View
101
Download
0
Category
Preview:
Citation preview
Conflict of Interest in Drug
Research
Dr. Mansij Biswas
SYR, Dept. of Pharmacology & Therapeutics,
Seth GS Medical College & KEM Hospital.
Definition
“Circumstances that create a risk that professional
judgments or actions regarding a primary interest can
be unduly influenced by a secondary interest”
“It is a risk, a condition… not necessarily a behavior
or the existence of a biased judgment or action”
20/09/14Richard Smith, Editor, BMJ
• “Conflicts of interests are situations in which financial
or other personal considerations may compromise, or
have the appearance of compromising, an
investigator’s judgment in conducting or reporting a
research.”
(AAMC, 1990)
• “A conflict of interest in research exists when the
individual has interests in the outcome of the research
that may lead to a personal advantage and that might
therefore, in actuality or apparently compromise the
integrity of the research.”
(NAS, Integrity in Scientific Research)
20/09/14
Significant financial interests:
Anything of monetary value, including but not limited
to, salary or other payment of services (e.g., consulting
fees, honoraria); equity interests (stocks, stock options
or other ownership interests); and intellectual property
rights (e.g., patents, copyrights and royalties from such
rights) when aggregated for the investigator and the
his/her spouse and dependent children, are greater than,
or equal to, $10,000 in value and 5% ownership
interest in any single entity
20/09/14PHS and NSF enacted regulations
‘Financial’ conflicts may be the easiest to
identify but they may not be the most influential
• Other sources of conflict are political, academic,
intellectual, religious, social and personal or
professional relationships; these may be just as
potent as financial conflicts are!!
20/09/14
Levels of COI
Conflict of Interest by Researchers (PI or CoI)
The REB should assess the likelihood that the
researcher’s judgment may be influenced, or appear to be influenced, by private or personal interests, and
assess the seriousness of any harm that is likely to result
from such influence or from the mere appearance of
undue influence
20/09/14
• Conflicts of Interest by REB Members
It is of the highest importance that members of the
REB avoid real or apparent conflicts of interest
For example:
• when their own research projects are under review by
their REB
or
• when they have been in direct academic collaboration
with the researcher whose proposal is under review
20/09/14
• Institutional Conflicts of Interest
• When the parent organization has a strong interest in
seeing a project approved before all ethical questions
are resolved.
• When REB is not acting independently from the
parent organization.
• The institution disrespects the autonomy of the REB
and fails to ensure that it has appropriate financial
and administrative independence to fulfill its primary
duties.
20/09/14
What comprises COI?
• Stock ownership
• Paid employment or board membership
• Patent (pending or actual)
• Research grants (from whatever source)
• Travel grants and honoraria for speaking or participation at meetings
• Gifts or membership of lobbying organizations
• Relationship with the IEC/IRB, or with possible reviewers of the paper
• Relationship with organizations and funding bodies or Membership of a government advisory board
20/09/14
• 33% of guideline authors have financial interests in the
drug(s)
• 50% guidelines had no COI documentation
• 34% of guidelines stated no COIs
• 50% had at least one author receiving research support
• 43% had at least one author who had been a paid speaker
for the company
20/09/14Nature; Vol 437 | Issue no. 7062 | 20 October 2005
Some data…
COIs may result in:
• Loss of objectivity
• Reordering of priorities towards research
• Degradation of the nature of science as an open and
collegial enterprise
• Exploitation of trainees
• Transfer of time and interest to commercial ventures
20/09/14
• Protection of human subjects may be compromised
• Integrity of research may be at risk
• The public may lose trust in research findings
• The investigator/faculty member may lose the respect
of the academic community
• Violation of scientific norms may result
• May violate terms of research grants, contracts and
federal regulations
20/09/14
• University may lose public support and funding for academic research
• Research results may be excessively delayed or not published
• Students may be negatively impacted, which may lead to inability to pursue their research interests
• University resources may be improperly used
• Increased government regulations may result
• Scandals or negative media attention may occur
20/09/14
Conflicts Can Occur at all Levels of Research:-
• In awarding a grant
• In ethical reviews
• In recruitment of participants
• During the actual study conduct
• In analysis of data
• In presentation/publication of data
20/09/14
Three Guiding Principles:
The investigator must:
conduct research activities objectively
operate with transparency
be accountable to all stakeholders, especially
when relationships with industry exist
20/09/14FASEB COI Toolkit 2007
All investigators conducting a research (industry funded or
not) have a professional obligation to the integrity of their
studies:
• Intellectual honesty in proposing and conducting the
research
• Report research results to public and scientific
community
• Lack of influence by other competing secondary
interests, primarily money
20/09/14
How to maintain objectivity?
