Financial Conflicts of Interest in Human Subjects Research: The Problem of Institutional Conflicts

Lemonick M.D. Goldstein A. , “At Your Own Risk,” Time, April 14, 2002, at 40–49.

Ironically, in certain respects, animal research is more stringently regulated than is human subjects research. For example, while federal regulations require the Institutional Animal Care and Use Committee (IACUC) — the committee within each medical institution charged with ethics review of animal research projects undertaken at that institution — to review animal research protocols every six months, the continuing review requirement for human research trials may be fulfilled by annual reviews. Moreover, while IACUCs have long been subject to accreditation requirements, attention is only now being directed to accreditation of Institutional Review Boards (IRB).

See Steinbrook R. , “Improving Protection for Research Subjects,” N. Engl. J. Med., 346 (2002): 1425–30;.

White E. , “House Bill Aims to Protect Human Subjects, Establish Voluntary Accreditation Process,” BNA Medical Research, Law & Policy, 1:5 (2002): 124–25.

In this document, the terms “investigator” and “researcher” are used interchangeably, and include, for all purposes of this article, research staff exercising independent judgment over data gathering, monitoring, analysis, and interpretation, and those involved in the informed consent process with research subjects.

See Office of Human Research Protections, Letters to the University of Oklahoma Health Sciences Center, “Re: Human Research Subject Protections Under Multiple Project Assurance (MPA) M-1448,” dated June 29, 2000, July 7, 2000, July 13, 2000, and October 19, 2000.

See also Cohen J. , “Share and Share Alike is Not Always the Rule in Science,” Science, 268 (1995): 1715–18.

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Thompson D.F. , “Understanding Financial Conflicts of Interest,” N. Engl. J. Med., 329 (1993): 573–76, at 573.

Rothman K.J. , “Conflicts of Interest: The New McCarthyism in Science,” JAMA, 269 (1993): 2782–84.

Cohen J.J. , “Trust Us to Make a Difference: Ensuring Public Confidence in the Integrity of Clinical Research,” Academic Medicine, 76 (2001): 209–14.

See Thompson , supra note 18, at 574.

See generally Goldner J.A. , “Dealing With Conflicts of Interest in Biomedical Research: IRB Oversight as the Next Best Solution to the Abolitionist Approach,” Journal of Law, Medicine & Ethics, 28, no. 4 (2000): 379–404;.

Barnes M. Krauss S. , “Conflicts of Interest in Human Research: Risks and Pitfalls of ‘Easy Money’ in Research Funding,” BNA's Health Law Report, 9:35 (2000): 1378–86.

Barnes M. Florencio P.S. , “Investigator, IRB and Institutional Financial Conflicts of Interest in Human Subjects Research: Past, Present and Future,” Seton Hall Law Review (publication anticipated in 2003).

IRB member conflicts of interest are regulated, theoretically, for all conflict of interest purposes, both financial and nonfinancial. Yet the Public Health Service and the Food and Drug Administration regulations that apply this “zero-tolerance” policy to IRB member conflict of interests are written generally, without exact definitions of what constitutes either a financial or nonfinancial conflict of interest for these purposes.

Association of American Universities, Task Force Report on Individual and Institutional Conflicts of Interest (Washington, D.C.: Association of American Universities, October, 2001): 1–22, at 10, available at <http://www.aau.edu/research/COI.01.pdf>.

Korn D. , “Conflicts of Interest in Biomedical Research,” JAMA, 284 (2000): 2234–37.

National Human Research Protections Advisory Committee, Letter to the Honorable Tommy G. Thompson , Secretary of the U.S. Department of Health and Human Services, “Re: HHS' Draft Interim Guidance: Financial Relationships in Clinical Research: Issues for Institutions, Clinical Investigators and IRBs to Consider When Dealing With Issues of Financial Interests and Human Subject Protection,” dated August 8, 2001, at 9 (on file with author).

