 [1] - 1:20

8

80 [2] - 194:19,

194:23

80107 [1] - 182:21

80142 [1] - 180:21

80202 [2] - 2:6, 2:13

83107 [1] - 186:21

83112 [1] - 188:7

85121/88516 [1] -

184:23

86-375-14 [1] -

191:20

9

9 [1] - 187:12

90067-6048 [1] -

2:16

92660 [1] - 1:17

95 [1] - 45:8

A

A&M [4] - 6:25,

64:20, 64:23, 113:21

ABACK [1] - 60:20

ABANDONED [2] -

96:8, 96:23

ABBREVIATED [1] -

163:12

ABDOMINAL [3] -

124:12, 181:6, 207:6

ABERRATIONAL [1]

- 44:12

ABILITY [12] - 71:24,

86:23, 126:17, 127:2,

133:6, 148:13, 157:3,

158:1, 158:5, 168:18,

185:8, 185:12

ABLATION [1] -

167:15

ABLE [12] - 3:14, 5:8,

44:3, 89:20, 102:12,

120:22, 139:10,

165:1, 167:21,

167:25, 168:10,

174:14

ABNORMAL [3] -

64:12, 115:25, 129:14

ABNORMALITIES

[6] - 79:5, 81:6,

152:11, 152:20,

152:24, 174:1

ABNORMALITY [1] -

201:2

ABORTION [3] -

193:12, 193:13, 203:5

ABORTIONS [7] -

80:14, 81:9, 81:10,

109:20, 179:13,

193:9, 203:17

ABOVE-ENTITLED

[1] - 208:1

ABSENCE [3] -

138:20, 148:18,

160:21

ABSENT [1] - 36:15

ABSOLUTELY [11] -

115:3, 121:18,

123:10, 123:19,

143:8, 149:2, 180:2,

180:6, 196:17,

198:21, 202:23

ABSORBANCE [1] -

157:6

ABSORBED [1] -

157:4

ACADEMIC [1] - 81:3

ACCEPT [5] -

142:23, 152:19,

163:8, 167:3, 194:6

209

ACCEPTABLE [2] -

153:9, 202:5

ACCEPTANCE [6] -

12:4, 23:5, 23:7,

23:10, 84:14, 84:20

ACCEPTED [28] -

12:3, 16:8, 23:6,

23:13, 23:15, 29:25,

32:8, 36:9, 42:10,

48:10, 51:16, 52:10,

52:16, 52:18, 53:25,

59:1, 63:11, 88:25,

92:17, 94:2, 125:4,

137:4, 142:5, 142:9,

146:16, 173:9,

173:18, 192:21

ACCESS [5] - 57:4,

126:17, 130:19, 157:7

ACCORDING [9] -

14:4, 16:11, 85:14,

154:2, 154:4, 180:3,

193:14, 195:25,

202:21

ACCOUNT [6] - 47:2,

86:8, 86:14, 105:15,

105:16, 105:17

ACCOUNTS [1] -

46:2

ACCUMULATE [1] -

149:23

ACCURATE [1] -

184:13

ACCUSED [3] -

60:23, 99:25, 100:2

ACCUTANE [4] -

35:17, 172:21,

173:15, 173:18

ACHIEVE [1] -

181:24

ACHIEVED [1] -

193:2

ACHIEVES [1] -

194:7

ACID [3] - 35:17,

172:20, 172:21

ACIDS [1] - 115:6

ACKNOWLEDGED

[2] - 77:15, 178:20

ACKNOWLEDGES

[1] - 56:15

ACQUITTED [1] -

35:2

ACT [4] - 35:10,

35:18, 78:16, 129:10

ACTING [3] - 78:11,

78:12, 78:15

ACTION [26] - 14:13,

42:22, 43:5, 98:13,

99:20, 107:11,

117:25, 126:14,


129:11, 141:6, 141:7,

141:12, 141:16,

142:2, 142:7, 144:11,

144:21, 144:22,

150:22, 151:4,

152:22, 153:6, 154:8,

162:4

ACTIVELY [1] -

62:19

ACTIVITY [2] -

157:12, 158:2

ACTUAL [2] - 40:3,

156:7

ACTUALITY [2] -

132:8, 201:25

ADD [3] - 38:9,

150:14, 168:17

ADDED [1] - 34:25

ADDITION [9] -

33:13, 36:11, 126:25,

127:1, 140:12, 141:9,

173:11, 176:24,

178:16

ADDITIONAL [7] -

93:19, 141:19,

150:13, 182:16,

190:6, 193:23, 200:11

ADDITIONALLY [15]

- 116:18, 117:15,

119:9, 131:13, 134:6,

141:3, 147:24,

157:10, 162:6, 165:4,

165:24, 171:3, 178:1,

200:19, 201:4

ADDRESS [4] -

30:10, 32:13, 41:13,

53:24

ADDRESSING [2] -

29:10, 92:6

ADEQUATE [4] -

198:5, 198:11, 199:1,

199:9

ADHERE [1] - 30:12

ADJOURNED [1] -

207:23

ADJUNCT [1] - 7:19

ADJUST [1] - 94:20

ADJUSTMENT [2] -

45:17, 46:6

ADMINISTERED [2] -

79:5, 152:12

ADMINISTRATION

[1] - 181:14

ADMISSIBILITY [2] -

85:17, 93:15

ADMISSION [3] -

21:3, 40:11, 76:6

ADMIT [1] - 23:9

ADMITTED [1] -

84:21

ADMITTEDLY [2] -

31:4, 31:11

ADMITTING [1] -

85:17

ADVANCE [1] - 38:4

ADVANCED [1] -

91:16

ADVANCES [2] -

25:2, 29:25

ADVANCING [2] -

51:24, 107:9

ADVERSE [48] -

20:12, 21:5, 24:10,

54:14, 61:11, 64:7,

65:11, 70:21, 128:17,

130:20, 133:19,

134:2, 134:3, 134:23,

134:24, 135:6,

135:10, 135:18,

135:21, 137:7,

137:10, 140:4,

140:14, 140:15,

140:17, 140:18,

141:16, 141:22,

142:23, 145:14,

154:13, 155:4,

155:14, 156:8,

156:24, 163:4,

167:23, 171:1, 171:7,

171:18, 175:19,

187:25, 198:10,

198:23, 200:3, 202:9,

203:9, 206:16

ADVERSELY [6] -

98:16, 100:18, 130:9,

131:8, 131:9, 142:25

ADVERSITY [1] -

43:7

ADVISED [1] - 190:1

ADVISORY [1] - 85:9

AFFAIRS [1] - 74:12

AFFECT [11] - 39:14,

42:24, 98:16, 98:25,

99:3, 130:15, 130:24,

131:8, 131:9, 142:25,

173:1

AFFECTED [5] -

100:17, 128:19,

130:9, 130:12, 138:17

AFFECTS [3] -

66:18, 98:13, 105:25

AFFINITIES [2] -

157:24, 158:1

AFFINITY [1] - 154:4

AFFIRMED [3] -

36:13, 51:12, 52:6

AFFORD [1] - 5:9

AFTERNOON [3] -

83:22, 83:24, 175:18

AGE [1] - 19:20

AGENCIES [3] -

32:1, 32:5, 33:9

AGENCY [5] - 12:17,

12:18, 117:1, 117:4,

140:12

AGENT [4] - 36:6,

36:18, 36:20, 128:22

AGENTS [7] - 35:2,

55:2, 128:15, 128:19,

128:20, 129:9, 131:12

AGO [4] - 71:24,

72:2, 77:19, 88:8

AGREE [15] - 53:24,

65:4, 67:24, 150:16,

150:25, 152:8,

152:14, 171:11,

176:4, 197:4, 203:19,

204:5, 205:2, 205:19,

206:5

AGREED [1] - 77:17

AGREES [8] - 20:16,

43:11, 54:16, 68:25,

76:17, 81:19, 110:3,

146:17

AHA [2] - 16:4, 31:19

AHEAD [1] - 147:10

AIDED [1] - 1:25

ALABAMA [1] - 92:5

ALCOHOL [1] - 20:7

ALLEGEDLY [1] -

43:19

ALLOWED [3] - 75:3,

75:6, 75:21

ALLOWS [2] -

140:20, 145:23

ALLUDED [1] -

142:13

ALMOST [6] - 13:2,

57:4, 87:7, 160:9,

184:2, 194:7

ALONE [5] - 35:9,

45:15, 52:12, 77:6,

79:15

ALPHABETICAL [4]

- 6:12, 6:22, 6:23, 7:6

ALTER [7] - 76:2,

136:1, 147:15, 149:3,

158:2, 158:6, 161:24

ALTERATION [3] -

98:15, 124:2, 163:9

ALTERATIONS [3] -

144:14, 158:12,

164:19

ALTERED [3] -

160:16, 163:10, 165:6

ALTERING [2] -

145:17, 148:8

ALTERNATIVE [1] -

140:20

ALWAN [13] - 42:19,

42:20, 42:21, 43:1,

45:22, 46:17, 49:6,

99:6, 102:6, 105:10,

106:4

ALYSTOCK [5] -

83:5, 83:6, 92:15,

112:17, 174:25

AMBIENT [1] -

142:17

AMERICAN [4] -

33:25, 34:1, 111:17,

115:12

AMOUNT [2] -

170:14, 202:5

AMOUNTS [1] -

149:11

ANAL [3] - 31:9,

52:2, 103:14

ANALYSES [3] -

46:4, 46:14, 119:2

ANALYSIS [21] -

10:9, 18:21, 18:23,

23:11, 33:4, 37:22,

45:23, 71:19, 103:8,

118:13, 118:20,

120:6, 120:21,

121:13, 121:14,

173:6, 179:2, 193:24,

200:8, 200:9, 200:20

ANALYZE [11] - 11:8,

26:25, 40:17, 41:3,

75:14, 98:24, 120:18,

120:22, 135:1,

176:15, 178:3

ANALYZED [2] -

154:23, 179:15

ANALYZES [2] -

42:3, 98:23

ANALYZING [5] -

48:11, 111:21, 136:6,

159:9, 200:7

ANATOMY [3] - 7:15,

7:21, 51:7

AND-A-HALF [2] -

57:22, 88:8

ANENCEPHALI [1] -

102:18

ANGELES [1] - 2:16

ANICK [14] - 6:12,

58:23, 58:24, 60:10,

64:2, 76:14, 77:8,

80:11, 80:20, 80:23,

84:5, 96:5, 98:19,

108:18

ANIMAL [46] - 10:23,

27:20, 27:21, 28:4,

28:11, 28:19, 56:3,

56:7, 75:1, 75:8,

78:12, 81:25, 82:11,

82:12, 116:14,

210

116:20, 117:15,

120:7, 127:2, 141:1,

141:9, 151:18, 155:1,

155:9, 167:4, 168:4,

168:5, 168:7, 168:15,

168:17, 169:8,

170:25, 177:1, 177:3,

177:11, 181:11,

184:13, 184:17,

191:2, 197:12, 198:3,

198:10, 199:18,

200:12, 203:7, 203:14

ANIMALS [30] -

27:22, 27:23, 75:2,

82:18, 117:18,

134:14, 139:7,

142:22, 155:20,

177:7, 177:23, 178:3,

181:2, 181:3, 182:14,

183:10, 183:12,

187:5, 187:7, 190:15,

190:21, 190:25,

191:23, 192:1,

192:20, 193:2, 200:7,

201:12, 203:11,

206:11

ANOMALITIES [1] -

121:2

ANOMALOUS [2] -

44:17, 50:6

ANOMALY [1] -

109:2

ANSWER [10] -

39:20, 87:20, 101:20,

102:2, 104:23,

117:12, 145:8,

189:21, 190:2

ANSWERING [1] -

22:9

ANSWERS [1] -

135:11

ANTAGONIST [1] -

157:11

ANTHONY [2] -

69:13

ANTI [1] - 64:8

ANTI-

DEPRESSANT [1] -

64:8

ANTICIPATED [1] -

5:20

ANTIDEPRESSANT

[3] - 26:14, 80:16,

154:2

ANTIDEPRESSANT

S [11] - 17:11, 37:13,

62:17, 64:3, 73:12,

73:17, 80:2, 101:24,

109:7, 153:24, 154:3

ANTIEPILEPTIC [5] -


75:22, 115:7, 117:13,

139:17, 139:19

ANTIEPILEPTICS [1]

- 139:25

ANTIOXIDANTS [1] -

139:7

ANYWAY [1] - 83:16

AORTIC [2] - 159:5,

165:8

AORTICOPULMON

ARY [1] - 165:8

APOLOGIES [1] -

38:4

APOLOGIZE [6] -

31:4, 48:22, 73:24,

77:19, 92:7, 97:15

APPARENT [2] -

49:25, 100:25

APPEAR [2] - 44:12,

47:23

APPEARANCES [2] -

1:11, 2:1

APPLICABLE [1] -

54:8

APPLIED [7] - 70:11,

71:6, 87:15, 87:17,

94:8, 124:23, 154:14

APPLIES [2] - 70:24,

112:11

APPLY [12] - 68:25,

93:7, 93:22, 94:7,

94:22, 95:6, 95:11,

96:2, 101:15, 109:8,

125:20

APPLYING [1] - 97:7

APPROACH [3] -

35:12, 65:22, 117:16

APPROPRIATE [7] -

76:25, 78:13, 132:16,

144:19, 152:22,

153:4, 154:10

APPROPRIATELY

[2] - 41:12, 67:1

APPROVAL [3] -

75:20, 76:10, 177:12

APPROVED [6] -

13:10, 28:7, 77:20,

77:22, 77:23, 77:24

APRIL [1] - 63:25

ARCH [1] - 2:19

ARCHES [1] - 165:8

ARCHIVE [1] -

118:25

AREA [3] - 146:2,

146:24, 155:11

AREAS [1] - 70:15

ARGUE [6] - 17:17,

69:8, 69:9, 73:23,

151:24

ARGUED [1] - 73:3

ARGUING [2] -

14:17, 144:6

ARGUMENT [6] -

23:17, 61:20, 84:5,

170:2, 176:14, 202:1

ARGUMENTS [6] -

3:19, 10:6, 87:4, 87:6,

91:16, 92:6

ARNOLD [1] - 5:25

ARRAY [3] - 31:3,

38:6, 50:13

ARRIVE [3] - 119:8,

122:22, 122:23

ARRIVED [3] - 97:9,

108:15, 108:16

ARRIVING [1] -

147:6

ART [2] - 70:22, 71:6

ARTHUR [2] - 94:23,

105:5

ARTICLE [4] - 20:20,

26:5, 26:12, 66:22

ARTICLES [6] -

12:12, 30:16, 56:16,

62:14, 63:12, 147:5

ARTICULATED [1] -

44:19

ARTIFACT [1] -

194:6

ARTIFICIAL [1] -

21:15

ARTRIAL [1] - 167:7

ASBESTOS [1] -

128:1

ASCRIBE [1] - 93:20

ASIDE [1] - 17:18

ASPECTS [1] - 129:1

ASSAY [2] - 141:17,

141:18

ASSAYS [3] -

140:21, 141:5, 141:6

ASSERTED [1] -

87:5

ASSESS [1] - 44:6

ASSESSED [1] -

86:8

ASSESSING [1] -

35:24

ASSIGNED [2] -

4:12, 77:2

ASSIST [1] - 85:18

ASSISTANCE [1] -

62:22

ASSISTED [1] - 6:9

ASSISTING [1] -

120:21

ASSOCIATE [2] -

66:13, 67:18

ASSOCIATED [12] -

20:11, 25:13, 33:6,

36:18, 37:22, 102:18,

104:4, 108:8, 111:3,

162:13, 181:15,

206:17

ASSOCIATION [31] -

13:22, 34:1, 34:20,

37:5, 38:12, 38:21,

39:8, 44:7, 44:8,

45:24, 46:24, 47:22,

48:4, 48:7, 49:25,

54:6, 94:5, 94:17,

94:20, 95:1, 95:7,

95:13, 97:12, 97:19,

98:7, 103:16, 103:20,

104:11, 205:22

ASSOCIATIONS [12]

- 11:4, 30:11, 32:5,

39:13, 39:23, 39:24,

44:7, 46:15, 46:18,

103:8, 103:10, 103:18

ASSUME [6] - 78:15,

78:20, 78:21, 132:6,

142:2, 151:11

ASSUMED [3] - 43:7,

79:3, 152:10

ASSUMING [2] -

147:1, 180:21

ASSURE [1] - 21:18

ASYMMETRICAL [1]

- 148:2

ASYMMETRY [2] -

68:2, 148:3

ASYMPTOMATIC [1]

- 47:12

ATLANTIC [1] - 2:18

ATRESIA [3] - 31:9,

52:2, 103:14

ATTACHED [2] -

65:8, 94:13

ATTACKED [2] -

60:4

ATTACKING [1] -

84:5

ATTACKS [1] - 96:22

ATTEMPTED [1] -

38:8

ATTEMPTING [1] -

24:17

ATTEMPTS [1] - 20:2

ATTENTION [2] -

69:17, 75:11

ATTENTIVE [1] -

95:20

ATTORNEY [1] -

1:14

ATTORNEY'S [1] -

52:14

ATTORNEYS [2] -

4:15, 9:5

ATTRIBUTED [3] -

46:19, 202:13, 202:16

ATTRIBUTES [3] -

31:6, 38:7, 99:19

AUBREY [2] - 79:18,

204:9

AUDIENCES [1] -

55:25

AUSTIN [7] - 7:5,

64:15, 87:15, 87:18,

113:12, 125:6, 129:16

AUTHOR [5] - 42:20,

50:16, 54:23, 69:14,

90:21

AUTHORED [1] -

65:6

AUTHORITIES [2] -

22:24, 77:25

AUTHORS [7] -

11:12, 30:4, 34:16,

45:9, 48:23, 51:11,

51:19

AUTISM [1] - 151:19

AUTISM-TYPE [1] -

151:19

AVAILABILITY [1] -

24:3

AVAILABLE [8] -

3:13, 17:12, 32:19,

141:8, 145:12, 150:6,

154:19, 205:10

AVANDIA [5] - 22:4,

27:15, 41:24, 87:16,

88:12

AVENUE [2] - 2:9,

2:15

AVOID [2] - 139:15,

139:22

AVOIDED [1] - 79:8

AVOIDING [1] -

196:12

AWARD [10] - 64:2,

64:5, 64:6, 65:7, 67:8,

67:11, 111:20,

111:21, 111:24,

112:13

AWARDED [1] - 67:6

AWARDS [2] - 67:5,

111:25

AWARE [8] - 4:13,

30:14, 84:8, 125:13,

125:16, 147:1,

203:21, 203:25

AXIS [1] - 147:25

AYLSTOCK [5] - 2:2,

2:2, 6:10, 58:6, 83:24

B

B-E-R-A-R-D [1] -

6:13

211

BABIES [3] - 20:9,

201:17, 202:18

BABY [2] - 20:9,

37:16

BACKGROUND [8] -

17:13, 18:1, 32:22,

37:20, 38:22, 151:18,

182:17, 190:9

BACTERIA [1] -

183:8

BAD [9] - 21:12,

40:8, 93:12, 99:8,

100:22, 101:12,

106:20, 107:16,

111:16

BAKER [2] - 50:16,

50:18

BALL [1] - 147:22

BARTLE [1] - 88:7

BASE [1] - 125:5

BASED [35] - 10:13,

14:5, 14:11, 31:3,

34:19, 38:2, 43:6,

82:3, 87:13, 88:10,

106:19, 119:4, 120:5,

121:3, 121:5, 123:3,

133:23, 153:3, 154:7,

161:6, 165:25,

167:22, 168:21,

170:24, 171:1, 171:6,

180:18, 184:10,

186:17, 188:2,

193:11, 202:15,

203:13, 205:14,

206:20

BASES [2] - 54:10,

56:12

BASIC [1] - 169:3

BE-ALL [1] - 111:2

BEACH [1] - 1:17

BEARD [2] - 121:25,

122:4

BEARING [2] -

19:20, 24:18

BEAVER [1] - 100:2

BECKER [1] - 84:24

BECOME [3] - 89:7,

159:15

BECOMES [1] - 3:22

BECOMING [1] -

106:1

BEGAN [3] - 108:22,

120:5, 190:20

BEGIN [3] - 8:10,

38:24, 191:23

BEGINNING [4] -

30:20, 65:15, 66:2,

137:20

BEGINS [1] - 8:10

BEGUN [1] - 69:8


BEHALF [2] - 70:2,

123:7

BEHAVIOR [6] -

20:5, 151:16, 151:19,

188:19, 189:5, 190:17

BEHAVIORAL [1] -

119:5

BEHAVIORS [1] -

138:14

BELABOR [2] -

88:13, 109:25

BELIEF [1] - 66:24

BELIEVES [6] -

69:22, 73:2, 77:13,

96:25, 97:2, 204:3

BELL [1] - 2:18

BELONGING [2] -

82:6, 205:18

BELOW [1] - 204:8

BENCH [2] - 44:24,

65:24

BENEFICIAL [1] -

115:8

BENEFITS [2] -

198:14, 198:19

BENMANSOUR [1] -

162:7

BENZODIAZEPINE

[4] - 79:3, 152:9,

152:17, 153:10

BERARD [131] -

6:12, 6:13, 7:25,

10:19, 10:25, 11:2,

12:16, 12:23, 16:19,

17:18, 20:16, 25:2,

25:6, 25:11, 25:17,

25:25, 26:6, 26:12,

29:14, 29:20, 30:23,

31:2, 31:6, 31:23,

32:7, 32:12, 32:16,

33:12, 33:14, 33:17,

34:10, 35:7, 35:9,

35:11, 35:18, 37:7,

37:25, 38:7, 39:19,

40:3, 40:9, 40:12,

40:15, 42:6, 42:12,

43:2, 43:4, 43:8,

43:23, 44:1, 44:3,

45:9, 45:11, 46:8,

47:2, 48:17, 49:2,

50:4, 50:17, 51:9,

51:17, 52:3, 52:7,

53:22, 53:24, 55:6,

56:24, 57:1, 58:23,

58:24, 60:10, 60:16,

61:4, 61:8, 61:12,

61:17, 61:21, 62:3,

64:2, 66:1, 72:23,

76:15, 77:8, 78:18,

79:9, 79:15, 80:1,

80:11, 80:20, 80:23,

81:2, 82:10, 82:22,

84:3, 84:5, 84:14,

85:2, 85:5, 85:21,

86:9, 86:22, 87:23,

88:20, 89:19, 92:19,

93:20, 94:9, 96:5,

98:19, 101:14,

102:12, 104:16,

106:14, 107:2,

107:13, 107:22,

108:9, 108:18, 109:4,

109:10, 109:16,

109:24, 110:10,

111:13, 112:2, 112:5,

161:1, 203:23

BERARD'S [7] -

23:1, 24:21, 32:8,

81:14, 147:1, 203:15,

204:7

BESIDE [1] - 23:2

BEST [3] - 44:18,

68:8, 78:14

BETTER [4] - 17:10,

37:13, 72:1, 131:3

BETWEEN [26] -

13:20, 24:23, 25:20,

34:21, 37:5, 37:9,

37:11, 39:24, 41:5,

42:13, 47:24, 48:5,

50:1, 53:11, 53:16,

54:7, 55:9, 56:21,

69:22, 80:17, 97:12,

103:8, 103:10,

103:11, 194:18,

205:22

BEYOND [1] - 87:25

BI [1] - 148:1

BI-SYMMETRICAL

[1] - 148:1

BIAS [8] - 39:14,

44:16, 46:22, 46:24,

47:3, 47:4, 95:25,

105:16

BIFIDA [1] - 174:4

BIG [3] - 71:4,

106:13, 199:23

BIND [1] - 136:3

BIOLOGIC [3] - 72:8,

98:14, 101:6

BIOLOGICAL [6] -

28:22, 28:24, 133:7,

135:2, 136:5, 155:6

BIOLOGICALLY [2] -

135:3, 154:21

BIOLOGIST [3] -

7:17, 67:14, 70:18

BIOLOGISTS [1] -

147:20

BIOLOGY [10] - 7:9,

7:12, 7:21, 66:17,

67:17, 67:19, 67:22,

67:23, 68:4, 172:25

BIOSTATISTICS [1] -

6:14

BIRNBAUM [10] -

2:8, 9:20, 9:21, 30:1,

31:18, 32:14, 42:7,

43:12, 63:17, 73:25

BIRTH [189] - 10:14,

11:21, 12:15, 13:1,

13:3, 13:21, 14:21,

15:12, 15:21, 16:5,

16:8, 16:12, 17:4,

17:8, 17:13, 17:19,

17:20, 17:21, 17:22,

17:23, 17:24, 18:1,

18:6, 18:10, 18:11,

18:15, 18:16, 18:19,

18:25, 19:10, 19:16,

20:14, 21:4, 23:15,

25:23, 26:18, 27:10,

30:19, 30:20, 31:3,

31:6, 31:14, 32:3,

32:6, 32:21, 32:25,

35:7, 35:14, 35:21,

36:7, 36:8, 36:9,

36:17, 37:6, 37:11,

37:16, 37:19, 38:6,

38:10, 39:25, 40:4,

42:16, 48:11, 50:8,

50:9, 50:11, 50:13,

51:1, 51:5, 52:8,

53:18, 54:7, 54:13,

55:2, 55:4, 55:11,

55:18, 55:21, 56:1,

56:11, 57:1, 57:3,

60:14, 61:7, 62:18,

63:1, 63:21, 64:1,

64:4, 64:9, 64:15,

64:17, 65:1, 66:12,

67:9, 67:12, 68:13,

70:3, 70:22, 74:21,

75:15, 76:21, 76:24,

78:20, 78:21, 78:22,

79:19, 79:24, 80:5,

80:6, 81:11, 82:13,

86:25, 89:15, 89:25,

93:2, 97:16, 99:2,

99:3, 99:7, 100:16,

102:4, 104:3, 109:6,

109:20, 110:7,

110:15, 111:4,

113:22, 114:16,

114:20, 114:23,

115:2, 115:5, 115:15,

116:1, 116:4, 116:9,

118:16, 118:19,

118:21, 118:22,

119:10, 120:6, 120:7,

120:9, 120:10,

120:12, 120:16,

120:19, 122:11,

122:16, 127:20,

128:9, 128:23, 138:9,

138:12, 139:2, 139:3,

145:4, 146:24, 147:2,

148:9, 150:21,

156:25, 171:10,

172:3, 173:19,

181:21, 181:23,

182:3, 182:5, 182:10,

189:15, 191:24,

192:1, 192:4, 192:10,

192:17, 193:1, 194:4,

196:7, 196:24,

201:15, 204:10,

205:22

BIRTHDAY [1] -

108:19

BIT [11] - 30:2, 42:8,

50:7, 59:25, 62:3,

81:22, 84:7, 84:9,

87:19, 161:11, 172:7

BLACK [1] - 31:21

BLIP [1] - 44:17

BLOCK [1] - 104:18

BLOOD [13] - 119:1,

120:20, 144:17,

144:18, 149:6,

149:10, 149:24,

149:25, 157:20,

157:22, 162:5, 181:5,

181:6

BOARD [2] - 115:19,

115:23

BODIES [1] - 137:7

BODY [20] - 13:2,

21:4, 31:8, 31:16,

32:11, 43:19, 50:14,

65:17, 71:8, 77:6,

86:22, 88:19, 104:16,

124:5, 136:13,

150:14, 154:18,

156:9, 169:20, 175:20

BOLSTER [1] - 88:14

BONDING [1] - 20:9

BONE [9] - 148:5,

151:20, 183:11,

183:13, 183:16,

186:4, 186:6, 186:10

BONES [3] - 110:13,

183:13, 186:7

BOOK [8] - 35:16,

43:3, 66:5, 79:22,

129:2, 158:8, 204:8,

204:13

BORN [9] - 20:9,

47:13, 47:19, 151:9,

151:12, 181:2, 187:9,

188:21, 192:6

212

BORNE [1] - 151:2

BOSTON [1] - 79:21

BOTTOM [5] -

142:14, 144:9,

148:11, 193:24,

204:15

BOUNDS [3] - 39:25,

51:9, 51:10

BOX [7] - 31:21,

54:5, 158:5, 180:20,

181:19, 182:20,

186:19

BRADFORD [29] -

54:2, 54:8, 87:15,

87:18, 88:1, 88:6,

88:22, 88:23, 92:20,

93:22, 94:3, 94:12,

94:19, 94:22, 94:23,

95:9, 95:12, 95:14,

95:18, 97:7, 97:18,

101:15, 105:6, 107:5,

109:9, 134:25, 135:8,

145:15

BRAIN [7] - 149:4,

149:9, 149:21,

151:13, 165:14,

185:15, 207:8

BREAK [10] - 57:21,

58:1, 58:19, 99:10,

114:21, 141:23,

174:11, 175:17,

177:10

BREYER [2] - 21:9,

21:10

BRIAN [3] - 6:9,

81:1, 82:21

BRIEF [10] - 3:23,

8:7, 8:25, 21:10,

22:14, 52:25, 58:1,

58:13, 94:13, 126:5

BRIEFING [5] - 3:19,

5:24, 84:4, 87:5, 87:6

BRIEFLY [7] - 10:24,

17:20, 24:21, 50:8,

54:9, 154:14, 197:20

BRIEFS [5] - 22:20,

24:7, 24:8, 78:18,

88:3

BRING [1] - 69:17

BRINGS [2] - 163:4,

169:12

BROAD [2] - 31:3,

34:19

BROAD-BASED [1] -

34:19

BROKEN [1] - 38:17

BROUGHT [2] - 71:4,

75:10

BRYAN [1] - 2:2

BUILD [3] - 136:7,


136:8, 195:8

BULLET [2] - 129:19,

130:7

BUMP [1] - 185:21

BUNCH [2] - 77:2,

142:15

BURDEN [5] - 10:1,

10:12, 76:1, 95:12

BUSH [1] - 7:10

BUSINESS [2] -

56:6, 77:16

BUSY [5] - 31:4,

31:5, 31:11, 38:5

C

CA [2] - 1:17, 2:16

CABRERA [54] -

6:23, 6:24, 8:1, 29:15,

55:17, 60:11, 60:15,

61:4, 64:10, 65:9,

65:20, 70:9, 70:20,

70:25, 71:5, 71:11,

72:11, 73:19, 76:16,

78:19, 79:9, 81:7,

81:25, 82:10, 85:3,

92:18, 98:10, 112:22,

112:23, 113:7,

117:10, 119:20,

123:24, 143:15,

144:25, 147:11,

150:7, 150:25, 151:8,

156:18, 156:23,

161:15, 170:3,

171:24, 172:2,

176:24, 189:15,

189:19, 196:21,

201:14, 206:8,

206:15, 207:11

CALCAGNIE [1] -

1:16

CALCULATE [1] -

134:4

CALIFORNIA [2] -

118:25, 119:16

CANADA [4] - 6:14,

62:9, 62:24, 109:5

CANADIAN [6] -

34:7, 62:21, 96:6,

109:2, 109:18, 111:18

CANCER [1] - 48:6

CANNIBALIZE [2] -

187:9, 187:10

CANNIBALIZED [3] -

186:24, 187:6, 187:7

CANNOT [14] - 5:10,

19:24, 24:3, 43:6,

43:19, 46:2, 49:3,

49:14, 56:2, 82:3,

90:5, 95:8, 106:19,

205:15

CAPABLE [10] -

55:21, 62:18, 66:24,

76:7, 79:4, 131:7,

137:23, 145:4,

152:10, 206:21

CAPTURE [1] - 38:6

CARDIAC [24] - 25:8,

31:13, 34:22, 50:23,

104:5, 104:6, 104:7,

105:10, 105:20,

108:8, 146:8, 148:5,

159:13, 159:16,

160:18, 163:14,

164:12, 164:25,

165:2, 165:4, 170:13,

171:14, 172:5, 173:22

CARDIACS [1] -

38:17

CARDINAL [3] -

182:24, 183:18, 184:3

CARDIO [2] - 31:15,

173:24

CARDIOLOGIST [1]

- 153:17

CARDIOMYOCYTE

[2] - 158:16, 163:15

CARDIOMYOCYTE

S [2] - 159:17, 164:6

CARDIOVASCULA

R [12] - 20:22, 26:7,

124:12, 142:20,

142:25, 169:15,

169:24, 169:25,

171:3, 200:20, 201:3,

207:4

CARE [5] - 23:18,

124:18, 130:4, 163:3,

201:17

CAREER [2] - 63:10,

68:9

CAROLINA [2] -

7:24, 66:12

CARRY [1] - 110:14

CARRYING [1] - 76:7

CASCADE [1] -

130:6

CASCADES [1] -

139:4

CASE [66] - 8:13,

9:23, 21:9, 24:5, 24:8,

24:10, 24:12, 24:16,

36:6, 36:13, 43:17,

43:24, 51:12, 52:5,

57:8, 57:9, 59:7,

59:19, 60:3, 61:6,

61:21, 62:15, 62:17,

62:24, 63:13, 66:6,

66:16, 68:12, 70:3,

72:11, 73:18, 77:9,

78:9, 80:9, 84:3,

85:16, 86:21, 87:3,

87:12, 87:13, 88:23,

90:9, 90:23, 92:6,

94:10, 94:21, 95:3,

96:3, 101:15, 109:4,

114:10, 122:20,

123:7, 123:11,

123:21, 145:7, 153:9,

154:6, 154:14,

154:16, 160:5,

166:15, 167:5, 181:5,

207:21

CASES [5] - 3:18,

3:23, 4:11, 4:14,

181:5

CATASTROPHIC [1]