How to operate with transparency?
• Transparency in academia-industry relationships is
important to advance research and promote trust of
colleagues and the public
• What is Transparency?
- Openness and willingness to accept scrutiny & criticism
• How can you be more transparent?
Full and regular internal reporting
External disclosure
Perception in reality
20/09/14
How to be accountable?
• Investigators are accountable to all stakeholders
including the public, sponsor, institution, research
team, and human subjects or patients
• What is Accountability?
Obligation to take responsibility for one’s actions, may berequired to explain them to others
• Who are you accountable to?
State or Federal sponsors
All study co-ordinators
Human Subjects in Clinical Trials
20/09/14
Steps to resolve
• Disclosure / transparency
• Stringent analysis of COI
• Review of contracts between funding agencies and researchers
• Elimination of the conflicting interest (e.g., divestment of
financial interest or removal from project)
• Substitution of non-interested personnel in the project
• Close external monitoring by independent reviewers
• Blinding of study, when possible
• Restrict review of colleague’s work
• Peer review of manuscripts
20/09/14
Recommendations: Individual-level conflicts
• Adopt conflict of interest policies for individuals
• Make disclosures specific enough to identify and
assess risks of relationships
• Create conflict of interest committee to review
disclosures and determine response to conflicts
• Avoid unnecessary administrative burdens
20/09/14
Recommendations:Institution-level conflicts
• Create board-level policies and procedures to identify
and respond to conflicts of interest at the institutional
level
• Develop rules for grantees on institutional conflicts of
interest
20/09/14
Recommendations:Standardize disclosure
• Broad-based consensus process to develop standard categories and formats for disclosure of conflict of interests to institutions
Goals: • Reduce burden on researchers• Improve information to assess relationships
Problem:
Some researchers need to make disclosures to multiple institutions (university, granting agencies, journals, CME courses), each with different requirements and format
20/09/14
Recommendations:Report company payments
Pharmaceutical, medical device, and
biotechnology companies should publicly report
payments to physicians, researchers, and medical
institutions (e.g. teaching institutions, professional
societies, providers of continuing medical
education etc)
20/09/14
Recommendations: Clinical research
• Research institutions: adopt policy that investigators
generally may not conduct research with human
subjects if they have a significant conflict of
interesst in the outcome of the research
• Exceptions: investigator essential, conflict managed
20/09/14
Recommendations: Medical education
• Academic medical centers should:
Prohibit gifts, ghostwriting, speakers bureaus
Limit drug samples, consulting, sales reps
Provide education on conflicts of interest
End or restrict relationships with risk but little
benefit
20/09/14
28
Recommendations: Medical practice
• Physicians should:
Not accept gifts, ghostwriting, speakers bureaus
Limit drug samples, sales reps, consulting
• Professional societies and health care providers
should amend policies to support these
recommendations
20/09/14
The Conflict of Interests Committee
• Determines if a conflict exists, evaluates, manages COI
in research, and ensures that the institution’s COI
policies and regulations are met
• A “real” and a “perceived” COI: both are treated equally
• Encourage investigators to submit a conflict of interests
statement even if there is uncertainty of whether or not a
conflict exists
The COI Committee…contd.
• Significant financial interests are reviewed as per
federal guidelines
• If COI is determined, then it must have an
acceptable management plan. The investigator
submits a proposed management plan depending on
the nature of the conflict. The COI Committee
reviews the plan and accepts or rejects it
20/09/14
May 2004…
Pfizer agreed to pay $430 million to settle a lawsuit by aformer employee turned whistle-blower, who was joinedin the lawsuit by the U.S. federal government and 11other state governments.