Stolberg S.G. , “The Biotech Death of Jesse Gelsinger,” New York Times Magazine, Nov. 28, 1999, available at <http://nytimes.com/library/magazine/home/19991128mag*stolberg.html>.

Beardsley T. , “Gene Therapy Setback: A Tragic Death Clouds the Future of an Innovative Treatment Method,” Scientific American, 282 (2000): 36–37.

See Lemonick , supra note 1.

American Society of Gene Therapy, Policy of the American Society on Gene Therapy on Financial Conflict of Interest in Clinical Research (Adopted April 5, 2000), available at <http://www.asgt.org/policy/index.html>.

45 C.F.R. §; 46.107(e) (2002);

21 C.F.R. §; 56.107(e) (2002).

Wilson D. Heath D. , “With a Year or Two to Live, Woman Joined Test in Which She Was Misled — and Died,” Seattle Times, March 13, 2001, at A1;.

Wilson D. Heath D. , “The Hutch Zealously Guards its Secrets,” Seattle Times, March 15, 2001,): at A1.

(“[h]ow can [academic medical institutions] justify rigorous conflict of interest policies for individual researchers when their own ties are so extensive? Some academic institutions have entered into partnerships with drug companies to set up research centers and teaching programs in which students and faculty members essentially carry out industry research”).

Kassirer J.P. , “Medicine at Center Stage,” N. Engl. J. Med., 328 (1993): 1268–69;.

Shalala D. , “Protecting Research Subjects — What Must be Done,” N. Engl. J. Med., 343 (2000): 808–10.

Kassirer J.P. Angell M. , “Financial Conflicts of Interest in Biomedical Research,” N. Engl. J. Med., 329 (1993): 570–71, at 571 (“when researchers [and research institutions] choose to invest in health-related companies rather than in other types of business, it raises the question of whether they are attempting to profit from the specialized knowledge they gain in the course of performing research”).

Kassirer J.P. , “Pseudoaccountability,” Annals of Internal Medicine, 134 (2001): 587–90.

In fact, some calls for federal oversight have already been made. The U.S. National Bioethics Advisory Commission, for example, has called for federal legislation to create a National Office for Human Research Oversight to oversee all research involving human subjects, including disclosure and management of conflicts of interest. See National Bioethics Advisory Commission, Ethical and Policy Issues in Research Involving Human Participants (Rockville, Maryland: The Commission, 2001), available at <http://www.georgetown.edu/research/nrcbl/human/overvoll.html>.

See also Wood A.J.J. Stein C.M. Woosley R. , “Making Medicines Safer — The Need for an Independent Drug Safety Board,” N. Engl. J. Med., 339 (1998): 1851–54.

Association of American Universities, supra note 25, at 12.

During the editorial process, the Association of American Medical Colleges released a report on institutional financial interests in human subjects research.

See Association of American Medical Colleges (October 2002): 1–14, available at <http://www.aamc.org/members/coitf/2002coireport.pdf>.

National Association of Securities Dealers, NASD Rule 2711, Research Analysts and Research Reports, available at <http://www.nasdr.com/pdf-text/rf02_21_final.pdf>; Securities and Exchange Commission, Amendments to NYSE Rules 472 and 351, available at <http://www.nyse.com/regulation/regulation.html>.

Association of American Universities, supra note 25, at 13.

Id.

Internal Revenue Service, Excise Taxes on Excess Benefit Transactions, 65 Federal Register at 3076 et seq. (January 23, 2002). 44. The intermediate sanctions rules provide that when a disqualified person benefits from an excess benefit transaction, that disqualified person will be liable for an excise tax equal to 25 percent of the excess benefit. If the excess benefit is not corrected (i.e., returned to the institution), the disqualified person can be liable for an additional excise tax of 200 percent of the excess benefit.

See Id.

Korn , supra note 26.

Moore v. Regents of the University of California, 793 P.2d 479 (Cal. 1990).

