PHARMACEUTICALS CONFERENCE NAAG, MAY 11, 2007

FINANCIAL CONFLICTS: CONSEQUENCES, PROPOSALS

Jerome P. Kassirer, M.D.Distinguished Professor, Tufts University

School of MedicineEditor-in-Chief Emeritus, New England

Journal of Medicine

Assumption:• EVEN SMALL GIFTS INFLUENCE

BEHAVIORPrinciples:• FINANCIAL CONSIDERATIONS NEVER

COMPROMISE MD DECISION-MAKING• MEDICAL INFORMATION FREE OF BIAS

FROM FINANCIAL INDUCEMENTS• PROFESSION ACCOUNTABLE FOR

INORDINATELY HIGH COST OF CARE• ALL FINANCIAL ARRANGEMENTS OPEN

AND TRANSPARENT

Not all incentives are financial…

Nina Easton from Fortune Magazine was asked how she can be objective as a Fox News TV commentator when discussing John McCain’s presidential candidacy, given that her husband is McCain’s media advisor. She replied, “Disclosure is the great disinfectant.”

( NPR, April 1st 2007)

Not all incentives are financial…

PHYSICIANS’ FERVENT BELIEFS IN THEIR OBJECTIVITY

• TRAINED IN THE SCIENTIFIC METHOD

• RELIGIOUS ADHERENCE TO EVIDENCE-BASED MEDICINE

THE CANDY EXPERIMENT AT CORNELL’S HOTEL SCHOOL

THE GIFT THE TIPNO CANDY ONE PIECETWO PIECESONE PLUS ONE

THE CANDY EXPERIMENT AT CORNELL’S HOTEL SCHOOL

THE GIFT THE TIPNO CANDY 19.0%ONE PIECETWO PIECESONE PLUS ONE

THE CANDY EXPERIMENT AT CORNELL’S HOTEL SCHOOL

THE GIFT THE TIPNO CANDY 19.0%ONE PIECE 19.6%TWO PIECESONE PLUS ONE

THE CANDY EXPERIMENT AT CORNELL’S HOTEL SCHOOL

THE GIFT THE TIPNO CANDY 19.0%ONE PIECE 19.6%TWO PIECES 21.6%ONE PLUS ONE

THE CANDY EXPERIMENT AT CORNELL’S HOTEL SCHOOL

THE GIFT THE TIPNO CANDY 19.0%ONE PIECE 19.6%TWO PIECES 21.6%ONE PLUS ONE 23.0%

WHEN FINANCIAL CONFLICTS TRANSLATE INTO BIAS, WHAT DO

THEY “COST”?

COLLEGE LOAN SCANDAL

Financial aid officers: fees based on loan volume, expense-paid trips to exotic locations, stock in company, paid as consultants, advisory board positions.

Students steered to “preferred lists.”

Result: Students and parents ripped off.

THEY CAN INFLUENCE TREATMENT OF MILLIONS

THERAPEUTICS INITIATIVE U.B.C.Statins have not been shown to provide an overall health benefit for primary prevention

NCEP GUIDELINESAggressive LDL lowering for high risk patients (primary prevention) with lifestyle changes (diet, exercise) and statins

NCEP PANEL’S FINANCIAL CONFLICTS(Personal income - honoraria and/or consulting

fees- from all 5 statin companies)

Grundy 5 Hunninghake 4Pasternak 5 Merz 3Stone 5 Smith 0Brewer 4 Cleeman 0Clark 4

FOLLOW-UP OCTOBER 2006

• 2004 NCEP GUIDELINES QUESTIONED• EVIDENCE BASE FOR ORIGINAL

RECOMMENDATIONS WAS WEAK AND BASED ON SECONDARY PREVENTION

• SOME ORIGINAL AUTHORS BACK OFF (NYT)

(Ann. Intern. Med 2006;145:520-530; Lancet 2007;369:168-169)

THEY CAN AFFECT THE OBJECTIVITY OF PHYSICIANS

INTERPRETATION OF CHEST X-RAYS

492 abnormal chest X-rays, according to 30 plaintiff-hired “B” readers (hirees). Films re-read by 6 blinded “B” readers (independents).

(“B” readers are certified by NIOSH; all used standard DHSS form OMB No. 0920-0020)

Gitlin et al Acad. Radiol 2004;11:843-856

RESULTS (%)hirees

independents-------

---------------- Parench. abn. 96 5Pneumocon. 97 6Pleural abn 26 8Film normal 0 38

THEY CAN RAISE THE COST OF CARE AND INCREASERISK

WE PAY FOR EXPENSIVE, INEFFECTIVE, AND RISKY DRUGS

NYT 5/9/07

THEY CAN JEOPARDIZE PATIENT CARE

1997: Rezulin withdrawn from market in England because of liver failure

In U.S., cases of death from liver failure continued to increase

1999: FDA advisory committee voted 11:1 to keep drug on the market. Nearly all members had financial ties to drug maker.