- 132:13

CATEGORIES [6] -

14:3, 31:12, 38:8,

197:19, 197:20,

197:21

CATEGORIZATION

[1] - 154:1

CATEGORIZED [2] -

63:18, 154:3

CATEGORY [26] -

14:2, 14:3, 14:7, 14:8,

14:12, 14:16, 15:6,

15:7, 38:9, 43:13,

43:15, 74:14, 74:17,

74:23, 75:23, 75:25,

197:1, 197:22, 198:1,

198:2, 198:9, 198:17,

198:21, 200:2

CAUDAL [1] - 185:15

CAUGHT [1] - 75:24

CAUSAL [12] - 15:11,

37:5, 42:13, 50:25,

53:10, 53:15, 55:1,

97:12, 97:19, 98:7,

103:20, 143:6

CAUSALITY [1] -

135:2

CAUSALLY [1] -

51:25

CAUSATION [23] -

10:16, 13:20, 13:23,

24:18, 27:10, 29:2,

30:19, 35:23, 35:24,

37:11, 52:4, 52:19,

53:1, 86:18, 87:9,

87:20, 88:10, 89:2,

93:3, 94:1, 94:9, 95:4,

95:5

CAUSATION-

RELATED [1] - 35:23

CAUSED [8] - 18:19,

21:4, 49:4, 49:16,

64:17, 65:2, 104:3,

186:14

CAUSES [38] -

10:14, 12:15, 12:20,

12:25, 13:3, 16:5,

17:3, 17:24, 19:16,

23:15, 27:17, 31:3,

32:2, 33:11, 33:15,

42:16, 50:13, 52:8,

53:14, 53:18, 54:13,

56:1, 56:5, 56:25,

63:2, 63:20, 64:11,

76:12, 81:9, 81:18,

114:22, 115:24,

116:1, 116:9, 133:2,

139:3, 149:25, 166:18

CAUSING [13] -

44:16, 55:21, 62:18,

66:24, 76:23, 79:4,

82:13, 145:4, 152:10,

159:13, 201:15,

203:17, 206:21

CAUTION [1] - 30:5

CAVITY [1] - 181:6

CELEXA [6] - 88:23,

90:4, 163:1, 199:14,

200:2, 200:12

CELL [33] - 7:1, 7:21,

66:3, 116:19, 118:1,

129:20, 129:25,

130:7, 131:15, 136:9,

136:10, 136:11,

146:1, 146:4, 146:8,

146:10, 146:13,

148:22, 148:23,

149:1, 154:24,

158:10, 158:11,

159:8, 159:24, 160:6,

160:7, 163:11, 164:7,

165:2, 167:11, 167:12

CELLS [49] - 71:25,

100:8, 100:15,

100:17, 106:1,

116:20, 129:12,

129:23, 130:2,

130:12, 130:14,

136:2, 136:11, 141:4,

142:22, 145:24,

146:2, 146:5, 146:6,

147:22, 148:17,

148:22, 157:14,

158:9, 158:13,

158:14, 158:17,

158:20, 159:15,

159:18, 159:19,

160:18, 162:8,

163:13, 163:14,

163:16, 164:3, 164:4,

164:17, 164:24,

164:25, 165:5,

165:10, 166:5,

213

166:11, 173:1

CELLULAR [22] -

65:17, 66:17, 67:23,

71:16, 72:1, 72:16,

130:6, 134:19,

140:21, 141:8,

145:25, 146:18,

154:21, 158:8,

159:12, 159:23,

163:5, 163:7, 163:8,

164:15, 164:21,

172:24

CELLULARLY [1] -

161:4

CENTER [6] - 6:25,

7:11, 7:23, 64:19,

66:12, 79:20

CENTRAL [4] -

124:13, 173:5, 174:3,

207:8

CENTURY [1] - 68:5

CERTAIN [7] - 20:14,

50:6, 86:25, 138:24,

138:25, 139:8, 158:2

CERTAINLY [12] -

31:9, 39:17, 55:13,

56:14, 57:4, 87:23,

88:24, 88:25, 93:21,

95:16, 98:14, 151:13

CERTAINTY [8] -

82:17, 102:11, 104:2,

123:4, 124:1, 194:23,

206:9, 206:20

CERTIFIED [1] -

115:20

CERTIFY [1] -

207:24

CHAIN [2] - 135:2,

143:6

CHAIR [6] - 6:19,

7:10, 62:10, 62:11,

92:25, 112:7

CHAIRED [2] - 5:25,

6:1

CHAIRS [1] - 32:16

CHALLENGE [1] -

60:7

CHALLENGED [1] -

59:14

CHALLENGING [2] -

59:11, 91:22

CHANCE [19] -

39:14, 44:15, 44:18,

44:22, 45:3, 45:6,

45:8, 45:15, 45:20,

45:24, 46:1, 46:7,

46:9, 46:16, 46:19,

87:22, 102:9, 102:10,

102:12

CHANGE [14] -


22:24, 25:24, 74:13,

89:21, 93:23, 96:14,

106:19, 107:15,

107:22, 108:1,

133:13, 133:14,

183:24, 184:1

CHANGED [8] - 26:2,

55:9, 55:14, 80:22,

107:19, 108:2,

190:17, 201:12

CHANGES [17] -

16:3, 20:6, 126:25,

127:1, 136:2, 144:17,

146:9, 162:1, 162:12,

162:17, 165:15,

185:24, 185:25,

186:11, 186:12,

188:19, 189:5

CHANGING [1] -

146:4

CHANNELS [1] -

76:25

CHANTIX [1] - 91:13

CHAPEL [1] - 66:12

CHAPTER [5] -

35:16, 43:2, 55:3,

55:6, 89:9

CHARGE [1] - 4:14

CHART [4] - 31:11,

71:9, 135:15, 137:20

CHARTER [1] - 76:7

CHARTS [1] - 137:12

CHECK [1] - 58:11

CHEFFO [29] - 2:8,

8:23, 8:24, 9:10, 9:17,

9:22, 10:8, 12:10,

13:4, 15:9, 17:1,

25:21, 29:4, 29:8,

57:11, 57:13, 63:17,

85:10, 87:3, 93:18,

99:25, 102:7, 106:13,

107:18, 112:5,

171:20, 174:15,

175:17, 176:2

CHEFFO'S [1] -

92:23

CHEMICAL [39] -

15:12, 15:13, 15:17,

16:14, 18:25, 42:14,

42:16, 42:17, 42:23,

53:11, 53:12, 53:16,

72:15, 126:18,

129:19, 129:23,

129:24, 130:6, 130:9,

130:24, 131:7,

131:16, 135:20,

135:24, 136:9,

136:19, 138:21,

140:18, 141:24,

143:25, 144:2, 144:6,

154:2, 157:1, 157:2,

157:4, 167:16, 183:23

CHEMICALS [37] -

21:16, 43:19, 71:24,

114:17, 115:8, 115:9,

116:17, 116:21,

117:18, 117:25,

118:8, 118:9, 124:24,

126:9, 126:15,

127:18, 127:19,

129:21, 129:22,

138:14, 138:17,

139:8, 141:13,

141:19, 141:20,

141:21, 142:1, 144:1,

144:12, 144:21,

165:1, 168:11,

168:22, 177:25,

181:15, 191:8

CHERRY [9] - 11:5,

30:5, 39:21, 40:2,

40:8, 50:6, 53:3,

96:15, 103:5

CHERRY-PICKED

[1] - 96:15

CHERRY-PICKING

[4] - 39:21, 40:2, 53:3,

103:5

CHERRY-PICKS [1]

- 30:5

CHICKS [4] - 56:12,

56:13, 56:18, 155:7

CHIEF [1] - 110:3

CHILD [1] - 19:20

CHILDREN [6] -

21:6, 47:7, 47:8,

47:19, 128:8, 203:11

CHOOSE [1] - 91:17

CHOSE [2] - 89:17,

89:21

CHOSEN [1] - 84:4

CHRONIC [2] -

162:7, 162:11

CIRCUIT [11] - 36:5,

36:14, 43:16, 43:17,

51:12, 52:6, 84:18,

84:25, 85:14, 90:16

CITE [4] - 12:17,

26:23, 89:9, 89:11

CITED [3] - 63:5,

67:2, 201:23

CITES [2] - 30:2,

40:6

CITING [1] - 90:23

CITRIN [1] - 34:12

CLAIM [3] - 21:3,

23:2, 25:17

CLAIMS [3] - 25:17,

31:2, 40:3

CLASS [73] - 11:16,

14:1, 14:14, 14:16,

15:5, 25:12, 39:21,

42:7, 42:8, 42:25,

43:5, 43:6, 43:9,

43:12, 72:21, 73:2,

73:3, 73:11, 73:15,

73:18, 74:25, 75:9,

75:23, 76:17, 77:13,

77:18, 78:22, 79:3,

80:11, 80:12, 80:18,

81:1, 81:5, 81:19,

82:7, 82:18, 98:20,

98:24, 99:13, 99:16,

99:18, 102:3, 105:9,

108:5, 108:20, 140:1,

142:1, 145:1, 145:3,

152:10, 152:17,

152:18, 152:19,

152:25, 153:10,

157:10, 161:24,

162:24, 169:23,

171:10, 171:13,

173:19, 175:20,

197:4, 203:6, 203:16,

203:24, 204:3,

205:18, 205:25,

206:10

CLASS-BASED [1] -

43:6

CLASSES [4] - 77:5,

80:16, 144:20, 153:1

CLASSIFY [1] -

73:13

CLEAR [5] - 3:16,

24:16, 41:16, 76:9,

84:25

CLEARLY [5] -

13:22, 149:3, 167:14,

181:10, 181:25

CLEFT [3] - 106:10,

157:15, 173:11

CLERK [5] - 3:1,

58:15, 83:20, 112:25,

175:11

CLIENT [1] - 9:6

CLINICAL [8] - 62:7,

91:18, 113:17,

115:17, 115:20,

120:4, 120:6, 205:12

CLOSE [3] - 171:17,

174:19, 194:6

CLOSURE [1] -

192:23

CLUB [5] - 31:10,

103:14, 183:15,

186:14, 207:2

CLUSTERING [1] -

100:18

CNS [1] - 150:9

CO [5] - 2:6, 2:13,

65:6, 124:19, 194:18

CO-AUTHORED [1] -

65:6

CO-FOUNDER [1] -

124:19

CO-RELATIONS [1] -

194:18

COAUTHOR [1] -

114:9

COGNITIVE [1] -

109:21

COHERENCE [2] -

94:6, 98:7

COHORTS [1] - 98:4

COLLABORATION

[2] - 120:14, 120:21

COLLEAGUE [2] -

3:5, 121:18

COLLEAGUES [3] -

26:5, 26:16, 106:25

COLLECTIVELY [2]

- 164:13, 164:14

COLLEGE [2] - 7:21,

34:1

COLUMN [1] - 38:19

COLVIN [3] - 41:5,

105:11, 106:4

COMBINED [2] -

91:22, 92:1

COMING [5] - 4:25,

11:2, 60:24, 61:23,

107:24

COMMERCIALLY [1]

- 173:15

COMMITTEE [4] -

5:25, 6:1, 85:9, 92:25

COMMITTEES [2] -

5:24, 32:17

COMMON [13] - 3:6,

17:23, 142:6, 142:8,

144:10, 151:4, 151:6,

153:4, 153:8, 153:11,

154:7, 155:8, 202:9

COMMONLY [5] -

90:24, 124:21, 134:1,

154:22, 201:23

COMMUNICATE [4] -

145:24, 148:17,

148:19, 148:20

COMMUNICATED

[1] - 66:20

COMMUNITY [13] -

12:3, 12:5, 19:14,

23:10, 25:4, 30:1,

32:10, 36:19, 44:5,

49:1, 52:11, 57:6,

142:23

COMPANIES [4] -

64:18, 65:22, 70:6,

117:6

214

COMPANY [3] - 70:4,

70:5, 76:1

COMPARATOR [2] -

101:22, 101:25

COMPARE [1] -

183:20

COMPARED [3] -

52:10, 104:17, 205:12

COMPARING [1] -

101:23

COMPARISON [1] -

45:1

COMPARISONS [7] -

45:12, 45:20, 45:23,

46:3, 46:14, 46:21,

99:11

COMPELLING [1] -

56:8

COMPLEMENTARY

[1] - 52:18

COMPLETE [1] -

58:18

COMPLETELY [1] -

30:6

COMPLEX [2] -

50:20, 121:1

COMPLEXITY [1] -

136:8

COMPLIMENT [1] -

100:3

COMPOSED [1] -

136:13

COMPOUND [10] -

15:18, 16:14, 65:24,

117:10, 126:18,

132:15, 137:11,

139:15, 164:9, 178:6

COMPOUNDS [8] -

15:17, 64:17, 140:2,

143:22, 145:18,

178:25, 186:9, 198:21

COMPROMISE [1] -

86:7

COMPROMISES [1]

- 47:1

COMPUTER [2] -

1:25, 1:25

COMPUTER-AIDED

[1] - 1:25

CONCEDE [1] -

28:23

CONCENTRATE [1]

- 10:19

CONCENTRATION

[3] - 54:17, 158:13,

163:10

CONCENTRATION

S [11] - 144:15,

147:15, 149:7,

157:17, 158:3, 158:6,


158:18, 162:2, 163:9,

164:20, 165:16

CONCEPT [6] -

30:11, 33:17, 44:18,

45:12, 50:3, 92:9

CONCEPTUS [2] -

127:8, 131:19

CONCERN [3] -

21:22, 24:10, 182:25

CONCERNED [5] -

24:14, 61:10, 63:20,

71:8, 81:8

CONCERNING [3] -

4:12, 30:25, 43:18

CONCLUDE [4] -

36:19, 132:17,

195:18, 196:22

CONCLUDED [4] -

89:13, 196:1, 196:4,

203:22

CONCLUDES [1] -

203:16

CONCLUDING [1] -

42:4

CONCLUSION [15] -

12:13, 12:14, 32:2,

49:2, 56:23, 75:2,

75:15, 82:15, 90:2,

90:14, 91:2, 91:9,

106:9, 197:15, 205:5

CONCLUSIONS [34]

- 11:3, 11:11, 11:12,

30:3, 30:9, 32:9,

39:19, 44:4, 51:14,

51:15, 51:19, 52:21,

60:7, 61:23, 68:15,

68:16, 69:5, 70:17,

72:19, 81:5, 90:25,

95:21, 147:6, 152:23,

154:16, 156:4,

156:17, 168:19,

170:11, 170:20,

191:13, 195:16,

203:19

CONCLUSIVELY [4]

- 79:23, 80:4, 204:10,

204:22

CONCLUSORY [1] -

56:21

CONDITION [1] -

151:18

CONDITIONS [1] -

178:24

CONDUCT [8] - 6:8,

44:23, 45:6, 61:19,

62:1, 121:10, 124:23,

197:22

CONDUCTED [9] -

45:10, 54:12, 101:18,

118:18, 170:9,

191:21, 193:23,

199:10, 200:5

CONDUCTING [3] -

44:20, 45:2, 182:13

CONFER [1] - 107:9

CONFERENCE [1] -

3:12

CONFIDENCE [4] -

38:13, 38:16, 38:21,

39:8

CONFIRMED [1] -

143:10

CONFIRMING [2] -

8:17, 145:16

CONFOUNDED [1] -

50:2

CONFOUNDER [3] -

48:19, 86:17, 183:9

CONFOUNDERS [3]

- 95:25, 103:6, 105:15

CONFOUNDING [12]

- 39:14, 44:16, 47:21,

47:22, 48:4, 48:9,

48:18, 48:25, 49:12,

49:20, 50:3, 183:6

CONFRONTED [1] -

80:9

CONFUSED [1] -

126:22

CONGENITAL [45] -

25:7, 33:6, 34:9, 36:1,

37:2, 37:23, 49:3,

49:15, 50:1, 79:4,

81:5, 97:13, 97:23,

98:1, 104:21, 108:11,

109:2, 109:20, 118:3,

121:2, 124:4, 126:23,

132:7, 133:6, 148:21,

149:15, 152:11,

152:20, 152:24,

153:5, 153:11,

160:24, 167:22,

172:22, 178:23,

179:11, 181:10,

181:25, 187:8,

187:25, 190:22,

194:12, 194:20,

199:4, 201:1

CONGRESS [1] -

76:8

CONNECTION [1] -

37:5

CONNECTIONS [1] -

69:20

CONNIE [1] - 9:6

CONSENSUS [1] -

57:23

CONSEQUENCES

[2] - 21:6, 22:1

CONSERVATION [2]

- 168:19, 168:23

CONSERVED [4] -

155:5, 155:8, 167:3,

169:6

CONSIDER [14] -

23:16, 126:6, 131:5,

132:20, 141:2, 155:5,

155:13, 157:3, 167:2,

170:15, 170:16,

176:8, 192:13, 198:18

CONSIDERATION

[2] - 170:18, 198:14

CONSIDERED [10] -

35:19, 37:24, 52:22,

53:4, 53:23, 67:10,

86:13, 101:8, 155:16,

155:23

CONSISTENCIES [1]

- 105:23

CONSISTENCY [17]

- 36:12, 36:21, 36:23,

36:24, 37:3, 38:14,

38:25, 39:11, 40:4,

40:5, 94:5, 97:25,

98:5, 105:3, 106:12,

109:16, 109:17

CONSISTENT [29] -

25:1, 30:8, 34:3,

34:10, 36:15, 72:24,

72:25, 82:11, 82:14,

88:6, 98:8, 98:11,

103:25, 105:1,

105:19, 106:2,

134:25, 161:3, 167:8,

169:14, 180:2, 184:3,

184:7, 186:16, 191:5,

191:7, 197:2, 205:25,

206:6

CONSISTENTLY [4]

- 35:21, 35:25, 37:1,

97:20

CONSORTIUM [1] -

140:14

CONSTANT [1] -

18:11

CONSTELLATION

[3] - 29:24, 44:11, 57:1

CONSTITUTES [1] -

24:17

CONTAGIOUS [1] -

183:8

CONTAINED [1] -

10:10

CONTESTED [1] -

72:22

CONTEXT [5] -

15:23, 23:22, 38:22,

54:3, 168:24

CONTEXTS [1] -

87:17

CONTINUE [1] - 69:9

CONTINUED [2] -

2:1, 198:19

CONTINUES [1] -

16:20

CONTINUING [2] -

62:21, 79:14

CONTINUOUS [1] -

130:12

CONTINUUM [1] -

151:11

CONTRACEPTION

[1] - 110:25

CONTRADICT [1] -

42:4

CONTRARY [7] -

25:2, 32:9, 41:4, 42:1,

44:4, 85:12, 107:16

CONTRAST [1] -

25:6

CONTRIBUTE [3] -

87:25, 138:4, 158:14

CONTRIBUTIONS

[2] - 67:11, 164:7

CONTROL [4] -

49:23, 183:18,

183:21, 190:5

CONTROLLED [6] -

91:23, 181:7, 198:5,

198:12, 199:1, 199:9

CONTROLS [1] -

187:12

CONTROVERSIAL

[3] - 146:14, 195:1,

195:4

CONVENTIONAL [2]

- 162:24, 162:25

CONVERGE [1] -

70:19

CONVEY [1] - 148:15

COPIED [1] - 71:10

COPULATION [1] -

191:24

COPY [4] - 3:11,

175:18, 176:8, 176:17

COPYRIGHTED [1] -

55:9

CORD [1] - 207:9

CORE [1] - 96:25

CORPORATE [1] -

1:16

CORRECT [11] -

8:21, 52:1, 97:23,

131:23, 137:13,

144:23, 159:8,

179:12, 182:9, 196:9,

207:24

CORRESPOND [2] -

28:8, 193:5

COST [1] - 5:7

215

COTE [2] - 149:12,

160:21

COUNSEL [7] - 3:3,

4:16, 5:12, 8:16, 9:8,

55:12, 71:3

COUNT [1] - 192:4

COUNTRY [3] -

21:24, 70:4, 79:17

COUNTS [1] - 14:25

COUPLE [8] - 22:7,

23:3, 84:9, 122:18,

166:6, 170:22,

187:11, 201:9

COURAGE [2] -

96:21, 96:24

COURSE [16] - 5:5,

27:13, 38:22, 38:25,

40:8, 47:19, 48:7,

56:13, 99:11, 100:21,

101:11, 102:14,

102:15, 176:10,

189:17, 206:13

COURT [116] - 1:1,

1:22, 3:1, 3:2, 3:4,

3:6, 4:8, 4:19, 5:6,

5:16, 5:23, 8:14, 8:16,

8:22, 9:9, 9:16, 9:18,

11:7, 11:19, 14:18,

14:19, 23:23, 24:10,

24:16, 24:22, 27:14,

29:7, 33:17, 39:16,

57:8, 57:11, 57:14,

57:19, 58:3, 58:10,

58:15, 58:17, 58:22,

59:2, 59:15, 59:24,

60:24, 68:6, 69:11,

70:7, 71:2, 75:14,

83:3, 83:8, 83:15,

83:20, 83:22, 83:25,

84:8, 84:25, 85:14,

86:19, 87:5, 87:8,

87:13, 87:14, 87:15,

89:1, 90:5, 90:8,

91:25, 94:3, 95:6,

96:4, 96:9, 96:14,

101:20, 109:23,

111:23, 112:2,

112:10, 112:17,

112:20, 113:3,

114:12, 116:11,

123:2, 124:17,

135:16, 143:17,

143:19, 145:11,

150:3, 156:21, 166:7,

172:4, 174:13,

174:20, 174:22,

175:5, 175:8, 175:11,

175:13, 175:15,

175:25, 176:6,

176:18, 176:22,


177:3, 179:15, 186:2,

188:9, 188:13,

190:11, 191:16,

207:13, 207:20,

207:23, 208:5

COURT'S [2] - 3:7,

9:11

COURTHOUSE [2] -

1:22, 58:13

COURTROOM [22] -

1:7, 13:6, 24:23,

24:24, 25:1, 26:19,

30:13, 44:14, 59:5,

65:4, 68:9, 68:24,

73:1, 73:3, 76:18,

77:13, 84:15, 89:12,

96:21, 107:20,

107:25, 110:19

COURTS [5] - 5:4,

43:17, 43:25, 80:9,

91:17

COVER [2] - 8:25,

40:15

COVERED [1] -

164:16

CRANIOFACIAL [4] -

124:11, 148:4, 174:1,

206:23

CRANIOSYNOSTO

SIS [3] - 31:10,

102:19, 106:5

CRAZY [3] - 79:10,

98:22, 117:21

CREATE [6] - 21:7,

87:22, 126:12, 136:1,

136:12, 146:11

CREATED [7] - 40:5,

54:20, 91:15, 93:1,

191:13, 191:16,

192:14

CREATES [1] -

149:18

CREATION [1] -

92:25

CREDENTIALS [2] -

59:11, 59:14

CREDIBILITY [3] -

91:11, 92:3, 197:10

CREDIBLE [1] -

199:7

CREDIT [1] - 67:25

CREST [13] - 100:15,

100:17, 158:14,

160:18, 163:13,

163:14, 164:4, 164:7,

164:25, 165:4,

165:10, 167:11,

167:12

CRITERIA [24] -

34:14, 35:24, 52:16,

52:19, 53:5, 54:8,

69:16, 69:18, 87:14,

87:16, 89:3, 92:21,

93:22, 94:19, 94:22,

95:12, 96:2, 97:8,

97:18, 101:15, 109:9,

145:15

CRITERION [1] -

36:25

CRITICAL [4] -

44:13, 44:15, 126:21,

128:18

CRITICISM [3] -

67:2, 201:13, 201:19

CRITICISMS [1] -

191:12

CRITIQUE [1] - 42:1

CROSS [19] - 8:12,

9:15, 23:18, 23:19,

23:24, 24:1, 24:3,

31:7, 85:10, 85:12,

91:11, 91:20, 112:4,

112:5, 174:16, 188:7,

188:8, 188:13, 188:20

CROSS-

EXAMINATION [2] -

8:12, 9:15

CROWDED [1] -

148:14

CRUNCHING [1] -

45:1

CULMINATES [1] -

161:3

CULTURE [3] -

54:11, 154:24, 155:19

CURE [3] - 60:14,

61:7, 61:12

CURRENT [6] -

25:11, 34:2, 34:13,

35:6, 82:1, 205:13

CURVE [2] - 19:2,

19:6

CUT [1] - 87:7

CYNTHIA [4] - 1:9,

76:25, 110:4, 171:9

D

DAM [1] - 134:8

DAMS [4] - 179:2,

188:21, 190:17,

190:19

DANISH [2] - 120:10,

120:12

DATA [110] - 11:5,

11:6, 11:8, 11:14,

11:17, 11:18, 12:13,

12:14, 13:19, 14:5,

14:11, 14:25, 15:2,

15:3, 25:12, 25:18,

25:20, 25:22, 27:14,

27:20, 27:21, 28:14,

30:2, 30:5, 30:7,

30:18, 30:24, 31:1,

31:24, 32:14, 32:18,

32:25, 33:5, 33:13,

33:14, 33:18, 33:19,

33:23, 33:25, 34:2,

35:5, 35:6, 37:4, 37:9,

37:17, 39:15, 40:3,

40:4, 40:23, 41:14,

44:10, 44:25, 45:2,

45:5, 48:16, 50:6,

50:9, 53:7, 53:19,

57:5, 88:4, 88:14,

90:14, 90:17, 90:19,

90:21, 90:24, 91:1,

91:4, 91:6, 91:18,

91:22, 91:24, 92:1,

92:2, 96:15, 97:17,

103:25, 104:24,

105:14, 106:15,

106:17, 108:21,

109:18, 110:14,

120:22, 121:15,

141:1, 141:7, 141:12,

142:9, 142:16, 155:2,

165:1, 170:20,

170:21, 178:4, 187:2,

194:13, 194:15,

194:16, 195:2, 203:14

DATABASES [1] -

98:4

DATE [4] - 25:21,

77:19, 180:22, 208:4

DAUBERT [34] -

1:10, 10:2, 21:13,

21:17, 22:3, 22:4,

22:5, 22:6, 22:18,

23:6, 23:8, 23:11,

23:22, 28:17, 29:1,

54:1, 56:8, 56:22,

57:9, 84:2, 84:16,

85:6, 85:8, 87:17,

88:9, 91:12, 93:5,

93:6, 93:13, 94:8,

95:2, 105:4, 107:17

DAVIS [1] - 1:16

DAY-TO-DAY [3] -

71:11, 93:11, 114:13

DAYS [3] - 29:19,

194:1, 196:16

DEAD [9] - 182:6,

182:10, 186:23,

187:6, 187:9, 192:8,

203:2, 203:8, 203:11

DEAL [5] - 10:22,

48:19, 86:20, 106:13,

122:7

DEALING [2] - 10:4,

33:5

DEATH [22] - 20:3,

81:11, 124:10,

126:25, 132:2, 132:9,

132:13, 132:20,

133:1, 133:2, 133:9,

133:11, 181:4,

181:16, 188:1, 188:3,

193:12, 195:19,

195:24, 196:1, 202:4,

206:21

DEATHS [3] - 74:22,

187:4, 196:25

DEBATE [2] - 90:20,

188:16

DEBATED [1] - 14:19

DEBILITATING [1] -

19:18

DECADE [1] - 70:4

DECADES [2] -

156:3, 185:2

DECEMBER [2] -

13:11, 110:11

DECHERT [1] - 2:18

DECIDED [3] - 62:15,

104:8, 185:6

DECIDES [1] - 112:5

DECISION [6] -

14:20, 22:5, 84:24,

87:16, 90:4

DECISIONS [3] -

21:25, 22:4, 24:15

DECLINE [1] - 95:21

DECREASE [5] -

149:8, 149:9, 149:25,

180:25

DECREASED [7] -

74:20, 74:21, 149:11,

179:21, 180:13,

196:23, 196:24

DECREASES [2] -

149:7, 157:22

DEDICATED [3] -

60:12, 60:13, 70:5

DEEMED [1] - 44:20

DEFECT [40] - 17:24,

31:14, 37:16, 47:14,

50:11, 51:2, 53:18,

56:5, 64:15, 66:12,

70:3, 81:11, 92:14,

93:2, 97:16, 100:9,

108:5, 115:5, 115:15,

116:4, 118:10,

118:17, 122:16,

126:13, 128:23,

132:10, 138:12,

156:9, 164:12, 171:4,

175:20, 181:21,

181:23, 184:4, 184:8,

185:1, 185:13,

216

185:14, 185:20,

189:15

DEFECTS [249] -

10:15, 11:22, 12:15,

13:1, 13:2, 13:3,

13:21, 14:21, 15:12,

15:21, 16:6, 16:8,

16:12, 17:4, 17:8,

17:13, 17:19, 17:20,

17:22, 17:23, 18:1,

18:7, 18:10, 18:11,

18:15, 18:16, 18:19,

18:25, 19:5, 19:10,

19:16, 20:14, 21:4,

23:15, 25:23, 26:18,

27:11, 30:19, 30:20,

31:4, 31:6, 32:3, 32:6,

32:11, 32:21, 33:1,

34:22, 35:7, 35:14,

35:15, 35:21, 36:8,

36:9, 36:17, 37:6,

37:11, 37:19, 38:6,

38:10, 39:4, 39:25,

40:4, 42:16, 47:11,

47:12, 48:12, 50:8,

50:9, 50:13, 50:15,

50:18, 50:20, 50:23,

50:25, 51:5, 51:6,

52:8, 54:7, 54:14,

55:2, 55:4, 55:11,

55:18, 55:22, 56:1,

56:11, 57:1, 57:3,

60:14, 61:7, 62:18,

63:1, 63:21, 64:1,

64:4, 64:9, 64:17,

65:2, 66:23, 66:25,

67:9, 67:12, 68:13,

70:23, 75:15, 76:21,

76:24, 78:20, 78:21,

78:22, 79:19, 79:24,

80:5, 80:6, 80:13,

82:13, 86:25, 89:15,

89:25, 99:2, 99:3,

99:7, 100:10, 100:16,

100:19, 100:23,

102:4, 103:9, 103:11,

103:14, 104:3, 104:7,

105:8, 105:10,

105:20, 105:22,

106:3, 109:6, 110:7,

110:15, 111:4,

113:22, 114:16,

114:20, 114:23,

115:2, 115:11, 116:1,

116:9, 117:22,

118:11, 118:19,

118:21, 118:22,

119:10, 120:6, 120:7,

120:9, 120:16,

120:19, 122:11,

124:11, 124:12,


124:13, 127:20,

128:9, 138:9, 138:19,

139:2, 139:3, 145:4,

146:24, 147:2, 148:9,

150:21, 155:3, 156:9,

156:13, 156:16,

156:17, 156:25,

160:17, 160:19,

160:20, 160:25,

161:9, 161:12, 165:9,

165:15, 165:18,

167:6, 167:7, 167:8,

167:9, 167:17,

167:18, 167:19,

169:15, 170:13,

171:3, 171:5, 171:6,

171:10, 171:14,

171:23, 172:4, 172:9,

172:17, 172:19,

173:11, 173:20,

173:22, 173:24,

174:8, 182:3, 182:5,

182:10, 182:16,

190:6, 190:7, 190:23,

196:7, 200:11,

200:17, 201:3, 201:4,

201:15, 204:3,

204:11, 204:25,

205:23, 206:23,

206:25, 207:4, 207:6,

207:8, 207:9

DEFEND [6] - 61:19,

61:25, 112:6, 112:7,

112:8, 112:9

DEFENDANT [3] -

22:15, 62:24, 84:4

DEFENDANT'S [1] -

8:13

DEFENDANTS [6] -

8:7, 9:22, 69:18, 70:3,

91:8, 94:11

DEFENDANTS' [1] -

57:16

DEFENSE [7] -

65:22, 91:3, 117:3,

202:1, 202:17, 202:19

DEFICIENCY [1] -

149:14

DEFICIT [1] - 132:3

DEFINE [1] - 24:17

DEFINED [3] - 99:19,

103:19, 188:2

DEFINITELY [1] -

193:19

DEFINITIVE [1] -

150:5

DEGRADATION [1] -

136:4

DEGREE [9] - 62:6,

62:7, 82:17, 104:1,

124:1, 131:12,

133:18, 197:10, 206:9

DEGREES [1] - 89:6

DELETERIOUS [1] -

20:18

DELIVERING [1] -

9:21

DELIVERY [1] -

181:16

DELL [4] - 7:2,

64:22, 113:11, 113:13

DELUISE [6] - 77:1,

110:4, 110:5, 110:8,

110:9, 171:9

DELVE [1] - 133:7

DEMAND [2] -

107:11, 112:1

DEMANDS [1] -

112:1

DEMISE [1] - 179:25

DEMONSTRATE [9]

