Conflict of Interests in Health Research

Ghaiath M. A. HusseinMBBS, MHSc. (Bioethics)

Outline

• What is an interest?• What is the Conflict of Interests (COI)?• What are the levels of COI?• What comprises COI?• Is it always “bad”?• Practical Steps to avoid and manage COI

Integrity in Scientific Research: Creating an Environment that Promotes Responsible Conduct

“For the individual scientist, integrity embodies above all a commitment to intellectual honesty and personal responsibility for one’s actions …”Accessed at www.nap.edu/openbook/0309084792/html/5.html

What is an interest?

• An interest may be defined as a commitment, goal, or value held by an individual or an institution.

• Examples include a research project to be completed, gaining status through promotion or recognition, and protecting the environment. Interests are pursued in the setting of social interactions.

What is COI?• COI exists when two or more contradictory interests relate

to an activity by an individual or an institution.

• Conflicts of interest are “situations in which financial or other personal considerations may compromise, or have the appearance of compromising, an investigator’s judgement in conducting or reporting 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 appearance compromise the integrity of the research.” NAS, Integrity in Scientific Research

Levels of COI

• Researchers• The REB should assess the likelihood that the

researcher’s judgement 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 (TCPS, 200)

Levels of COI

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 conflict or collaboration with the researcher whose proposal is under review.

Levels of COI

Institutional Conflicts of Interest• Situations may arise where the parent organization

has a strong interest in seeing a project approved before all ethical questions are resolved.

• The REB must act independently from the parent organization.

• Institutions must respect the autonomy of the REB and ensure that the REB has the appropriate financial and administrative independence to fulfill its primary duties.

What comprises COI?

• Stock ownership• Paid employment Board membership • Patent applications (pending or actual) • Research grants (from whatever source) • Travel grants and honoraria for speaking or

participation at meetings • Gifts Membership of lobbying organizations• Relationship with the National Research Ethics

Review Committee, or with possible reviewers of the paper

• Relationship with organizations and funding bodies Membership of a government advisory board

Is it always bad?

• 33% of guideline authors have financial interests in the drug

• 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 Derived from National Guideline Database

Nature, Oct 20,2005

Is it always bad?

• COIs may result in: 1. Loss of objectivity 2. Reordering of priorities towards applied research 3. Degradation of the nature of science as an open and collegial enterprise 4. Exploitation of trainees 5. Transfer of time and interest to Commercial ventures

• In May 2004, the pharmaceutical giant Pfizer agreed to pay $430 million to settle a lawsuit by a former employee turned whistle-blower, who was joined in the lawsuit by the U.S. federal government and 11 state governments.

• The lawsuit exposes various marketing practices by the company Warner-Lambert – later bought by Pfizer.

• Leading academic researchers were paid to deliver promotional lectures at educational events and to publish favourable reports on the off-label use of its epilepsy drug, Neurontonin.

L. Kowalczyk “Pfizer Drug Strategy Probed: States Question Marketing Tactics for Neurontin,” Boston Globe, October 18, 2002,

Conflicts Can Occur at all Levels of Research

• In reviews/awarding of grant• In ethics review of grant• In recruitment of participants• In analysis of data• In presentation of data

The Case of Nancy Oliveiri

• In 1996, Olivieri found that the drug she was researching (deferiprone, active iron-chelating agent ) at the Hospital for Sick Children in Toronto was showing unexpected potential risks to some patients in the trials.

• The drug company sponsoring her research abruptly terminated the trials and issued warnings of legal action against Olivieri should she inform her patients at the Hospital for Sick Children of the risks, or publish her findings.

The Case of Nancy Oliveiri

• The manufacturer (Apotex) issued more legal warnings to deter Dr Olivieri from communicating this second unexpected risk of L1 to anyone.

• However, she published her findings in the New England Journal of Medicine and

• She was subsequently dismissed from her position as Director of the Hospital for Sick Children Program of Hemoglobinopathies.

• Apotex was planning to donate USD 100 Million to the University of Toronto

The Case of Nancy Oliveiri

• After more than seven years of legal battle, an independent committee of inquiry into the matter vindicated Olivieri 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 at the Hospital for Sick Children and her actions have also been vindicated by several other independent reports.

The other side of the story

• Deferiprone which is the only effective orally active iron-chelating agent licensed for the treatment of patients with thalassaemia major and other disorders of transfusional iron overload.

• It is the only alternative to deferoxamine—a drug that has to be given by daily subcutaneous infusions and fails in many patients worldwide because of lack of compliance, high cost, toxicity, or hypersensitivity.

The other side of the story

• No other clinicians using the drug had found evidence for long-term liver damage and her interpretation of the data was immediately questioned in letters to the New England Journal of Medicine.

• Four of her patients in whom liver fibrosis had been suggested also had hepatitis C and all five had iron overload—both causes of liver fibrosis.

LET’S DEBATE…!

What do you think?

OR ?

Practical Steps to resolve

• Disclosure / transparency • Stringent analysis of COI, • Review of contracts between funders and

researchers• Close external monitoring• Blinding of study, when possible• Restrict review of colleague’s work• Peer review of manuscripts

“It is a condition and not a behaviour, and there is nothing wrong with having a conflict of interest. It is common.”

Richard Smith Editor, BMJ

DISCUSSION… Q & AThank you