2000: Rezulin withdrawn from market; 63 deaths in U.S. by then.

THEY MAY JEOPARDIZE RESEARCH SUBJECTS

In 1999, 17 year old Jesse Gelsinger died at Penn 4 days into gene therapy experiment

Safety issues of experiment questionableBoth institution and investigator had stake

in company that might profit from resultsInvestigator claimed money was not a factorSome on Penn task force skeptical

THEY MUDDLE INTERPRETATION OF THE OPINIONS OF CONFLICTED EXPERTS

Are they true believers;objective?Subconscious influences: what do

they really believe?Are their actions actually

conscious?

THEY CAN BIAS PRACTICE GUIDELINES

NCEP (NIH, AHA, ACC)ANDROPAUSE (ENDOCRINE

SOCIETY)ALTEPLASE IN ACUTE STROKE (AHA)NKF ON USE OF EPO FOR ANEMIAHEART RHYTHM SOC. ON ICM USESCCM ON XIGRIS, WITH BUNDLING

OTHER RECENT EXAMPLES

Treatment of age-related macular degeneration

Editor of Neuropsychopharmacology publishes ghostwritten paper touting Vagus nerve stimulation

MGH psychiatrists didn’t disclose industry ties in article on drugs in pregnancy

AtriCure procedure at Cleveland Clinic

Cartoons, television (ER, Simpsons)

THEY DENIGRATE PROFESSIONALISM

“EPIDEMIOLOGY”NEJM April 26,2007

Survey of1662 MDs(FP, IM, PedCard, AnesSurg)

MAIN POINTS

Industry used educational grants for marketing, especially for off-label uses

Excessive industry influence over content of CME programs

Lack of adequate oversight by ACCME of educational grant programs

DISCLOSURE:“THE GREAT DISINFECTANT”

IS DISCLOSURE THE SOLUTION TO “MANAGING” CONFLICTS OF

INTEREST?

THE BROUHAHA OVER LACK OF DISCLOSURE

2003 NEJM, Annals, JAMA

2005 Devices at Cleveland Clinic

2006 JAMA 3 instances

2006 Editor of Neuropsychoparmacology

2007 PHS Guideline on drugs for smoking cessation

DISCLOSURE’S DEFICIENCIES

Disclosure is often incomplete

Difficult to detect bias even when conflict of interest is known

Naming a company may not identify drug named in print or in a lecture

Requires assessing someone’s motives

DISCLOSURE:“THE GREAT DISINFECTANT”

LACK OF DISCLOSURE IS NOT THE PROBLEM

THEN WHAT IS THE PROBLEM?

The conflict is the real problem, not whether or not it is disclosed.

Pretending that disclosure ‘manages” the conflict doesn’t eliminate the conflict (“necessary but not sufficient”).

(Kassirer JP. A cure for public distrust. Boston Globe, July 27, 2006)

DISCLOSURE’S FLAWS

“It has become a truism onWall Street that conflicts ofinterest are unavoidable. In fact, most of them only seem so, because avoiding them makes it harder to get rich. That’s why full disclosure is so popular: it requires no substantive change.”

Surowiecki J. The talking cure. The New Yorker Dec. 9, 2002

IS THERE A BETTER WAY?

RELY ON UNCONFLICTED EXPERTSINDEPENDENCE AND DIVERSITYEXPERTISE: YES, BUT EXPERTS IN

DATA ANALYSISMINIMIZE CONFLICTED EXPERTSCONFLICTED EXPERTS ALLOWED TO

TESTIFY

THE SLIPPERY

SLOPE

REPRINTS FROM THE REPS PENS AND COFFEE CUPS TEXTBOOKS AND STETHOSCOPES LUNCHES AND PIZZA DINNERS AND TRAVEL CONTINUING MED. EDUCATION SPEAKER’S BUREAUS STOCK AND OPTIONS CONSULTANCIES/MARKETING CONSULTANCIES/SCIENCE JOINT RESEARCH

THE SLIPPERY

SLOPE

REPRINTS FROM THE REPS PENS AND COFFEE CUPS TEXTBOOKS AND STETHOSCOPES LUNCHES AND PIZZA DINNERS AND TRAVEL CONTINUING MED. EDUCATION SPEAKER’S BUREAUS STOCK AND OPTIONS CONSULTANCIES/MARKETING CONSULTANCIES/SCIENCE JOINT RESEARCH