- 12:15, 17:3, 35:25,

37:1, 54:13, 61:3,

72:13, 197:24, 198:4

DEMONSTRATED

[4] - 35:21, 162:6,

168:14, 169:10

DEMONSTRATING

[3] - 37:10, 97:11,

115:14

DEMONSTRATIVE

[1] - 176:10

DENSE [1] - 161:14

DENSITY [1] -

186:11

DENVER [2] - 2:6,

2:13

DEPARTMENT [4] -

7:3, 7:9, 65:22, 117:3

DEPARTS [1] - 52:3

DEPARTURES [1] -

59:1

DEPENDENT [2] -

147:23, 186:5

DEPOSITION [4] -

12:16, 29:19, 48:17,

96:16

DEPOSITIONS [1] -

41:18

DEPRESSANT [1] -

64:8

DEPRESSED [3] -

21:25, 48:18, 110:18

DEPRESSION [22] -

10:5, 13:12, 13:14,

16:18, 16:22, 17:22,

19:17, 19:22, 19:23,

19:24, 20:1, 20:11,

20:17, 26:3, 48:13,

48:14, 49:9, 49:11,

49:21, 111:5

DEPRESSIVE [1] -

47:6

DEPTH [1] - 10:8

DERIVED [1] - 166:3

DESCRIBE [5] -

26:25, 40:17, 41:3,

166:24, 183:14

DESCRIBED [19] -

102:23, 128:14,

129:9, 130:19,

131:11, 132:23,

135:18, 135:20,

144:3, 145:22,

145:25, 157:11,

165:13, 171:6, 184:2,

184:19, 185:20,

191:18, 196:23

DESCRIBES [3] -

128:17, 142:17,

147:12

DESCRIBING [2] -

164:17, 185:1

DESCRIPTION [1] -

185:10

DESERVE [1] -

111:25

DESIGN [8] - 26:24,

49:13, 65:25, 121:8,

121:12, 139:5, 141:3,

141:5

DESIGNED [7] -

46:5, 98:3, 141:17,

157:5, 180:9, 180:19,

202:2

DESIGNS [2] - 98:2,

170:10

DESPITE [7] - 40:2,

46:19, 51:21, 56:4,

98:2, 198:15, 198:20

DESTROY [1] -

21:22

DETAIL [6] - 11:5,

22:19, 85:19, 85:20,

129:1, 200:23

DETAILED [2] -

41:25, 200:19

DETAILS [3] - 15:15,

29:5, 179:6

DETECTION [3] -

47:3, 47:4, 105:16

DETERMINATION

[5] - 15:20, 42:13,

53:10, 53:15, 89:23

DETERMINATIONS

[4] - 51:1, 52:21, 53:1,

93:3

DETERMINE [8] -

3:8, 14:20, 27:10,

81:13, 124:24,

135:23, 182:7, 192:6

DETERMINED [2] -

32:5, 33:15

DETERMINES [1] -

70:22

DETERMINING [4] -

46:23, 52:17, 137:5,

137:7

DETRIMENTAL [1] -

115:9

DEVELOP [2] -

138:22, 146:7

DEVELOPED [7] -

124:20, 125:3,

126:13, 151:13,

151:14, 166:10, 168:3

DEVELOPING [14] -

42:24, 101:10,

114:18, 117:16,

126:19, 129:12,

130:20, 145:19,

147:16, 152:3, 159:6,

165:11, 165:22, 183:3

DEVELOPMENT [47]

- 50:19, 51:7, 54:25,

64:12, 66:18, 98:9,

98:12, 98:16, 100:12,

100:21, 110:7, 111:4,

114:19, 118:2,

122:12, 122:14,

124:3, 129:14,

130:11, 131:10,

132:2, 133:8, 133:17,

133:23, 140:20,

146:5, 148:5, 148:6,

150:10, 151:5,

151:11, 158:12,

158:20, 163:24,

164:5, 165:17,

166:13, 178:2, 178:6,

181:18, 183:2,

183:15, 183:16,

192:22, 192:23, 200:4

DEVELOPMENTAL

[20] - 7:11, 7:17,

67:14, 67:17, 67:19,

68:4, 126:10, 128:16,

132:9, 147:19,

151:20, 172:24,

177:6, 177:17,

178:11, 202:10,

202:12, 202:13,

202:16

DEVELOPMENTAL

LY [4] - 146:3, 147:13,

166:9, 173:2

DEVELOPMENTS

[2] - 115:25, 122:12

DEVELOPS [2] -

65:10, 93:9

217

DEVIANT [10] -

132:2, 132:9, 133:8,

133:17, 133:23,

133:25, 180:5,

187:25, 188:3, 193:14

DEVOTED [1] -

122:15

DEXTRACARDIO [1]

- 167:18

DIABETES [1] - 67:7

DIAGRAM [1] - 94:19

DIANE [2] - 8:25,

62:2

DIANNE [1] - 1:12

DIAV [1] - 34:12

DIAV-CITRIN [1] -

34:12

DICE [1] - 45:4

DICTATE [1] - 7:13

DIDACTIC [1] - 120:3

DIE [1] - 160:2

DIED [4] - 179:25,

181:12, 190:19,

202:18

DIET [2] - 88:8,

115:12

DIFFER [3] - 170:9,

170:10

DIFFERENCE [3] -

14:23, 15:16, 110:9

DIFFERENCES [3] -

15:19, 143:25, 170:7

DIFFERENT [54] -

15:8, 15:18, 16:13,

16:14, 19:13, 26:20,

31:12, 31:14, 33:20,

42:24, 59:6, 69:16,

69:22, 70:15, 73:6,

74:8, 78:24, 80:17,

86:12, 90:25, 91:9,

93:10, 98:4, 102:9,

118:11, 124:4,

127:17, 127:22,

138:13, 143:22,

144:1, 144:2, 144:3,

144:6, 144:7, 145:4,

146:6, 146:10,

146:13, 151:9, 153:1,

164:17, 165:13,

172:21, 173:3, 173:7,

173:24, 174:8,

178:16, 191:22,

195:15, 197:19

DIFFERENTIATION

[1] - 146:3

DIFFERENTLY [4] -

42:25, 90:9, 98:3,

130:25

DIFFICULT [4] -

48:11, 49:23, 148:15,


190:18

DIFFICULTY [1] -

4:21

DINNER [1] - 207:19

DIRECT [3] - 43:20,

113:4, 174:20

DIRECTLY [1] -

133:3

DIRECTOR [5] -

7:10, 66:11, 74:11,

76:19, 113:15

DISAGREE [1] - 90:3

DISAGREED [1] -

80:1

DISAGREES [1] -

90:7

DISCLOSURE [1] -

24:13

DISCONNECT [1] -

56:20

DISCRETE [1] -

175:20

DISCUSSED [2] -

41:1, 41:4

DISCUSSES [1] -

24:11

DISCUSSION [3] -

11:15, 22:14, 40:18

DISEASE [5] - 19:19,

27:17, 49:4, 49:16,

49:17

DISEASE-

RELATED [1] - 49:17

DISEASES [2] -

127:19, 165:24

DISHES [2] - 154:24,

155:19

DISMISS [1] - 94:25

DISMISSED [2] -

29:18, 95:10

DISPLAYED [1] -

192:3

DISRUPT [2] -

162:10, 165:10

DISRUPTING [2] -

148:8, 148:21

DISRUPTION [2] -

165:9, 167:10

DISTILLED [1] -

52:19

DISTINCT [4] -

11:21, 50:15, 50:16,

178:16

DISTINCTION [2] -

41:12, 69:25

DISTINGUISH [1] -

24:23

DISTINGUISHED [3]

- 37:9, 39:23, 111:21

DISTRICT [6] - 1:1,

1:2, 43:17, 59:15,

59:16, 92:5

DISTURBANCES [1]

- 56:11

DISTURBS [1] -

56:10

DIVERSE [4] - 118:2,

118:3, 138:15, 153:7

DIVIDE [3] - 56:21,

100:8

DIVIDED [2] - 5:23,

58:7

DIVIDING [1] - 106:1

DNA [2] - 136:1,

146:10

DOC [1] - 66:8

DOCKET [1] - 4:12

DOCTOR [7] - 29:19,

29:21, 41:25, 50:17,

197:20, 198:24,

203:21

DOCTORAL [2] -

120:8, 120:15

DOCTORATE [2] -

62:4, 89:5

DOCTORS [3] -

21:24, 66:1, 93:12

DOCUMENT [4] -

76:11, 77:10, 150:2,

201:21

DOCUMENTED [3] -

99:17, 149:21, 151:21

DOCUMENTS [5] -

22:14, 22:17, 22:22,

22:23

DOMINANCE [1] -

149:24

DONE [36] - 11:2,

13:24, 31:15, 39:21,

41:21, 45:21, 55:13,

60:7, 62:20, 63:4,

75:13, 75:17, 78:5,

86:3, 115:6, 115:21,

117:2, 117:5, 117:7,

123:12, 123:17,

134:11, 134:14,

137:12, 142:21,

143:3, 143:6, 154:24,

156:3, 179:3, 179:8,

180:21, 182:18,

188:14, 190:1

DOSAGE [1] -

133:18

DOSE [22] - 28:5,

28:9, 28:10, 54:18,

74:2, 74:5, 127:4,

127:5, 133:19,

133:25, 134:3, 134:7,

180:18, 183:19,

184:12, 186:22,

186:23, 187:13,

187:14, 190:8, 202:2

DOSES [4] - 28:8,

54:15, 187:3, 202:10

DOUBLE [1] - 201:9

DOUBLED [2] -

201:11

DOUBLING [3] -

184:2, 184:5, 184:6

DOW [1] - 36:6

DOWN [17] - 19:12,

38:17, 70:13, 70:16,

73:25, 84:12, 85:6,

114:21, 141:23,

144:5, 158:3, 161:11,

177:11, 180:20,

181:20, 186:24

DOWNLOADED [1] -

4:24

DOWNSTREAM [5] -

159:2, 162:18,

162:21, 165:12,

167:21

DOZEN [1] - 38:23

DOZENS [1] - 199:5

DR [275] - 6:12, 6:13,

6:23, 6:24, 7:7, 7:15,

7:16, 7:25, 8:1, 8:2,

8:3, 10:19, 10:24,

11:2, 12:16, 12:23,

16:19, 17:18, 20:16,

23:1, 24:21, 25:2,

25:6, 25:11, 25:17,

25:25, 26:5, 26:12,

29:14, 29:20, 30:23,

31:2, 31:6, 31:23,

32:7, 32:12, 32:16,

33:12, 33:14, 33:17,

34:10, 35:7, 35:9,

35:11, 35:15, 35:16,

35:18, 37:7, 37:25,

38:7, 39:19, 40:3,

40:9, 40:12, 40:15,

42:6, 42:11, 42:19,

42:21, 43:1, 43:2,

43:3, 43:4, 43:8,

43:23, 44:1, 44:3,

45:9, 45:11, 46:8,

46:17, 47:2, 48:17,

49:2, 50:4, 50:17,

51:9, 51:17, 52:3,

52:6, 53:21, 53:24,

54:10, 54:14, 54:16,

54:20, 54:22, 55:6,

55:17, 56:9, 56:11,

56:15, 56:24, 57:1,

58:24, 60:10, 60:11,

60:15, 60:16, 60:17,

61:4, 61:8, 61:12,

61:17, 61:21, 62:3,

63:18, 63:23, 64:2,

64:10, 65:3, 65:6,

65:9, 65:20, 66:1,

66:18, 67:13, 67:20,

69:19, 70:1, 70:9,

70:13, 70:20, 70:25,

71:5, 71:10, 71:11,

71:22, 72:11, 72:23,

73:19, 73:20, 78:18,

78:19, 79:9, 79:15,

80:1, 81:1, 81:7,

81:14, 82:10, 82:22,

84:2, 84:5, 84:14,

85:2, 85:3, 85:5,

85:21, 86:9, 86:21,

87:23, 88:19, 89:19,

91:2, 91:3, 91:4,

91:17, 91:22, 92:1,

92:12, 92:18, 92:19,

92:25, 93:19, 93:25,

94:9, 98:10, 98:19,

100:7, 101:14,

102:12, 104:7,

104:16, 106:14,

107:1, 107:13,

107:22, 108:9, 109:4,

109:10, 109:16,

109:23, 110:4, 110:8,

110:9, 110:10,

111:13, 112:2, 112:5,

112:21, 113:19,

113:20, 114:1, 114:7,

114:9, 115:10,

115:16, 115:20,

116:24, 117:10,

119:20, 120:25,

121:24, 122:18,

122:22, 123:24,

124:16, 125:13,

128:25, 129:2,

136:23, 143:15,

144:25, 146:20,

146:23, 147:1,

147:10, 150:7,

150:25, 151:7,

153:12, 153:23,

155:11, 156:18,

156:23, 161:1,

161:15, 163:20,

170:3, 171:24, 172:2,

176:24, 189:15,

189:19, 191:12,

191:19, 196:21,

201:14, 203:15,

203:22, 203:23,

204:1, 204:7, 206:5,

206:8, 206:15, 207:11

DRAMATICALLY [1]

- 18:14

DRAW [7] - 51:13,

69:5, 95:21, 152:23,

218

168:18, 170:11,

197:15

DRAWN [3] - 51:14,

51:16, 197:15

DRILL [1] - 161:11

DRIVE [1] - 1:16

DRIVEN [2] - 26:21,

93:14

DRIVING [1] - 68:2

DROP [1] - 68:2

DRS [1] - 29:14

DRUG [66] - 12:5,

12:6, 12:24, 13:3,

13:10, 13:17, 18:19,

19:15, 27:17, 27:25,

35:20, 43:20, 65:22,

69:1, 69:4, 70:4, 70:6,

71:14, 74:24, 75:2,

75:8, 75:23, 76:1,

77:20, 78:15, 78:25,

79:2, 81:9, 81:13,

82:6, 87:2, 88:8,

99:20, 110:17,

110:18, 110:20,

110:23, 111:1, 111:3,

111:19, 117:22,

123:8, 131:21,

132:17, 137:11,

139:15, 149:20,

174:7, 180:11,

180:25, 189:3, 189:6,

189:8, 189:10,

189:18, 189:20,

190:10, 192:7,

193:18, 196:18,

198:20, 201:15,

202:18, 204:18,

205:18

DRUGS [23] - 14:23,

14:24, 20:7, 35:1,

55:4, 55:18, 73:8,

73:15, 74:17, 79:6,

89:13, 99:16, 110:14,

115:7, 117:14,

139:17, 139:19,

144:20, 152:25,

198:1, 198:15,

199:14, 204:14

DTRA [1] - 117:2

DUE [17] - 17:23,

44:21, 45:3, 45:8,

45:20, 47:24, 115:11,

133:12, 140:18,

149:13, 152:20,

155:3, 161:9, 165:15,

178:24, 188:19, 192:7

DURING [43] - 9:25,

16:18, 16:23, 17:11,

19:22, 20:11, 20:17,

20:23, 21:25, 23:14,


26:9, 34:8, 37:14,

37:15, 64:8, 79:5,

79:7, 80:15, 82:4,

82:19, 110:23,

111:10, 118:2, 125:4,

131:10, 133:8,

139:23, 152:12,

158:20, 163:24,

165:17, 176:7, 178:2,

180:11, 181:12,

181:17, 190:19,

191:6, 196:6, 196:11,

197:24, 205:16,

206:11

DUTY [1] - 116:8

DYING [2] - 82:14,

203:11

E

EARLY [19] - 26:15,

34:21, 66:16, 100:7,

101:21, 103:16,

118:1, 122:11,

130:13, 130:14,

136:20, 146:5,

147:22, 166:11,

173:2, 181:18,

188:17, 192:21, 198:3

EARS [2] - 88:4,

100:17

EARTH [5] - 106:21,

106:23, 107:1,

107:19, 110:2

EAST [2] - 2:3, 7:22

EASTERN [2] - 1:2,

59:16

EASY [1] - 61:21

EATING [1] - 201:18

ECONOMIC [1] -

21:14

EDITION [3] - 55:2,

55:9, 85:25

EDITOR [2] - 66:13

EFEXOR [1] - 110:6

EFFECT [78] - 11:16,

14:1, 14:14, 25:12,

39:21, 42:7, 42:8,

42:25, 43:12, 43:18,

49:8, 54:19, 72:7,

72:21, 72:22, 73:2,

73:3, 74:1, 74:4,

76:17, 77:13, 77:18,

80:11, 80:12, 80:18,

81:1, 81:5, 81:20,

82:2, 86:7, 89:20,

94:25, 95:5, 99:20,

100:25, 101:2,

106:16, 108:5,

108:21, 127:5,

129:22, 132:19,

133:19, 134:2, 134:3,

143:5, 149:6, 152:19,

160:10, 160:12,

161:8, 161:20,

171:10, 171:13,

184:18, 184:22,

188:17, 189:4, 189:8,

189:10, 189:22,

190:24, 192:24,

193:19, 193:20,

194:3, 194:21, 197:4,

197:12, 198:1,

198:11, 201:15,

203:13, 203:16,

203:24, 204:3, 205:14

EFFECTIVE [2] -

13:11, 13:12

EFFECTS [29] -

20:18, 28:3, 43:6,

47:7, 54:14, 87:22,

87:25, 115:15,

122:13, 122:14,

133:25, 136:16,

150:9, 151:6, 162:5,

162:23, 163:10,

177:9, 178:5, 180:3,

194:23, 198:23,

200:3, 200:4, 202:10,

202:12, 202:15, 203:8

EFFICIENT [1] -

176:2

EFFORT [1] - 79:14

EGG [1] - 167:1

EIGHT [4] - 52:24,

62:20, 69:15, 125:11

EITHER [14] - 8:19,

90:22, 97:3, 97:4,

133:13, 134:8,

159:17, 159:20,

164:10, 164:18,

169:23, 185:10,

187:25, 193:11

ELEMENT [1] -

126:12

ELEVATED [5] -

88:18, 97:20, 105:1,

109:14, 160:17

ELI [2] - 78:5, 150:7

ELIMINATE [1] -

21:20

ELUCIDATED [1] -

56:17

EMANUEL [1] - 2:9

EMBARRASSES [1]

- 6:16

EMBRYO [15] -

54:11, 54:15, 54:19,

114:18, 131:6, 131:7,

131:9, 131:17, 134:9,

145:19, 147:16,

147:23, 189:10,

198:8, 200:3

EMBRYOGENESIS

[1] - 136:20

EMBRYOLOGICAL

[1] - 129:1

EMBRYOLOGIST [4]

- 7:17, 66:5, 70:18,

100:7

EMBRYOLOGY [5] -

7:16, 66:6, 100:24,

101:8, 129:3

EMBRYONIC [8] -

54:25, 56:10, 116:19,

124:3, 159:5, 166:11,

192:22

EMBRYOS [2] -

155:2, 179:24

EMPHASIZE [2] -

16:25, 132:24

EMPHASIZED [1] -

43:25

EMPLOY [1] - 70:8

EMPLOYED [11] -

30:13, 30:14, 34:17,

59:19, 59:23, 61:5,

63:8, 64:21, 68:20,

123:11, 154:16

EMPLOYING [1] -

125:25

ENABLED [1] -

156:3

ENCEPHALOCELE

[1] - 185:7

ENCOUNTERED [1]

- 46:11

END [19] - 10:24,

28:21, 33:14, 37:4,

58:12, 65:15, 66:3,

105:4, 105:5, 111:2,

137:21, 138:25,

139:1, 161:1, 166:20,

171:19, 184:20,

203:9, 207:14

END-ALL [1] - 111:2

ENDED [1] - 76:25

ENDING [1] - 173:5

ENDORSED [1] -

41:16

ENDOWED [1] - 7:10

ENDPOINT [2] -

126:23, 142:8

ENDPOINTS [3] -

126:21, 126:25, 127:3

ENDS [1] - 77:17

ENGAGED [2] -

54:23, 60:15

ENGAGING [1] -

61:22

ENGINE [1] - 21:19

ENGINES [1] -

146:13

ENGLAND [5] - 99:6,

99:8, 102:7, 102:15,

103:7

ENGLISH [2] - 6:15,

6:17

ENROLLED [1] -

120:17

ENTIRE [12] - 3:13,

3:14, 43:9, 68:9, 77:6,

86:22, 88:19, 102:11,

104:16, 169:20,

190:21, 190:23

ENTIRETY [1] -

141:7

ENTITLED [1] -

208:1

ENVIRONMENT [5] -

64:18, 114:17,

127:10, 127:19,

141:20

ENVIRONMENTAL

[6] - 64:20, 116:16,

119:5, 122:13,

138:14, 140:12

ENVIRONMENTAL

LY [1] - 121:1

ENVIRONMENTAL

LY-INDUCED [1] -

121:1

EPA [4] - 65:21, 71:7,

71:10, 137:8

EPI [4] - 142:16,

142:19, 143:2, 170:21

EPIDEMIOLOGIC [6]

- 43:25, 51:7, 86:5,

86:17, 87:8, 102:13

EPIDEMIOLOGICA

L [12] - 17:2, 27:14,

27:16, 27:19, 28:20,

35:22, 36:16, 49:23,

86:10, 86:21, 104:1,

136:16

EPIDEMIOLOGIST

[15] - 10:20, 10:25,

11:1, 61:9, 61:10,

61:13, 61:19, 61:25,

62:5, 70:19, 77:1,

97:3, 121:19, 153:18,

161:2

EPIDEMIOLOGIST

S [11] - 88:17, 93:12,

95:17, 99:23, 101:2,

109:13, 121:11,

121:16, 122:7, 122:9,

122:10

EPIDEMIOLOGY [37]

- 6:13, 12:1, 35:25,

219

37:1, 66:1, 71:18,

72:4, 72:6, 72:10,

72:17, 76:19, 81:24,

85:24, 87:12, 97:4,

110:3, 121:6, 121:7,

121:8, 122:6, 136:20,

137:22, 141:1,

143:10, 147:2, 155:2,

155:23, 161:3,

169:12, 169:13,

170:4, 170:8, 186:13,

203:10, 203:12, 206:6

EQUIVALENT [1] -

54:18

ERADICATE [1] -

115:11

ERROR [1] - 46:25

ERRORS [2] - 10:9,

95:22

ESPECIALLY [2] -

36:2, 46:3

ESPOUSED [2] -

42:11, 126:24

ESQ [9] - 1:15, 1:18,

2:2, 2:5, 2:8, 2:8,

2:11, 2:14, 2:17

ESQUIRE [1] - 1:12

ESSENTIAL [1] -

126:11

ESSENTIALLY [7] -

30:21, 54:4, 61:1,

61:22, 65:12, 70:13,

193:9

ESTABLISH [3] -

13:16, 23:13, 30:19

ESTABLISHED [4] -

140:16, 141:12,

141:15, 172:15

ESTABLISHES [1] -

10:14

ESTABLISHMENT

[2] - 147:24, 148:2

ESTIMATE [2] -

51:24, 199:3

ESTIMATES [1] -

51:22

ETHICALLY [1] -

168:10

ETIOLOGY [1] -

101:7

EUROPE [2] - 77:24,

77:25

EVALUATE [3] -

39:13, 48:16, 95:5

EVALUATED [3] -

45:23, 86:15, 86:22

EVALUATING [3] -

86:5, 89:2, 92:22

EVENING [1] -

207:14


EVENT [4] - 10:25,

141:12, 147:19,

147:21

EVENTS [6] - 16:15,

129:13, 135:3,

140:17, 140:22, 202:8

EVIDENCE [50] -

3:20, 10:14, 13:17,

14:5, 14:10, 17:3,

23:21, 24:18, 26:22,

27:9, 27:19, 27:20,

28:4, 28:10, 33:1,

34:13, 43:18, 43:20,

44:9, 51:23, 51:24,

53:2, 54:17, 56:17,

71:19, 75:6, 75:12,

85:13, 85:18, 85:25,

86:5, 86:21, 88:10,

91:10, 92:22, 97:11,

107:14, 154:18,

156:8, 169:20, 180:1,

184:12, 184:16,

184:18, 189:22,

198:17, 205:10,

205:22, 206:1, 206:6

EVOLVE [1] - 108:23

EVOLVED [1] - 107:1

EVOLVING [1] -

106:20

EXACT [5] - 79:12,

87:6, 88:7, 123:12,

171:18

EXACTLY [6] - 77:8,

109:10, 110:8,

115:22, 170:23, 206:2

EXAMINATION [11] -

8:12, 9:15, 23:18,

24:2, 24:3, 85:10,

85:12, 91:11, 91:20,

112:4, 113:4

EXAMINE [5] - 23:20,

23:24, 112:5, 115:25,

118:12

EXAMINED [4] -

7:25, 8:1, 8:2, 8:4

EXAMPLE [12] -

5:25, 12:18, 47:11,

47:12, 51:6, 51:20,

71:17, 101:21,

127:25, 139:10,

173:10, 174:6

EXAMPLES [3] -

40:14, 41:8, 80:3

EXCEEDED [1] -

39:25

EXCEEDS [2] - 51:9,

51:10

EXCELLENCE [1] -

65:7

EXCEPT [2] - 69:18,

182:25

EXCEPTION [2] -

26:15, 85:8

EXCEPTIONS [2] -

47:17, 169:21

EXCERPTS [1] -

73:7

EXCESS [2] -

148:16, 160:21

EXCHANGE [1] -

171:21

EXCLUDE [3] -

49:14, 90:6, 91:17

EXCLUSION [1] -

91:20

EXCLUSIVELY [1] -

122:16

EXCUSE [1] - 51:10

EXCUSED [1] -

83:12

EXERCISE [2] - 57:8,

79:12

EXHIBIT [4] - 94:14,

107:6, 191:14, 191:16

EXHIBITS [2] -

163:22, 171:22

EXIST [2] - 105:18,

167:4

EXISTING [7] -

90:24, 106:15, 156:1,

161:19, 167:24,

168:22

EXPAND [1] - 77:21

EXPECT [19] - 5:12,

18:18, 19:2, 78:7,

83:4, 150:12, 150:22,

151:5, 152:1, 160:8,

165:15, 168:25,

169:6, 170:24, 188:2,

193:11, 193:17,

194:24, 202:21

EXPECTATION [2] -

161:7, 161:8

EXPECTED [23] -

3:21, 73:6, 103:20,

118:2, 118:10, 137:6,

138:22, 140:17,

141:22, 144:22,

145:15, 150:14,

152:20, 155:3, 167:9,

170:14, 171:4, 171:6,

181:13, 186:17,

202:3, 203:1, 203:13

EXPECTING [1] -

35:3

EXPECTS [1] -

174:14

EXPERIENCE [4] -

7:18, 19:22, 35:17,

79:2

EXPERIENCED [2] -

179:21, 180:13

EXPERIMENTAL [2]

- 107:7, 183:20

EXPERIMENTALLY

[1] - 135:23

EXPERT [30] - 10:10,

10:13, 21:3, 23:24,

29:11, 37:8, 54:21,

55:15, 59:21, 60:8,

61:24, 69:13, 78:9,

84:19, 88:9, 90:3,

90:7, 90:13, 90:15,

90:18, 90:19, 91:3,

91:6, 93:1, 93:9, 96:8,

106:19, 107:13,

153:12

EXPERT'S [1] - 90:6

EXPERTISE [2] -

70:15, 93:14

EXPERTS [54] - 8:19,

10:16, 10:21, 22:12,

27:6, 27:15, 28:13,

28:15, 28:23, 29:17,

41:13, 50:23, 54:10,

56:20, 56:25, 57:2,

59:6, 59:12, 59:14,

60:1, 60:6, 60:10,

60:12, 60:23, 61:4,

61:16, 61:22, 63:6,

63:12, 63:18, 63:22,

65:14, 65:20, 66:6,

68:8, 68:10, 68:19,

72:23, 73:10, 82:16,

84:15, 85:2, 85:5,

85:22, 88:13, 89:2,

89:20, 90:24, 92:17,

97:5, 99:2, 112:3,

147:6

EXPLAIN [28] - 11:8,

15:9, 27:1, 40:17,

40:25, 41:3, 47:3,

62:1, 65:10, 70:10,

70:20, 70:25, 71:6,

72:5, 73:20, 131:3,

143:16, 147:10,

148:7, 150:3, 163:21,

163:23, 164:12,

166:7, 177:19, 186:2,

192:11, 197:19

EXPLAINED [3] -

68:1, 121:4, 172:4

EXPLAINS [1] - 11:6

EXPLANATION [1] -

133:5

EXPLANT [1] - 155:1

EXPLETIVE [1] -

4:21

EXPOSED [18] -

36:2, 56:3, 108:12,

127:22, 128:1, 128:8,

128:22, 138:23,

139:8, 173:8, 177:24,

188:18, 188:21,

188:23, 192:20,

195:20, 196:11

EXPOSING [1] -

189:24

EXPOSURE [30] -

25:9, 34:2, 36:18,

54:17, 97:12, 97:22,

97:25, 101:9, 101:10,

128:17, 129:1,

131:13, 138:21,

139:12, 140:18,

151:14, 152:20,

161:10, 162:7,

162:11, 167:5,

178:25, 188:24,

191:22, 192:7, 193:5,

193:25, 195:24,

196:12, 205:23

EXPOSURES [7] -

51:4, 128:5, 139:9,

192:12, 192:13,

192:14, 196:14

EXPRESS [2] -

129:23, 164:17

EXPRESSED [6] -

55:25, 129:25,

165:12, 165:17,

165:20, 165:21

EXPRESSING [1] -

130:2

EXPRESSION [7] -

146:9, 146:11, 159:4,

162:12, 162:13,

165:19, 165:20

EXTENSIVE [1] -

97:10

EXTENSIVELY [1] -

12:6

EXTENT [4] - 50:10,

53:7, 86:6, 119:4

EXTRAORDINARIL

Y [1] - 77:14

EXTRAPOLATE [1] -

90:24

EXTREMELY [2] -

50:5

EYE [2] - 44:13,

44:15

F

FACE [1] - 100:16

FACILITY [1] -

113:15

FACT [39] - 24:15,

30:4, 30:23, 32:16,

220

47:24, 48:6, 48:12,

54:14, 56:4, 77:12,

84:16, 85:7, 85:18,

85:20, 85:23, 86:2,

86:11, 89:1, 89:17,

89:24, 94:8, 96:16,

97:15, 98:16, 98:22,

100:4, 101:18,

103:18, 104:9, 110:3,

112:1, 166:2, 170:12,

170:19, 182:25,

183:1, 202:21, 205:11

FACTOR [8] - 23:9,

23:11, 47:22, 48:10,

53:13, 93:14, 94:6,

170:15

FACTORS [15] -

23:8, 39:1, 46:23,

49:5, 49:17, 51:8,

81:12, 94:7, 94:8,

94:14, 118:21, 119:3,

119:5, 120:16, 120:19

FACTS [1] - 72:18

FACULTY [1] - 6:20

FAILED [4] - 10:1,

179:22, 197:24, 198:4

FAILING [1] - 44:6

FAILS [1] - 30:12

FAILURE [1] - 56:6

FAIR [8] - 116:6,

131:20, 132:14,

135:4, 135:5, 148:24,

184:10, 199:7

FAIRLY [3] - 163:22,

172:8, 172:14

FALL [1] - 108:3

FALLACY [5] -

11:22, 14:1, 39:21,

42:9, 43:5

FALSE [10] - 11:4,

30:11, 39:13, 39:23,

39:24, 44:6, 46:24,

47:22, 74:9, 195:10

FAMILIAR [9] - 70:2,

94:3, 129:2, 146:20,

146:23, 153:15,

153:20, 185:18,

204:13

FAMILIES [1] - 35:4

FAMODISIN [1] -

113:22

FAMOUS [4] - 65:5,

68:23, 79:16, 94:24

FAR [14] - 56:20,

95:19, 121:19,

122:12, 138:11,

144:4, 144:7, 158:3,

158:25, 165:19,

168:25, 170:8,

174:15, 184:11


FASHION [1] - 137:1

FAVOR [1] - 94:11

FDA [47] - 12:18,

13:10, 13:19, 13:20,

13:24, 14:1, 14:4,

14:8, 14:9, 14:10,

14:13, 15:4, 16:12,

28:3, 28:7, 34:18,

43:11, 74:3, 74:10,

74:15, 74:16, 74:24,

74:25, 75:7, 75:11,

75:12, 75:13, 75:21,

75:24, 76:2, 76:4,

76:6, 89:13, 89:23,

90:8, 99:12, 99:15,

100:13, 100:14,

111:5, 177:12,

178:22, 197:7, 197:11

FDA'S [3] - 27:24,

74:19, 76:10

FEBRUARY [2] -

106:14, 108:2

FEDERAL [2] -

119:12

FELLOWSHIP [1] -

66:8

FEMALES [1] -

177:24

FERTILITY [2] -

74:21, 196:24

FETAL [7] - 14:5,

14:10, 98:9, 98:12,

98:16, 100:21, 200:3

FETUS [18] - 20:18,

42:25, 100:12,

114:18, 131:6, 131:8,

131:10, 131:17,

134:9, 145:19,

147:16, 152:3,

189:11, 189:12,

197:24, 198:5, 198:7,

198:11

FEW [3] - 40:15,

179:2, 185:2

FIELD [12] - 12:1,

52:9, 67:12, 112:14,

125:2, 158:15,

163:21, 163:23,

164:2, 164:4, 164:11,

185:1

FIELDS [1] - 164:8

FIFTH [2] - 133:23,

187:24

FIGURE [7] - 69:1,

69:4, 94:20, 116:8,

123:8, 161:2, 190:2

FILED [1] - 114:10

FILL [2] - 137:11,

137:15

FINAL [1] - 47:21

FINALLY [5] - 5:22,

34:24, 67:5, 76:11,

82:15

FINANCIAL [1] -

21:20

FINDINGS [30] -

11:3, 26:24, 27:1,

30:8, 30:9, 40:6,

40:25, 41:4, 41:7,

43:23, 46:6, 51:18,

74:20, 78:6, 78:8,

82:1, 82:12, 86:7,

104:13, 119:7,

150:11, 150:13,

186:25, 189:16,

192:11, 196:22,

197:11, 205:13,

205:24

FINE [6] - 9:16,

25:14, 26:17, 156:21,

200:21

FINGERTIPS [2] -

48:5, 48:8

FINISH [6] - 174:20,

175:2, 175:4, 175:6,

175:7, 175:9

FINNELL [38] -

64:14, 65:3, 65:6,

113:16, 113:19,

113:20, 114:1, 114:7,

114:9, 114:13,

115:10, 115:16,

115:20, 116:2, 116:3,

116:7, 116:24, 117:5,

117:11, 120:23,

121:19, 121:21,

121:23, 121:24,

121:25, 122:5,

122:15, 122:19,

122:22, 134:12,

134:16, 134:20,

136:23, 137:2,

137:25, 189:14,

189:16

FINNELL'S [1] -

120:25

FIRM [1] - 1:19

FIRST [59] - 1:22,

6:12, 6:17, 9:1, 9:3,

10:18, 16:22, 16:23,

18:9, 18:14, 20:1,

20:23, 22:10, 22:13,

23:4, 23:7, 25:9,

25:15, 25:21, 26:3,

26:8, 27:25, 29:13,

32:13, 34:8, 37:24,

59:3, 59:19, 68:1,

68:21, 70:9, 75:12,

79:6, 79:7, 84:12,

97:8, 108:13, 110:21,

112:19, 114:21,

115:21, 123:1, 127:7,

127:11, 129:19,

131:18, 138:10,

143:12, 152:12,

158:5, 165:3, 166:25,

170:6, 193:5, 195:19,

196:2, 197:25, 205:23

FIRST-LINE [5] -

16:22, 16:23, 20:23,

25:15, 26:8

FIRST-TRIMESTER

[2] - 193:5, 205:23

FISH [5] - 56:13,

56:18, 155:7, 169:4

FIVE [7] - 19:21,

44:22, 66:15, 144:5,

174:18, 174:19, 175:8

FIVE-MINUTE [1] -

175:8

FL [1] - 2:3

FLASKS [1] - 154:24

FLAT [4] - 106:21,

106:23, 107:20, 110:2

FLAW [2] - 86:16,

91:19

FLAWED [4] - 10:17,

86:4, 92:2, 95:23

FLAWS [11] - 10:9,

29:11, 29:24, 85:22,

86:2, 86:6, 86:8,

86:11, 104:24, 105:17

FLEXIBLE [1] - 94:7

FLIES [1] - 169:4

FLOOR [2] - 1:22,

2:9

FLOW [7] - 71:9,

135:15, 137:20,

176:13, 176:14

FLUOXETINE [2] -

150:6, 151:23

FLUVOXAMINE [1] -

205:11

FLY [1] - 29:1

FOCUS [8] - 12:4,

43:4, 84:2, 84:25,

90:2, 95:17, 122:10,

156:20

FOCUSED [2] - 10:8,

85:15

FOCUSES [1] -

120:25

FOISTED [1] - 87:4

FOLATE [2] - 115:4,

115:11

FOLATES [1] -

115:15

FOLD [2] - 104:5,

108:8

FOLLOW [4] - 10:8,

20:8, 171:23, 172:2

FOLLOWING [5] -

9:14, 99:19, 124:6,

176:19, 197:14

FOLLOWS [1] -

136:18

FOOT [7] - 31:10,

103:14, 183:13,

183:15, 186:14, 207:2

FORBID [1] - 59:2

FORCED [1] - 175:22

FOREGOING [1] -

207:24

FOREST [2] -

104:18, 109:12

FORGOT [1] - 82:23

FORM [6] - 30:23,

100:7, 136:11, 137:1,

153:1, 159:25

FORMAL [2] - 87:19,

87:20

FORMATION [2] -

147:25, 164:11

FORMED [1] - 97:24

FORMING [3] -

100:11, 147:4, 169:19

FORMS [1] - 56:18

FORTH [4] - 66:23,

77:3, 103:1, 140:15

FORUM [1] - 78:11

FORWARD [1] -

85:11

FOSTERING [4] -

188:7, 188:8, 188:13,

188:20

FOUNDED [1] -

29:24

FOUNDER [1] -

124:19

FOUR [15] - 6:11,

8:11, 28:9, 53:15,

59:6, 60:6, 63:12,

66:15, 68:10, 132:1,

132:15, 144:4, 180:5,

188:2, 195:20

FOURTH [4] - 11:14,

38:9, 130:17, 130:18

FRAME [2] - 97:24,

100:21

FRAMEWORK [4] -

22:3, 52:4, 135:1,

135:17

FRANKLY [6] -

30:23, 48:11, 54:3,

73:21, 78:13, 88:5

FRAUD [1] - 24:12

FREEDOM [1] -

107:10

FRENCH [2] - 6:15,

96:6

221

FRENCH-

SPEAKING [1] - 96:6

FREQUENCY [3] -

36:1, 37:2, 133:18

FREQUENTLY [1] -

13:18

FROGS [5] - 56:12,

56:13, 56:18, 155:7,

169:5

FRONTS [1] - 196:1

FRYE [2] - 3:20,

23:12

FULFILL [2] - 21:17,

145:15

FULFILLED [2] -

34:13, 34:14

FULL [2] - 62:8,

112:25

FULLY [4] - 34:10,

59:6, 151:13

FUNCTION [8] -

24:22, 57:9, 109:21,

131:6, 150:10,

157:12, 177:23

FUNCTIONAL [3] -

127:2, 132:3, 132:10

FUNCTIONS [1] -

21:18

FUNDED [2] -

116:25, 119:14

G

GALLERY [1] -

174:24

GAME [2] - 138:25,

139:1

GAPS [1] - 137:15

GARNERED [1] -

166:9

GASTROINTESTIN

AL [1] - 106:3

GASTRULATION [2]

