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Investigator ResponsibilitiesInvestigator Responsibilities

Regulation and Clinical TrialsRegulation and Clinical Trials

FDAS 2012 Clinical Investigator Training CourseCynthia F. Kleppinger, M.D.

Division of Good Clinical Practice Compliance

Office of Scientific Investigations

Office of Compliance, CDER

November 14, 2012

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2

ObjectivesObjectives

Discuss specific problems seen during FDA inspections

at clinical sites

Discuss specific problems seen during FDA inspections

at clinical sites

Identify the federal regulations coveringclinical research and clinical investigator obligations

Identify the federal regulations covering

clinical research and clinical investigator obligations

Discuss various methods that can be used to ensure

compliance with federal regulations and study

protocol requirements

Discuss various methods that can be used to ensure

compliance with federal regulations and study

protocol requirements

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3

Who is an Investigator?Who is an Investigator?An individual who actually conducts a

study

(i.e. under whose immediatedirection the drug is dispensed to a

subject.)In the event an investigation isconducted by a team of individuals, theinvestigator is the responsible leader

ofthe team.

[21 CFR 312.3]

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4

SponsorSponsor--InvestigatorInvestigatorA

in

n individual who both initiates and conducts an

vestigation, and under whose immediatedirection the investigational drug is administeredor dispensed.

The term does not include any person otherthan an individual.

The requirements applicable to a sponsor-

investigator under this part include both thoseapplicable to an investigator and a sponsor.

[21 CFR 312.3]

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Question ?Question ?Does the investigator have to be a medical

doctor?

ANSWER: NO A physician can be asubinvestigator to perform those studyfunctions requiring the appropriate level of

medical expertise.[21 CFR 312.53(a)]

5

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Legal FrameworkLegal Framework

i

Gu

FA

C

ederal Food, Drug, and Cosmetic Act (FD&Cct)

Section 505(i) is the statutory authority for FDAsoversight of clinical investigations to test safety andeffectiveness

ode of Federal Regulations (CFR)Regulations promulgated under Section 505(i)describing FDAs authority over the conduct of clinicalnvestigations including

Sponsor responsibilitiesClinical Investigator responsibilities

idances Advisory only, to assist clinical investigators and

sponsors in complying with the regulations

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Clinical Trial EnvironmentClinical Trial Environment

SponsorSponsor

InstitutionInstitution

IRBsIRBs

OHRPOHRP

FDAFDA

Study SubjectsStudy Subjects

InvestigatorInvestigator

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FDA Expectations of ClinicalFDA Expectations of ClinicalInvestigatorsInvestigators

Adherence to Code of Federal Regulations

Knowledge of Clinical Investigatorregulations

Understanding of Clinical Investigator

responsibilities

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Statement of InvestigatorStatement of Investigator

Form FDA 1572Form FDA 1572

No investigator may participate in aninvestigation until he/she provides thesponsor with a completed, signed

Statement of Investigator, Form FDA1572

[21 CFR 312.53(c)].

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Form Approved: OMB No. 0910-0014.PUBLIC HEALTH SERVICE Expiration Date: January 31, 2006.

See OMB Statement on Reverse.FOOD AND DRUG ADMINISTRATION

STATEMENT OF INVESTIGATOR NOTE: No investigator may participatein an investigation until he/she provides

(TITLE 21, CODE OF FEDERAL REGULATIONS (CFR) Part 312)the sponsor with a completed, signed

(See instructions on reverse side.)Statement of Investigator, Form FDA1572 (21 CFR 312.53(c))

1. NAME AND ADDRESS OF INVESTIGATOR

2. EDUCATION, TRAINING, AND EXPERIENCE THAT QUALIFIES THE INVESTIGATOR AS AN EXPERT IN THE CLINICAL INVESTIGATION OF THE DRUG FOR THE USEUNDER INVESTIGATION. ONE OF THE FOLLOWING IS ATTACHED.

