Beyond unease and acknowledgements:

Addressing the impact of conflicts of interest on research and scientific integrity

by Eric Racine, PhD and Danaë Larivière-Bastien*
Neuroethics Research Unit
Institut de recherches cliniques de Montréal (IRCM)
* The authors would like to thank Dr. Emily Bell for helpful feedback on this manuscript.

Over the past few years, the pages of medical and scientific journals have been steadily reporting the modern challenges posed to scientific integrity. In our current context, there are many occasions where the primary interest of clinical researchers to generate knowledge can conflict with secondary interests, notably financial interests.

This situation led Maria Angell, editor of the New England Journal of Medicine, to write the following in a recent article published in the Journal of the American Medical Association entitled “Industry-sponsored clinical research: A broken system�?: “Over the past two decades, the pharmaceutical industry has gained unprecedented control over the evaluation of its own products. Drug companies now finance most clinical research on prescription drugs, and there is mounting evidence that they often skew the research they sponsor to make their drugs look better and safer."[1]

Angell argued in the same commentary that drug companies often design the studies, conduct data analysis, write the publications, and decide how and when they will be published; sometimes preventing investigators to access all of their own data.

“Looking at this picture altogether, it would be naïve to conclude that bias is only a matter of a few isolated instances. It permeates the entire system," she further remarked. “Physicians can no longer rely on the medical literature for valid and reliable information. This is the conclusion I reluctantly reached toward the end of my two decades as an editor of the New England Journal of Medicine, and it has been reinforced in subsequent years."[1]

In support of this claim, a study published in Nature examining different forms of scientific misconducts reported that 15.5 per cent of the 3,247 surveyed scientists admitted “changing the design, methodology or results of a study in response to pressure from a funding source."[2] Although it was not clear that these were necessarily private sources of funding, the results highlight the fragility of scientists when they are exposed to external pressures that can shape their research. The high prevalence of scientific misconduct has been confirmed by several other studies, including one showing that “one in four articles demonstrated misapplication of authorship criteria and inappropriate assignment of authorship."[3]

Conflicts of interest
Conflicts of interest can be generally defined as “a set of conditions in which professional judgment concerning a primary interest tends to be unduly influenced by a secondary interest."[4] They can involve wide ranging practices, including the use of pharmaceutical samples, drug formularies, funding for continuing medical education, funds for physician travel, speakers bureaus and ghostwriting, and consulting and research contracts.[5]

Financial conflicts of interest have been the focus of much of the discussion although other interests (such as prestige and promotion) can lure clinical scientists like all other professionals.

The task force of the American Association of Medical Colleges (AAMC) has rightfully highlighted that: “financial interests in human subjects research are distinct from other interests inherent in academic life that might impart bias or induce improper behavior, because, financial interests are discretionary, and because the perception is widespread that they may entail special risks. Specifically, opportunities to profit from research may affect – or appear to affect – a researcher’s judgments about which subjects to enroll, the clinical care provided to subjects, even the proper use of subject’s confidential health information."[6]

The task force also mentioned that “financial conflicts of interest also threaten scientific integrity when they foster real or apparent biases in study design, data collection and analysis, adverse event reporting, or the presentation and publication of research findings."[6]

In its companion paper on institutional financial conflicts of interest, the task force clarified that “an institution may have a conflict of interest in human subjects research whenever the financial interests of the institution, or of an institutional official acting within his or her authority on behalf of the institution, might affect – or reasonably appear to affect – institutional processes for the conduct, review, or oversight of human subjects research."[7]

Conflicts of interests can threaten and jeopardize scientific integrity, which has been defined by the European Science Foundation as “at the heart of the trust on which scientific communication and collaboration depend."[8]

The European Science Foundation has listed some principles that should be followed in order to foster scientific integrity, including the “highest professional standards in designing and conducting investigations" and “frankness and fairness with regard to the contributions of partners, competitors, and predecessors."[8] Scientific integrity is opposed to scientific misconduct which includes, “fabrication, falsification, or plagiarism in proposing, performing or reviewing research, or in reporting research results"[9] as well as “redundant publication"[10], “inhumane research"[10], “failure to obtain informed consent, breach of patient confidentiality, improper award"[11], or “failing to present data that contradict one’s own previous research".[2]

In Canada, the well known cases of Nancy Olivieri and David Healy have sparked debates on the potential of the industry to influence the integrity of research and the independence of research institutions.