- 147:18

GATEKEEPING [3] -

21:18, 24:22, 57:9

GENE [4] - 138:13,

139:11, 146:9, 162:12

GENERAL [27] -

11:16, 11:18, 14:16,

18:2, 23:4, 23:7, 23:9,

25:22, 26:22, 32:22,

47:17, 53:22, 84:13,

84:20, 86:18, 86:24,

89:14, 97:13, 99:10,

103:16, 104:2,

104:10, 105:20,

106:18, 127:15,

135:17, 139:23

GENERALLY [42] -


12:3, 16:7, 23:6,

23:13, 23:14, 29:25,

31:17, 32:8, 33:19,

33:24, 42:10, 52:10,

59:4, 67:10, 88:24,

92:17, 94:1, 114:15,

121:11, 124:14,

128:6, 137:4, 140:1,

141:4, 142:6, 142:16,

143:12, 144:13,

148:7, 154:24,

168:18, 172:16,

173:9, 173:18,

179:18, 180:19,

181:1, 182:24,

183:20, 192:13,

192:21, 195:13

GENERATE [1] -

21:19

GENERATING [1] -

121:15

GENERATIONAL [1]

- 178:4

GENES [7] - 79:22,

138:24, 138:25,

146:11, 166:9,

166:12, 166:13

GENETIC [32] - 7:12,

7:23, 64:20, 79:20,

115:3, 115:14,

115:19, 116:15,

118:20, 118:21,

119:1, 119:3, 120:25,

126:6, 126:7, 127:16,

128:6, 128:11, 138:7,

138:11, 138:15,

138:19, 138:20,

139:3, 139:21,

149:12, 149:14,

149:16, 151:17,

166:8, 167:16

GENETICALLY [4] -

121:2, 138:15,

138:18, 139:14

GENETICIST [6] -

113:17, 115:16,

115:17, 115:18,

115:20, 204:9

GENETICISTS [1] -

79:17

GENETICS [2] -

131:19, 170:7

GENOME [3] -

137:25, 138:3, 138:4

GENOMIC [1] - 64:23

GENOMICS [1] -

113:15

GENOTYPE [1] -

127:8

GENTILE [1] - 34:5

GESTATIONAL [1] -

196:5

GESTATIONALLY

[1] - 178:2

GIVEN [11] - 62:16,

62:25, 64:5, 76:8,

80:19, 91:14, 107:11,

108:21, 109:1,

112:13, 198:3

GLAD [2] - 63:17,

156:15

GLASSES [1] - 122:1

GLAXOSMITHKLIN

E [1] - 63:3

GOAL [5] - 114:13,

114:15, 116:7, 116:8,

116:13

GOD [1] - 111:9

GOD'S [1] - 68:7

GODFREY [1] - 67:8

GOSPEL [2] - 90:19,

90:20

GOVERNMENT [3] -

62:21, 76:22, 119:12

GRADED [1] - 63:11

GRADUATE [1] -

115:5

GRANT [2] - 62:23,

67:7

GRANTS [3] - 61:16,

62:16, 119:11

GRATEFUL [1] -

71:3

GREAT [5] - 22:19,

58:20, 82:25, 85:19,

86:20

GREATER [6] -

38:13, 38:16, 38:21,

39:8, 45:8, 85:20

GREAUX [2] - 36:13,

52:5

GREENSTONE [2] -

2:16, 2:20

GREENWOOD [2] -

7:23, 7:24

GROSS [2] - 132:8,

132:11

GROUNDS [1] - 95:1

GROUP [25] - 30:18,

50:18, 62:12, 68:8,

98:23, 99:16, 99:24,

101:8, 101:12, 104:6,

104:7, 169:25,

183:19, 183:21,

187:13, 191:22,

192:18, 192:19,

193:4, 194:1, 195:20,

195:21, 195:22

GROUPED [5] -

32:11, 104:8, 152:17,

154:7, 193:24

GROUPING [6] -

100:19, 100:23,

101:1, 101:5, 102:19,

160:20

GROUPS [14] -

16:25, 51:6, 179:21,

180:13, 180:15,

180:16, 183:21,

190:21, 190:23,

193:25, 194:1,

195:19, 195:22, 196:2

GROW [1] - 151:12

GROWTH [8] -

127:1, 132:2, 132:10,

150:9, 151:21, 186:6,

186:7, 186:10

GSK [5] - 89:17,

89:18, 89:22, 93:1

GUESS [5] - 108:9,

121:10, 147:9,

165:22, 201:23

GUESSWORK [1] -

13:7

GUIDANCE [4] -

52:15, 99:14, 99:15,

99:18

GUIDE [2] - 85:24,

176:15

GUIDED [1] - 63:9

GUIDELINES [6] -

178:21, 178:22,

202:4, 202:15, 202:22

GUIDEPOSTS [1] -

53:23

GUT [1] - 165:14

GUY [2] - 64:13,

121:25

GUYS [3] - 60:9,

122:6, 137:25

GYNECOLOGISTS

[1] - 34:2

H

HALF [2] - 57:22,

88:8

HALLMARK [2] -

36:4, 36:11

HAND [3] - 81:4,

107:2, 176:11

HANDFUL [1] -

22:14

HANDING [1] -

174:15

HANDLE [1] - 82:22

HAPPY [4] - 3:5, 4:8,

5:19, 58:8

HARD [4] - 5:21,

25:19, 31:5, 176:8

HARDENING [1] -

186:7

HARDER [2] -

200:22, 201:1

HARMONIZATION

[1] - 178:22

HARVARD [8] - 7:8,

62:4, 67:15, 67:16,

67:19, 79:21, 89:6,

112:12

HEAD [9] - 31:9,

35:12, 89:3, 116:18,

185:4, 185:15,

185:17, 185:21,

185:22

HEADED [1] - 113:24

HEALTH [16] - 6:25,

10:3, 21:5, 21:7,

21:14, 22:1, 47:7,

57:7, 66:9, 71:7,

79:22, 117:1, 137:8,

140:13, 142:25,

183:10

HEALY [1] - 91:2

HEAR [16] - 5:11,

27:7, 27:22, 27:23,

28:22, 39:4, 61:17,

75:6, 85:9, 86:9,

88:20, 97:6, 98:9,

99:1, 100:6, 101:11

HEARD [14] - 39:3,

60:10, 66:4, 67:13,

78:17, 84:10, 87:13,

88:2, 91:9, 94:4,

111:6, 201:13, 201:19

HEARING [15] - 1:10,

6:8, 22:11, 22:18,

22:21, 22:25, 23:14,

23:22, 42:21, 59:3,

68:14, 75:5, 85:1,

85:11, 96:5

HEARINGS [5] - 3:9,

9:25, 22:5, 76:18,

94:4

HEART [61] - 7:13,

13:1, 13:2, 50:2,

50:18, 50:19, 50:20,

50:25, 51:6, 56:4,

56:5, 66:23, 66:25,

68:3, 71:18, 80:5,

80:13, 100:16, 108:5,

108:11, 146:7,

156:13, 156:16,

156:17, 158:11,

158:15, 158:16,

158:17, 158:20,

159:5, 159:6, 160:3,

160:11, 160:17,

160:24, 161:9,

161:12, 163:15,

222

163:16, 163:21,

163:23, 163:24,

163:25, 164:2, 164:5,

164:8, 164:11, 165:9,

165:14, 165:17,

165:22, 165:24,

167:6, 168:3, 183:3,

192:23, 200:21,

204:2, 204:24

HEARTBURN [2] -

76:12, 76:13

HEARTS [1] - 156:20

HEAVY [1] - 10:12

HEIM [3] - 2:17,

83:12, 83:17

HELD [3] - 3:10,

43:18, 107:2

HELP [6] - 21:18,

59:21, 96:19, 102:2,

131:3, 143:16

HELPED [1] - 143:15

HELPFUL [5] - 4:24,

72:4, 73:13, 176:10,

176:13

HELPING [3] - 111:2,

115:11, 137:21

HELPS [4] - 65:25,

101:1, 121:14, 139:5

HENCE [1] - 109:21

HERRING [1] - 54:3

HERSELF [6] -

16:19, 45:11, 101:18,

110:11, 110:12,

111:13

HETEROGENEOUS

[1] - 50:19

HETEROGENOUS

[1] - 51:7

HIDE [1] - 110:10

HIERARCHICAL [1] -

136:6

HIERARCHY [1] -

27:8

HIGH [13] - 41:12,

85:7, 94:18, 95:12,

148:15, 157:5,

157:24, 180:18,

183:19, 187:3,

187:14, 202:2, 202:6

HIGHER [3] - 19:19,

80:14, 157:17

HIGHEST [1] - 63:13

HIGHLIGHT [2] -

41:11, 52:25

HIGHLIGHTED [5] -

31:18, 144:9, 192:10,

192:11, 193:4

HIGHLY [4] - 80:18,

108:21, 112:3, 183:8

HILL [30] - 54:2,


54:8, 66:13, 87:15,

87:18, 88:1, 88:6,

88:22, 88:23, 92:20,

93:22, 94:3, 94:12,

94:19, 94:22, 94:23,

95:9, 95:12, 95:14,

95:18, 97:7, 97:18,

101:15, 105:6, 107:5,

109:9, 134:25, 135:8,

145:15

HIRES [1] - 116:23

HISTORICAL [1] -

12:7

HISTORY [1] - 67:22

HOLD [1] - 43:7

HOLDER [1] - 6:19

HOLDING [1] - 7:10

HOLDS [1] - 62:10

HOLE [2] - 160:2,

160:11

HONEST [1] - 68:7

HONOR [52] - 3:3,

5:15, 8:6, 8:21, 9:10,

9:17, 15:14, 21:10,

29:3, 29:16, 31:13,

32:7, 38:22, 39:9,

40:15, 41:8, 41:11,

41:12, 41:15, 41:24,

48:22, 50:3, 53:9,

54:1, 56:23, 57:10,

57:13, 57:15, 57:25,

58:7, 58:21, 59:9,

60:12, 83:1, 83:12,

83:17, 83:25, 87:2,

88:12, 112:7, 112:19,

113:2, 156:14,

161:13, 171:18,

174:10, 175:1,

175:16, 176:16,

176:21, 207:12

HONORABLE [1] -

1:9

HONORS [16] - 8:24,

9:20, 19:9, 24:3,

26:20, 28:16, 29:9,

35:10, 57:8, 60:13,

65:10, 74:18, 84:1,

84:23, 92:10, 113:23

HOOD [6] - 63:18,

63:21, 63:23, 191:12,

191:19, 192:25

HOOPER [3] - 2:11,

9:3, 9:4

HOPE [2] - 135:4,

174:21

HOPEFULLY [1] -

74:9

HORMONE [1] - 91:7

HORRIBLE [1] -

111:16

HOTLY [2] - 14:19,

72:22

HOUR [4] - 57:17,

57:21, 57:22, 83:9

HOURS [1] - 96:7

HOUSEKEEPING [1]

- 9:1

HOUSTON [3] - 1:20,

64:21, 120:2

HUMAN [29] - 14:5,

14:10, 14:11, 27:14,

27:19, 28:9, 34:15,

35:1, 36:15, 36:20,

52:8, 54:18, 65:19,

66:3, 66:18, 116:20,

121:3, 121:5, 122:12,

137:25, 138:3, 138:4,

141:10, 155:4,

172:15, 198:18,

204:18, 204:21

HUMANS [19] -

56:14, 56:19, 82:18,

86:3, 124:25, 168:11,

168:16, 181:15,

193:6, 194:13,

194:21, 194:24,

198:12, 198:13,

199:1, 199:9, 203:17,

206:10

HUNDREDS [3] -

17:25, 63:7, 120:18

HURTING [1] -

111:18

HYDROCHLORIDE

[1] - 1:4

HYOID [1] - 183:12

HYPERTENSION [1]

- 81:17

HYPOTHESES [1] -

29:2

HYPOTHESIS [5] -

46:6, 55:21, 55:22,

88:1, 94:25

HYPOTHESIZED [1]

- 34:5

HYPOTHESIZES [1]

- 56:5

I

I.E [1] - 52:8

IDEA [10] - 75:11,

79:9, 88:2, 94:16,

106:18, 114:12,

116:12, 127:21,

145:11, 174:16

IDEALLY [1] - 45:17

IDENTIFICATION [1]

- 7:12

IDENTIFIED [6] -

32:12, 139:13,

139:18, 164:3, 165:3,

190:16

IDENTIFIES [1] -

144:16

IDENTIFY [10] - 56:2,

56:7, 133:2, 133:7,

138:23, 139:10,

139:21, 178:23,

179:4, 196:10

IDENTIFYING [2] -

144:8, 176:9

IGNORE [6] - 42:2,

107:10, 107:14,

108:9, 108:13, 108:14

IGNORED [1] - 39:22

IGNORING [2] - 30:6,

103:5

II [2] - 182:20, 188:6

III [3] - 186:20, 188:9,

188:11

ILLICIT [1] - 20:7

ILLUSION [1] - 40:5

IMMUNOLOGICAL

[1] - 120:16

IMPACT [31] - 48:15,

49:22, 63:13, 98:8,

98:12, 124:3, 129:12,

131:19, 136:2,

136:14, 142:21,

144:11, 144:17,

145:19, 147:16,

151:23, 158:9,

158:19, 159:7, 160:8,

166:1, 166:4, 166:12,

167:12, 167:20,

169:7, 177:22, 178:2,

183:12, 186:10

IMPACTFUL [1] -

67:21

IMPACTS [10] - 64:7,

113:22, 136:9,

144:16, 145:17,

152:1, 158:3, 160:16,

162:8, 164:24

IMPAIRED [1] - 20:9

IMPLANTATION [2] -

192:4, 192:16

IMPLANTED [1] -

179:24

IMPLEMENT [2] -

135:7, 166:8

IMPLEMENTATION

[1] - 121:12

IMPLEMENTED [1] -

134:25

IMPLICATED [5] -

55:1, 77:4, 110:7,

148:3, 148:6

IMPLICATIONS [1] -

20:5

IMPORTANCE [14] -

10:2, 10:3, 126:21,

140:9, 140:25,

143:19, 147:12,

169:17, 177:19,

187:2, 187:6, 188:15,

192:19, 199:24

IMPORTANT [57] -

3:24, 4:1, 10:6, 13:9,

14:11, 14:14, 15:23,

18:3, 18:7, 18:8, 21:1,

21:17, 23:8, 23:10,

39:1, 39:10, 46:12,

47:10, 48:22, 49:6,

49:9, 50:4, 50:5,

54:24, 61:9, 63:6,

64:1, 66:5, 67:6, 69:3,

71:21, 72:6, 77:14,

81:15, 85:4, 102:1,

102:16, 131:25,

132:4, 132:5, 132:23,

135:16, 138:9,

140:24, 147:9,

147:17, 147:20,

149:10, 150:4,

169:18, 170:15,

186:3, 186:25,

187:22, 191:17,

200:5, 201:22

IMPORTANTLY [5] -

12:2, 25:25, 56:15,

67:20, 196:9

IMPOSSIBLE [1] -

49:12

IMPROPER [1] - 24:9

IN-DEPTH [1] - 10:8

INABILITY [4] - 49:7,

56:7, 148:19, 148:20

INACCURATE [1] -

184:15

INACTIVE [2] -

101:22, 101:24

INADMISSIBLE [1] -

29:13

INAPPLICABLE [1] -

54:4

INAPPROPRIATE [1]

- 22:25

INC [3] - 1:16, 2:10,

2:13

INCENTIVES [1] -

21:20

INCEPTION [1] -

119:18

INCIDENCE [2] -

114:20, 120:19

INCIDENTALLY [3] -

116:3, 117:19, 197:18

INCLUDE [7] - 91:17,

223

132:9, 137:19, 146:1,

148:21, 177:7, 177:22

INCLUDED [6] -

38:10, 68:24, 72:15,

163:12, 166:25, 169:4

INCLUDES [6] -

55:3, 97:19, 104:7,

154:21, 178:12,

186:12

INCLUDING [16] -

10:15, 21:13, 29:18,

30:7, 34:17, 55:11,

64:18, 75:1, 124:2,

124:5, 155:7, 160:19,

160:24, 167:6,

196:13, 200:4

INCOMPATIBLE [2] -

133:14, 133:15

INCOMPLETE [1] -

107:7

INCONSISTENT [8] -

11:3, 27:2, 40:10,

40:18, 41:14, 53:8,

84:10, 186:16

INCORRECT [1] -

195:21

INCREASE [29] -

20:21, 26:7, 34:9,

35:14, 35:15, 36:1,

37:2, 51:5, 98:1,

105:10, 108:8,

133:17, 149:8,

149:20, 149:21,

182:14, 182:15,

187:3, 187:4, 187:5,

190:3, 190:5, 190:6,

190:7, 195:19,

195:23, 200:14,

201:8, 203:5

INCREASED [32] -

18:14, 25:7, 25:10,

36:17, 49:3, 49:15,

51:23, 74:21, 74:22,

79:4, 102:20, 103:17,

104:13, 106:2,

108:11, 110:15,

139:12, 139:24,

142:19, 152:11,

170:13, 179:23,

180:14, 182:23,

183:17, 196:1,

196:24, 196:25,

200:6, 200:10,

200:16, 200:25

INCREASES [10] -

17:13, 32:20, 33:2,

36:7, 37:19, 45:2,

100:24, 133:18,

186:22, 186:23

INCREASING [4] -


40:19, 109:19, 134:7,

169:24

INCREDIBLY [1] -

71:22

INCRIMINATED [1] -

35:1

INDEED [8] - 86:17,

95:7, 95:16, 99:12,

106:25, 107:4,

107:13, 112:13

INDEPENDENT [7] -

12:11, 32:9, 38:20,

39:7, 90:17, 108:16,

109:11

INDEPENDENTLY

[3] - 59:8, 68:11, 74:25

INDICATE [1] - 183:2

INDICATED [3] -

43:5, 192:16, 202:7

INDICATES [1] -

192:12

INDICATION [8] -

26:13, 48:18, 49:12,

49:21, 77:21, 183:14,

198:1

INDICATIONS [1] -

50:2

INDIVIDUAL [2] -

103:8, 166:10

INDIVIDUALS [1] -

127:16

INDUCE [5] - 167:6,

173:19, 173:22,

174:1, 174:3

INDUCED [1] - 121:1

INDUCING [2] -

150:21, 169:15

INDUCTING [1] -

174:7

INDUCTION [1] -

171:14

INDUSTRY [4] -

99:14, 121:22, 138:3,

178:21

INEFFECTIVELY [1]

- 148:17

INEVITABLE [1] -

86:3

INEVITABLY [1] -

145:19

INFAMOUS [1] -

34:25

INFANT [1] - 181:16

INFANTS [2] - 47:5,

108:12

INFECTION [1] -

183:7

INFECTIONS [1] -

190:25

INFECTIOUS [3] -

127:18, 130:23

INFERENCE [1] -

88:14

INFLUENCE [6] -

61:15, 128:17,

130:20, 130:21,

164:4, 183:9

INFLUENCED [1] -

158:17

INFLUENTIAL [1] -

71:22

INFORM [3] - 22:6,

59:21, 139:13

INFORMATION [14] -

17:7, 17:9, 17:12,

24:14, 32:20, 34:3,

39:2, 41:14, 49:11,

57:6, 82:3, 102:16,

191:21, 205:15

INGA [1] - 92:4

INGESTED [2] -

82:19, 206:11

INGRAINED [3] -

89:4, 89:7, 89:9

INHERENTLY [2] -

29:13, 43:10

INHIBIT [3] - 73:9,

158:1, 165:2

INHIBITING [2] -

149:5, 157:16

INHIBITION [2] -

162:2, 167:20

INHIBITORS [3] -

74:13, 143:24, 197:3

INHIBITS [1] -

157:12

INITIAL [1] - 179:20

INITIATE [3] -

129:13, 130:5, 162:20

INJECTIONS [1] -

165:23

INJURIES [1] - 10:15

INJURY [1] - 97:16

INNS [1] - 5:5

INQUIRED [1] - 5:7

INSIDE [1] - 5:3

INSISTENCE [1] -

41:19

INSPIRED [1] - 13:7

INSTANCE [3] -

158:12, 160:4, 169:2

INSTEAD [3] - 30:9,

42:3, 160:1

INSTITUTE [3] -

64:22, 64:23, 113:14

INSTITUTES [3] -

66:9, 113:11, 117:1

INSTITUTION [1] -

7:2

INSTRUCT [1] -

87:24

INSTRUCTIONS [1] -

20:8

INSTRUCTIVE [4] -

31:23, 33:20, 55:14,

104:25

INSTRUCTOR [3] -

67:16, 67:17

INSTRUMENTAL [1]

- 115:10

INSULIN [1] - 139:7

INTELLECTUAL [1] -

79:10

INTEND [2] - 6:11,

9:14

INTENTLY [1] - 29:4

INTERACT [6] -

117:25, 126:15,

126:18, 135:25,

157:10, 166:13

INTERACTION [6] -

71:15, 71:16, 131:18,

135:23, 154:8, 159:7

INTERACTIONS [8] -

71:9, 114:17, 126:16,

130:24, 138:14,

157:8, 157:9, 157:23

INTERACTS [4] -

127:9, 129:19,

129:24, 135:24

INTEREST [4] -

62:11, 120:15,

156:13, 177:25

INTERESTED [6] -

117:17, 154:20,

158:10, 158:11,

159:9, 192:2

INTERESTING [3] -

27:5, 92:23, 94:15

INTERFERE [1] -

149:1

INTERFERENCE [1]

- 100:15

INTERIM [1] - 176:7

INTERNAL [1] -

177:1

INTERNALIZING [1]

- 162:8

INTERNALLY [2] -

76:17, 76:24

INTERNATIONAL [2]

- 62:13, 140:11

INTERPRETATION

[1] - 137:21

INTERPRETED [1] -

51:23

INTERRUPT [2] -

159:23, 164:10

INTERVAL [4] -

38:13, 38:16, 38:21,

39:8

INTERVENTION [1] -

139:5

INTERVIEW [1] -

114:1

INTIMATELY [1] -

70:2

INTRAUTERINE [2] -

124:10, 206:21

INTRODUCE [4] -

9:1, 9:5, 9:13, 113:6

INTRODUCED [1] -

65:16

INTRODUCTION [4]

- 72:15, 136:19,

148:24, 159:10

INVESTIGATING [1]

- 64:7

INVESTIGATORS [1]

- 51:22

INVESTOR [1] -

24:14

INVITATION [1] - 4:6

INVITE [1] - 59:24

INVITED [1] - 4:2

INVOKED [1] - 43:2

INVOKING [1] - 74:3

INVOLVE [1] - 3:18

INVOLVED [2] -

10:4, 54:22

INVOLVING [1] -

124:4

IPAD [1] - 4:21

IRONY [2] - 36:22,

37:3

IRRELEVANT [1] -

90:1

ISLAND [9] - 52:13,

58:25, 59:4, 59:5,

61:21, 72:24, 79:11,

98:21, 110:1

ISSUE [19] - 3:22,

14:18, 15:13, 23:24,

24:11, 38:1, 42:15,

43:7, 48:11, 53:12,

53:17, 59:16, 61:16,

64:1, 72:21, 109:6,

109:8, 164:21

ISSUES [13] - 10:3,

59:7, 62:14, 62:16,

63:1, 63:13, 66:16,

68:12, 76:5, 80:8,

91:15, 95:24, 111:22

ITSELF [21] - 49:4,

49:18, 51:14, 86:16,

88:22, 88:24, 106:20,

107:15, 107:16,

135:20, 148:10,

157:2, 160:6, 162:19,

163:16, 164:1,

224

165:16, 166:2,

167:12, 186:4, 188:25

J

JAMES [4] - 2:11,

68:23, 124:17, 124:19

JELLINEK [1] -

100:23

JIM [1] - 9:3

JIMENEZ [5] -

104:12, 105:13,

106:4, 108:10

JIMINEZ [3] - 41:1,

41:5, 49:25

JIMINEZ-SOLEM [3]