DAB v. Brown, 570 N.W2d 168 (Minn. Ct. App. 1997).

Rodwin M.A. , “Physicians' Conflicts of Interest: The Limitations of Disclosure,” N. Engl. J. Med., 321 (1989): 1405–08;.

Miller T.E. Sage WM ., “Disclosing Physician Financial Incentives,” JAMA, 281 (1999): 1424–30.

Miller T.E. Horowitz C.R. , “Disclosing Doctors' Incentives: Will Consumers Understand and Value the Information?,” Health Affairs, 19 (2000): 149–55.

Kassirer J.P. , “Financial Conflict of Interest: An Unresolved Ethical Frontier,” American Journal of Law & Medicine, 27, nos. 2&3 (2001): 149–62, at 151.

Moses H. Martin J.B. , “Academic Relationships With Industry: A New Model for Biomedical Research,” JAMA, 285 (2001): 933–35.

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See Bodenheimer , supra note 52.

See Id.

Chalmers I. , “Underreporting Research is Scientific Misconduct,” JAMA, 263 (1990): 1405–08.

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Slater E.E. , “IRB Reform,” N. Engl. J. Med., 346 (2002): 1402–04 at 1403 (noting that “… the increasing number and complexity of protocols are taxing the capability of local IRBs.”).

Emanuel E.J. Steiner D. , “Institutional Conflict of Interest,” N. Engl. J. Med., 332 (1995): 262–67 at 265 (“… some members of the [IRB] might work for the department that stood to benefit financially from the clinical research, and others might benefit indirectly from the institution's royalties. Finally, the public perceives these boards as internal rather than external bodies. Just as citizens may be suspicious of the thoroughness of a government agency's review of its own behavior, there may be little confidence in an [IRB's] judgment when the institution has a financial interest in the research”).

(“[c]onflict of interest analysis should take account of, and contain ‘compelling and necessary’ exceptions for, situations in which physicians who treat unusual conditions invent new devices or develop other interventions, and yet have significant financial interests in those techniques, interventions, or devices. In these cases, guidance should not discourage these physicians from inventing new devices and developing new interventions and therapies, and should not prohibit these physicians from acting as clinical investigators, particularly in the initial stages of investigation, since they may be in the best position to undertake critical research with a high assurance of safety for research subjects”).

See Association of American Medical Colleges, Protecting Subjects, Preserving Trust, Promoting Progress —- Policy and Guidelines for the Oversight of Individual Financial Interests in Human Subjects Research (December 2001): 1–25, at 7, available at <http://www.aamc.org/members/coitf/firstreport.pdf>,(“[i]n the event of compelling circumstances, an individual holding significant financial interests in human subjects research may be permitted to conduct the research. Whether the circumstances are deemed compelling will depend in each case upon the nature of the science, the nature of the interest, how closely the interest is related to the research, and the degree to which the interest may be affected by the research”).

See Kassirer , supra note 50, at 151. This searchable registry could be extended to also list corporate and personal institutional financial conflicts of interest when disclosure to the sponsor is recommended by the IRP.

As we noted above, the editors of many leading biomedical journals have adopted the position that they must reveal to readers the financial incentives underlying the articles they publish so that readers can interpret the findings presented in the articles in light of the financial incentives. When recommended by the independent review panel, significant institutional financial incentives might also be disclosed to journal editors who could then publish this information alongside the article.

Miller F.G. Rosenstein D.L. DeRenzo E.G. , “Professional Integrity in Clinical Research,” JAMA, 280 (1998): 1449–54;.

Yarborough M. Sharp R.R. , “Restoring and Preserving Trust in Biomedical Research,” Academic Medicine, 77 (2002): 8–14.

Palmisano P. Edelstein J. , “Teaching Drug Promotion Abuses to Health Care Profession Students,” Journal of Medical Education, 55 (1980): 453–55.

See Blumenthal , supra note 6.