CURRICULUM VITAE OTHER STATEMENT OF QUALIFICATIONS

3. NAME AND ADDRESS OF ANY MEDICAL SCHOOL, HOSPITAL, OR OTHER RESEARCH FACILITY WHERE THE CLINICAL INVESTIGATION(S) WILL BE CONDUCTED.

4. NAME AND ADDRESS OF ANY CLINICAL LABORATORY FACILITIES TO BE USED IN THE STUDY.

5. NAME AND ADDRESS OF THE INSTITUTIONAL REVIEW BOARD (IRB) THAT IS RESPONSIBLE FOR REVIEW AND APPROVAL OF THE STUDY(IES).

6. NAMES OF THE SUBINVESTIGATORS (e.g., research fellows, residents, associates) WHO WILL BE ASSISTING THE INVESTIGATOR IN THE CONDUCT OF THE INVESTIGATION(S).

7. NAME AND CODE NUMBER, IF ANY, OF THE PROTOCOL(S) IN THE IND FOR THE STUDY(IES) TO BE CONDUCTED BY THE INVESTIGATOR.

FDA 1

572

1/03)

REVIO

US EDITION ISOBSOLETE

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Commitments on 1572Commitments on 1572Personally conduct or supervise investigation

Follow protocol- only make changes afternotifyin

g the sponsor unless subject at riskEnsure all persons assisting with the study are

informed of obligationsInform subjects that drugs are being used forinvestigational purposes

Ensure informed consent (21 CFR Part 50) anIRB review, approval and reporting (21 CFRPart 56)Report to sponsor adverse events (21 CFR312.64)

d

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Commitments (cont.)Commitments (cont.)Maintain adequate and accurate records

(21 CFR 312.62) and make them availablefor inspection in accordance with 21 CFR312.68Ensure initial and continuing review by an

IRB and report all changes to researchand unanticipated problems involving risksto subjects, not make any changes without

IRB approval except where necessary toeliminate immediate hazardsComply with other requirements in 21 CFR312

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Form FDA 1572Form FDA 1572If a clinical study is conducted outside of the

U.S. and is not conducted under an IND, thenthe investigator need not sign a 1572

If a foreign clinical study is conducted under anIND, then all FDA IND regulations, including therequirement to obtain a signed 1572, must be

metIf la

ocal laws or regulations prohibit the signing of1572, FDA would expect the sites to operate

as non-IND sites

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E6: Good Clinical Practice:E6: Good Clinical Practice:Consolidated GuidelineConsolidated Guideline

Published as official

guidance in U.S. FederalRegister (May 1997)

The objective of this ICH GCPguidance is to provide a unifiedstandard for the European

Union (EU), Japan, and theUnited States to facilitate themutual acceptance of clinical

data by the regulatory authoritiesin these jurisdictions.

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Answer: Not really butAnswer: Not really butFDA has no regulations concerning delegation of

this duty

Discussed in the FDA Information Sheets: FDA doesnot require the investigator to personally conduct the

consent interview.

http://www.fda.gov/RegulatoryInformation/Guidances/ucm126431.htm

ICH allows the delegation of the informedconsent process to a designee

The investigator, or a person designated by the

investigator, should fully inform the subject

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Question ?Question ?Does the investigator have to sign the

informed consent?

ANSWER: NO Signing/dating by personconducting the informed consentdiscussion

is part of ICH-GCP but not FDA

regulations

20

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Role of Clinical InvestigatorsRole of Clinical Investigators

Good Clinical Practice(GCP)

in FDA-regulatedresearch is not the same as

good clinical practice incaring for patients

For example, FDAregulations have veryspecific requirements forfollowing the protocol,recordkeeping, and drug

accountability

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Important Caveat forImportant Caveat forClinical InvestigatorsClinical Investigators

Standards for clinical care of patients

Standards for academic research

Standards for FDA regulated research

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Historical PerspectiveHistorical Perspective1961-1962: Thalidomide tragedyExposed loopholes in Food, Drug andCosmetic Act of 1938: Companies coulddistribute unapproved drugs for experimentalpurposes