- 41:1, 41:5, 49:25

JOB [1] - 87:7

JOE [5] - 6:2, 6:5,

6:10, 8:2

JOHNSON [1] - 92:5

JOINER [2] - 21:9,

90:23

JOKE [1] - 5:3

JOSEPH [1] - 2:5

JOURNAL [7] -

66:14, 67:3, 99:6,

99:8, 102:7, 102:15,

103:7

JOURNALS [2] -

63:14, 67:24

JR [1] - 1:15

JUDGE [17] - 3:7,

3:14, 3:17, 4:3, 4:5,

4:13, 4:17, 5:17, 5:18,

5:20, 23:11, 84:24,

88:7, 91:8, 92:4,

181:21, 188:7

JUDGE'S [2] - 52:13,

52:14

JUDGES [5] - 3:8,

3:10, 3:25, 21:17,

123:17

JUDGMENT [1] -

90:17

JULY [1] - 108:18

JUMP [1] - 81:4

JUNK [1] - 99:21

JURY [6] - 59:2,

74:9, 92:4, 95:4,

112:4, 112:8

JUSTICE [2] - 21:8,

21:10

JUVENILE [5] -

77:22, 78:1, 151:8,

151:14, 152:1

JUVENILES [2] -

77:22, 77:23


K

KAHN [1] - 91:3

KAHN'S [1] - 91:4

KALLEN [1] - 46:10

KAYE [1] - 2:15

KEEP [1] - 18:3

KEEPS [2] - 157:17,

157:20

KEY [6] - 29:10,

52:3, 52:20, 86:6,

140:22, 141:12

KID [1] - 189:17

KIELER [1] - 81:18

KIMMEL [2] - 153:13,

153:23

KIMMEL'S [1] -

35:16

KIND [22] - 8:25,

16:5, 28:16, 38:9,

44:11, 50:11, 89:8,

89:10, 116:12, 119:4,

138:10, 142:14,

143:9, 143:10,

146:12, 148:10,

157:6, 166:9, 179:5,

185:4, 185:6, 185:21

KINDS [1] - 20:14

KINGDOM [3] -

155:9, 167:4, 169:8

KNOCKOUT [3] -

151:17, 166:15,

166:17

KNOWLEDGE [3] -

17:17, 107:9, 107:10

KNOWN [10] - 7:12,

25:25, 75:21, 81:21,

98:8, 98:11, 172:8,

172:14, 183:9, 204:18

KNOWS [3] - 5:23,

87:14, 111:9

KOREN [1] - 34:24

KORNUM [5] -

49:14, 104:4, 104:8,

105:11, 108:7

KRAMER [1] - 91:17

KREIS [1] - 2:2

L

LAB [30] - 64:14,

114:13, 115:10,

116:2, 116:3, 116:7,

116:23, 117:5,

118:14, 119:19,

120:23, 120:24,

121:17, 121:21,

122:5, 122:15, 125:6,

129:16, 134:12,

134:16, 134:20,

136:23, 137:2,

137:14, 137:19,

138:1, 189:14

LABEL [24] - 28:6,

28:7, 73:7, 74:7, 74:8,

74:9, 74:18, 75:4,

76:2, 78:25, 81:18,

89:21, 145:18, 149:3,

152:6, 152:14,

161:24, 184:11,

184:19, 191:22,

192:12, 195:17,

196:4, 199:8

LABELED [2] -

74:23, 197:1

LABELS [1] - 22:24

LABORATORY [8] -

65:25, 113:25,

116:11, 120:5,

120:25, 121:20,

121:23, 134:12

LACK [1] - 37:10

LACTATION [4] -

6:20, 62:11, 181:12,

181:18

LANDSCAPE [1] -

16:4

LANGUAGE [3] -

6:16, 6:17, 185:8

LARGE [5] - 27:1,

45:22, 46:13, 66:20,

80:19

LARGELY [1] - 132:5

LARGEST [1] - 115:4

LAST [11] - 24:6,

63:24, 67:18, 68:5,

106:22, 110:11,

126:20, 127:4,

155:10, 156:3, 165:22

LATE [2] - 16:21,

192:13

LATE-TERM [1] -

192:13

LATERALITY [5] -

147:25, 167:9, 183:3,

184:4, 184:7

LAUGHED [1] -

185:5

LAUGHING [1] -

110:2

LAUNCH [1] - 60:2

LAW [21] - 1:19,

13:5, 36:14, 51:12,

82:21, 82:22, 84:16,

84:23, 88:5, 89:8,

90:8, 90:12, 90:16,

90:22, 91:4, 91:14,

93:9, 93:24, 95:14,

112:1

LAWYER [1] - 89:7

LAWYERS [5] - 5:5,

5:9, 80:22, 96:14,

207:17

LAYERED [1] -

147:22

LEAD [7] - 1:14,

20:1, 20:17, 99:2,

100:15, 100:18,

100:19

LEADING [4] - 20:3,

62:9, 63:19, 67:24

LEADS [1] - 160:18

LEARN [4] - 4:2, 4:7,

89:4, 89:6

LEAST [9] - 16:11,

43:11, 59:25, 67:25,

68:15, 76:9, 129:16,

171:24, 204:2

LEAVE [3] - 4:20,

15:6, 100:1

LEAVING [1] - 160:2

LEBER [2] - 196:21,

197:4

LEFT [10] - 68:2,

92:13, 106:21,

121:19, 135:19,

147:25, 148:2,

182:24, 183:17,

185:17

LEGAL [3] - 22:3,

52:4, 84:7

LEGITIMATE [2] -

73:22, 81:3

LENGTH [1] - 57:16

LESS [5] - 30:10,

37:5, 39:23, 44:22,

56:19

LETHAL [1] - 54:15

LETHALITY [2] -

133:20, 134:8

LETTER [3] - 74:10,

162:13, 196:20

LETTERS [1] - 4:17

LEVEL [24] - 28:5,

28:11, 72:1, 74:2,

74:5, 130:6, 133:19,

134:2, 135:1, 135:24,

136:8, 136:10,

136:17, 137:23,

145:13, 145:16,

154:20, 158:21,

163:8, 168:2, 168:4,

184:12

LEVELS [8] - 148:8,

149:4, 149:6, 149:13,

149:17, 149:19,

165:7, 190:5

LEVIN [25] - 5:25,

7:7, 8:2, 29:14, 56:9,

56:11, 56:15, 60:11,

60:17, 61:5, 67:13,

70:13, 71:11, 71:22,

73:20, 76:16, 79:10,

85:3, 92:18, 98:10,

147:9, 155:11, 203:23

LEVIN'S [2] - 67:20,

146:23

LEVINE [1] - 76:3

LEXAPRO [4] -

88:23, 90:5, 163:1,

199:20

LIABILITY [2] - 1:4,

21:19

LIABLE [1] - 107:8

LIBERAL [1] - 85:16

LIFE [9] - 10:2,

19:18, 21:13, 56:18,

60:13, 123:9, 133:14,

147:19, 147:21

LIGANDS [1] -

135:25

LIKELIHOOD [1] -

100:25

LIKELY [6] - 37:15,

45:5, 45:13, 45:23,

87:24, 189:20

LIKEWISE [5] -

153:5, 167:15,

168:20, 170:8, 172:19

LILLY [2] - 78:5,

150:7

LIMB [5] - 103:13,

172:17, 173:11,

206:25

LIMIT [1] - 57:4

LIMITATION [2] -

49:7, 86:16

LIMITATIONS [4] -

45:19, 86:12, 103:4,

105:18

LIMITED [4] - 30:2,

124:5, 132:11, 205:11

LINE [8] - 16:22,

16:23, 20:23, 25:15,

26:3, 26:8, 37:24,

107:24

LINK [1] - 203:10

LINKED [2] - 20:21,

26:6

LIP [1] - 106:10

LISA [1] - 3:7

LIST [6] - 34:25,

66:7, 124:7, 160:13,

173:4, 206:16

LISTED [2] - 191:20,

197:21

LISTEN [1] - 96:21

LISTENING [2] -

29:3, 61:20

LISTS [3] - 52:18,

225

80:2, 81:13

LITERALLY [1] -

166:22

LITERATELY [1] -

63:10

LITERATURE [46] -

30:15, 38:2, 39:12,

45:17, 50:24, 51:13,

51:14, 51:15, 55:24,

62:1, 67:4, 69:20,

76:20, 76:21, 76:23,

77:4, 77:7, 78:15,

86:22, 88:19, 99:4,

99:24, 102:5, 104:17,

108:6, 109:8, 135:22,

145:6, 145:7, 145:12,

146:20, 151:2,

151:22, 153:15,

153:21, 154:19,

154:20, 156:2, 156:7,

161:19, 167:24,

168:22, 170:16,

172:18, 173:10,

176:25

LITHIUM [1] - 80:3

LITIGATION [39] -

1:4, 15:25, 16:11,

17:25, 25:11, 26:21,

30:21, 35:24, 41:23,

42:6, 54:21, 55:16,

55:23, 56:21, 60:24,

61:1, 61:13, 69:19,

69:21, 69:23, 70:6,

88:8, 88:23, 90:10,

93:2, 93:4, 93:10,

93:14, 93:23, 94:1,

107:23, 108:15,

108:17, 109:11,

125:13, 125:17,

125:21, 125:25

LITIGATION-

DRIVEN [2] - 26:21,

93:14

LIVE [2] - 27:22,

192:6

LIVES [2] - 93:11,

110:17

LIVING [4] - 27:20,

27:21, 96:11, 113:8

LLC [3] - 1:13, 2:16,

2:20

LLP [3] - 2:5, 2:9,

2:12

LOGICALLY [2] -

136:18, 197:9

LOGO [1] - 106:22

LONDON [1] - 5:4

LONG-TERM [1] -

162:23

LONG-TIME [1] -


113:17

LONGSHORE [2] -

74:11, 196:21

LOOK [107] - 11:17,

14:25, 15:2, 15:3,

15:12, 17:8, 18:8,

18:22, 19:8, 19:9,

19:10, 25:19, 27:10,

28:6, 30:10, 33:18,

33:19, 33:22, 37:17,

39:1, 39:11, 40:22,

42:17, 42:25, 43:9,

44:2, 44:6, 45:4, 50:5,

53:6, 53:14, 53:19,

59:17, 59:20, 65:14,

65:16, 65:17, 71:14,

71:15, 71:16, 71:18,

76:19, 76:20, 78:14,

81:23, 81:24, 84:17,

85:11, 88:17, 88:18,

91:6, 94:16, 95:10,

95:25, 96:1, 96:19,

97:20, 98:5, 98:20,

99:9, 99:12, 99:24,

101:2, 102:8, 102:14,

104:25, 105:7,

106:17, 109:8,

109:13, 119:2, 119:3,

130:16, 131:13,

132:8, 132:12, 133:3,

133:24, 134:19,

135:19, 135:22,

136:15, 138:7,

138:13, 139:3,

144:20, 151:16,

152:22, 154:18,

155:6, 166:23, 168:8,

172:17, 176:3, 178:5,

180:9, 181:20, 190:6,

192:5, 192:19,

194:11, 203:10

LOOKED [46] -

31:23, 31:24, 32:1,

32:17, 39:23, 48:24,

55:7, 59:16, 74:25,

86:12, 87:6, 96:18,

101:16, 101:17,

102:5, 102:9, 102:22,

103:21, 103:22,

103:23, 104:16,

104:17, 104:20,

105:7, 105:10,

105:11, 105:12,

106:22, 110:8,

142:21, 143:4,

151:24, 158:5,

161:23, 164:23,

169:19, 186:15,

199:5, 200:8, 200:22,

200:23, 201:1

LOOKING [49] -

15:11, 18:15, 18:24,

32:24, 44:10, 47:9,

47:18, 66:17, 73:19,

76:5, 76:22, 90:16,

93:18, 102:20,

103:15, 105:23,

109:6, 114:16,

114:19, 114:22,

115:1, 115:7, 117:14,

118:20, 120:6, 120:9,

120:15, 126:16,

127:5, 129:21, 130:1,

132:25, 136:5, 136:8,

140:14, 140:17,

153:23, 154:25,

155:1, 155:2, 157:1,

157:7, 160:15,

161:19, 162:17,

167:3, 169:21,

180:11, 199:4

LOOKS [4] - 76:23,

99:4, 102:23, 105:19

LOOP [1] - 171:17

LOOPING [1] -

163:25

LORENZO [1] -

32:24

LOS [1] - 2:16

LOSE [1] - 190:23

LOSS [23] - 160:18,

179:23, 180:14,

181:2, 181:17,

184:20, 184:21,

187:1, 188:17,

190:15, 190:21,

190:24, 191:4, 191:6,

191:7, 192:8, 192:15,

193:2, 193:11, 194:3,

202:7

LOST [2] - 192:7,

202:14

LOUIK [8] - 46:1,

51:21, 51:24, 102:22,

103:7, 105:12, 106:4

LOUISIANA [1] -

1:19

LOW [11] - 149:13,

149:17, 149:19,

160:22, 160:23,

166:18, 180:18,

187:3, 187:13,

201:24, 202:3

LOWER [4] - 56:18,

109:20, 109:21, 169:2

LOWERING [1] -

134:3

LOWEST [1] -

133:25

LUMP [6] - 14:24,

30:22, 50:9, 50:12,

50:24, 53:19

LUMPED [8] - 30:18,

30:24, 31:15, 31:16,

31:17, 32:11, 38:18,

39:24

LUMPER [3] - 30:24,

100:1, 100:3

LUMPERS [1] -

30:22

LUMPING [6] -

11:22, 33:16, 50:8,

50:22, 100:5, 100:19

LUMPS [1] - 11:21

LUMPY [2] - 100:1,

100:5

LUNCH [7] - 57:18,

58:4, 58:8, 58:9,

58:19, 83:9, 83:13

LUNCHEON [1] -

83:19

LUNG [1] - 48:5

LUST [1] - 36:5

M

MADISON [1] - 2:9

MAGNITUDE [1] -

87:24

MAIN [2] - 2:3, 10:25

MAINTAIN [1] - 3:14

MAJOR [18] - 12:20,

18:10, 18:15, 18:16,

25:7, 25:8, 33:2,

33:11, 33:15, 34:9,

35:2, 49:19, 82:2,

99:7, 104:21, 109:20,

182:25, 205:13

MAJORITY [5] -

47:14, 47:17, 115:5,

118:7, 118:9

MAKER [1] - 63:3

MAKEUP [2] - 126:8,

127:16

MALES [1] - 177:23

MALFORMATION [9]

- 56:4, 97:23, 98:1,

132:2, 133:6, 181:10,

181:25, 187:8, 188:1

MALFORMATIONS

[61] - 12:20, 19:7,

19:11, 19:12, 20:22,

25:8, 26:7, 33:3, 33:7,

33:12, 33:16, 34:9,

34:22, 36:1, 37:2,

37:23, 40:19, 49:4,

49:16, 50:1, 97:14,

101:6, 101:7, 104:5,

104:6, 104:21, 108:9,

108:11, 109:20,

118:4, 124:4, 126:23,

130:15, 132:7, 132:8,

132:11, 132:25,

133:12, 148:21,

149:15, 153:5,

153:11, 160:24,

167:15, 167:22,

169:24, 170:1,

172:22, 172:25,

173:3, 173:5, 174:4,

178:24, 179:11,

181:8, 182:17,

189:24, 194:12,

194:20, 199:5

MALFORMED [1] -

187:8

MALM [4] - 41:1,

41:5, 46:13, 49:19

MAMMAL [1] - 27:23

MAMMAL-TYPE [1] -

27:23

MAMMALS [3] -

56:14, 56:19, 169:7

MAMMILLARY [1] -

167:2

MAN [1] - 169:7

MANAGER [1] - 7:1

MANIFESTATION [1]

- 133:22

MANIFESTATIONS

[2] - 132:1, 133:17

MANNER [2] - 92:1,

127:9

MANUAL [6] - 36:23,

44:9, 48:2, 85:25,

86:2

MANUFACTURED

[1] - 21:15

MAP [1] - 137:25

MARGARET [2] -

74:11, 196:21

MARGINS [1] - 134:5

MARGOLISA [1] -

103:15

MARGULIS [3] -

34:16, 34:17

MARK [10] - 1:15,

2:8, 6:2, 6:3, 6:8,

7:25, 8:2, 8:4, 82:24,

171:21

MARKET [17] - 1:13,

1:23, 12:9, 12:24,

12:25, 15:24, 18:5,

18:15, 18:17, 18:18,

19:11, 28:1, 31:21,

110:20, 177:13,

189:18

MARKETED [2] -

74:17, 75:22

MARKETING [1] -

77:16

226

MASSACHUSETTS

[2] - 119:1, 119:16

MASSIVELY [1] -

94:18

MASTERS [1] - 62:7

MATERIAL [2] - 27:5,

85:10

MATERIALITY [1] -

24:12

MATERNAL [15] -

34:21, 49:8, 49:21,

102:17, 131:12,

149:10, 149:17,

150:1, 160:22,

166:18, 201:25,

202:3, 202:4, 202:6,

202:11

MATH [1] - 195:2

MATHEMATICALLY

[1] - 195:5

MATRIX [3] - 24:8,

24:9, 24:17

MATRIXX [1] - 87:12

MATTEO [1] - 9:6

MATTER [9] - 26:14,

79:7, 91:20, 101:10,

142:18, 143:3,

170:18, 183:19, 208:1

MATTERS [3] - 92:3,

93:8, 143:20

MATTHEW [2] -

112:23, 113:7

MAXIMUM [1] - 28:9

MCGILL [2] - 6:14,

62:6

MD'S [1] - 120:4

MDL [5] - 1:3, 4:1,

87:4, 91:7, 123:7

MEAN [23] - 11:6,

17:1, 69:11, 89:23,

106:8, 115:1, 119:8,

119:24, 129:20,

130:10, 133:21,

140:23, 141:14,

141:24, 142:8, 160:4,

166:7, 166:21, 179:1,

182:11, 195:2, 200:22

MEANING [3] -

22:17, 117:20, 143:4

MEANINGFUL [2] -

14:3, 15:19

MEANS [16] - 14:8,

14:9, 18:23, 28:24,

60:25, 91:19, 127:14,

127:15, 128:21,

131:20, 146:3,

166:22, 186:2, 192:8,

197:12

MEANT [5] - 101:19,

104:23, 185:4, 185:9,


188:9

MEASURE [1] -

183:25

MEASURES [1] -

49:22

MECHANICAL [1] -

10:21

MECHANISM [31] -

27:6, 42:22, 54:10,

56:2, 57:2, 65:14,

73:15, 73:16, 78:7,

78:11, 78:16, 98:13,

99:2, 99:20, 105:25,

117:24, 129:8,

141:16, 142:1, 142:6,

142:7, 142:17,

144:11, 144:21,

144:22, 150:12,

150:22, 152:22,

153:6, 154:7, 162:4

MECHANISM-

RELATED [2] - 78:7,

78:11

MECHANISMS [15] -

64:12, 68:2, 98:15,

115:24, 118:1,

126:14, 129:11,

141:7, 151:4, 155:6,

155:8, 167:4, 168:25,

172:23

MECHANISTIC [3] -

126:16, 141:3, 143:5

MEDICAL [19] - 6:24,

12:19, 17:17, 29:19,

29:21, 30:1, 32:10,

51:13, 51:15, 62:5,

72:19, 89:4, 93:12,

102:5, 119:23,

119:24, 120:2, 120:3,

173:9

MEDICATION [3] -

26:14, 139:23, 183:23

MEDICATIONS [8] -

6:19, 21:2, 62:10,

62:12, 79:23, 80:4,

154:2, 204:10

MEDICINE [17] - 7:8,

7:22, 10:3, 21:23,

29:22, 31:20, 43:13,

64:20, 64:23, 66:10,

67:22, 95:9, 99:6,

99:8, 102:7, 102:15,

103:8

MEDICINES [3] -

30:25, 43:15, 49:10

MEDIUM [3] -

180:18, 187:3, 187:13

MEEK [1] - 140:8

MEET [5] - 9:3,

23:25, 24:1, 113:19,

116:12

MEETING [3] -

57:18, 64:6, 109:21

MEETS [1] - 77:16

MEMBER [7] - 32:16,

42:12, 53:22, 78:21,

111:14, 119:19,

152:18

MEMBERS [6] - 6:9,

9:2, 79:3, 140:11,

140:14, 152:9

MEMBERSHIP [1] -

106:24

MEMO [1] - 171:8

MEN [1] - 19:19

MENTION [3] - 55:5,

55:7, 82:20

MENTIONED [11] -

63:16, 131:25,

157:19, 162:5, 166:6,

167:2, 181:24, 183:6,

186:4, 190:19, 195:18

MENTOR [1] -

113:17

MERELY [2] - 28:24,

94:25

MERRILL [1] - 36:6

MERRILL-DOW [1] -

36:6

MESODERMAL [1] -

159:18

MESSAGES [1] -

148:16

MET [3] - 9:6,

113:20, 122:18

META [2] - 33:4,

37:22

META-ANALYSIS [2]

- 33:4, 37:22

METABOLIC [1] -

144:3

METABOLISM [3] -

139:18, 144:5, 144:8

METACARPALS [1] -

186:12

METHOD [5] - 22:11,

40:11, 134:24,

140:16, 140:17

METHODOLOGIC

[1] - 104:24

METHODOLOGICA

L [6] - 10:9, 29:11,

29:24, 91:19, 95:24,

105:17

METHODOLOGICA

LLY [1] - 10:16

METHODOLOGIES

[2] - 30:17, 60:5

METHODOLOGY

[42] - 11:25, 23:1,

51:16, 52:9, 52:10,

54:1, 59:1, 59:18,

59:22, 60:2, 61:5,

63:9, 65:12, 68:16,

68:18, 68:19, 68:22,

68:25, 70:8, 72:18,

85:1, 85:3, 85:4, 85:5,

85:13, 86:15, 88:25,

90:2, 92:21, 96:3,

101:4, 111:16,

112:10, 123:11,

123:12, 123:20,

137:4, 156:16,

156:19, 171:23, 172:3

METHODS [1] -

153:2

MICE [4] - 168:8,

178:15, 194:12, 195:6

MICHAEL [1] - 7:7

MICROTHALMIA [2]

- 181:9, 181:23

MICROTIA [1] -

173:4

MIDDLE [2] - 38:19,

121:25

MIGHT [11] - 3:12,

8:16, 33:20, 39:14,

44:12, 48:6, 55:1,

95:8, 170:11, 174:22,

174:23

MIGRATE [1] - 165:7

MIGRATING [1] -

148:23

MIGRATION [5] -

146:1, 148:22,

158:19, 164:3, 167:13

MIKE [1] - 76:16

MILESTONES [1] -

68:4

MILLIONS [2] -

22:15, 128:1

MILUNSKY [3] -

79:18, 80:1, 204:9

MIND [3] - 18:4,

107:22, 193:22

MINE [1] - 58:8

MINIMAL [1] - 202:10

MINIMUM [2] - 53:23,

69:16

MINORITY [1] -

36:10

MINUTE [11] - 9:12,

12:4, 25:5, 39:10,

43:22, 53:1, 61:18,

78:4, 97:21, 98:6,

175:8

MINUTES [4] - 57:17,

57:21, 58:11, 83:6

MISAPPROPRIATE

LY [1] - 198:3

MISCONDUCT [1] -

61:23

MISLEADING [2] -

111:17

MISS [3] - 62:2,

63:17, 73:25

MISSING [1] - 33:9

MITCHELL [3] - 43:3,

43:4, 100:12

MITCHELL'S [1] -

35:16

MODE [1] - 141:11

MODEL [5] - 149:12,

155:13, 160:23, 169:5

MODELS [18] -

115:3, 115:6, 115:14,

116:14, 116:15,

116:16, 116:17,

117:15, 120:7, 121:3,

121:4, 166:8, 167:16,

168:15, 168:18, 177:8

MODERN [1] - 21:13

MODES [2] - 129:11,

141:6

MODIFIED [2] -

107:8, 121:2

MODIFIER [1] -

115:4

MODIFIERS [3] -

114:19, 115:1, 138:12

MOLECULAR [20] -

65:17, 67:13, 68:1,

70:18, 71:15, 71:25,

72:16, 134:19,

135:24, 136:10,

139:4, 141:8, 154:22,

157:7, 157:9, 159:11,

161:7, 161:18, 163:3,

164:21

MOLECULARLY [1]

- 161:4

MOLECULE [7] -

65:16, 135:19,

145:22, 147:18,

153:8, 169:3

MOLECULES [3] -

15:16, 126:15, 161:20

MOLLY [1] - 9:6

MOLMOL [1] -

151:17

MOM [5] - 189:6,

189:8, 202:18,

202:19, 202:24

MOMENT [2] - 16:4,

31:19

MOMS [3] - 47:8,

188:22

MONDAY [2] - 1:6,

57:18

MONEY [6] - 61:15,

227

62:23, 62:25, 80:21,

96:13, 107:23

MONITORING [2] -

118:24, 119:10

MONTREAL [4] -

6:21, 29:21, 62:8,

63:5

MORNING [29] - 3:2,

3:3, 4:5, 5:15, 5:16,

5:17, 5:18, 8:24, 9:8,

9:9, 9:20, 29:9, 60:4,

60:19, 60:22, 63:16,

64:13, 84:11, 86:1,

88:2, 89:13, 90:15,

91:10, 92:9, 96:22,

111:7, 135:5, 171:8,

175:24

MORPHOGENESIS

[1] - 148:5

MORPHOLOGICAL

[1] - 34:3

MORPHOLOGY [1] -

151:21

MORPHY [1] - 9:6

MORTALITY [1] -

142:20

MOST [36] - 5:6,

15:7, 17:23, 37:14,

56:15, 63:4, 63:25,

64:2, 65:5, 66:6,

67:10, 67:20, 67:21,

67:23, 69:3, 76:12,

79:16, 86:2, 97:5,

102:24, 103:24,

103:25, 105:14,

111:20, 114:6,

126:11, 127:22,

147:20, 150:5,

164:16, 170:15,

183:12, 196:7, 196:9

MOSTLY [1] - 67:14

MOTHER [8] - 20:18,

54:16, 131:6, 131:19,

148:25, 201:16,

202:14

MOTHER'S [3] -

131:8, 188:19, 189:5

MOTHERS [3] - 35:3,

47:19, 108:12

MOTION [1] - 3:17

MOTOR [2] - 58:2,

58:3

MOUSE [6] - 115:6,

116:15, 116:17,

121:2, 121:4

MOUSES [1] -

194:19

MOVE [6] - 4:20,

9:18, 83:13, 157:6,

157:13, 164:21


MOVED [2] - 198:9,

200:9

MOVEMENT [1] -

146:2

MULTI [1] - 46:6

MULTI-

HYPOTHESIS [1] -

46:6

MULTIFACTORIAL

[1] - 84:18

MULTIGENERATIO

N [1] - 178:5

MULTIGENERATIO

NAL [1] - 178:6

MULTIPLE [15] -

45:17, 46:11, 46:21,

51:18, 51:19, 97:14,

100:11, 105:23,

106:6, 117:22,

118:11, 132:22,

145:16, 169:22, 172:9

MUST [11] - 23:25,

24:5, 24:22, 39:13,

43:25, 52:9, 74:23,

94:24, 107:22,

107:23, 197:1

MUSTER [1] - 28:17

MUTANT [5] -

151:16, 151:20,

166:6, 166:7, 166:15

MUTANTS [2] -

165:19, 181:14

MUTATE [2] - 166:9,

166:11

MUTATION [2] -

186:8, 186:9

MUTATIONS [2] -

7:13, 136:1

MYLES [1] - 37:21

MYLEY [1] - 33:4

MYRIAD [2] - 13:1

N

NAKHAI [1] - 203:4

NAKHAI-POUR [1] -

203:4

NAME [7] - 9:21,

113:1, 113:7, 165:25,

166:2, 166:3, 173:15

NAMED [4] - 68:23,

69:13, 79:18, 153:12

NANOMOLAR [1] -

158:1

NAST [12] - 1:12,

5:15, 5:17, 5:19, 6:5,

8:15, 8:21, 57:15,

57:23, 58:5, 62:2

NASTLAW [1] - 1:13

NATAL [1] - 184:21

NATIONAL [8] - 66:9,

67:9, 116:25, 118:16,

118:18, 118:22,

119:9, 120:17

NATIVE [1] - 6:15

NATURE [5] - 67:23,

130:21, 131:11,

169:6, 202:2

NCC [1] - 163:13

NEARLY [1] - 19:21

NECESSARILY [6] -

38:17, 89:3, 92:2,

93:20, 167:1, 195:10

NECESSARY [5] -

74:13, 94:6, 111:7,

179:4

NEED [16] - 36:3,

36:20, 36:21, 36:24,

50:11, 58:12, 72:4,

77:25, 78:1, 89:9,

100:20, 102:2,

110:18, 111:18,

111:24, 176:18

NEEDING [1] - 89:11

NEEDS [3] - 72:18,

85:14, 131:21

NEGATIVE [2] -

49:22, 93:14

NEGATIVES [1] -

195:10

NEONATAL [1] -

195:24

NERVOUS [4] -

124:13, 173:5, 174:3,

207:8

NET [3] - 160:10,

160:12

NETWORK [2] -

67:9, 109:3

NEURAL [18] -

100:15, 100:16,

100:17, 105:22,

115:11, 158:14,

160:18, 163:13,

163:14, 164:3, 164:7,

164:25, 165:4,

167:11, 185:13,

185:14, 185:20,

192:22

NEUROLOGICALL

Y [1] - 144:15

NEURON [1] -

157:18

NEURONAL [1] -

144:16

NEURONS [2] -

157:14, 162:4

NEURONTIN [2] -

87:1, 87:2

NEVER [7] - 47:16,

54:24, 54:25, 94:12,

100:2, 111:5, 185:20

NEW [17] - 2:10,

16:3, 22:23, 25:18,

25:20, 25:22, 32:1,

76:21, 95:8, 99:6,

99:8, 102:7, 102:15,

103:7, 107:14, 188:22

NEWBORN [1] -

81:17

NEWPORT [1] - 1:17

NEWS [1] - 52:12

NEXT [20] - 6:22, 9:3,

10:7, 18:20, 24:20,

46:22, 130:7, 136:8,

145:20, 157:6, 158:8,

158:20, 160:13,

180:20, 182:20,

184:23, 185:23,

186:19, 186:20, 188:6

NICE [1] - 83:15

NIGHT [1] - 106:22

NIH [2] - 119:10,

119:14

NIKFAR [1] - 80:13

NINE [2] - 69:16,

125:11

NINTH [1] - 36:5

NOAEL [1] - 134:1

NOBEL [1] - 166:9

NOBODY [3] - 60:4,

69:17, 110:19

NOMINAL [1] - 46:20

NONE [4] - 12:21,

33:14, 202:5

NONPROFIT [1] -

117:7

NONRANDOM [1] -

46:25

NONRANDOMIZED

[1] - 49:13

NONRODENT [2] -

168:12, 194:17

NONSIGNIFICANT

[1] - 88:14

NONSUBSTANTIV

E [1] - 8:8

NONZOLOFT [3] -

11:14, 11:17, 31:1

NORMALLY [1] -

138:22

NORTH [1] - 66:12

NORTHERN [1] -

92:5

NORWEGIAN [2] -

120:9, 120:12

NOTABLY [1] -

183:12

NOTED [2] - 20:20,

26:6

NOTES [2] - 85:9,

176:11

NOTHING [14] - 23:1,

32:1, 55:23, 69:24,

75:16, 85:23, 87:25,

91:1, 100:4, 101:3,

107:19, 108:1

NOTICE [1] - 84:3

NOTION [2] - 36:6,

42:8

NTD [2] - 185:7,

185:13

NUMBER [29] -

18:25, 27:1, 45:20,

45:22, 46:13, 48:21,

50:14, 53:10, 54:5,

74:21, 80:7, 80:19,

101:9, 108:22,

121:23, 143:21,

177:21, 181:11,

182:14, 182:21,

183:11, 187:19,

190:7, 192:4, 192:6,

193:8, 201:12, 203:21

NUMBERS [6] - 45:1,

179:10, 186:24,

190:6, 191:19, 196:25

NUMEROUS [2] -

104:7, 104:13

NUTRACEUTICALS

[2] - 117:16, 139:6

NUTRITION [2] -

20:8, 115:2

NUTRITIONAL [5] -

7:4, 114:19, 114:25,

115:4, 139:20

NY [1] - 2:10

O

O'CLOCK [3] - 58:4,

83:9, 83:10

O'DONNELL [1] -

2:12

OAKLEY [1] - 67:8

OATH [2] - 33:12,

44:2

OBESITY [1] -

151:19

OBJECTIONS [1] -

8:18

OBSERVABLE [2] -

133:19, 134:2

OBSERVATIONAL

[1] - 107:7

OBSERVE [1] -

80:16

OBSERVED [3] -

45:24, 46:15, 95:1

OBSERVING [1] -

228

199:11

OBSTETRICIANS [1]

- 34:1

OBSTRUCTIONS [1]

- 103:13

OBTAIN [1] - 84:20

OBVIOUSLY [1] - 8:6

OCCASIONS [1] -

117:9

OCCUR [5] - 50:21,

70:23, 128:23, 196:8,

202:10

OCCURRED [2] -

46:7, 202:8

OCCURS [2] - 101:9,

103:19

OCTOBER [1] -

109:1

ODD [2] - 95:7, 100:4

ODDS [6] - 88:18,

97:20, 104:9, 104:19,

109:14, 194:13

OFFERING [1] - 52:7

OFFICIAL [2] - 1:22,

208:5

OFFSPRING [2] -

34:23, 149:15

OFFSPRING'S [1] -

149:16

OFTEN [8] - 13:18,

30:4, 47:12, 147:20,

155:6, 166:8, 187:9,

201:24

OLD [2] - 60:16,

114:4

OLMSTEN [2] -

91:22, 92:1

OMPHALOCELE [3]

- 52:1, 102:19, 103:11

ONCE [3] - 141:11,

141:15, 187:1

ONE [117] - 3:21,

3:22, 4:15, 5:8, 12:22,

14:17, 16:16, 17:5,

17:10, 18:24, 19:21,

23:8, 24:6, 24:24,

27:13, 32:6, 35:24,

37:13, 38:20, 39:6,

44:12, 44:20, 47:12,

49:19, 50:21, 51:20,

59:5, 60:11, 60:23,

61:4, 61:17, 62:9,

63:4, 63:7, 63:18,

63:21, 64:1, 64:25,

65:1, 65:5, 65:20,

66:14, 66:16, 67:6,

67:10, 67:24, 68:4,

68:8, 68:9, 68:10,

68:21, 71:21, 72:12,

73:8, 74:16, 75:10,


78:10, 78:11, 78:21,

78:22, 79:16, 80:2,

80:11, 81:10, 81:12,

82:16, 83:9, 90:2,

90:6, 93:16, 93:17,

93:18, 94:6, 97:4,

97:16, 99:19, 104:19,

109:14, 110:6,

115:13, 117:22,

118:10, 121:13,

126:10, 127:4, 127:6,

131:4, 132:15,

141:24, 144:9,

144:12, 145:17,

146:2, 147:5, 153:2,

155:10, 157:24,

170:17, 173:12,

173:17, 174:7,

179:20, 180:4,

180:17, 181:6, 182:2,

183:20, 186:11,

186:20, 188:3,

193:14, 195:7,

199:14, 201:13,

204:1, 204:7

ONES [11] - 21:22,

102:4, 102:25,

103:23, 103:24,

104:15, 141:21,

157:25, 166:14,

199:23

ONGOING [4] -

117:13, 118:19,

119:17, 119:18

OPEN [1] - 107:15

OPENING [9] - 5:13,

8:7, 9:22, 10:24,

57:15, 58:19, 96:5,

142:13, 152:5

OPENINGS [3] - 8:9,

9:12, 9:19

OPENS [1] - 3:1

OPERATE [2] -

93:11, 98:11

OPERATES [1] -

91:5

OPINE [1] - 57:2

OPINED [2] - 54:24,

56:25

OPINES [2] - 50:12,

56:9

OPINION [50] - 11:7,

11:9, 11:10, 21:3,

23:6, 40:13, 41:7,

42:2, 42:5, 52:7, 63:1,

67:1, 75:19, 77:3,

80:22, 84:14, 87:1,

88:9, 89:11, 90:6,

91:24, 93:23, 96:14,

97:8, 97:9, 97:10,

98:21, 104:1, 106:14,

106:19, 107:15,

107:23, 108:16,

108:22, 109:17,

110:10, 110:13,

111:14, 112:6,

123:25, 124:8, 147:4,

169:18, 169:19,

171:9, 172:10,

189:19, 206:8, 206:19

OPINIONS [37] -

10:16, 12:2, 22:12,

23:19, 25:2, 26:21,

27:2, 29:12, 30:6,

32:8, 39:19, 41:15,

54:11, 54:20, 55:14,

55:25, 56:12, 56:21,

58:25, 59:7, 60:24,

61:2, 69:23, 94:9,

103:2, 108:15,

108:16, 110:5, 112:3,

122:23, 123:2, 123:3,

123:24, 124:14, 172:5

OPPORTUNITY [4] -

9:3, 55:13, 91:14,

112:9

OPPOSED [2] - 36:8,

39:5

OPPOSITE [4] -

42:5, 93:5, 93:13,

112:2

OPPOSITION [1] -

22:13

ORAL [1] - 55:24

ORALLY [1] - 157:5

ORDER [18] - 6:12,

6:22, 6:23, 7:6, 27:24,

35:19, 88:11, 116:20,

124:23, 139:20,

141:6, 145:15,

157:15, 168:12,

178:23, 179:3,

182:15, 195:8

ORGAN [17] - 65:18,

71:17, 72:16, 97:14,

100:11, 101:9,

102:20, 118:11,

118:12, 124:5,

126:13, 128:19,

141:9, 158:22,

158:25, 161:5, 168:2

ORGAN/TISSUES

[1] - 130:8

ORGANISM [6] -

130:14, 130:24,

136:14, 160:13,

160:15, 160:16

ORGANISMS [5] -

136:15, 155:13,

155:14, 169:2, 169:4

ORGANIZATION [15]