THE SLIPPERY

SLOPE

REPRINTS FROM THE REPS PENS AND COFFEE CUPS TEXTBOOKS AND STETHOSCOPES LUNCHES AND PIZZA DINNERS AND TRAVEL CONTINUING MED. EDUCATION SPEAKER’S BUREAUS STOCK AND OPTIONS CONSULTANCIES/MARKETING CONSULTANCIES/SCIENCE JOINT RESEARCH

THE SLIPPERY

SLOPE

REPRINTS FROM THE REPS PENS AND COFFEE CUPS TEXTBOOKS AND STETHOSCOPES LUNCHES AND PIZZA DINNERS AND TRAVEL CONTINUING MED. EDUCATION SPEAKER’S BUREAUS STOCK AND OPTIONS CONSULTANCIES/MARKETING CONSULTANCIES/SCIENCE JOINT RESEARCH

THE SLIPPERY

SLOPE

REPRINTS FROM THE REPS PENS AND COFFEE CUPS TEXTBOOKS AND STETHOSCOPES LUNCHES AND PIZZA DINNERS AND TRAVEL CONTINUING MED. EDUCATION SPEAKER’S BUREAUS STOCK AND OPTIONS CONSULTANCIES/MARKETING CONSULTANCIES/SCIENCE JOINT RESEARCH

THE SLIPPERY

SLOPE

REPRINTS FROM THE REPS PENS AND COFFEE CUPS TEXTBOOKS AND STETHOSCOPES LUNCHES AND PIZZA DINNERS AND TRAVEL CONTINUING MED. EDUCATION SPEAKER’S BUREAUS STOCK AND OPTIONS CONSULTANCIES/MARKETING CONSULTANCIES/SCIENCE JOINT RESEARCH

THE SLIPPERY

SLOPE

REPRINTS FROM THE REPS PENS AND COFFEE CUPS TEXTBOOKS AND STETHOSCOPES LUNCHES AND PIZZA DINNERS AND TRAVEL CONTINUING MED. EDUCATION SPEAKER’S BUREAUS STOCK AND OPTIONS CONSULTANCIES/MARKETING CONSULTANCIES/SCIENCE JOINT RESEARCH

THE SLIPPERY

SLOPE

REPRINTS FROM THE REPS PENS AND COFFEE CUPS TEXTBOOKS AND STETHOSCOPES LUNCHES AND PIZZA DINNERS AND TRAVEL CONTINUING MED. EDUCATION SPEAKER’S BUREAUS STOCK AND OPTIONS CONSULTANCIES/MARKETING CONSULTANCIES/SCIENCE JOINT RESEARCH

THE SLIPPERY

SLOPE

REPRINTS FROM THE REPS PENS AND COFFEE CUPS TEXTBOOKS AND STETHOSCOPES LUNCHES AND PIZZA DINNERS AND TRAVEL CONTINUING MED. EDUCATION SPEAKER’S BUREAUS STOCK AND OPTIONS CONSULTANCIES/MARKETING CONSULTANCIES/SCIENCE JOINT RESEARCH

THE SLIPPERY

SLOPE

REPRINTS FROM THE REPS PENS AND COFFEE CUPS TEXTBOOKS AND STETHOSCOPES LUNCHES AND PIZZA DINNERS AND TRAVEL CONTINUING MED. EDUCATION SPEAKER’S BUREAUS STOCK AND OPTIONS CONSULTANCIES/MARKETING CONSULTANCIES/SCIENCE JOINT RESEARCH

THE SLIPPERY

SLOPE

REPRINTS FROM THE REPS PENS AND COFFEE CUPS TEXTBOOKS AND STETHOSCOPES LUNCHES AND PIZZA DINNERS AND TRAVEL CONTINUING MED. EDUCATION SPEAKER’S BUREAUS STOCK AND OPTIONS CONSULTANCIES/MARKETING CONSULTANCIES/SCIENCE JOINT RESEARCH

THE SLIPPERY

SLOPE

REPRINTS FROM THE REPS PENS AND COFFEE CUPS TEXTBOOKS AND STETHOSCOPES LUNCHES AND PIZZA DINNERS AND TRAVEL CONTINUING MED. EDUCATION SPEAKER’S BUREAUS STOCK AND OPTIONS CONSULTANCIES/MARKETING CONSULTANCIES/SCIENCE JOINT RESEARCH