Did not require notification to patients ofinvestigational status

Did not require companies or doctors tokeep track of distribution

Did not require FDA to be notified ofexperimental use

Did not require records to be kept

Did not require demonstration of drugeffectiveness

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1962: Kefauver-Harris Amendments Approval based on demonstration of efficacy as

well as safety

Expanded inspectional authority -

FDA can inspectcompany records regarding development and

clinical testing FDA must be notified before clinical trials could be

conducted

Rulemaking authority over Investigational NewDrugs

Expansive rulemaking authority over clinical trials

Gave FDA the power to halt clinical trials

ActionAction

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Additional ActionsAdditional ActionsIND Regulations of 1963

Created the current framework ofclinical trials

Investigations must be adequate

and well-controlled

Investigators qualified by scientific

training and experience

Recordkeeping requirements

Informed Consent

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WhoWhos in Charge at the Study Site?s in Charge at the Study Site?Clinical investigators are in charge and held

accountable

FDA regulations permit sponsors to delegate theirresponsibilities to Contract Research Organizations(CROs) but do not permit clinical investigators to

delegate their general responsibilities to CROs orsite management organizations, subinvestigators, orstudy staff

Penalties for significant noncompliance Warning Letters (posted on FDA website)

Disqualifications/Restrictions/Debarments (posted on

FDA website) Criminal prosecutions/prison/fines

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General Clinical InvestigatorGeneral Clinical InvestigatorResponsibilities [ 21 CFR 312.60]Responsibilities [ 21 CFR 312.60]Ensuring that an investigation is conducted according to

the Signed investigator statement (Form 1572)

Investigational plan

Applicable regulations

Protecting

the rights, safety, and welfare of subjects

under the investigator's care

Control of drugs under investigationEnsuring that informed consent is adequately obtainedaccording to 21 CFR 50

Ensuring IRB review, approval and reportingrequirements are met per 21 CFR 56

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Investigator ResponsibilitiesInvestigator ResponsibilitiesControl of investigational drug (312.61)Record keeping and retention (312.62)

An investigator is responsible for:

Maintaining adequate records of the disposition of the drug

Accurate case histories that record all observations, and

Other data pertinent to the investigation on each individual

administered the investigational drug or employed as a control inthe investigation

An investigator is required to maintain investigationrecords for:

2 years following the date a marketing application is approved forthe drug for the indication for which it is being investigated

2 years after the investigation is discontinued and FDA is notified ifno application is to be filed or if the application has not been

approved for such indication

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Responsibilities (cont.)Responsibilities (cont.)

Investigator reports (312.64)

Progress reports to sponsor Safety reports

Immediately report any adverse event that is alarming (e.g.

an unexpected event that is serious or life-threatening)Record nonserious adverse events and report them to thesponsor according to the timetable for reporting specified inthe protocol

Final report to sponsor

Financial disclosure to sponsorPromptly update as needed during the course of theinvestigation and for 1 year following study completion

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ClinicalTrials.govClinicalTrials.govU.S. Public Law 110-85 (Food and Drug Administration

Amendments Act of 2007 or FDAAA), Title VIII, Section

801 mandates that a "responsible party" (i.e., the sponsoror designated principal investigator) register and reportresults of certain applicable clinical trials

Trials of Drugs and Biologics: controlled clinical investigations,other than Phase 1 investigations, subject to FDA regulation

Trials of Devices: Controlled trials with heath outcomes of devicessubject to FDA regulation, other than small feasibility studies,

andpediatric postmarket surveillance

FDA requires a statement in the informed consentregarding ClinicalTrials.gov.

http://clinicaltrials.gov/ct2/manage-recs/fdaaa

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QuestionQuestionWhat documents must be submitted to the

IRB for review?