- 12:18, 17:6, 32:15,

32:19, 63:20, 71:7,

135:2, 136:6, 137:8,

137:24, 140:13,

154:21, 154:22,

158:21

ORGANIZATIONS

[6] - 12:11, 31:25,

32:4, 33:10, 52:15,

117:8

ORGANIZE [1] -

135:18

ORGANIZED [1] -

135:1

ORGANOGENESIS

[8] - 100:5, 100:20,

101:12, 103:19,

105:24, 106:12,

178:12, 196:7

ORGANS [9] - 7:14,

68:3, 97:24, 100:7,

106:2, 130:13,

136:12, 136:13,

165:11

ORIGINAL [1] -

62:14

ORIGINALLY [1] -

68:22

OSSIFICATION [6] -

183:11, 185:24,

185:25, 186:6,

186:12, 201:5

OTHERWISE [3] -

73:23, 111:8, 138:21

OTIS [7] - 17:6,

32:14, 32:15, 32:16,

32:17, 37:12

OTTAWA [1] -

108:25

OTTOWA [1] -

109:18

OUTCOME [43] -

15:13, 39:5, 42:14,

49:22, 53:11, 53:16,

53:17, 53:20, 65:11,

70:21, 118:10,

134:23, 134:24,

135:6, 135:10,

135:18, 135:21,

137:7, 137:10, 140:4,

140:16, 141:16,

141:21, 141:22,

142:24, 143:4,

145:14, 153:8,

154:13, 155:4,

155:14, 156:8,

156:24, 163:4,

166:24, 167:23,

171:1, 171:7, 171:18,

175:19, 187:25,

193:14, 203:9

OUTCOMES [23] -

20:12, 31:14, 38:11,

38:12, 38:15, 38:19,

39:6, 42:1, 50:11,

61:11, 118:3, 129:14,

132:9, 132:13,

132:15, 140:15,

140:18, 179:10,

180:5, 180:11, 188:3,

206:16

OUTFLOW [8] -

103:12, 158:15,

160:19, 164:5, 167:7,

167:14, 167:19, 171:4

OUTSET [1] - 8:17

OUTSIDE [10] -

24:24, 30:13, 44:14,

73:1, 73:2, 76:17,

76:18, 77:13, 162:10,

164:6

OUTSTANDING [1] -

8:18

OVERALL [9] -

17:11, 32:19, 33:2,

34:13, 37:9, 80:18,

82:1, 108:20, 205:12

OVERCOME [1] -

139:20

OVERHOLTZ [1] -

2:2

OVERLOOKED [1] -

48:1

OVERLOOKS [1] -

30:8

OVERNIGHT [1] -

175:21

OVERSTATED [1] -

19:25

OVERTURES [1] -

3:7

OVERVIEW [2] -

9:24, 17:6

OVERWHELMING

[1] - 170:17

OVO [1] - 166:25

OWN [11] - 25:3,

30:7, 38:3, 76:6,

77:16, 86:11, 90:19,

92:17, 110:3, 140:12,

162:10

P

P.M [1] - 207:23

PAGES [4] - 22:13,

22:15, 170:22, 170:23

PAID [1] - 61:2

PALATE [2] - 106:10,

229

173:11

PALSGRAF [1] -

89:10

PAM [1] - 9:4

PAMELA [1] - 2:14

PANOPLY [1] - 66:2

PAPER [38] - 4:23,

18:22, 27:13, 32:24,

34:5, 34:12, 34:17,

34:19, 34:25, 35:23,

36:25, 42:20, 46:10,

50:18, 64:9, 66:22,

69:14, 69:19, 80:23,

81:14, 87:18, 94:12,

94:16, 94:24, 101:5,

102:11, 107:6,

125:15, 125:16,

140:6, 140:8, 140:9,

140:10, 142:11,

149:12, 160:21,

203:3, 203:4

PAPERS [10] - 60:3,

60:21, 63:8, 63:10,

64:24, 65:1, 66:15,

79:19, 115:14, 125:24

PARAGRAPH [2] -

184:20

PAROXETINE [10] -

80:4, 82:2, 82:5,

103:12, 151:25,

204:15, 204:21,

205:14, 205:17,

205:23

PART [16] - 33:16,

42:19, 113:11,

114:21, 114:25,

118:24, 119:10,

129:16, 138:3,

161:18, 163:3,

165:23, 178:13,

185:17, 187:17, 200:5

PARTICIPATE [5] -

3:9, 79:11, 118:16,

121:8, 121:10

PARTICIPATING [1]

- 122:6

PARTICLE [1] -

142:18

PARTICULAR [34] -

28:17, 36:17, 40:22,

84:2, 84:5, 84:23,

85:2, 86:24, 90:5,

98:12, 99:22, 102:4,

104:3, 105:9, 105:21,

106:18, 118:1,

126:13, 129:21,

136:3, 137:11,

139:11, 139:14,

140:21, 141:15,

143:3, 151:18,


158:10, 160:4,

166:14, 169:1, 181:4,

183:7, 186:11

PARTICULARLY [10]

- 21:16, 31:22, 44:10,

47:10, 149:4, 149:10,

151:4, 158:14,

185:15, 195:17

PARTICULATES [1]

- 142:24

PARTIES [1] - 65:4

PARTS [3] - 100:16,

190:4, 192:23

PARTUM [1] - 20:4

PASS [4] - 27:24,

28:17, 54:5, 207:12

PASSED [1] - 112:11

PAST [6] - 60:16,

60:17, 62:20, 64:21,

70:3, 117:2

PASTE [1] - 87:7

PATHOGENESIS [1]

- 100:24

PATHOLOGICAL [1]

- 133:4

PATHOLOGICALLY

[1] - 185:9

PATHOLOGIST [1] -

185:3

PATHOLOGY [4] -

133:3, 179:4, 185:12,

185:22

PATHWAY [18] -

135:18, 135:22,

136:18, 137:10,

140:5, 140:16,

140:22, 145:14,

155:14, 156:9,

156:24, 161:6, 163:4,

167:23, 171:1, 171:7,

171:19, 203:10

PATHWAYS [12] -

56:17, 65:11, 70:21,

134:23, 134:24,

135:6, 135:11, 137:8,

142:24, 154:13,

155:4, 175:20

PATIENT [2] -

118:20, 138:7

PATIENTS [3] -

29:23, 119:2, 138:21

PATRICK [1] - 1:18

PATTERN [2] -

35:20, 36:9

PATTERNING [1] -

92:13

PATTERNS [2] -

64:12, 115:24

PAUL [2] - 196:21,

197:4

PAXIL [32] - 14:2,

14:6, 14:16, 15:7,

16:10, 16:11, 16:13,

20:20, 20:24, 25:7,

25:11, 25:13, 25:18,

26:6, 26:9, 26:16,

26:18, 37:8, 37:9,

43:13, 63:3, 64:9,

80:25, 89:18, 93:1,

101:23, 106:14,

106:16, 150:20,

162:25, 199:16

PEAKS [1] - 19:20

PEANUT [1] - 174:24

PEDERSEN [1] -

46:5

PEDERSON [4] -

80:12, 103:21, 108:3

PEDERSON'S [1] -

204:1

PEDIATRIC [5] - 7:2,

34:7, 64:22, 113:11,

113:13

PEDIATRICS [1] -

7:19

PEER [25] - 12:12,

12:19, 16:20, 16:21,

20:19, 26:5, 26:12,

30:15, 33:10, 45:16,

50:24, 55:23, 56:16,

63:8, 64:24, 65:1,

66:22, 67:1, 67:3,

79:18, 84:20, 97:10,

99:23, 108:5, 125:24

PEER-REVIEWED

[7] - 63:8, 64:24, 65:1,

66:22, 67:3, 97:10,

108:5

PEERS [8] - 20:25,

24:25, 26:11, 108:25,

109:18, 109:24,

111:14, 112:13

PENDING [1] - 3:17

PENDULUM [1] -

95:19

PENNSYLVANIA [3]

- 1:2, 23:12, 59:16

PENSACOLA [1] -

2:3

PEOPLE [20] - 12:8,

17:7, 47:17, 61:15,

72:17, 117:9, 117:15,

121:13, 126:22,

127:21, 127:25,

128:1, 128:4, 132:6,

138:17, 138:24,

140:5, 143:1, 143:6,

186:14

PERCENT [17] -

17:14, 18:2, 32:21,

44:22, 45:4, 45:8,

133:20, 134:8,

183:18, 183:19,

187:12, 187:13,

187:14, 192:16,

194:19, 194:23, 202:4

PERCENTAGE [1] -

192:6

PERFECTLY [1] -

26:17

PERFORM [1] -

146:13

PERFORMED [5] -

28:8, 46:14, 55:19,

105:19, 177:7

PERFORMING [1] -

24:22

PERFORMS [1] -

146:10

PERHAPS [1] - 56:15

PERINATAL [12] -

6:18, 61:8, 61:9,

61:12, 61:18, 61:25,

65:25, 99:22, 101:1,

109:13, 122:7, 122:9

PERIOD [4] - 19:1,

103:19, 192:21, 196:5

PERIODS [1] -

128:18

PERITONEUM [1] -

181:5

PERMISSION [1] -

9:11

PERMIT [1] - 112:2

PERMITTED [1] -

57:2

PERSISTENCE [3] -

182:23, 183:17, 184:2

PERSISTENT [1] -

167:17

PERSON [5] - 7:6,

56:6, 96:12, 96:15,

96:20

PERSONALLY [1] -

88:21

PERSPECTIVE [5] -

21:12, 52:5, 52:13,

52:14

PERTURBATIONS

[1] - 148:12

PETERSON [1] -

105:12

PFIZER [49] - 2:10,

2:13, 58:22, 61:14,

62:24, 65:7, 67:6,

68:24, 69:6, 69:7,

69:15, 72:25, 73:1,

73:2, 74:20, 76:16,

77:12, 77:15, 79:1,

84:13, 87:2, 87:3,

89:17, 89:22, 91:13,

91:21, 92:5, 96:8,

108:13, 110:10,

123:12, 150:16,

152:6, 152:8, 152:23,

153:12, 171:9,

175:18, 177:11,

179:16, 184:11,

189:14, 191:12,

195:25, 196:21,

197:7, 197:11, 200:13

PFIZER'S [8] - 74:11,

75:1, 78:3, 80:21,

96:5, 110:3, 152:14,

177:1

PH.D [12] - 6:13,

6:24, 7:7, 7:15, 64:19,

66:7, 89:5, 97:4,

119:20, 119:21,

119:22, 119:25

PHARMACEUTICA

L [7] - 3:18, 64:18,

90:10, 116:16,

122:14, 141:20, 157:4

PHARMACEUTICA

LS [1] - 177:24

PHARMACOEPIDE

MIOLGISTS [1] -

109:12

PHARMACOEPIDE

MIOLOGIC [1] - 49:20

PHARMACOEPIDE

MIOLOGY [5] - 6:18,

43:3, 48:20, 62:4,

62:13

PHARMACOKINETI

C [1] - 42:23

PHARMACOLOGIC

[4] - 43:6, 99:13,

99:16, 99:18

PHARMACOLOGIC

AL [1] - 16:15

PHARMACY [1] -

6:20

PHENOTYPE [3] -

166:20, 166:21,

166:22

PHENOTYPICALLY

[1] - 166:23

PHILADELPHIA [6] -

1:7, 1:14, 1:23, 2:19,

3:6, 4:12

PHOCOMELIA [1] -

172:16

PHYSICAL [1] -

130:23

PHYSICALLY [1] -

166:24

PHYSIOLOGIC [2] -

99:20, 133:13

230

PHYSIOLOGICAL

[1] - 140:22

PHYSIOLOGICALL

Y [1] - 157:19

PHYSIOLOGY [1] -

131:9

PICKED [3] - 50:6,

96:15, 103:24

PICKING [5] - 39:21,

40:2, 40:8, 53:3,

103:5

PICKS [3] - 11:5,

11:6, 30:5

PICTURE [1] - 19:13

PIECE [1] - 153:20

PINEDA [2] - 84:24,

85:16

PITCH [1] - 148:15

PLACE [8] - 13:6,

68:9, 70:14, 70:19,

74:8, 82:5, 159:3,

205:17

PLACED [2] - 14:2,

113:24

PLACEMENT [1] -

68:3

PLACENTA [1] -

131:16

PLACENTAL [1] -

131:14

PLAINTIFF'S [3] -

4:15, 23:17, 112:23

PLAINTIFFS [22] -

1:17, 1:20, 2:4, 2:7,

10:1, 10:11, 10:20,

11:1, 22:8, 22:13,

22:21, 23:2, 23:4,

24:5, 24:7, 25:17,

28:2, 29:16, 30:21,

31:15, 41:21, 112:21

PLAINTIFFS' [8] -

9:14, 10:10, 22:12,

28:15, 28:23, 29:11,

41:19, 96:13

PLANE [1] - 4:25

PLATELET [1] -

149:7

PLATELETS [3] -

149:22, 157:20,

157:21

PLAUSIBILITY [4] -

28:22, 28:24, 72:8,

98:14

PLAY [3] - 24:2,

48:14, 87:22

PLAYS [1] - 54:24

PLAZA [1] - 1:16

PLEAS [1] - 3:6

PLEASED [1] - 68:7

PLLC [1] - 2:2


PLOT [1] - 109:12

PLUG [1] - 156:6

PLUGS [1] - 191:24

PLURAL [1] - 66:23

POINT [13] - 15:22,

22:7, 23:2, 27:8,

31:18, 39:16, 60:3,

88:13, 109:25,

126:20, 129:19,

130:7, 142:11

POINTED [5] - 24:9,

89:16, 108:19, 144:1,

205:9

POINTS [8] - 17:2,

21:21, 30:2, 33:14,

33:25, 37:4, 39:15,

44:10

POLICY [1] - 85:16

POOR [3] - 20:7,

190:13, 190:14

POPULATING [1] -

160:1

POPULATION [21] -

10:5, 18:2, 32:22,

36:3, 47:18, 48:1,

66:3, 119:6, 121:3,

121:5, 136:15,

136:16, 138:15,

138:24, 139:21,

139:24, 155:5,

158:10, 161:8,

170:10, 189:24

POPULATIONS [11]

- 98:2, 118:1, 118:20,

138:7, 138:15,

158:11, 163:11,

173:8, 194:19,

198:23, 199:11

PORTION [1] -

140:19

PORTRAYED [1] -

58:24

POSITION [5] - 7:13,

18:22, 27:13, 35:23,

176:14

POSITIVE [15] - 14:4,

14:10, 38:12, 38:20,

39:7, 44:7, 44:20,

45:3, 45:7, 72:7,

143:3, 160:7, 170:18,

170:20

POSITIVELY [1] -

130:2

POSSIBILITIES [1] -

28:25

POSSIBILITY [3] -

46:1, 49:15, 105:16

POSSIBLE [5] - 13:5,

28:24, 28:25, 46:14,

161:16

POSSIBLY [2] -

15:20, 107:21

POST [7] - 20:4,

62:4, 66:8, 120:8,

120:14, 184:21,

192:16

POST-DOC [1] - 66:8

POST-NATAL [1] -

184:21

POST-PARTUM [1] -

20:4

POSTIMPLANTATI

ON [6] - 179:23,

180:14, 192:3,

192:15, 193:1, 194:3

POSTNATAL [3] -

181:2, 191:7, 200:3

POSTPONE [2] -

83:8, 107:11

POTENTIAL [20] -

31:14, 47:3, 49:12,

55:18, 64:7, 82:6,

116:21, 117:17,

124:24, 135:20,

139:5, 140:14, 178:5,

183:8, 198:14,

198:16, 198:19,

198:20, 205:17,

205:25

POTENTIALLY [11] -

46:7, 80:25, 114:20,

132:12, 136:1,

139:21, 181:16,

183:15, 185:7,

192:14, 193:12

POTENTIALS [1] -

189:23

POTENTIATE [1] -

127:20

POUR [1] - 203:4

POWER [13] - 170:9,

182:15, 190:3,

193:24, 195:9, 200:6,

200:10, 200:14,

200:16, 200:25,

201:8, 201:11, 201:12

POWERED [3] -

179:9, 182:2, 182:11

POWERFUL [1] -

21:19

POWERPOINT [2] -

143:16, 175:18

POWERPOINTS [2] -

171:21, 176:9

POZNER [1] - 2:5

PPHN [3] - 10:15,

81:16, 97:14

PRACTICALLY [3] -

18:16, 125:18, 135:7

PRACTICE [4] -

88:17, 120:4, 125:22,

134:6

PRE [2] - 117:14,

157:15

PRE-SCREENING

[1] - 117:14

PRE-SYNAPTIC [1] -

157:15

PRECEDENT [1] -

85:14

PRECEDENTS [1] -

140:11

PRECEDES [1] -

97:22

PRECISE [1] - 66:16

PRECISELY [1] -

42:5

PRECLINICAL [4] -

177:5, 197:23, 206:1,

206:5

PREDECESSORS

[1] - 159:18

PREDICTABLE [1] -

194:20

PREDICTIVE [1] -

141:21

PREDICTORS [1] -

168:16

PREDOMINANTLY

[3] - 116:14, 172:15,

177:7

PREFERENCE [1] -

85:17

PREGNANCY [45] -

6:19, 14:2, 16:18,

16:23, 17:11, 19:22,

20:11, 20:17, 20:23,

21:25, 26:9, 26:15,

32:18, 34:8, 34:21,

37:14, 37:15, 37:25,

49:22, 61:11, 62:10,

62:12, 64:8, 74:13,

74:23, 80:15, 82:5,

82:19, 103:16, 109:6,

110:23, 111:8,

111:10, 115:8,

139:23, 179:22,

180:10, 180:14,

196:12, 197:19,

197:25, 200:1,

205:16, 206:11,

206:16

PREGNANT [17] -

10:5, 20:4, 26:3, 79:5,

110:17, 111:2,

111:18, 117:17,

148:25, 152:12,

155:21, 178:3,

179:22, 180:11,

198:6, 198:15, 198:22

PRELIMINARY [1] -

8:5

PRENATAL [1] - 97:3

PREPARED [1] -

191:19

PREPARING [1] -

5:21

PRESCRIBE [1] -

29:22

PRESCRIBED [3] -

16:2, 16:17, 18:5

PRESCRIPTIONS [2]

- 18:9, 18:13

PRESENCE [5] -

148:16, 149:2, 186:8,

186:9, 194:20

PRESENT [14] -

41:2, 56:19, 119:5,

132:16, 149:15,

155:4, 162:9, 170:19,

172:19, 178:24,

179:5, 181:11,

182:16, 190:25

PRESENTATION

[13] - 9:14, 55:24,

58:18, 84:1, 84:13,

85:12, 108:25, 109:1,

118:3, 161:9, 168:7,

175:19, 180:10

PRESENTATIONS

[2] - 84:10, 173:7

PRESENTED [8] -

55:22, 62:16, 88:3,

109:24, 119:9,

144:10, 192:25,

195:17

PRESENTING [2] -

41:6, 172:16

PRESENTS [2] -

151:19, 194:21

PRESTIGIOUS [2] -

64:2, 67:11

PRESUMABLY [2] -

55:5, 128:12

PRESUMPTUOUS

[1] - 39:18

PRETTY [1] - 174:19

PREVENT [2] - 65:2,

115:2

PREVENTABLE [2] -

114:16, 139:2

PREVENTING [2] -

114:15, 139:2

PREVENTION [6] -

63:20, 66:12, 67:9,

118:17, 118:19,

118:22

PREVIOUSLY [1] -

34:10

PRICE [1] - 5:7

231

PRIMARILY [1] -

27:15

PRIMARY [7] -

42:20, 81:17, 163:21,

163:23, 164:2,

164:10, 164:11

PRIMER [4] - 20:10,

42:19, 46:17, 51:3

PRINCIPLE [20] -

89:8, 127:7, 127:11,

128:13, 128:14,

129:7, 129:8, 129:15,

130:17, 130:18,

131:18, 131:24,

133:16, 133:23,

134:10, 138:10,

138:11, 180:4,

187:19, 187:24

PRINCIPLES [45] -

42:10, 52:4, 52:20,

52:22, 52:24, 59:18,

59:22, 68:21, 68:22,

69:2, 69:5, 69:7,

69:10, 70:9, 70:24,

81:10, 84:8, 89:6,

92:10, 92:11, 92:16,

92:18, 93:3, 93:21,

93:25, 96:9, 96:23,

102:13, 109:22,

124:21, 124:22,

125:1, 125:5, 125:8,

125:14, 125:17,

125:21, 126:1, 126:4,

135:8, 135:12, 170:7,

187:17, 197:14

PRINT [1] - 79:15

PRIVATE [1] - 117:6

PRIZE [1] - 166:10

PROBABILITY [5] -

36:7, 44:21, 45:3,

45:7, 194:7

PROBLEM [14] -

53:14, 74:6, 78:3,

131:22, 149:16,

149:18, 159:23,

183:2, 183:5, 183:15,

184:25, 188:25,

191:1, 201:19

PROBLEMS [17] -

20:14, 21:7, 46:11,

47:15, 49:19, 100:9,

110:15, 115:12,

133:1, 151:20,

151:21, 159:13,

181:3, 181:15,

183:11, 183:16, 201:5

PROCEDURE [1] -

144:24

PROCEED [6] - 5:12,

9:24, 113:2, 175:14,


176:1, 176:21

PROCEEDING [1] -

90:1

PROCEEDINGS [2] -

1:25, 207:25

PROCESS [3] -

41:16, 50:20, 130:12

PROCESSES [3] -

56:10, 145:25, 148:4

PROCESSING [1] -

121:15

PRODUCE [17] -

78:7, 129:13, 130:8,

130:15, 133:9,

133:25, 134:8,

150:12, 163:16,

167:14, 167:17,

167:21, 172:21,

172:25, 173:2, 191:6,

202:3

PRODUCED [2] -

1:25, 22:16

PRODUCES [6] -

141:16, 148:20,

160:17, 160:24,

165:23, 188:25

PRODUCING [5] -

133:19, 142:7, 153:5,

153:11, 195:10

PRODUCT [5] -

15:25, 16:13, 17:19,

18:24, 21:23

PRODUCTION [4] -

21:21, 132:11,

149:14, 166:17

PRODUCTS [1] - 1:4

PROFESSION [1] -

55:17

PROFESSIONAL [9]

- 12:18, 16:24, 30:12,

31:25, 32:4, 33:9,

60:13, 116:8, 123:9

PROFESSOR [7] -

6:18, 7:8, 7:19, 7:20,

62:8, 67:19, 113:21

PROFESSORSHIP

[1] - 67:7

PROFFERED [1] -

29:17

PROGRAM [7] -

113:23, 116:18,

118:24, 118:25,

119:10, 119:13,

119:17

PROHIBITED [1] -

90:15

PROHIBITS [1] -

13:6

PROJECT [3] - 7:1,

138:4

PROLIFERATION [6]

- 146:1, 148:22,

158:19, 163:15,

165:2, 167:13

PRONG [1] - 46:22

PROOF [5] - 29:1,

29:2, 34:14, 43:25,

88:1

PROPENSITY [1] -

86:23

PROPER [2] - 70:8,

73:10

PROPERLY [3] -

86:14, 87:8, 148:19

PROPERTIES [6] -

42:23, 99:17, 144:2,

144:3, 144:7

PROPOSED [2] -

162:3, 200:7

PROPOSITION [1] -

84:17

PROTECTION [2] -

117:1, 140:12

PROTEIN [7] -

129:24, 129:25,

136:3, 162:12, 169:1

PROTEINS [3] -

136:2, 146:12

PROTOCOL [5] -

180:20, 182:21,

184:23, 188:6, 191:19

PROTUBERANCE

[5] - 185:4, 185:8,

185:17, 185:21,

185:22

PROVE [13] - 11:19,

21:16, 74:8, 84:13,

86:18, 87:9, 94:17,

94:21, 95:3, 95:4,

150:20, 170:5

PROVED [2] -

186:13, 189:3

PROVEN [1] - 28:25

PROVIDE [1] - 42:12

PROVIDED [2] -

120:20, 178:21

PROVIDING [3] -

10:12, 139:7, 176:8

PROVINCE [1] - 92:4

PROVING [1] - 95:13

PROZAC [5] - 150:7,

150:20, 163:1,

199:22, 199:23

PSC [2] - 5:23, 6:7

PSYCHIATRIC [1] -

33:25

PSYCHOLOGICAL

[1] - 47:6

PUBLIC [7] - 5:10,

10:3, 21:7, 22:1, 57:7,

111:17, 111:18

PUBLICATION [1] -

63:12

PUBLICATIONS [2] -

38:3, 145:13

PUBLICLY [1] -

154:19

PUBLISH [1] - 119:8

PUBLISHED [20] -

12:19, 16:3, 30:8,

33:10, 34:11, 39:12,

55:3, 55:23, 56:16,

62:14, 63:7, 66:22,

67:4, 98:15, 99:4,

99:23, 108:6, 115:13,

169:22, 176:24

PUBLISHING [1] -

63:12

PULL [1] - 157:15

PULLED [1] - 110:20

PULMONARY [1] -

81:17

PUP [7] - 74:21,

74:22, 181:22, 187:7,

187:9, 196:24, 196:25

PUPILS [1] - 95:20

PUPS [15] - 82:13,

180:12, 181:1,

181:12, 181:17,

182:6, 182:10,

186:24, 188:17,

188:20, 188:23,

189:1, 192:6, 203:2,

203:8

PURPOSE [3] - 17:8,

143:13, 177:19

PURPOSES [4] -

17:16, 99:15, 99:18,

185:22

PUSHED [1] - 16:15

PUT [26] - 15:6, 15:7,

15:23, 17:21, 40:12,

66:23, 69:6, 69:7,

69:15, 71:24, 73:11,

86:1, 92:16, 110:10,

111:13, 112:13,

135:14, 139:11,

143:16, 171:22,

184:11, 187:19,

199:8, 199:21,

206:14, 206:15

PUTS [3] - 21:11,

102:24, 110:12

PUTTING [2] -

107:23, 140:15

Q

QUALIFICATIONS

[4] - 8:19, 59:20,

59:21, 60:1

QUALIFIED [4] -

59:7, 68:11, 97:5,

112:3

QUALITY [1] -

190:11

QUERIED [1] -

154:19

QUESTIONNAIRES

[1] - 119:4

QUESTIONS [4] -

87:20, 135:12, 145:8,

187:11

QUICKLY [3] - 27:3,

27:5, 197:19

QUILLEN [1] - 7:21

QUINN [1] - 2:9

QUITE [7] - 10:6,

15:23, 24:16, 69:6,

73:21, 78:13, 166:22

QUOTE [4] - 21:8,

52:7, 86:1, 95:13

R

RABBIT [3] - 177:8,

182:21, 195:13

RABBITS [3] - 27:23,

28:8, 178:15

RADICAL [1] - 58:25

RAIL [2] - 111:15,

111:20

RARE [2] - 178:24,

179:10

RARELY [1] - 79:7

RAT [5] - 181:22,

182:6, 182:10, 203:2,

203:8

RATE [3] - 19:5,

19:19, 37:20

RATES [6] - 35:14,

35:15, 179:22,

180:14, 182:17, 190:9

RATHER [8] - 35:15,

49:5, 49:17, 57:25,

77:6, 85:8, 90:18,

154:3

RATIO [3] - 104:9,

104:19, 109:14

RATIOS [2] - 88:18,

97:20

RATS [12] - 28:8,

74:22, 165:24, 168:9,

177:7, 178:15,

186:20, 194:12,

195:6, 196:15,

196:25, 201:9

RAU [10] - 3:7, 3:14,

3:17, 4:3, 4:5, 4:13,

4:17, 5:17, 5:18,

232

23:11

RE [1] - 1:3

REACH [11] - 30:3,

30:4, 39:19, 44:4,

51:20, 72:19, 90:13,

91:2, 154:16, 156:4,

156:17

REACHED [2] - 4:15,

106:9

REACHING [3] -

14:20, 110:5, 131:7

REACTION [2] -

24:10, 65:18

READ [17] - 4:25,

8:17, 21:8, 22:20,

31:5, 41:10, 49:1,

78:17, 84:22, 94:12,

94:15, 124:8, 125:15,

125:16, 141:13,

150:4, 204:12

READ-ACROSS [1] -

141:13

READILY [2] -

142:23, 146:16

READY [1] - 94:24

REAL [9] - 14:18,

19:1, 19:8, 24:23,

29:1, 70:24, 125:21,

135:8

REALITY [3] - 75:7,

80:22, 198:7

REALLY [24] - 4:7,

10:8, 14:14, 18:19,

19:24, 21:11, 35:7,

37:25, 39:5, 44:19,

48:22, 56:24, 65:13,

68:20, 69:12, 69:18,

73:11, 74:10, 77:11,

92:20, 101:19, 102:1,

110:9, 179:6

REAR [1] - 188:23

REASON [16] -

19:14, 28:18, 35:9,

44:3, 54:3, 59:13,

69:17, 73:4, 73:10,

73:13, 76:1, 76:20,

81:8, 91:6, 98:24,

176:12

REASONABLE [7] -

82:17, 104:1, 123:4,

124:1, 175:25, 206:9,

206:20

REASONS [3] -

10:17, 81:4, 132:22

REBUTTAL [2] -

41:20, 41:22

RECEIVED [6] -

62:5, 62:23, 65:7,

67:5, 67:8, 119:21

RECENT [2] - 33:24,


35:6

RECENTLY [3] -

66:21, 75:21, 75:24

RECEPTOR [5] -

154:5, 154:9, 160:7,

162:22, 165:16

RECEPTORS [12] -

130:3, 135:25, 159:2,

159:4, 159:21,

162:19, 162:20,

164:18, 165:6,

165:12, 167:21, 186:5

RECESS [7] - 57:12,

58:13, 58:14, 83:18,

83:19, 175:9, 175:10

RECOGNIZABLE [1]

- 36:2

RECOGNIZE [3] -

16:20, 19:15, 45:19

RECOGNIZED [6] -

16:19, 16:24, 45:11,

48:2, 50:4, 89:1

RECOGNIZES [4] -

23:23, 46:8, 64:6,

86:11

RECOGNIZING [1] -

80:24

RECOMMEND [1] -

16:24

RECOMMENDED [2]

- 82:4, 205:16

RECORD [11] - 5:4,

65:8, 113:1, 115:22,

150:4, 171:22,

171:24, 175:23,

188:10, 206:14,

207:25

RECORDED [1] -

1:25

RED [1] - 54:3

REDIRECT [1] - 8:12

REDUCE [2] - 21:20,

114:20

REDUCING [1] -

115:15

REDUCTION [2] -

103:13, 117:4

REDUCTIONS [1] -

103:13

REFER [6] - 91:8,

114:15, 129:10,

132:18, 147:20, 159:3

REFERENCE [7] -

36:23, 44:8, 48:2,

66:7, 85:24, 140:10

REFERENCED [1] -

148:11

REFERENCES [2] -

86:9, 163:17

REFERENCING [1] -

64:8

REFERRED [19] -

124:21, 128:6,

128:18, 130:18,

134:1, 138:2, 138:5,

139:1, 140:1, 141:5,

143:23, 144:13,

146:4, 154:22, 164:1,

172:16, 178:13,

179:18, 181:1

REFERRING [1] -

92:24

REFINED [2] - 69:11,

179:3

REFLECT [2] -

45:24, 46:15

REFLECTED [1] -

35:22

REFLECTS [1] -

205:11

REGARD [8] - 24:15,

27:7, 71:23, 115:14,

174:9, 177:8, 199:6,

200:1

REGARDED [1] -

32:15

REGARDING [3] -

55:4, 88:10, 196:23

REGARDS [2] -

130:1, 145:13

REGENERATIVE [1]

- 7:11

REGION [2] - 185:15,

185:16

REGISTRIES [3] -

120:10, 120:13,

120:17

REGISTRY [2] -

89:17, 89:18

REGULATES [1] -

145:24

REGULATIONS [1] -

14:4

REGULATORY [11] -

12:17, 31:25, 32:4,

32:5, 71:8, 74:11,

75:5, 77:16, 77:24,

137:7

REILLY [1] - 2:5

REIS [1] - 46:10

REJECT [1] - 59:2

REJECTED [1] -

91:16

REJECTS [1] -

102:11

RELATED [20] -

31:1, 35:23, 38:23,

47:25, 49:4, 49:17,

51:25, 63:1, 78:7,

78:11, 92:9, 92:10,

93:2, 93:4, 133:5,

150:12, 180:25,

186:22, 186:23,

190:10

RELATIONS [1] -

194:18

RELATIONSHIP [6] -

15:11, 42:13, 47:24,

53:11, 53:16, 143:5

RELATIVELY [2] -

64:25, 142:9

RELEASED [1] -

157:16

RELEVANCE [1] -

147:13

RELEVANT [2] -

22:18, 166:14

RELIABILITY [2] -

24:4, 92:3

RELIABLE [10] -

10:13, 24:18, 85:4,

86:15, 88:11, 101:4,

103:24, 105:15,

112:10

RELIANCE [1] -

51:15

RELIED [6] - 11:3,

45:9, 50:17, 77:12,

91:3, 169:19

RELIES [7] - 11:14,

30:9, 43:23, 45:18,

47:4, 85:21, 102:25

RELY [12] - 27:15,

28:15, 28:18, 51:17,

76:2, 85:22, 88:13,

92:18, 103:2, 140:25,

141:1, 154:1

RELYING [2] - 11:13,

24:7

REMAIN [8] - 4:11,

18:11, 18:16, 19:3,

58:15, 75:4, 83:20,

175:11

REMAINED [3] -

16:6, 19:7, 107:20

REMAINS [4] - 14:7,

14:12, 18:7, 34:6

REMARK [1] - 8:7

REMEDIES [1] -

139:9

REMEMBER [3] -

73:24, 79:25, 94:19

REMIND [1] - 87:21

REMOVAL [2] -

167:11, 167:13

REMOVED [1] -

12:25

RENDER [2] - 29:12,

59:7

REPEATED [1] -

36:15

REPEATEDLY [3] -

51:17, 80:10, 96:16

REPLACEMENT [1] -

91:7

REPLICATED [1] -

97:12

REPLY [2] - 94:13,

107:6

REPORT [21] -

25:10, 25:18, 29:23,

37:8, 38:12, 40:13,

40:16, 40:17, 40:21,

41:2, 41:21, 65:6,

77:10, 102:23, 103:5,

106:17, 109:3, 114:9,

123:25, 150:2, 171:25

REPORTED [3] -

39:7, 56:3, 185:23

REPORTER [2] -

1:22, 208:5

REPORTING [1] -

119:7

REPORTS [11] -

4:24, 10:10, 24:11,

26:23, 29:11, 29:17,

30:8, 38:20, 41:17,

41:20, 41:22

REPRESENTED [1] -

87:3

REPRESENTS [1] -

31:11

REPRODUCTION [4]

