Iain Hrynaszkiewicz - Research Integrity: Integrity of the published record
RESEARCH Integrity
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Transcript of RESEARCH Integrity
Patricia Kerby, MPA Office of Research Compliance April 8, 2010
Tiger Woods "lived a lie“
Bernard Madoff lost $50 billion invested with him
President of business indicted in Deutsche Bank fire linked to companies with rich N.Y. contracts
John Edwards, the disgraced former Democratic presidential candidate.
Jesse James Seems 'Very Upset‘ Badge Stops Bullet: Former Cop
Charged With Lying
FDA Warns Against Use Of Zocor
Merck unit held liable in Australian Vioxx case
Massachusetts doctor pleads guilty to research fraud
Top Pain Scientist fabricated data in studies
The Office of Research Integrity (ORI)
oversees and directs Public Health Service (PHS) research integrity activities on behalf of the Secretary of Health and Human Services with the exception of the regulatory research integrity activities of the Food and Drug Administration.
National Institutes of Health.
The Centers for Disease Control and Prevention
The Food and Drug Administration
The Substance Abuse and Mental Health Services Administration
The Health Resources and Services Administration
The Agency for Healthcare Research and Quality.
The Agency for Toxic Substances and Disease Registry
The Indian Health Service
Office of Regional Health Administrators
protecting the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products, medical devices, our nation’s food supply, cosmetics, dietary supplements, and products that give off radiation
Research misconduct means fabrication, falsification or plagiarism in proposing, performing or reviewing research, or in reporting research results.
42 CFR 93.103
_______ is making up data or results and recoding or reporting them.
Fabrication is making up data or results and recoding or reporting them
________ is manipulating research
materials, equipment, or processes or changing or omitting data or results such that the research is not accurately represented in the research record
Falsification is manipulating research materials, equipment, or processes or changing or omitting data or results such that the research is not accurately represented in the research record
________ is the appropriation of
another person’s ideas, processes, results, or words without giving appropriate credit.
Plagiarism is the appropriation of
another person’s ideas, processes, results, or words without giving appropriate credit.
Innocent Ignorance- misconduct of the uninformed kind
Noncompliance is 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
Backdating the subject’s signature on a consent form
Discarding source documents after accurate transcription and reporting transcribed data as original.
Using Case Report Forms as only source document
Surprising Sloppiness- misconduct of
the lazy kind Noncompliance is due to inaction,
inattention to detail, inadequate staff, lack of supervision. The act itself may be intentional or unintentional and is usually repeated.
Consent forms inadvertently not obtained from subjects
Blood pressures rounded to the nearest 5mm
Data estimated rather than actually measured
Data inaccurately transcribed as recorded
Protocol ignored or shortcuts taken
In FDA’s review of the source
documents for the records audited during the inspection, there were numerous instances where either (a) information entered into the case report forms (CRFs) did not match the information in the source documents or (b) information in the source documents was changed after the subject had completed the study, up to two years post-completion, and it could not be determined where the information related to the change was derived.
Surprising Sloppiness
Four subjects signed the 2002 ICD
version in 2004. The 2002 ICD version did not include updated data regarding sample purity rates, subject pregnancy rates, malformation rates and changes in success rates that would have been available to subjects had the proper version been used.
Innocent Ignorance
In FDA’s review of 12 of 12 subject
records, there were numerous study visits where your site’s records do no indicate that your site conducted the protocol specified physical exams and at either the screening visit, during study treatment visits and/or termination visits. In addition, in review of your site’s records, documentation could not be found to verity comments made in the CRF that a physical exam was done.
Surprising sloppiness
Our investigation indicates that you
permitted individuals to conduct study tasks which they had not been delegated the authority to execute, and that your supervision of personnel to whom you delegated study tasks was not adequate to ensure that the clinical trials were conducted according to the signed investigator statement, the investigational plan, and applicable regulations and in a manner that protected the rights, safety and welfare of human subjects.
Innocent Ignorance
The case history for Subject #002 had two different copies of CRF page 12 from Visit 1. One copy was a pink duplicate copy of CRF page 12, signed and dated as having been completed by Barbara Harris on May 10, 2007. The second copy was a photocopy of CRF page 12 also signed and dated as having been completed by Barbara Harris on May 10, 2007 but apparently filled out by a different person (as evidenced by different handwriting) and contains different information.