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AnswerAnswerFDA: The IRB should receive and review all researchactivities

Copies of all research proposals reviewed, scientific evaluations, if any,that accompany the proposals, approved sample consent documents,

progress reports submitted by investigators, and reports of injuries tosubjects

FDA Guidance: The documents reviewed should includethe complete documents received from the clinical

investigator, such as the protocol, the investigator'sbrochure, a sample consent document and anyadvertising intended to be seen or heard by prospectivestudy subjects.

ICH specifically requires IRB submission of: informed consent, protocol/amendments, and advertisements Written information provided to subjects Information about subject payment/compensation

Investigators Brochure

Investigator's current CV and/or qualifications

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Sponsor ResponsibilitiesSponsor ResponsibilitiesSponsors are responsible for (312.50): Selecting qualified investigators

Providing them with the information they needto conduct the investigation properly

Ensuring proper monitoring of the investigation

Ensuring that the investigation is conducted inaccordance with the general investigational

plan Maintaining an effective IND

Ensuring that the FDA and all participating

investigators are promptly informed ofsignificant new adverse effects or risks

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Guidance (cont.)Guidance (cont.)Outlines FDA expectations for protecting

the rights, safety, and welfare of subjects

Provision of reasonable medical care forissues related to study participation (e.g.

to manage an adverse event) Facilitation of care for other health

issues that might arise during the studyAvoiding exposure of subjects to

unreasonable risks

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QuestionCan the investigator delegate the activities

around investigational product?

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AnswerAnswerFd

DAele

hagati

The inindiviis qua

s no regulation concerningon of these duties

vestigator should ensure that anydual to whom a task is delegatedlified by education, training, and

experience (and state licensure where

relevant) to perform the delegated task(per FDA Investigator Guidance 2009).

ICH allows the delegation of study drugdispensing, patient counselling, and drugaccountability to an appropriate

designee

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In SummaryIn SummaryFollow the current

protocol

Personally

conduct or superviseinvestigation(s)

Ensure that all persons assisting inconduct of studies are informed of theirobligations

Ensure informed consent (21 CFR 50) andIRB review, approval , and reporting (21

CFR 56) requirements are met

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In Summary (cont.)In Summary (cont.)Obtain the informed consent of each

human subject to whom the drug isadministered

Notify the sponsor before making changesin the protocol

Notify the IRB and obtain IRB approval

before making changes in the protocolReport adverse events to the sponsor

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In Summary (cont.)In Summary (cont.)Maintain adequate and

accurate recordsMake records available forinspection

Comply with all otherrequirements in 21 CFR

312Report Financial Interests

to the Sponsor

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DONDONTTOver-delegate to non-physicians (e.g., diagnosis thatqualifies/determines eligibility for entry into the study)

Erase, white-out or obliterate original data entryAccept suggested changes to study data withoutchecking the source documents or without justificationfor such changes

Backdate the consent forms and signatures

Forget to obtain IRB approval of consent form revisions

Revise the protocol without obtaining the sponsorswritten concurrence

Use your staff as subjects in a study not having thecondition(s) under investigation

Destroy study records

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Regulatory Authority toRegulatory Authority toConduct Inspections/AuditsConduct Inspections/Audits

Section 505(k)(2) of the Food, Drug, andCosmetic Act mandates that FDA shall haveaccess to and copy and verify the requiredclinical study records.21 CFR 312.68

An investigator shall upon request from any

properly authorized officer or employee ofFDA, at reasonable times, permit such officeror employee to have access to, and copy andverify any records or reports made by theinvestigator

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Typical Questions in an InterviewTypical Questions in an Interview

Delegation of authority: Who, when, where:

Screening of subjects

Interpreting screening results/admitting to the study

Informed Consent of subjects

Receipt of test article; handling; administration; return

Reporting (including safety reporting) /transcribingdata

Clinical laboratory

Archiving study data

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Inspections Overseen by OSI *Inspections Overseen by OSI *

(CDER, FY 2003 -

FY 2011)