- 28:4, 28:7, 198:4,

198:10

REPRODUCTIVE

[12] - 20:12, 150:10,

177:6, 177:16,

177:17, 177:20,

177:22, 178:8,

178:10, 178:17,

179:9, 183:10

REPUTATION [2] -

96:10, 107:24

REQUEST [1] -

182:14

REQUIRE [2] - 23:7,

88:9

REQUIRED [11] -

41:16, 86:18, 87:9,

87:12, 88:24, 88:25,

102:25, 162:22,

177:12, 179:7, 202:24

REQUIREMENT [2] -

90:13, 91:2

REQUIREMENTS [3]

- 24:4, 24:13, 53:23

REQUIRING [1] -

41:13

RESEARCH [46] -

233

6:19, 7:2, 7:3, 55:7,

56:12, 62:10, 62:16,

62:25, 64:3, 64:6,

64:15, 64:22, 65:7,

65:21, 65:25, 66:19,

67:20, 67:21, 76:5,

81:3, 113:22, 116:4,

116:12, 116:19,

118:6, 120:5, 120:9,

120:15, 120:25,

122:16, 124:23,

125:6, 137:2, 137:12,

137:15, 137:19,

139:16, 143:5, 143:9,

143:10, 146:23,

147:2, 164:23,

182:13, 189:15

RESEARCHER [7] -

67:3, 68:1, 69:12,

81:19, 81:22, 91:25,

205:4

RESEARCHERS [6]

- 63:5, 66:17, 67:2,

72:25, 80:8, 203:22

RESEQUENCE [1] -

138:6

RESEQUENCING [2]

- 138:2, 138:6

RESERVOIR [1] -

149:24

RESOLVE [1] - 47:15

RESPECT [25] -

30:25, 33:23, 35:7,

39:12, 40:4, 47:22,

48:11, 50:25, 52:2,

52:8, 52:13, 75:8,

81:15, 81:16, 124:14,

145:8, 146:18,

156:24, 161:11,

161:20, 163:7, 171:9,

171:14, 172:3, 204:2

RESPOND [2] - 3:7,

162:8

RESPONSE [10] -

78:3, 127:4, 140:6,

158:22, 158:25,

159:12, 160:14,

160:15, 187:15,

191:11

RESPONSES [2] -

3:10, 134:7

RESPONSIBILITY

[2] - 74:19, 76:4

RESPONSIBLE [1] -

119:15

RESPONSIVE [5] -

159:20, 163:11,

163:18, 163:19,

164:19

REST [3] - 44:5,


66:25, 169:8

RESULT [7] - 13:6,

29:12, 44:15, 45:6,

46:25, 193:13

RESULTED [1] -

181:4

RESULTING [2] -

124:3, 180:12

RESULTS [18] -

46:2, 46:24, 80:12,

80:17, 98:5, 105:1,

105:3, 105:19,

105:23, 106:6,

107:21, 108:4,

108:20, 109:16,

109:17, 150:23,

179:20, 194:8

RESUME [1] - 65:8

RETAINED [2] - 37:8,

55:15

RETARDATION [2] -

132:3, 132:10

RETINOIC [2] -

172:20

RETINOID [2] -

173:14, 173:16

RETINOIDS [6] -

172:13, 172:20,

173:13, 173:17,

173:19

REUPTAKE [3] -

74:12, 143:24, 197:3

REVIEW [10] - 12:12,

13:19, 16:21, 45:1,

84:21, 99:24, 122:19,

145:6, 170:24, 189:16

REVIEWED [39] -

12:19, 13:19, 20:20,

26:5, 26:12, 30:15,

33:10, 45:16, 50:24,

52:18, 55:24, 56:16,

63:8, 63:10, 64:24,

65:1, 66:22, 67:1,

67:3, 79:18, 97:10,

108:5, 125:25, 150:2,

151:3, 152:6, 156:1,

169:14, 177:1,

179:18, 191:2,

199:13, 199:14,

199:16, 199:18,

202:11, 204:8,

205:24, 206:4

REVIEWING [2] -

12:13, 89:24

RICHARD [1] -

113:16

RICK [1] - 65:3

RIGHTLY [1] - 93:20

RISE [2] - 130:13,

146:6

RISK [54] - 14:5,

14:10, 17:13, 17:14,

18:1, 18:6, 18:9,

19:24, 20:21, 25:7,

25:10, 26:7, 32:21,

33:2, 34:9, 36:17,

37:19, 40:19, 49:3,

49:15, 51:23, 79:4,

80:14, 88:18, 98:1,

102:9, 102:21,

103:18, 104:5,

104:14, 105:1, 106:2,

108:8, 109:19,

110:15, 115:5,

118:21, 119:3, 119:5,

120:16, 120:19,

139:22, 139:24,

142:19, 151:15,

152:11, 169:24,

170:13, 197:24,

198:4, 198:7, 198:17,

203:5, 205:10

RISKS [15] - 16:12,

25:13, 32:22, 34:4,

51:5, 80:17, 108:10,

110:22, 111:3,

115:15, 138:12,

151:14, 152:24,

198:16, 198:20

ROAD [2] - 70:14,

70:16

ROBERT [6] - 2:17,

6:23, 76:15, 112:22,

112:23, 113:7

ROBINSON [10] -

1:15, 1:16, 6:2, 6:3,

8:1, 8:2, 8:4, 82:25,

175:3

ROBUST [10] -

12:13, 13:16, 80:19,

102:1, 102:25,

103:25, 104:24,

105:14, 108:21,

141:18

ROBUSTNESS [1] -

145:11

RODENT [3] -

168:11, 194:17, 195:7

ROLE [2] - 54:24,

114:13

RONALD [1] - 63:21

ROOM [1] - 148:14

ROUGHLY [1] -

193:5

ROUND [1] - 107:1

ROUTES [1] - 131:12

ROUTINE [1] - 26:14

ROWS [2] - 144:4,

144:5

RUFE [1] - 1:9

RULE [7] - 23:25,

24:1, 49:3, 49:13,

85:8, 102:12, 103:1

RULED [2] - 46:3,

102:10

RULES [2] - 78:24,

207:16

RUN [3] - 111:8,

111:15, 111:19

RUNS [1] - 79:20

RUTHERFORD [1] -

100:1

S

S-E-R-T [1] - 144:13

SADLER [29] - 7:15,

7:17, 8:4, 29:14,

54:10, 54:14, 54:16,

54:22, 55:6, 60:11,

60:17, 61:4, 66:4,

66:18, 70:13, 71:12,

73:20, 76:15, 78:19,

79:10, 85:3, 92:12,

92:19, 98:10, 100:7,

128:25, 147:9,

163:20, 203:23

SADLER'S [4] -

54:20, 72:20, 129:2,

146:20

SAFE [2] - 13:11,

13:12

SAFETY [3] - 75:20,

117:18, 134:4

SAKE [1] - 9:10

SALES [1] - 19:10

SAMPLES [4] -

119:1, 120:20, 121:15

SANCTITY [1] - 74:3

SATISFY [4] - 10:1,

10:11, 24:5

SAVE [1] - 4:22

SAVES [1] - 176:10

SAVING [2] - 10:2,

110:17

SAW [12] - 19:21,

89:19, 90:14, 92:9,

101:16, 102:6,

109:16, 152:5,

165:18, 179:15,

186:13

SCARCE [1] - 205:11

SCHEDULE [1] -

3:15

SCHOLAR [1] - 7:23

SCHOLER [1] - 2:15

SCHOOL [6] - 7:8,

62:5, 66:10, 89:5,

120:2, 120:3

SCIENCE [49] - 3:9,

6:1, 6:7, 6:9, 6:24,

6:25, 16:6, 16:7,

21:12, 22:11, 24:23,

44:25, 62:7, 64:11,

70:1, 72:13, 72:19,

88:5, 91:5, 93:6, 93:7,

93:13, 93:24, 95:9,

95:15, 99:8, 99:21,

100:4, 100:22, 101:3,

101:12, 101:13,

105:5, 106:20, 107:1,

107:16, 110:2,

111:16, 119:24,

125:25, 137:15,

142:20, 168:14,

169:10

SCIENCES [2] - 7:4,

119:23

SCIENTIFIC [59] -

10:13, 12:3, 12:4,

13:7, 13:19, 16:4,

16:25, 19:14, 22:11,

22:12, 22:22, 23:10,

23:25, 25:3, 25:22,

26:22, 27:9, 30:1,

30:13, 32:10, 34:13,

40:10, 44:5, 44:9,

49:1, 51:16, 52:20,

53:2, 55:25, 57:5,

59:1, 59:18, 59:22,

61:22, 61:23, 63:9,

63:19, 67:24, 71:19,

78:14, 79:12, 82:17,

85:25, 90:20, 96:8,

96:23, 97:11, 102:10,

107:6, 107:8, 120:5,

123:4, 124:1, 142:23,

185:18, 197:10,

206:9, 206:20

SCIENTIFICALLY

[13] - 28:25, 42:9,

52:23, 78:13, 78:14,

99:17, 117:21,

132:16, 136:19,

142:5, 142:10, 197:9,

199:7

SCIENTIST [8] - 7:3,

23:5, 27:9, 61:10,

73:22, 96:1, 182:12,

204:19

SCIENTISTS [21] -

11:23, 11:25, 12:11,

12:12, 16:21, 17:18,

31:25, 32:3, 33:23,

44:14, 76:5, 93:7,

93:11, 94:6, 99:22,

109:5, 135:6, 135:11,

142:15, 146:15,

194:10

SCREEN [11] -

234

69:15, 71:4, 73:5,

120:8, 120:23,

141:19, 146:15,

172:12, 187:20,

201:21, 203:3

SCREENING [2] -

117:14

SCREENS [1] -

176:19

SEAN [5] - 1:18, 6:3,

6:8, 8:1

SEATED [7] - 3:4,

58:15, 58:17, 83:20,

83:23, 175:11, 175:13

SEC [1] - 24:13

SECOND [16] - 6:15,

65:12, 76:22, 85:25,

114:25, 126:10,

128:13, 128:14,

129:18, 131:2, 151:7,

155:10, 181:19,

185:25, 201:14

SECONDARY [6] -

158:15, 163:21,

163:23, 164:2,

164:10, 164:11

SECTION [3] - 40:16,

41:6, 188:6

SECTIONING [2] -

200:20, 200:21

SECULAR [2] -

18:21, 18:23

SECURITIES [1] -

24:11

SEE [104] - 11:24,

17:1, 18:13, 19:6,

21:17, 26:23, 27:7,

28:2, 29:23, 31:7,

31:13, 33:19, 38:16,

44:12, 58:12, 74:15,

78:10, 78:11, 82:14,

83:15, 86:10, 88:20,

89:20, 95:10, 96:25,

97:1, 97:21, 104:20,

104:25, 105:8,

106:24, 107:3,

109:16, 119:2,

133:22, 133:24,

143:22, 143:24,

147:17, 149:8, 149:9,

151:25, 155:7,

157:23, 160:17,

162:16, 163:10,

164:12, 164:24,

165:1, 165:5, 165:10,

165:17, 168:19,

169:7, 170:21,

170:24, 171:2, 171:3,

173:14, 177:21,

179:10, 179:19,


179:21, 180:25,

181:5, 181:8, 182:5,

182:6, 182:10,

182:11, 182:15,

183:24, 183:25,

185:25, 186:8,

186:10, 186:11,

186:22, 187:1, 187:2,

188:23, 190:4, 190:7,

190:9, 192:24,

192:25, 193:8,

193:17, 194:2, 194:6,

194:11, 194:22,

194:24, 195:22,

197:6, 197:11,

198:10, 198:12,

200:2, 201:24,

202:21, 204:7, 204:15

SEEING [1] - 81:11

SEES [1] - 105:19

SEGMENT [14] -

178:12, 179:19,

180:7, 180:8, 180:9,

180:20, 181:19,

182:20, 184:23,

186:20, 188:6, 188:9,

188:11

SELECTED [5] -

26:24, 30:9, 35:15,

51:18

SELECTIVE [1] -

143:23

SELECTIVELY [1] -

40:6

SELF [1] - 145:23

SELFISH [1] - 176:12

SELL [1] - 27:25

SEMINAL [2] - 84:24,

115:13

SEND [1] - 140:6

SENIOR [2] - 7:3,

7:23

SENSE [1] - 95:8

SENSIBLE [1] - 72:9

SENT [2] - 4:17,

197:11

SEPARATE [2] -

49:7, 178:16

SEPTAL [12] - 19:5,

19:6, 34:22, 39:4,

47:11, 47:12, 47:14,

103:11, 160:19,

167:7, 167:18, 171:5

SEPTUM [3] -

159:25, 160:1, 165:8

SEQUENCE [1] -

129:13

SERIOUS [4] - 19:23,

20:5, 47:6, 111:3

SEROTONIN [107] -

54:24, 66:18, 73:9,

74:12, 98:13, 98:15,

98:25, 99:1, 102:3,

105:25, 124:2, 130:3,

143:23, 144:12,

144:14, 144:17,

145:17, 145:21,

145:22, 146:18,

146:21, 146:24,

147:12, 147:14,

147:15, 147:17,

147:23, 148:3, 148:6,

148:8, 148:10,

148:12, 148:13,

148:17, 148:18,

149:4, 149:5, 149:7,

149:11, 149:13,

149:14, 149:17,

149:19, 149:22,

149:23, 149:24,

149:25, 154:4, 154:8,

157:11, 157:13,

157:15, 157:17,

157:21, 157:22,

158:2, 158:6, 158:13,

158:18, 159:1, 159:2,

159:7, 159:20,

159:21, 160:5,

160:16, 160:17,

160:22, 160:23,

161:25, 162:2, 162:7,

162:9, 162:10,

162:18, 162:20,

162:21, 162:22,

163:9, 163:10,

163:12, 163:19,

164:19, 165:6, 165:7,

165:12, 165:15,

165:21, 165:23,

165:25, 166:2,

166:16, 166:18,

167:5, 167:10,

167:12, 167:21,

169:3, 169:5, 169:10,

186:6, 197:3

SERT [17] - 130:2,

144:13, 151:16,

151:17, 151:20,

157:12, 157:13,

159:1, 160:7, 162:1,

165:19, 166:15,

167:20, 181:13,

186:5, 186:8, 186:9

SERT'S [1] - 165:20

SERTRALINE [17] -

1:4, 77:2, 80:3, 86:24,

103:10, 104:4, 108:7,

124:3, 124:14, 130:1,

150:12, 150:14,

150:22, 157:2,

188:18, 204:15,

204:21

SERUM [1] - 166:3

SERVANT [1] - 5:10

SERVES [2] - 6:17,

7:1

SERVICE [1] - 4:22

SESSION [3] - 58:16,

83:21, 175:12

SET [4] - 29:6, 58:1,

78:24, 103:1

SETS [1] - 141:18

SETTING [1] -

116:11

SETTINGS [1] -

49:24

SEVEN [3] - 5:24,

29:17, 66:15

SEVENTEENTH [1] -

2:12

SEVERAL [6] -

10:17, 20:12, 32:17,

49:22, 101:6, 124:4

SEVERE [1] - 151:15

SEVERITY [1] -

49:11

SHALEEN [1] - 77:6

SHALL [1] - 9:18

SHAPIRO [1] - 1:16

SHARE [3] - 42:22,

99:16, 100:24

SHARED [1] - 102:17

SHAW [1] - 101:5

SHEET [2] - 71:9,

135:15

SHEILA [3] - 2:8,

9:21, 29:8

SHIALI [5] - 69:13,

70:1, 92:25, 93:25

SHIALI'S [5] - 69:19,

125:13, 125:17,

125:20, 125:25

SHOCKED [1] -

61:14

SHORTER [1] -

58:19

SHOT [1] - 120:24

SHOTGUN [1] -

35:12

SHOW [16] - 12:10,

12:21, 13:5, 16:7,

16:19, 17:15, 18:20,

19:4, 25:21, 27:18,

28:15, 34:2, 37:4,

79:14, 117:18, 170:13

SHOWED [5] - 103:9,

110:14, 143:3, 150:9,

165:5

SHOWING [5] - 17:5,

36:16, 51:25, 109:19,

169:22

SHOWN [22] - 35:20,

79:23, 80:4, 82:6,

144:4, 147:17, 149:3,

149:12, 158:13,

163:17, 167:5,

167:14, 167:16,

184:11, 198:10,

198:13, 198:22,

200:1, 200:2, 204:10,

204:22, 205:18

SHOWS [9] - 40:3,

72:7, 93:19, 97:17,

143:21, 157:23,

165:1, 188:24, 203:5

SHUT [1] - 81:2

SIC [2] - 113:22,

151:17

SICK [7] - 127:23,

128:2, 128:4, 201:16,

202:18, 202:19,

202:24

SIDE [6] - 8:19,

73:22, 97:3, 97:4,

195:9, 195:12

SIDES [3] - 4:18,

5:21, 14:19

SIGNAL [1] - 160:2

SIGNALING [22] -

56:10, 56:17, 99:1,

100:9, 106:1, 124:2,

145:23, 146:18,

147:18, 147:23,

148:13, 149:1, 158:4,

158:6, 159:2, 159:24,

160:5, 160:6, 162:11,

162:18, 166:5, 169:3

SIGNALLING [3] -

162:21, 169:5, 186:5

SIGNALS [1] -

159:25

SIGNED [1] - 55:12

SIGNIFICANCE [13] -

39:22, 43:23, 44:2,

46:20, 87:11, 87:19,

87:21, 95:18, 105:3,

181:24, 183:25,

184:24, 193:3

SIGNIFICANT [28] -

21:5, 36:17, 43:24,

44:1, 44:21, 45:14,

45:19, 48:14, 48:15,

88:4, 102:24, 103:9,

103:17, 104:8,

104:10, 104:13,

105:2, 181:10, 184:1,

185:24, 190:4,

192:18, 192:24,

193:1, 193:8, 194:3,

194:8, 195:23

SIGNIFICANTLY [2]

235

- 37:22, 80:16

SILENCE [2] - 75:18,

76:10

SILLY [1] - 95:22

SIMILAR [19] - 8:7,

8:8, 42:22, 43:19,

45:2, 46:10, 69:6,

78:7, 89:7, 94:4, 94:7,

101:7, 139:16,

141:22, 150:13,

169:7, 172:9, 174:7,

174:9

SIMPLE [4] - 39:20,

127:14, 160:9, 169:4

SIMPLISTIC [2] -

159:22, 160:3

SIMPLY [13] - 35:10,

42:2, 88:5, 90:6,

90:18, 107:14,

127:15, 133:6, 160:6,

164:17, 182:17,

190:8, 200:7

SINGLE [5] - 50:21,

101:8, 104:22,

109:15, 170:4

SIT [1] - 198:25

SITES [2] - 148:22,

192:4

SITUATION [2] -

28:17, 202:9

SITUATIONS [1] -

202:12

SIX [7] - 66:15,

68:21, 69:2, 69:5,

124:21, 125:9, 126:4

SIXTH [2] - 133:16,

134:10

SKELETAL [5] -

183:14, 200:8, 200:9,

201:4, 206:25

SKELETAL/LIMB [1]

- 124:11

SKEPTICAL [2] -

142:15, 143:7

SKILLED [1] -

185:11

SLICE [1] - 45:4

SLIDE [28] - 10:18,

31:5, 38:5, 44:19,

74:1, 79:25, 82:8,

92:8, 92:10, 92:23,

108:24, 109:11,

109:22, 109:23,

124:10, 129:18,

131:2, 143:14,

143:19, 143:21,

145:20, 147:8,

175:23, 182:20,

199:21, 199:24,

206:15


SLIDES [3] - 84:22,

102:6, 175:19

SLIGHT [1] - 95:2

SMALL [1] - 79:15

SMALLER [2] - 71:1,

73:6

SMOKERS [1] - 48:8

SNAP [1] - 75:25

SNRI [2] - 77:5,

110:6

SOCIETY [23] -

15:10, 18:22, 27:13,

34:7, 42:11, 42:12,

52:16, 52:17, 53:21,

62:13, 63:15, 63:19,

63:25, 69:14, 69:21,

106:21, 106:23,

109:18, 110:2, 111:6,

111:12, 111:15,

124:20

SOCIETY'S [3] -

35:23, 42:18, 51:3

SOLD [1] - 16:1

SOLDO [2] - 43:17,

43:24

SOLE [2] - 23:9,

88:15

SOLELY [2] - 61:10,

122:15

SOLEM [3] - 41:1,

41:5, 49:25

SOLUBILITY [1] -

157:3

SOMEONE [1] - 48:5

SOMETIMES [7] -

74:16, 137:14,

152:21, 152:23,

153:3, 190:21, 190:23

SOMEWHAT [1] -

38:5

SOMEWHERE [3] -

66:7, 82:9, 122:3

SORRY [4] - 6:3,

51:10, 55:6, 188:11

SORT [13] - 13:7,

21:11, 22:25, 63:17,

65:21, 69:10, 88:15,

93:9, 117:21, 171:20,

175:20, 177:10, 191:3

SOUNDS [1] - 72:22

SOUTH [1] - 7:24

SP [1] - 132:14

SPAN [1] - 50:13

SPEAKER [1] - 6:15

SPEAKING [4] -

96:6, 148:14, 178:9,

178:10

SPECIAL [1] - 62:11

SPECIALISTS [1] -

17:7

SPECIALTY [1] -

155:11

SPECIES [8] - 155:7,

168:12, 168:20,

194:18, 195:7, 195:8,

195:11

SPECIFIC [53] -

11:21, 11:24, 15:13,

30:19, 32:14, 32:18,

33:13, 34:3, 35:5,

35:20, 36:9, 36:18,

37:21, 41:25, 42:1,

42:14, 50:10, 51:5,

53:12, 53:17, 53:18,

53:19, 91:18, 100:9,

101:5, 103:9, 105:8,

105:10, 117:20,

129:10, 129:20,

129:24, 129:25,

130:8, 130:22, 131:5,

132:7, 135:25,

140:22, 141:3,

159:13, 162:18,

166:12, 166:13,

169:23, 169:25,

172:23, 172:25,

183:3, 183:11

SPECIFICALLY [12]

- 32:25, 62:17, 81:2,

82:22, 84:6, 84:19,

89:15, 97:13, 99:17,

122:11, 126:15,

143:13

SPECIFICITY [7] -

36:3, 36:12, 36:20,

38:14, 38:25, 39:11,

53:13

SPECTRUM [2] -

100:10, 100:15

SPELL [1] - 112:25

SPELLED [1] - 22:19

SPEND [4] - 22:2,

24:7, 84:4, 96:7

SPENT [4] - 5:4,

22:13, 43:12, 58:22

SPINA [1] - 174:4

SPINAL [1] - 207:9

SPONTANEOUS [10]

- 80:14, 81:8, 81:9,

109:19, 179:13,

193:9, 193:12,

193:13, 203:5, 203:17

SPURIOUS [1] -

45:14

SSRI [45] - 11:18,

14:23, 14:24, 14:25,

16:5, 19:5, 19:6,

33:19, 33:23, 34:2,

34:7, 35:6, 37:24,

49:5, 49:8, 49:16,

49:18, 50:1, 55:20,

56:1, 73:18, 77:5,

78:10, 82:12, 88:23,

90:4, 90:23, 99:7,

99:10, 102:18,

104:10, 106:16,

108:5, 108:12, 110:6,

148:25, 149:2, 150:6,

161:10, 174:7,

199:13, 199:18,

205:9, 205:25, 206:13

SSRIS [119] - 11:16,

11:18, 14:7, 14:15,

14:17, 15:5, 15:6,

15:8, 15:17, 18:4,

20:13, 20:22, 21:2,

25:9, 25:12, 25:14,

26:8, 29:22, 31:17,

34:6, 34:15, 34:19,

34:21, 34:25, 37:9,

42:22, 42:24, 43:9,

43:14, 46:19, 47:5,

47:8, 47:19, 48:12,

48:13, 55:1, 55:5,

55:10, 57:4, 66:22,

66:24, 68:12, 72:15,

73:6, 73:13, 73:17,

76:21, 76:23, 80:13,

80:15, 80:17, 80:18,

82:4, 82:17, 86:23,

89:14, 97:12, 98:1,

98:20, 98:23, 99:10,

99:13, 99:24, 101:23,

102:3, 102:20, 103:9,

103:15, 104:2, 105:9,

105:20, 106:11,

106:17, 108:21,

109:19, 110:22,

124:2, 124:14, 128:8,

143:12, 143:23,

145:1, 145:3, 145:9,

147:15, 151:25,

152:2, 156:24,

157:10, 157:24,

159:7, 159:23,

161:20, 161:24,

162:11, 162:23,

162:24, 162:25,

163:19, 164:9,

169:14, 169:23,

170:13, 171:10,

171:14, 172:10,

186:14, 191:3, 191:9,

197:2, 203:6, 203:16,

204:2, 205:12,

205:16, 206:10,

206:17, 206:21

ST [1] - 2:12

STACKED [1] -

104:18

STAGE [6] - 3:25,

4:1, 5:20, 29:6,

126:10, 128:16

STAMP [1] - 75:20

STAND [6] - 73:22,

112:4, 112:6, 170:3,

207:16, 207:18

STANDARD [12] -

3:20, 24:12, 41:13,

68:25, 69:22, 85:7,

93:10, 94:18, 95:6,

95:22, 101:4

STANDARDS [3] -

23:25, 24:1, 30:13

STANDS [3] - 35:9,

38:2, 84:16

STARS [1] - 2:15

START [10] - 8:10,

8:11, 9:12, 29:13,

81:11, 123:23,

156:12, 157:1,

191:25, 207:14

STARTED [4] -

56:24, 59:10, 80:21,

80:24

STARTING [1] -

173:4

STATE [8] - 3:6, 3:8,

7:22, 17:17, 33:11,

70:21, 71:6, 112:25

STATEMENT [6] -

9:22, 51:21, 142:14,

152:5, 184:14, 199:8

STATEMENTS [3] -

5:13, 25:3, 107:25

STATES [4] - 1:1,

12:20, 28:1, 53:22

STATISTIC [1] - 20:3

STATISTICAL [12] -

13:22, 39:22, 43:22,

44:2, 46:20, 87:11,

88:10, 95:17, 105:3,

181:24, 183:25, 193:2

STATISTICALLY [18]

- 33:6, 36:16, 43:24,

44:1, 44:21, 45:14,

88:4, 103:17, 104:10,

104:13, 105:2, 181:9,

192:17, 192:24,

193:8, 194:2, 194:8,

195:23

STATISTICIANS [2] -

95:16, 95:21

STATISTICS [2] -

19:21, 62:7

STAYED [2] - 81:4,

183:1

STEERS [1] - 170:20

STEM [8] - 7:1,

65:21, 71:19, 116:19,

146:4, 146:8, 166:11

236

STEM-TO-STERN

[2] - 65:21, 71:19

STENOTYPE [1] -

1:25

STENOTYPE-

COMPUTER [1] - 1:25

STEP [4] - 44:23,

72:14, 72:17, 157:6

STEPS [2] - 27:25,

72:12

STERN [2] - 65:21,

71:19

STEVEN [1] - 153:13

STILL [6] - 38:2,

106:23, 138:3,

183:10, 201:18,

202:16

STILLBIRTHS [4] -

74:22, 186:23, 187:4,

196:25

STOCK [1] - 110:2

STOP [4] - 21:1,

26:13, 26:16, 94:21

STRATEGIES [2] -

139:6, 139:20

STREAM [1] - 158:3

STREET [5] - 1:13,

1:23, 2:3, 2:6, 2:19

STRENGTH [2] -

94:5, 97:19

STRENGTHENS [1] -

168:18

STRENGTHS [1] -

42:3

STRENUOUSLY [1] -

17:16

STRICTLY [4] - 92:4,

178:9, 178:10, 194:5

STRIKES [1] - 19:19

STROM [1] - 43:3

STRONG [4] - 21:20,

51:23, 85:17, 97:11

STRONGER [2] -

37:10, 103:18

STRUCTURAL [4] -

132:24, 133:12,

133:14, 153:10

STRUCTURE [5] -

136:7, 147:22, 153:3,

154:3, 171:19

STRUCTURES [5] -

42:23, 143:25, 153:4,

153:7, 168:7

STUDENTS [3] -

93:8, 96:12, 112:11

STUDIED [10] - 12:5,

13:18, 14:9, 17:10,

37:13, 48:1, 80:8,

80:19, 108:22, 190:22

STUDIES [172] -


11:9, 11:13, 13:17,

26:24, 27:16, 28:4,

28:7, 28:11, 30:3,

30:4, 30:7, 33:11,

35:22, 35:25, 36:16,

37:1, 37:14, 38:12,

38:15, 38:24, 39:7,

40:1, 40:13, 41:6,

42:1, 42:2, 44:10,

44:11, 44:19, 45:9,

45:18, 46:11, 46:19,

46:21, 48:18, 49:1,

49:20, 51:11, 51:18,

54:11, 54:13, 55:19,

62:25, 64:12, 66:1,

75:1, 75:14, 78:1,

81:25, 82:11, 85:21,

86:2, 86:10, 86:12,

86:17, 87:8, 91:8,

91:23, 95:23, 98:2,

98:3, 101:18, 102:24,

103:4, 104:15,

105:14, 106:8, 110:8,

121:3, 121:5, 121:6,

121:7, 121:9, 121:17,

122:6, 122:13,

136:17, 136:21,

137:22, 141:2, 141:4,

141:9, 141:10,

142:19, 143:2,

145:16, 150:20,

154:15, 154:23,

154:25, 155:1,

155:16, 155:20,

168:6, 169:13,

169:17, 169:22,

170:8, 170:12,

170:25, 177:1, 177:3,

177:5, 177:6, 177:9,

177:11, 177:15,

177:16, 177:18,

177:20, 178:4, 178:7,

178:8, 178:9, 178:11,

178:15, 178:17,

178:20, 179:8,

179:16, 179:17,

179:19, 179:20,

180:17, 180:19,

182:2, 184:13,

184:17, 186:13,

186:15, 186:18,

187:1, 190:3, 190:8,

190:12, 190:16,

190:20, 190:24,

191:3, 194:22, 195:6,

197:13, 197:23,

198:4, 198:6, 198:8,

198:10, 198:12,

198:13, 198:18,

199:1, 199:5, 199:9,

199:10, 199:19,

200:11, 200:12,

201:24, 201:25,

202:5, 202:6, 202:8,

202:11, 203:7,

203:12, 205:24

STUDY [89] - 12:7,

12:19, 16:3, 25:6,

37:12, 38:20, 44:7,

44:13, 45:9, 45:13,

46:5, 46:25, 48:16,

49:7, 49:23, 51:11,

56:2, 56:8, 61:11,

72:6, 77:6, 78:12,

80:12, 80:13, 86:16,

98:22, 98:23, 101:17,

101:21, 101:23,

101:25, 103:22,

104:22, 105:18,

108:20, 109:15,

115:24, 118:17,

118:19, 118:23,

142:21, 150:5,

150:13, 151:8,

166:25, 167:2, 170:4,

170:10, 178:13,

179:1, 179:5, 179:20,

180:7, 180:8, 180:9,

181:19, 182:1,

182:11, 182:15,

182:21, 182:23,

183:5, 183:7, 184:24,

184:25, 186:20,

188:7, 188:8, 188:13,

188:15, 188:24,

190:5, 191:20,

196:13, 197:6, 200:5,

200:6, 200:10,

200:25, 201:12,

202:2, 203:15, 204:1,

204:7

STUDY'S [1] - 86:6

STUDYING [1] -

113:21

STUFF [1] - 200:22

STUNNING [1] -

40:11

SUBJECT [5] - 8:5,

67:22, 68:9, 79:19,

84:20

SUBMITTED [2] -

37:7, 41:22

SUBNANOMOLAR

[1] - 157:25

SUBSTANCES [2] -

21:15, 21:21

SUBSTANTIALLY

[1] - 36:7

SUBSTITUTE [1] -

43:20

SUCCESSFUL [1] -

5:9

SUDDEN [5] - 16:3,

16:9, 31:20, 94:17,

181:16

SUFFER [1] - 10:5

SUFFERING [1] -

35:3

SUGGEST [20] -

17:12, 25:12, 32:20,

37:18, 69:24, 70:7,

72:23, 75:13, 80:12,

80:18, 82:1, 106:16,

108:4, 117:21,

138:16, 139:22,

152:15, 200:24,

205:13, 205:24

SUGGESTED [5] -

35:11, 35:18, 54:25,

127:2, 201:23

SUGGESTING [3] -

53:4, 72:10, 151:22

SUGGESTS [2] -

108:20, 204:2

SUICIDE [2] - 20:1,

20:3

SUICIDES [1] - 20:2

SUITE [6] - 1:13,

1:19, 2:3, 2:6, 2:12,

2:15

SULLIVAN [1] - 2:9

SUMMARIZED [1] -

177:8

SUMMARY [3] -

33:1, 123:23, 124:8

SUMMER [1] - 109:1

SUN [2] - 70:5,

104:22

SUPER [1] - 149:23

SUPERVISE [1] -

121:11

SUPPLANT [1] - 24:4

SUPPORT [12] -

11:9, 11:10, 34:3,

40:7, 41:7, 57:6,

86:21, 88:15, 97:18,

143:6, 161:19, 205:22

SUPPORTED [1] -

26:22

SUPPORTING [2] -

40:13, 70:5

SUPPORTIVE [2] -

25:24, 28:19

SUPPORTS [4] -

11:7, 16:7, 25:22,

30:6

SUPPOSED [9] -

41:17, 68:15, 68:16,

103:1, 149:19,

159:15, 159:24,

182:5, 182:6

SUPREME [5] -

23:23, 24:10, 24:16,

87:12, 90:8

SURELY [1] - 95:22

SURPRISE [1] -

201:6

SURPRISED [2] -

19:20, 20:2

SURPRISING [1] -

85:23

SURVEILLANCE [1]