Surprising sloppiness
Does not include honest error or differences of opinion
Malicious Malfeasance- misconduct of the sleazy kind
Usually noncompliance is due to
deliberate action to deceive or mislead: Falsification
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
Omitting data that were obtained and ordinarily would be recorded
The FDA is revamping its debarment anddisqualification procedures against clinicalinvestigators by increasing staff and centralizingcoordination, and will list investigators againstwhom it has completed proceedings on its
website.“The number of clinical investigators debarred will rise in the near term as the agency reviewscases,” said Matthew Warren of the agency's
Office of Research Integrity and Responsibility
Ref: Washington Drug Letter 41(32), 17 Aug 2009
The FDA Classification of the Inspections
is according to the following: NAI – No Action Indicated VAI – Voluntary Action Indicated OAI – Official Action Indicated Recommend that Study Data be
Disqualified Recommend Restrictions placed on the PI Recommend Disqualification of the PI Recommend that the PI be prosecuted
Defined as the deliberate reporting of false or misleading data or the withholding of reportable data.
Altered data - generating biased data or changing data
that is legitimately obtained. E.g. changing laboratory data,altering weights, breaking the blind and/or randomization
Omitted data - not reporting data that has an impact on
study outcome. E.g. removing subjects from a study forbogus reasons, disguising AEs, and replacing subjects
Manufactured data - Fabricating information or creating
results without performing the work. E.g. filling in values(BP, lab values, x-ray reports) for which no data wereobtained, photocopying data from one patient for another,and creating fictitious patients
From Restrictions to Disqualifications to Prosecution
“If an explanation is offered but not accepted by CDER orCBER, the investigator will be given an opportunity for aregulatory hearing under part 16 on the question ofwhether the investigator is entitled to receiveinvestigational new drugs”. Ref: 21 CFR 312.70(a)
An investigator who has been determined to be ineligibleto receive investigational drug may be reinstated aseligible when the commissioner is assured that theinvestigator will comply with all applicable regulations. Ref: 21 CFR 312.70(f)
Fortunately not common but one can check theFDA web sites for a listing of:
FDA Debarmentwww,fda.gov/ora/compliance_ref/
debar/ FDA Disqualified / Restrictedwww.fda.gov/ora/compliance_ref/
bimo/dis_res_assur.htm FDA Warning letterswww.fda.gov/foi/warning.htm
Signing a 1572 is the PI’s legally bindingcommitment in writing that she / he will
beresponsible for the study in question;totally responsible and for everything This means she / he agrees to follow: 21 CFR 50 - Protection of Human Subjects - IC process
21 CFR 56 - Institutional Review Board
21 CFR 312 - Investigational New Drug Application
21 CFR 312.64 - Investigator Reports - AE reporting
21 CFR 312.62 - Record keeping and retention
21 CFR 312.68 - Being audit ready
Truth of the MMR vaccine scandal After an epic misconduct hearing, the
doctors who caused panic over the vaccine are about to learn their fate. A report on the greatest health scare of recent times
Doctor pleads guilty to health care fraud
A Massachusetts doctor pleaded guilty to one count of health care fraud stemming from accusations that he faked research for a dozen in published studies that suggested after surgery benefits from painkillers including Vioxx and Celebrex. He agreed to repay $361,932 of research grants and forfeit assets worth atleast $50,000. Prosecutors have recommended up to 10 years in prison.
Cuomo: NY Research used actors to fake testimony
A former University of Buffalo addictions researcher hired professional actors to testify on his behalf in a investigation into whether he fabricated data in federally funded studies.
He paid 3 actors to speak by phone during a university misconduct hearing in 2007– and then sued the state for $4 million when their false testimony helped exonerate him. The Attorney General’s Office charged him with grand larceny, perjury, identity theft, and falsifying business records.
Accused Scientist Dies
A researcher who was suspected of fabrication data and who hired actors to lie at his misconduct trial in New York in 2004 was found dead last week.