44

*Based on inspection start date

[OSI database as of January 18, 2012]

IRB includes only CDER numbers

previously reported metrics may have used combined data acrossCDER, CBER and CDRH, Sponsor (GCP) includes Sponsor/CRO/Sponsor-Investigator

As of June 2011, Postmarketing Adverse Drug Event and Risk Evaluation and Mitigation Strategyinspection programs were incorporated into OSI

103136

89 106123 127 153

191 194

371353

366408 368

416

474 403

315

90 7562

30 4833

3740

156 136

124 77 10778

10098

103

2321

32 33 25 47

7562

45

72

1517

27

2003 2004 2005 2006 2007 2008 2009 2010 2011

Risk Evaluation and Mitigation Strategy

Postmarketing Adverse Drug Event

Sponsor (GCP)

Institutional Review Board/

Radiological Drug Research CommitteeGood Laboratory Practice

Clinical Investigator

Bioequivalence

743

671

721

654673701

773809839

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Clinical Investigator Inspections*Clinical Investigator Inspections*(All Centers, FY 2011)(All Centers, FY 2011)

CDER = Center for Drug Evaluation and Research, CBER = Center for Biologics Evaluation andResearch, CDRH = Center for Devices and Radiological Health*CDER numbers based on inspection start date

[OSI database as of July 25, 2012]

CDRH numbers based on inspection end date CBER numbers based on end date of classified inspections

CDER = 317

CBER = 62CDRH = 174

Total 553

CDRH

31%

CBER

11%

CDER58%

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Frequency of Clinical Investigatorrequency of Clinical InvestigatorRelatedelated

Deficiencies Based on Post

eficiencies Based on Post

Inspection

nspection

Correspondence Issued(CDER, FY 2011)*

211 Domestic Inspections,

101 Foreign Inspections

*Based on letter issue date; Inspections may have multiple deficiencies, [OSI database as of July 25, 2012]

Note that this does not denote number of inspections completed in FY 2011, but rather number of inspection reportsevaluated and closed in FY2011

46%

33%

10%

9% 7%4%

31%

17%

4%6%

1%3%

Protocol Records IRB Communication Consent Drug Accountability Adverse Events

Domestic

Foreign

309 Domestic Inspections,

98 Foreign Inspections

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Compliance ClassificationsCompliance ClassificationsNAI -

No Action Indicated

Inspected Entity is in compliance

VAI -

Voluntary Action Indicated

Minor deviation(s) from the regulations

Voluntary correction is requested

OAI -

Official Action Indicated

Serious non-compliance requiring regulatory oradministrative action by FDA

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Inspectional OutcomesInspectional OutcomesNo Action Indicated

Form FDA 483 15 business days to reply

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(total=312)

*Based on Letter Issue date; Includes OAI Untitled Letters, [OSI database as of July 25, 2012]

CDER Clinical Investigator InspectionsCDER Clinical Investigator InspectionsFinal Classification* (FY 2011)Final Classification* (FY 2011)

51%

7%

42%No Action Indicated

Official Action Indicated

Voluntary Action Indicated

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*OAI: Denotes Official Action Indicated (significant deficiencies found)**Based on letter issue date [OSI Database as of 1/18/2012]; Inspections may have multiple deficiencies, Includes OAIuntitled letters

Frequency of Clinical Investigator RelatedFrequency of Clinical Investigator RelatedDeficiencies Based on PostDeficiencies Based on Post--InspectionalInspectional

Correspondence Issued: OAI* Final Class (CDER,Correspondence Issued: OAI* Final Class (CDER,

FY2011)**FY2011)**

N=44 OAI

23 OAI Inspections

96%

70%

43%

26%22% 22%

13%

Protocol Records IRBCommunication

Consent DrugAccountabi lity

CI Supervision SubjectRights/Safety

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ReferenceReferenceInspection Observations

