Transcript RESEARCH MISCONDUCT - University of Tennessee Health


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 and
disqualification procedures against clinical
investigators by increasing staff and centralizing
coordination, and will list investigators against
whom it has completed proceedings on its website.
“The number of clinical investigators debarred
will rise in the near term as the agency reviews
cases,” 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
Fraud in Bioresearch Monitoring

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 for
bogus 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 were
obtained, 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 or
CBER, the investigator will be given an opportunity for a
regulatory hearing under part 16 on the question of
whether the investigator is entitled to receive
investigational new drugs”.
Ref: 21 CFR 312.70(a)

An investigator who has been determined to be ineligible
to receive investigational drug may be reinstated as
eligible when the commissioner is assured that the
investigator 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 Debarment
www,fda.gov/ora/compliance_ref/debar/
 FDA Disqualified / Restricted
www.fda.gov/ora/compliance_ref/bimo/dis_r
es_assur.htm
 FDA Warning letters
www.fda.gov/foi/warning.htm
Signing a 1572 is the PI’s legally binding
commitment in writing that she / he will be
responsible for the study in question;
totally responsible and for everything
This means she / he agrees to follow:
21
21
21
21
21
21
CFR
CFR
CFR
CFR
CFR
CFR
50 - Protection of Human Subjects - IC process
56 - Institutional Review Board
312 - Investigational New Drug Application
312.64 - Investigator Reports - AE reporting
312.62 - Record keeping and retention
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.