Fraud and Misconduct in Clinical Trials

Dr Arun Bhatt President ClinInvent Research Pvt Ltd

Research Misconduct
Royal College of Physicians 1999 Behavior by a researcher, intentional or not, that falls short of good ethical and scientific standards

Research Misconduct
UK Medical Research Council Research misconduct or fraud means fabrication, falsification, plagiarism, or deception in proposing, carrying out or reporting results of research and deliberate, dangerous or negligent deviations from accepted practices in carrying out research.

Misconduct - Categories
(Royal College of Physicians 199)

Fabrication : invention of data or cases Falsification: willful distortion of data Plagiarism : copying of ideas, data, or words without attribution Failing to get EC approval Conducting human research without consent Not including data on side effects in a trial Publication of post hoc analysis without declaration that they were post hoc Not attributing to other authors Not disclosing a conflict of interest
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Clinical Research Misconduct Global Scenario

USFDA serious problems in 3% of not for cause audits and over 26% in for cause audits Europe Serious research misconduct >1% of all clinical research Most common regulatory violations (36 FDA warning letters Feb 2002-Feb 2004 )
Misconduct including data fabrication in 8% Others
deviation from research plan, a flawed or nonexistent consent process, failure to report or late reporting of adverse events

Misconduct in Clinical Trials

Error
Unintentional deviation from truth or accuracy

Misconduct
Intentional wrongdoing

Fraud
Willful deception

Malpractices : Causes
Error
Innocent Ignorance

Misconduct
Surprising Sloppiness

Fraud
Malicious Malfeasance

Innocent Ignorance
Misconduct of the uninformed kind
Noncompliance based on lack of understanding the regulatory consequences of an action. The act itself is usually intentional but the noncompliance is unintentional, not usually done to deliberately deceive

Innocent Ignorance
Backdating the subjects signature on a consent form because the subject forgot to date the form originally and the monitor is coming tomorrow! Discarding source documents after accurate transcription and reporting transcribed data as original Creating source documents from CRFs

Surprising Sloppiness
Misconduct of the lazy kind
Noncompliance due to inaction, inattention to detail, inadequate staff, lack of supervision. The act itself may be intentional or unintentional, the noncompliance is unintentional and usually repeated

Surprising Sloppiness
Consent forms inadvertently not obtained from subjects Blood pressures rounded to the nearest 5mm Data estimated rather than actually measured Data inaccurately transcribed or recorded Protocol ignored or shortcuts taken

Malicious Malfeasance
Misconduct of the sleazy kind
Usually noncompliance due to deliberate action to deceive or mislead includes The F Word: Falsification

Malicious Malfeasance
creating data that were never obtained altering data that were obtained by substituting different data recording or obtaining data from a specimen, sample or test whose origin is not accurately described or in a way that does not accurately reflect the data

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(Mis)Informed Consent Form

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Misconduct Costs
Falsification places all subjects in that trial at possible safety risk and jeopardizes the reliability of submitted and/or published data Cost per error $50-80 and 15 minutes time

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Dealing with Misconduct

Prevention
Identify and eliminate/minimize risk factors for misconduct

Detection
Monitor and recognize signs of fraud

Correction
Promptly investigate and report fraud

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Prevention of Fraud
Make sure all study staff have the necessary resources and support needed to accomplish their tasks Dont place needless requirements or unreasonable demands on the site Monitor sites closely and pay attention to complaints from site personnel Minimize the use of enrollment incentives
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Monitoring : Detection of Fraud

Recruitment of patients at weekends or holidays Completion of a number of CRFs on the same date Use of same pen throughout the study Lack of variation in readings e.g. BP Similar handwriting on consent forms or diary cards Difficulty in obtaining original source documents Perfect source documents
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Clinical Investigator Sanctions

Warning Letters Formal Disqualification Clinical Hold Voluntary Agreements

Debarment Prosecution

Restriction Disqualification/total restriction

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Sanctions for Sponsors

Submission based sanctions
Application Integrity Policy Exclude data or delay approval Prosecution
Criminal misconduct

Debarment
removes individuals from approval process FDA will not accept or review applications from debarred individuals or companies

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The integrity, probity, skill and trustworthiness of scientific and medical researchers are essential if public confidence is to be assured Royal College of Physicians 1999

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