Spreadsheets summarizing the areas ofregulation cited on FDA's system-

generated 483s by fiscal year

http://www.fda.gov/ICECI/EnforcementAction

s/ucm250720.htm

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ReferenceReferenceInspections Classification Databaseand Search (Oct. 2008March 2012)

Final inspection classification for inspectionsrelated to currently marketed FDA-regulatedproducts. (Some information may be withheld

from posting as to not interfere with enforcementaction).

http://www.fda.gov/ICECI/EnforcementActions/ucm222557.htm

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Common mistakesCommon mistakes

Risk factors for nonRisk factors for non--compliancecompliancePoor supervision and training of study staff

Insufficient investigator involvement in studyconduct

Inappropriate delegation of study tasks tounqualified persons

Failure to adequate protect study subjects

Overworked investigator and study staff (e.g. toomany subjects, complex study with large datacollection, too many concurrent studies)

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Regulatory ActionsRegulatory ActionsWarning Letter

Notice of Initiation ofDisqualification Proceedingsand Opportunity to Explain(NIDPOE)

Disqualification of clinical investigator

Criminal Investigation by Office of CriminalInvestigations (OCI)

Debarment

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ReferenceReferenceList of Warning Letters

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/default.htm

Regulatory Procedures Manual Section onWarning Letters

http://www.fda.gov/ICECI/ComplianceManuals/RegulatoryProceduresManual/ucm176870.htm

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Investigator DisqualificationInvestigator Disqualification21 CFR 312.70

Repeated and deliberate failure to comply withthe requirements

FDA provides notice of matter to investigatorand provides opportunity to explain (informalhearing)

Opportunity for formal hearing

May result in ineligibility to receiveinvestigational drugs

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ReferenceReferenceNotice of Initiation of Disqualif ication Proceedingsand Opportunity to Explain (NIDPOE)

FDA believes it has evidence that the clinicalinvestigator repeatedly or deliberately violated FDA'sregulations governing the proper conduct of clinicalstudies involving investigational products or submitted

false information to the sponsor and is initiating anadministrative proceeding to determine whether theclinical investigator should be disqualified from receivinginvestigational products.

http://www.fda.gov/RegulatoryInformation/FOI/ElectronicReadingRoom/ucm092185.htm

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ReferenceReferenceDisRe

qualified/Restricted/ Restrictionsmoved/ Assurance Lists for Clinical

InvestigatorsRestricted from receiving investigational drugs,biologics, or devices if FDA determines that the

investigator has repeatedly or deliberately failed tocomply with regulatory requirements for studies or hassubmitted false information to the study's sponsor.

http://www.fda.gov/ICECI/EnforcementActions/ucm321308.htm

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ReferenceReferenceFDA Debarment List (Drug Product

Applications)

Firms or individuals convicted of a felony underFederal law for conduct (by a firm) relating to thedevelopment or approval of any drug product or

abbreviated drug application

http://www.fda.gov/ICECI/EnforcementActions/FDADebarmentList/ucm2005408.htm

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Failure to prepare and maintain adequate case historiesand retain records [21 CFR 312.62(b) and (c)]

eCRFs were source documents; Site data forinspection consisted of CD provided by sponsor, noevidence that CI prepared or maintained subjectrecords or signed off on subject data in real time

Clinical signs such as breath sounds and chest examwere assessed during phone call to subjects

Data in eCRF inaccurately carried over from visit to

visit

Case StudyCase StudyData Validation Inspection for New DrugData Validation Inspection for New DrugApplication (NDA)Application (NDA)

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Case Study: Lax SupervisionCase Study: Lax Supervision

Study coordinator enrolled ineligible subjects inoncology trials

Coordinator altered source records and createdfraudulent CRFs to make subjects appear eligibleData manipulations should have been apparent toattentive clinician

Subject who was ineligible due to poor renal andliver function was enrolled, dosed, and died as aresultStudy coordinator sentence to 71 months inprison and debarred from any future involvementin FDA regulated researchDr. Holland