The lawsuit exposes various marketing practices bythe company Warner-Lambert, later bought by Pfizer.
Leading academic researchers were paid to deliverpromotional lectures at educational events and topublish favourable reports on the off-label use of itsepilepsy drug, Neurontonin
20/09/14L. Kowalczyk “Pfizer Drug Strategy Probed: States Question
Marketing Tactics for Neurontin,” Boston Globe, October 18, 2004
The Case of Nancy Oliveiri
• 1996, Olivieri found that Deferiprone in a clinical trial at the
Hospital for Sick Children in Toronto was showing
unexpected potential risks to some patients as hepatic
fibrosis.
• The drug company sponsoring her research (Apotex)
abruptly terminated the trials and issued warnings of legal
action against Olivieri if she inform her patients or publish
her findings, as it would violate the confidentiality
agreement
• However, she published her findings in NEJM in 1998
• She was subsequently dismissed from her position as
Director of the Hospital for Sick Children Program of
Hemoglobinopathies 20/09/14
• After more than 7 years of legal battle, an independent committee
looked into the matter and concluded that neither the university nor
the hospital offered her appropriate support in her conflict with
the drug company.
• Olivieri was reinstated to her position
The other side of the story: publicity seeking??
• Deferiprone- effective orally active iron-chelating agent licensed for
the treatment of patients with thalassaemia major
• Only alternative to Deferoxamine- daily subcutaneous infusions, lack
of compliance, high cost, toxicity, hypersensitivity
• No other clinicians using Deferiprone found evidence for long-term
liver damage and her interpretation of the data was immediately
questioned in letters to NEJM
• 4 of her 5 patients in whom liver fibrosis was suggested also had
hepatitis C and all 5 had iron overload- both causes liver fibrosis
20/09/14
Vioxx: Merck Vs. FDA• March 2000: A new study found Vioxx patients had double the rate of serious
cardiovascular problems than those on naproxen, an older NSAID.
• November 2000: NEJM published the study, called VIGOR.
• February 2001: An advisory panel recommends that FDA require a label warning of the possible link to cardiovascular problems.
• September 2001: FDA warns Merck to stop misleading doctors about Vioxx'seffect on the cardiovascular system.
• April 2002: FDA tells Merck to add information about CV risk to Vioxx'slabel.
• August 2004: An FDA researcher presents results of a database analysis of 1.4 million patients; it concludes that Vioxx users are more likely to suffer a heart attack or sudden cardiac death than those taking Celebrex or an older NSAID.
• Sept. 23, 2004: Merck agrees on that patients taking Vioxx in a study were twice as likely to suffer a heart attack or stroke as those on placebo.
• Sept. 30, 2004: Merck withdraws Vioxx from the U.S. and more than 80 other countries in which it was marketed.
October 4, 2008
Emory University Psychiatrist Failed to Report Income From Drug Makers. Comes under fire for violating federal and university rules against financial conflicts of interest.
The New York Times reports that Charles B. Nemeroff, chairman of psychiatry department at Emory and former editor in chief of Neuropsychopharmacology, earned more than $2.8-million for consulting with drug companies from 2000 to 2007 and hid that income from university.
October 14, 2008
The National Institutes of Health halted a $9.3-million five-year research project at Emory University, pending an investigation into potential conflicts of interest by the project’s former leader, Dr. Nemeroff.
20/09/14
Indian scenario Diabetologist Dr. V. Mohan
Letter to PMO to ban Pioglitazone due to increase risk of
bladder cancer
IPA confronts health ministry- alliance of Dr. Mohan’s diabetes
education academy + PHFI + MSD which promote Sitagliptin,
newer & 10 times costlier than Pioglitazone
Mohan bounced back- Gliptins can’t be a replacement of
pioglitazone
MSD responds by saying it has no interest with the letter and the
diabetes traing programme is an independent pure academic
initiative by MSD, PHFI & Dr. Mohan’s academy
20/09/14
To conclude…
Take home message:-
there is nothing wrong in having a conflict of
interest, but one has to disclose it and proper
actions has to be taken to get rid of it…
“Knowing is not enough; we must apply…Willing is
not enough; we must do.”
— Goethe
20/09/14
Recommended