- 109:3

SURVIVAL [6] -

181:1, 192:3, 192:15,

192:17, 193:1, 194:4

SUSCEPTIBILITIES

[1] - 138:20

SUSCEPTIBILITY

[10] - 121:1, 126:5,

126:7, 127:7, 127:17,

128:7, 128:11,

128:15, 128:19,

139:12

SUSCEPTIBLE [2] -

126:9, 139:14

SUSPECT [1] - 39:16

SUSPECTED [1] -

101:7

SUZANNE [2] - 1:21,

208:4

SWITCH [1] - 174:11

SWORN [1] - 112:24

SWUNG [1] - 95:19

SYMMETRICAL [1] -

148:1

SYMPTOMS [1] -

19:23

SYNAPSIS [1] -

149:5

SYNAPTIC [1] -

157:15

SYNCYTIOTROPH

OBLAST [1] - 131:15

SYNDROME [2] -

36:2, 181:17

SYSTEM [18] - 13:2,

31:8, 32:11, 35:12,

124:13, 126:13,

126:19, 133:7,

149:11, 150:1,

151:15, 152:1, 156:9,

173:5, 174:3, 175:21,

183:2, 207:8

SYSTEMATIC [2] -

46:25, 162:5

SYSTEMICALLY [1]

- 144:15

SYSTEMS [15] -

13:4, 21:4, 31:16,

50:14, 97:14, 100:11,

237

101:9, 102:20,

118:11, 118:13,

124:5, 128:19, 148:1,

149:17, 165:13

T

TABLE [10] - 57:23,

79:16, 79:22, 191:18,

192:25, 204:10,

204:12, 204:13,

204:15, 204:18

TABLES [1] - 99:9

TAILORED [1] - 3:20

TAINTED [1] - 91:23

TAKEAWAY [1] -

37:18

TAKING [15] - 21:1,

37:15, 37:16, 44:23,

44:25, 47:5, 47:8,

49:10, 58:10, 105:15,

105:16, 110:23,

157:21, 201:17

TALKS [3] - 14:14,

36:24, 110:14

TALUS [1] - 183:13

TARGET [4] -

129:23, 140:21,

161:25, 162:23

TARGETING [1] -

153:7

TARGETS [2] -

159:8, 163:18

TASKS [2] - 146:10,

146:13

TAUGHT [2] -

112:12, 125:18

TE [1] - 149:17

TEACH [1] - 93:8

TEACHES [2] -

29:20, 96:12

TEACHING [1] - 62:9

TEAM [3] - 6:7, 6:9,

9:2

TECHNIQUE [1] -

166:10

TEDIOUSNESS [1] -

156:14

TEMPORALITY [2] -

94:5, 97:22

TEN [11] - 58:10,

63:4, 64:21, 66:11,

72:1, 77:18, 192:11,

192:20, 193:4, 202:4,

207:14

TENNESSEE [1] -

7:22

TERATOGEN [24] -

19:2, 19:8, 31:3,

35:19, 36:12, 36:20,


65:24, 69:1, 69:4,

75:2, 75:22, 81:12,

81:14, 117:12, 123:9,

123:14, 127:22,

132:17, 141:25,

172:15, 174:6,

189:21, 193:18,

204:19

TERATOGENESIS

[4] - 43:6, 43:8, 127:8,

151:5

TERATOGENIC [32]

- 28:3, 34:4, 35:2,

51:4, 74:1, 74:4, 82:2,

82:5, 100:25, 128:15,

129:9, 129:22,

132:18, 132:21,

139:25, 140:2,

150:21, 180:2,

184:18, 184:22,

189:22, 193:19,

193:20, 194:21,

194:22, 197:12,

198:1, 200:4, 205:10,

205:14, 205:17,

205:24

TERATOGENICITY

[19] - 12:1, 14:22,

15:4, 28:5, 33:21,

34:6, 34:15, 36:4,

42:9, 52:17, 75:8,

109:22, 116:21,

117:15, 144:23,

180:1, 184:12,

184:16, 203:9

TERATOGENS [20] -

34:20, 35:1, 35:10,

35:13, 82:13, 82:18,

98:8, 98:11, 117:20,

124:25, 137:5, 142:2,

145:1, 145:9, 172:8,

172:22, 173:1,

204:22, 206:10

TERATOLOGICAL

[5] - 67:11, 69:23,

178:9, 178:14, 194:11

TERATOLOGIST [13]

- 7:18, 64:10, 64:11,

68:23, 70:17, 73:14,

113:9, 113:10,

113:18, 154:11,

170:24, 185:2, 185:19

TERATOLOGISTS

[10] - 36:10, 36:19,

52:11, 65:5, 133:11,

144:19, 152:21,

168:8, 168:14, 195:6

TERATOLOGY [62] -

15:10, 17:7, 18:22,

20:10, 27:12, 28:10,

32:15, 35:22, 36:24,

42:10, 42:11, 42:12,

42:18, 46:17, 51:3,

52:9, 52:16, 52:19,

53:21, 63:15, 63:19,

64:11, 66:2, 66:14,

69:14, 69:20, 70:24,

78:16, 78:24, 81:15,

92:11, 92:22, 93:4,

111:13, 114:3,

115:22, 115:23,

124:20, 124:22,

124:23, 125:2,

125:14, 125:17,

125:18, 125:21,

125:22, 126:1, 126:4,

126:24, 127:3, 129:7,

129:15, 130:17,

131:24, 132:6, 132:7,

133:16, 134:11,

168:15, 173:10,

178:13, 179:7

TERATOLOGY-

RELATED [1] - 93:4

TERM [5] - 156:7,

162:23, 168:23,

185:18, 192:13

TERMS [8] - 33:20,

41:13, 41:17, 43:12,

48:25, 127:15,

148:13, 201:1

TERRIBLE [1] -

19:18

TEST [22] - 10:22,

27:16, 28:14, 44:20,

54:11, 54:12, 55:20,

56:6, 84:18, 116:16,

116:20, 118:10,

135:21, 139:19,

141:6, 141:17,

141:24, 155:18,

166:12, 168:10,

168:21, 193:24

TESTED [3] - 47:7,

55:20, 118:8

TESTIFIED [5] -

54:19, 70:2, 77:9,

206:2, 206:4

TESTIFIES [2] -

96:18, 97:21

TESTIFY [4] - 8:20,

12:23, 91:19, 97:1

TESTIMONY [9] -

8:9, 8:10, 10:13,

12:16, 23:25, 24:21,

84:19, 143:17, 176:8

TESTING [19] -

10:22, 10:23, 27:24,

28:16, 28:19, 46:6,

46:11, 55:18, 56:7,

116:14, 132:15,

134:17, 152:16,

168:13, 168:20,

183:23, 194:11

TESTINGS [1] -

45:17

TESTS [15] - 44:23,

44:24, 44:25, 45:2,

45:7, 45:10, 45:19,

45:20, 87:20, 87:21,

134:10, 134:11,

134:14, 168:21, 194:7

TEXAS [11] - 6:25,

7:4, 64:15, 64:20,

64:23, 113:12,

113:20, 118:25,

119:16, 120:1, 120:2

TEXTBOOK [3] -

54:23, 55:10, 79:16

TEXTBOOKS [1] -

79:20

THALIDOMIDE [8] -

19:9, 172:12, 172:13,

172:14, 172:19,

173:6, 173:10

THEMSELVES [8] -

47:15, 51:20, 73:1,

79:11, 95:21, 158:17,

164:6, 170:9

THEORIES [3] -

29:2, 40:7, 56:1

THEORY [4] - 23:12,

27:16, 66:23, 98:17

THERAPEUTIC [3] -

54:18, 144:10, 162:3

THERAPY [3] -

16:22, 20:23, 26:9

THERE [238] - 3:17,

8:9, 8:11, 8:18, 11:9,

11:15, 11:16, 12:21,

13:15, 13:16, 13:20,

13:21, 13:22, 14:15,

14:22, 14:23, 15:2,

16:2, 16:4, 16:10,

16:12, 18:1, 19:14,

21:5, 22:7, 25:7,

26:13, 28:3, 31:12,

31:13, 31:19, 32:1,

33:1, 33:8, 33:9,

34:20, 36:22, 37:4,

38:9, 38:11, 38:14,

38:19, 39:6, 39:11,

40:3, 40:14, 41:8,

41:18, 41:19, 41:20,

41:25, 44:8, 47:16,

48:7, 48:21, 50:6,

50:10, 50:11, 53:7,

54:6, 55:4, 56:16,

56:20, 57:7, 59:13,

59:15, 60:10, 69:12,

69:22, 69:25, 70:1,

70:15, 71:2, 72:14,

73:2, 73:3, 73:15,

73:16, 74:1, 74:4,

75:12, 76:14, 77:18,

78:23, 80:7, 80:10,

80:25, 81:3, 82:8,

84:9, 85:22, 86:1,

88:16, 90:20, 91:5,

92:17, 95:11, 97:10,

98:5, 98:14, 98:24,

100:4, 100:8, 101:2,

101:22, 101:24,

102:8, 102:16, 103:3,

103:5, 103:22, 106:5,

106:11, 106:12,

106:23, 106:25,

107:21, 108:1, 110:1,

110:11, 110:12,

110:16, 111:2, 111:4,

111:9, 113:13,

113:16, 114:14,

117:9, 119:3, 121:18,

123:1, 125:6, 125:9,

125:10, 125:11,

125:12, 129:16,

130:23, 131:5, 132:1,

132:22, 132:25,

134:12, 137:9,

138:11, 138:25,

140:5, 142:15,

142:19, 143:4,

143:24, 145:7,

145:10, 145:14,

145:16, 147:9,

148:12, 156:2,

157:23, 158:24,

160:1, 161:24,

162:20, 163:8, 164:1,

164:2, 165:3, 165:23,

169:20, 170:7,

170:16, 170:17,

170:19, 170:22,

171:13, 171:16,

172:8, 172:18,

173:12, 177:22,

178:1, 179:2, 179:5,

180:17, 180:24,

181:3, 181:20, 182:6,

182:22, 183:2, 183:5,

183:7, 184:12,

184:16, 184:18,

184:25, 185:23,

186:22, 186:25,

188:16, 189:22,

189:23, 190:15,

192:16, 192:25,

193:22, 193:25,

194:2, 194:15,

195:18, 195:23,

197:7, 197:12,

238

197:25, 198:5, 198:7,

198:11, 198:13,

198:17, 198:25,

199:2, 199:3, 199:8,

199:10, 203:21,

204:3, 205:21

THERE'S [10] - 9:5,

27:8, 89:10, 91:1,

105:23, 144:16,

162:12, 170:14, 181:7

THEREBY [1] - 47:1

THEREFORE [8] -

3:19, 21:16, 54:8,

91:24, 150:13, 158:6,

196:6, 201:16

THEREIN [1] - 51:16

THEY'RE [7] - 20:9,

78:8, 82:13, 176:9,

177:8, 179:18

THIRD [9] - 7:6,

11:11, 47:21, 85:14,

90:16, 129:7, 129:8,

129:15, 192:14

THIRD-TRIMESTER

[1] - 192:14

THOMAS [1] - 7:15

THOUSANDS [8] -

12:8, 16:1, 16:2, 18:6,

120:18, 127:25

THREAT [1] - 117:4

THREATENING [1] -

19:18

THREE [27] - 27:6,

29:18, 38:8, 46:22,

52:25, 53:10, 54:5,

57:2, 59:6, 60:5,

65:13, 66:15, 67:25,

80:3, 104:5, 104:9,

108:8, 147:6, 147:22,

156:3, 170:23,

176:19, 180:16,

195:19, 196:2

THREE-FOLD [2] -

104:5, 108:8

THREE-LAYERED

[1] - 147:22

THREE-PRONG [1] -

46:22

THRESHOLD [1] -

24:4

THROUGHOUT [10]

- 155:8, 165:13,

167:4, 168:19, 169:8,

172:24, 190:15,

195:21, 196:11,

196:13

THROW [1] - 23:19

TIMING [3] - 126:11,

128:15, 144:4

TINY [1] - 73:7


TIPS [1] - 48:9

TISSUE [13] - 65:18,

71:17, 72:16, 141:9,

146:7, 146:8, 159:8,

159:13, 159:16,

161:4, 161:5, 164:22,

164:23

TISSUES [10] -

129:12, 130:13,

130:20, 136:11,

136:12, 141:4,

142:22, 155:1, 165:2,

165:11

TITLE [1] - 92:24

TOBACCO [1] - 20:6

TODAY [35] - 3:10,

3:22, 5:8, 14:12, 41:9,

41:17, 43:15, 60:22,

61:3, 78:17, 78:20,

78:23, 84:1, 85:10,

85:15, 87:5, 96:17,

101:20, 102:3,

107:20, 109:23,

123:2, 123:18, 156:6,

174:14, 175:2, 175:4,

175:6, 175:7, 175:9,

197:16, 198:25,

199:8, 206:3, 207:17

TOE [2] - 31:10,

35:12

TOGETHER [17] -

14:24, 16:16, 17:21,

30:22, 38:18, 50:12,

50:22, 63:7, 73:11,

73:14, 99:12, 99:13,

104:9, 135:15,

143:16, 194:2, 199:21

TOM [4] - 60:17,

66:4, 72:20, 76:15

TOMORROW [4] -

96:17, 163:21, 176:5,

207:15

TONIGHT [3] -

175:17, 176:4, 207:18

TONIN [1] - 166:2

TOOK [2] - 163:3,

189:18

TOP [7] - 27:13,

63:4, 67:25, 120:24,

143:22, 179:19,

191:20

TOPAMAX [1] -

75:21

TOPIC [2] - 65:1,

195:1

TOPICS [1] - 174:11

TORT [1] - 21:19

TOTALITY [1] - 77:4

TOTALLY [1] - 24:9

TOUCHED [1] - 50:7

TOWARD [2] - 21:21,

205:13

TOWARDS [1] - 82:2

TOWER [1] - 2:18

TOXIC [2] - 71:8,

128:4

TOXICANT [2] -

71:14, 135:21

TOXICITY [16] - 78:1,

116:21, 151:8, 177:6,

177:16, 177:17,

177:20, 178:11,

178:17, 179:9,

201:25, 202:3, 202:6,

202:11, 202:13,

202:16

TOXICOLOGY [1] -

178:8

TOXIN [1] - 127:22

TPH1 [1] - 166:16

TRACER [1] - 71:24

TRACEY [43] - 1:18,

1:19, 6:3, 8:1, 57:25,

58:7, 58:18, 58:20,

71:5, 83:1, 83:3,

89:16, 92:13, 108:19,

112:18, 112:21,

113:2, 113:5, 156:12,

156:22, 161:13,

161:17, 171:17,

172:1, 174:10,

174:17, 174:21,

174:23, 175:2, 175:4,

175:7, 175:14,

175:16, 176:5,

176:16, 176:20,

176:23, 188:11,

188:12, 207:11,

207:19, 207:22

TRACT [7] - 103:12,

160:19, 164:5, 167:8,

167:14, 167:19, 171:4

TRACTS [1] - 158:15

TRAGEDY [1] - 57:7

TRAINED [3] - 65:3,

90:24, 113:17

TRAINING [5] -

24:15, 67:14, 115:19,

120:1, 141:18

TRANS [1] - 172:20

TRANSCRIPT [3] -

1:25, 3:11, 207:25

TRANSCRIPTION [1]

- 1:25

TRANSFER [1] -

131:14

TRANSLATED [1] -

146:12

TRANSPORT [4] -

131:16, 161:25,

162:19, 164:18

TRANSPORTER [11]

- 130:3, 144:12,

149:5, 149:23, 159:1,

162:1, 162:3, 162:9,

162:19, 165:21,

166:16

TRANSPORTERS

[2] - 159:4, 186:10

TRANSPORTS [1] -

159:20

TRAVEL [2] - 70:13,

70:16

TREAT [4] - 15:5,

20:13, 29:23, 191:25

TREATED [9] - 20:5,

74:24, 75:8, 99:12,

180:16, 181:11,

181:12, 183:12,

183:22

TREATISE [1] -

12:19

TREATISES [1] -

33:10

TREATMENT [11] -

13:11, 16:18, 16:22,

16:23, 26:3, 26:15,

26:17, 37:24, 190:18,

191:23, 191:25

TREATMENTS [3] -

25:15, 111:5, 190:19

TREND [4] - 18:21,

18:23, 82:1, 205:13

TRENDING [2] -

104:20, 106:11

TRENDS [1] - 88:16

TRIAL [4] - 75:7,

83:13, 85:11, 85:13

TRIALS [1] - 91:18

TRICYCLIC [1] -

101:24

TRIED [2] - 29:6,

38:6

TRIER [1] - 85:18

TRIES [2] - 51:17,

64:16

TRIGG [1] - 2:12

TRIMESTER [11] -

18:9, 25:9, 34:8, 79:6,

79:8, 108:13, 152:13,

192:14, 193:5,

197:25, 205:23

TRIP [1] - 5:6

TRIPLE [1] - 201:9

TROUBLING [2] -

31:22

TRUE [23] - 30:23,

32:10, 39:18, 39:24,

44:6, 44:8, 46:23,

54:6, 69:10, 73:4,

73:20, 74:6, 74:7,

77:14, 89:16, 95:13,

96:16, 108:2, 128:10,

170:5, 172:10, 172:11

TRUNCUS [2] -

165:9, 167:17

TRUTH [6] - 68:7,

69:25, 75:16, 90:20,

110:22, 126:24

TRY [13] - 4:20,

15:23, 22:21, 30:19,

58:18, 116:8, 123:8,

135:11, 141:23,

161:14, 161:15,

170:16, 190:2

TRYING [13] - 22:24,

27:10, 60:13, 61:6,

69:1, 69:3, 77:20,

77:21, 77:23, 138:23,

139:8, 139:19, 185:10

TUBE [13] - 10:22,

28:14, 54:11, 54:12,

100:16, 105:22,

115:11, 155:18,

163:25, 185:13,

185:14, 185:20,

192:23

TUCCORI [3] -

81:21, 205:4, 206:5

TUFTS [3] - 7:9,

7:11, 67:15

TURN [5] - 29:4,

29:14, 43:22, 54:9,

147:21

TURNS [1] - 63:24

TWICE [5] - 4:25,

47:7, 47:18, 47:20,

60:21

TWO [16] - 6:9, 9:2,

9:5, 29:19, 39:7,

39:10, 59:6, 63:5,

66:14, 67:5, 67:25,

99:21, 156:3, 170:17,

170:23, 196:1

TX [1] - 1:20

TYPE [12] - 17:24,

27:23, 79:12, 129:20,

130:1, 130:7, 146:7,

146:8, 151:19, 159:8,

159:9, 195:11

TYPES [9] - 36:8,

92:6, 138:24, 138:25,

146:6, 154:15,

169:25, 172:3, 173:24

TYPICALLY [8] -

51:4, 133:22, 134:6,

168:11, 179:3,

182:13, 183:24,

194:17

239

U

U.S [2] - 119:12,

140:12

UK [2] - 110:24

ULTIMATE [2] -

81:11, 84:14

ULTIMATELY [61] -

60:7, 114:18, 129:13,

130:8, 130:13,

130:15, 131:17,

133:1, 133:4, 133:8,

136:7, 136:12,

136:14, 139:5, 139:8,

139:19, 141:5,

144:14, 145:18,

146:6, 146:11, 148:4,

148:20, 149:6,

149:22, 149:25,

157:13, 157:22,

158:2, 158:18,

159:19, 160:5, 162:1,

162:11, 163:19,

165:7, 165:11,

165:16, 165:19,

166:12, 167:19,

169:21, 178:3,

179:24, 181:4,

183:14, 183:24,

184:1, 187:5, 188:20,

188:22, 188:23,

190:18, 191:20,

191:21, 191:25,

192:5, 197:23, 198:9,

198:14, 198:18

UNABLE [1] - 61:18

UNBORN [1] - 20:18

UNCHALLENGED

[1] - 68:20

UNCONTROLLED

[1] - 91:23

UNDEMONSTRATE

D [1] - 34:6

UNDER [18] - 10:1,

23:12, 24:12, 33:12,

44:1, 54:1, 56:8, 57:9,

65:3, 70:5, 80:4,

84:21, 86:15, 90:16,

95:9, 103:1, 104:22,

164:15

UNDERFUNDED [1]

- 76:6

UNDERGOES [1] -

163:25

UNDERGRADUATE

[1] - 113:20

UNDERLIE [1] -

52:20

UNDERLINED [1] -

140:19


UNDERLYING [4] -

34:18, 48:14, 49:8,

49:16

UNDERMINE [1] -

42:5

UNDERPINNINGS

[1] - 69:3

UNDERPOWERED

[3] - 178:23, 179:1,

190:20

UNDERSTANDABL

E [1] - 161:16

UNDERSTOOD [3] -

48:10, 48:24, 114:22

UNDERTAKING [1] -

121:17

UNDERTOOK [2] -

123:6, 145:6

UNDISPUTED [1] -

17:23

UNFAMILIAR [1] -

132:6

UNIFORMLY [1] -

35:14

UNIQUE [3] - 41:25,

126:7, 127:16

UNIQUELY [2] -

68:11, 126:8

UNITED [2] - 1:1,

28:1

UNIVERSITIES [1] -

62:9

UNIVERSITY [21] -

6:14, 6:21, 6:25, 7:4,

7:9, 7:16, 7:20, 7:22,

29:21, 62:6, 62:8,

63:5, 66:8, 66:10,

67:20, 79:21, 113:12,

113:21, 113:24,

120:1, 120:2

UNKNOWN [1] -

17:24

UNLESS [2] - 54:5,

193:18

UNLIKE [1] - 89:17

UNLIKELY [1] -

117:20

UNQUESTIONED [1]

- 28:2

UNQUOTE [1] -

95:13

UNRELIABLE [3] -

21:3, 29:12, 43:10

UNSAFE [1] - 16:1

UNTREATED [6] -

19:17, 19:24, 20:11,

20:17, 49:21, 183:21

UNTRUE [1] - 79:11

UNUSUAL [3] - 91:1,

101:3, 117:21

UP [34] - 19:2, 19:6,

19:10, 19:11, 43:14,

58:2, 60:18, 64:13,

69:6, 69:15, 76:24,

76:25, 81:2, 86:1,

93:2, 94:8, 104:18,

106:22, 112:4, 126:3,

131:15, 145:20,

146:14, 151:12,

161:1, 166:20, 170:3,

173:12, 189:25,

191:24, 202:4,

203:10, 205:21,

206:15

UPSET [1] - 107:8

UPTAKE [3] - 73:9,

154:4, 154:9

URGENCY [1] - 79:7

URQUHART [1] - 2:9

USERS [2] - 80:19,

108:22

USES [4] - 69:18,

70:23, 146:10, 186:5

UTAH [1] - 7:20

UTERO [9] - 100:8,

133:12, 184:20,

187:4, 188:18,

188:24, 189:4, 191:6,

193:12

UTERUS [2] -

179:24, 192:5

UTILIZED [1] - 121:3

V

VAGUE [1] - 185:11

VALID [6] - 40:10,

42:10, 45:12, 52:23,

59:23, 78:13

VALIDITY [2] - 47:1,

101:6

VALPROIC [2] -

35:17, 115:6

VALVE [3] - 160:17,

165:18, 165:24

VALVES [2] - 165:18,

167:7

VANNEVAR [1] -

7:10

VARIABILITIES [1] -

138:7

VARIABILITY [1] -

170:14

VARIABLE [1] -

47:25

VARIANTS [2] -

138:13, 139:18

VARIATION [1] -

45:25

VARIATIONS [1] -

46:16

VARIES [1] - 128:16

VARIETY [21] -

50:20, 99:3, 122:19,

132:8, 145:4, 145:25,

161:9, 167:6, 167:18,

167:22, 168:17,

171:2, 172:18,

172:21, 173:1, 173:2,

173:19, 174:7, 181:3,

181:7, 201:3

VARIOUS [8] - 14:23,

15:17, 124:5, 156:9,

168:19, 179:17,

199:4, 201:4

VARY [1] - 42:23

VARYING [1] - 98:2

VASCULAR [1] -

164:5

VASCULATURE [3] -

166:1, 166:4, 183:4

VAST [4] - 31:3,

38:6, 47:14, 50:13

VEHICLE [1] -

183:22

VEIN [3] - 182:24,

183:18, 184:3

VEINS [1] - 182:25

VENTRAL [2] -

167:7, 167:17

VENTRICLE [1] -

171:5

VENTRICULAR [2] -

103:12, 159:25

VERSE [1] - 89:9

VERSUS [5] - 35:8,

36:6, 76:3, 181:6,

183:18

VERTEBRAE [1] -

169:7

VETERINARIAN [1] -

185:3

VIABILITY [1] -

188:25

VIDEO [1] - 3:12

VIEW [4] - 25:22,

25:24, 46:3

VIEWPOINT [1] -

70:17

VIEWS [1] - 29:25

VIGOROUS [1] -

85:11

VIOLATE [1] - 52:22

VIRGINIA [3] - 7:16,

66:8, 66:10

VIRTUALLY [3] -

31:7, 105:18, 164:12

VISCERA [1] - 200:8

VISCERAL [2] - 7:14,

190:22

VISITING [2] - 5:4,

7:20

VITRO [8] - 28:14,

134:17, 140:21,

141:5, 154:23,

155:16, 168:20,

168:21

VIVO [4] - 134:17,

154:25, 155:20,

160:23

VOLUME [2] -

148:15, 179:5

VOLUNTARILY [1] -

89:21

VOLUNTEERED [1] -

55:11

VSD [1] - 31:9

VULNERABILITY [1]

- 196:6

W

WADE [2] - 36:13,

52:5

WADE-GREAUX [2]

- 36:13, 52:5

WAIT [6] - 76:22,

78:3, 107:3, 151:7,

201:14

WAITING [1] - 6:5

WALK [1] - 179:17

WALL [2] - 124:12,

207:6

WALLS [1] - 159:5

WARNED [1] -

110:25

WARNING [1] -

31:21

WARNS [1] - 51:13

WARRANT [2] -

198:15, 198:19

WATCH [1] - 71:25

WAYS [2] - 115:1,

129:10

WEAKNESSES [1] -

42:3

WEAR [1] - 5:8

WEARING [1] - 5:2

WEEK [7] - 3:12,

3:13, 3:15, 5:6, 10:7,

63:24, 171:19

WEIGHT [5] - 23:20,

91:10, 109:21, 202:7,

202:14

WEIGHTS [2] -

74:21, 196:24

WEIGHTY [1] - 85:7

WELCOME [2] - 3:5,

3:15

WELL-BEING [1] -

240

21:14

WELL-

CONTROLLED [2] -

199:1, 199:9

WELL-KNOWN [2] -

172:8, 172:14

WHEELER [1] - 2:12

WHITE [2] - 1:21,

208:4

WHOLE [11] - 54:11,

66:2, 95:8, 141:9,

154:25, 155:20,

168:5, 168:7, 177:11,

196:18, 205:25

WIDE [2] - 50:20,

57:1

WIDELY [4] - 16:17,

16:24, 125:4, 172:24

WIFE [1] - 113:23

WIGS [3] - 5:1, 5:2,

5:7

WIKIPEDIA [1] -

106:22

WILLING [1] - 152:18

WILSON [12] - 68:24,

81:13, 91:8, 92:16,

124:16, 124:17,

124:19, 126:24,

180:3, 193:15, 197:14

WILSON'S [19] -

68:21, 69:7, 69:10,

70:8, 70:23, 81:10,

92:11, 93:21, 124:21,

125:8, 135:7, 135:12,

138:11, 170:6, 180:4,

187:17, 187:19,

187:24

WINDOWS [1] -

191:22

WINGS [1] - 6:6

WISH [1] - 5:12

WISHED [1] - 3:9

WITHDRAWN [3] -

15:24, 15:25, 31:20

WITKIN [1] - 2:2

WITNESS [7] - 6:23,

8:3, 69:13, 70:10,

112:19, 112:24,

207:12

WITNESSES [4] -

6:11, 8:11, 9:13,

10:21

WOMAN [2] - 96:24,

152:12

WOMB [1] - 201:18

WOMEN [34] - 10:5,

16:1, 16:2, 18:6,

19:19, 19:21, 20:4,

20:6, 21:1, 21:6,

21:24, 26:3, 37:15,


37:16, 47:5, 47:6,

48:12, 48:18, 49:10,

79:5, 110:17, 110:21,

110:25, 111:2, 111:7,

111:10, 111:18,

120:18, 139:11,

139:13, 198:6,

198:15, 198:22

WOMEN'S [2] - 57:4,

110:17

WONDER [1] - 95:19

WONDERFUL [1] -

5:5

WORDINESS [1] -

92:7

WORDS [3] - 31:19,

42:15, 47:13

WORKS [7] - 22:6,

70:4, 121:21, 142:9,

142:17, 148:7, 195:2

WORLD [23] - 31:24,

32:7, 35:8, 48:25,

63:14, 64:1, 65:5,

66:20, 70:22, 70:23,

70:25, 71:7, 79:1,

79:17, 97:5, 99:23,

111:14, 125:21,

135:8, 137:5, 137:8,

140:13, 172:9

WORLD'S [2] -

33:22, 44:5

WORMS [1] - 56:18

WORRY [2] - 23:17

WORST [2] - 48:19,

189:23

WOW [2] - 26:1,

70:25

WRITING [5] - 20:24,

50:23, 55:6, 77:10,

176:11

WRITINGS [2] - 26:1,

46:8

WRITTEN [17] -

16:20, 20:16, 20:19,

22:4, 30:15, 38:1,

41:18, 42:19, 46:18,

53:25, 55:12, 66:5,

66:14, 68:22, 69:21,

79:19, 90:19

WRONGFULLY [1] -

74:17

WRONGLY [1] - 35:1

WROTE [9] - 21:13,

25:11, 25:18, 41:11,

73:25, 84:12, 85:6,

106:14, 153:21

WYETH [2] - 76:3,

90:9

X

XANAX [7] - 79:1,

79:3, 79:13, 152:9,

152:10, 152:17,

152:20

Y

YALE [1] - 67:7

YATES [2] - 2:14, 9:4

YEAR [7] - 12:8,

61:17, 67:18, 67:25,

88:8, 108:4, 110:11

YEARS [16] - 7:18,

18:1, 60:16, 60:17,

60:18, 62:20, 63:6,

64:22, 66:11, 71:24,

72:1, 74:17, 75:22,

77:18, 114:4, 121:23

YELLOW [2] - 48:5,

48:8

YELLOWFINGER [1]

- 48:9

YORK [1] - 2:10

YOUNG [1] - 64:25

YOURSELF [5] -

113:6, 135:7, 145:12,

154:15, 194:10

Z

ZEALAND [3] -

22:23, 76:22

ZEBRA [3] - 56:13,

56:18

ZERO [6] - 191:23,

191:25, 192:10,

192:20, 193:4

ZOLOFT [143] - 1:3,

3:18, 4:1, 4:12, 10:2,

10:14, 12:5, 12:14,

12:15, 12:20, 13:8,

13:21, 14:6, 14:11,

14:12, 14:15, 15:2,

15:3, 15:14, 15:24,

16:5, 16:8, 16:13,

16:17, 16:21, 17:3,

17:10, 17:12, 17:21,

18:4, 18:12, 18:13,

18:17, 18:18, 19:13,

20:13, 20:22, 21:2,

21:4, 23:15, 25:23,

26:2, 26:8, 28:6,

29:22, 30:25, 31:1,

31:2, 31:7, 32:2,

32:14, 32:18, 32:20,

32:25, 33:2, 33:5,

33:11, 33:13, 33:15,

33:21, 35:5, 37:6,

241

37:11, 37:13, 37:15,

37:17, 37:18, 37:21,

37:22, 37:23, 38:7,

38:23, 40:19, 42:16,

42:17, 43:14, 50:13,

51:25, 53:13, 53:14,

53:18, 54:7, 54:13,

54:17, 55:1, 55:5,

55:8, 55:11, 55:19,

55:20, 55:21, 56:1,

56:3, 56:5, 56:10,

56:25, 57:3, 57:5,

68:13, 72:15, 74:22,

75:15, 75:20, 77:20,

78:3, 78:7, 86:24,

89:14, 89:25, 97:13,

97:25, 104:2, 105:9,

105:20, 106:10,

106:18, 110:22,

111:1, 111:6, 111:7,

111:11, 123:14,

148:25, 156:24,

157:2, 157:9, 159:11,

162:25, 164:9,

169:15, 177:9,

177:13, 179:21,

180:13, 186:14,

197:1, 206:13,

206:17, 206:20

ZOLOFT-SPECIFIC

[4] - 32:18, 33:13,

35:5, 37:21

ZONIES [6] - 2:5,

6:2, 6:4, 6:10, 8:3


Documents

1 IN THE UNITED STATES DISTRICT COURT FOR THE ... - Zoloft …zoloftmdl.com › documents › Hearing Transcripts › Zoloft... · mdl called zoloft and it is an important stage and