In the first case, Olivieri was conducting a clinical trial of deferiprone (an iron chelator) in collaboration with Apotex for the treatment of thalassemia. Initial results were encouraging and a second trial was initiated. However, when Olivieri found out that there could be unexpected risks for subjects, and reported this to her research ethics committee, she faced legal lawsuits from Apotex and was poorly supported by her institution.[12]

David Healy is a well known British psychiatrist who was offered a senior position at the Centre for Addiction and Mental Health (CAMH). After he presented a critical talk on the role of the pharmaceutical industry in 2000, the offer he had received to direct the Mood and Anxiety Program (and full professorship) was revoked. There have been lingering fears of institutional conflicts of interests in this case since the manufacturer of Prozac, Eli Lilly, was the largest sponsor of CAMH at the time ($1 million).[13]

Emerging recommendations to handle conflicts of interest
The standard approach to conflicts of interest has been disclosure. This is well enshrined in major codes of ethics such as the Canadian Medical Association’s code stating that physicians must “recognize and disclose conflicts of interest that arise in the course of [their] professional duties and activities, and resolve them in the best interest of patients."[14] However, some commentators and professional associations have started to argue that disclosure is not enough and more stringent approaches are needed given the prevalence and potential impact of conflicts of interest.[5,6]

The AAMC task force has suggested that the default position should be to exclude those with conflicts of interest from research activities and to require proper examination and justification for their participation. Some of the key recommendations of the AAMC task force (see table below) include prior disclosing of all individual conflicts of interest to a special body within institutions and the implementation of rigorous monitoring processes.

These recommendations form a useful starting point for discussion on the management of conflicts of interest in the Canadian medical context to further promote scientific integrity.

References
1. Angell M. Industry-sponsored clinical research: a broken system. JAMA 300[9]:1069-1071, 2008.

2. Martinson BC, Anderson MS, de Vries R. Scientists behaving badly. Nature 435:737-738, 2005.

3. Flanagin A, et al. Prevalence of articles with honorary authors and ghost authors in peer-reviewed medical journals. JAMA 280[3]:222-224, 1998.

4. Thompson DF. Understanding financial conflicts of interest. NEJM 329[8]:573-576, 1993.

5. Brennan TA, et al. Health industry practices that create conflicts of interest: a policy proposal for academic medical centers. JAMA 295[4]:429-433, 2006.

6. Association of American Medical Colleges. Protecting subjects, preserving trust, promoting progress I: policy and guidelines for the oversight of individual financial interests in human subjects research. Academic Medicine 78[2]:225-36, 2003.

7. Association of American Medical Colleges. Protecting subjects, preserving trust, promoting progress II: principles and recommendations for oversight of an institution’s financial interests in human subjects research. Academic Medicine 78[2]:237-245, 2003.

8. European Science Foundation. Good scientific practice in research and scholarship. 2000 [cited 2008 October 28; Policy Briefing]. Available from: www.esf.org/index.php?eID=tx_nawsecuredl&u=0&file=fileadmin
/be_user/research_areas/social_sciences/documents/Good_research_practice.pdf&t=
1225314780&hash=581ab9766ac397b09e167d24b31e8adb.

9. Office of Research Integrity. Public Health Service Policies on Research Misconduct. Department of Health and Human Services, 28369-28400, 2005.

10. Walter G, Bloch S. Publishing ethics in psychiatry. Australian and New Zealand Journal of Psychiatry 35[1]:28-35, 2001.

11. Marcovitch H. Misconduct by researchers and authors. Gaceta Sanitaria 21[6]:492-499, 2007.

12. Gibson E, Baylis F, Lewis S. Dances with the pharmaceutical industry. CMAJ 166[4]:448-450, 2002.

13. Birmingham K. Dark clouds over Toronto psychiatry research. Nature Medicine 7[6]:643, 2001.

14. Canadian Medical Association. Code of Ethics. 2004 [cited 2008 October 28; CMA Policy]. Available from: http://policybase.cma.ca/ PolicyPDF/PD04-06.pdf.

© Copyright 2009. Canadian Psychiatry Aujourd’hui. All rights reserved.

Back to Table of Contents

General Inquiries:

Canadian Psychiatry Aujourd’hui
141 Laurier Avenue West
Suite 701
Ottawa, ON K1P 5J3
613-234-2815 ext. 235
Fax: 613-234-9857
E-mail: aujourdhui@cpa-apc.org

Display and Classified Ad Inquiries:

Smita Hamzeh
E-mail: advertising@cpa-apc.org