5 years probation, $500k restitutionto defrauded drug companies, disqualified

C St dC St d

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Case StudyCase Study

DR. P, age 58, pled guilty in federal court today

before U. S. District Judge to fifteen (15) counts of

failing to prepare and maintain records, with intent

to defraud and mislead, in connection with clinicaltrials to evaluate the efficacy and safety of Paxil in

children and adolescents with Obsessive-

Compulsive Disorder (OCD)

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Improve ProcessImprove Process BeBeProactiveProactive

Address human factors in systems Hire experienced, qualified staffAvoid conflicts of interest/financial

incentives Decrease number of times data are handled

Assess ability to comply with protocol visits;

laboratory testing; electronic systems fordata capture, archiving and transmission tosponsor; maintaining records, drugaccountability, inspections by FDA

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Improve ProcessImprove Process BeBeProactiveProactive

Create systems that limit opportunityfor errors Simplify protocol and outcomes assessed

Be realistic about the amount of data to becollected

Standardize systems and formats where possible Use validated instruments/definitions

Write down all procedures (SOPs). Use checklists.

Dont re-invent the wheel Keep amendments to a minimum and check the

CRFs and consent form against each change

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Improve ProcessImprove Process

Develop an integrated framework

Data and Safety Monitoring Plan, Data

Management Plan, Quality Assurance Plan,Data Analysis Plan

Insist on training and then test

it

Think very carefully about unblindingprocedures

Have a disaster plan (for staff turnover,

floods, etc.) Do beta-testing/dry-runs Have weekly team meetings/calls

Audit yourself

be open and honest

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Implement System to Detect andImplement System to Detect andCorrect Errors in Real TimeCorrect Errors in Real Time

Do real-time cleaning of the data

Pay attention to monitoring queries and

respond promptly Close loopsAudit trail of changes should make clear whatwas changed, who changed it, and why it

was changedEvaluate need for system wide correctionsand training

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Key MessagesKey MessagesClinical investigators play a critical role inensuring high quality studies

CGood care of patients is not the same as Good

linical Practices (GCP) in research

Ensure that all staff have a clearunderstanding of responsibilities under FDAregulations

tAt stake is public confidence and participation inhe clinical trials and ultimately the availability ofsafe and effective products

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The "cost of quality" isn't the price of

creating a quality product or service.It's the cost of NOT creating a quality

product or service.

**Principles of Quality Costs: Principles, Implementation, andUse, Third Edition, ed. Jack Campanella

FDA Sit f I t tFDA Sit f I t t

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FDA Sites of InterestFDA Sites of Interest

Running Clinical Trials

http://www.fda.gov/ScienceResearch/SpecialTopics/

RunningClinicalTrials/default.htm

FDA Basics for Industry

http://www.fda.gov/ForIndustry/FDABasicsforIndustry/default.htm

Sign up for Updates

http://www.fda.gov/ForIndustry/FDABasicsforIndustry/ucm234630.htm

FDA Sit f I t tFDA Sit f I t t

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FDA Sites of InterestFDA Sites of Interest

Replies to Inquiries to FDA on Good ClinicalPractice

Designed to simplify the search for copies of e-mailmessages (including the original inquiry andassociated reply(ies)) that have been submitted bythe public to the Good Clinical Practice Program'sgcp.questions@fda.hhs.gov

e-mail account.

http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/RepliestoInquiriestoFDAonGo

odClinicalPractice/default.htm

G id f I t tG id f I t t

mailto:gcp.questions@fda.hhs.govmailto:gcp.questions@fda.hhs.govmailto:gcp.questions@fda.hhs.govmailto:gcp.questions@fda.hhs.gov

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Guidances of InterestGuidances of Interest

FDA Inspections of Clinical Investigators-

Information sheet

http://www.fda.gov/downloads/RegulatoryInformatio

n/Guidances/UCM126553.pdf

Guidance for Industry-Investigator

Responsibilities

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM18777

2.pdf

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hank you for your attention