Spotlight on Compliance: HHS suggests analysis of conflicts of interest

Emphasis on identifying conflicts

By J. Mark Waxman, JD
General Counsel
CareGroup Healthcare System

The public is increasingly concerned about the integrity and ethical conduct of research. This has resulted in studies and guidelines by organizations such as the Association of American Medical Colleges, a multitude of articles, and even litigation. Now with the release of draft guidance "Financial Relationship and Interests in Research Involving Human Subjects: Guidance for Human Subject protection," published on March 31 by the Department of Health and Human Services Office of Public Health and Science (OPHS), the discussion will take on greater urgency and importance.

The heart of the draft guidance is a recommendation that IRBs, institutions, and investigators engaged in research undertake a meaningful analysis of whether specific financial relationships create financial interests in research studies that may adversely affect research subjects. It seeks to assist that review by presenting not only guidance as to general approaches to address the issues, but specific points and issues to be considered by each one of these groups.

The draft guidance, which replaces interim guidance published Jan. 10, 2001, makes clear that it does not change or seek to alter any existing requirements or impose any new requirements. It is noteworthy that no specific answers or bright lines are given in the draft guidance beyond citations to the existing requirements — which do not answer most of the difficult issues raised.

General approaches

The draft guidance begins by laying out "general approaches" to the financial conflict problem. These approaches are to be considered by each identified group — the IRBs, the institutions themselves, and the investigators. Sponsors apparently are not part of this process.

The first suggested approach is to identify those financial relationships and resulting financial interests that may cause potential or actual conflicts. This will require consideration of the multitude of potential arrangements — grants, gifts, retainers, honoraria, consulting arrangements, options, deferred compensation, patents, licenses, incentives, and enrollment bonus, to list but a few.

Second, the draft guidance asks at what levels are the interests meaningful? Here, the existing Public Health Service thresholds will be considered (42 CFR §50.603) — $10,000/year income or equity interests over $10,000 and 5% ownership in a company.

Third, there should be an understanding of what procedures will be useful to run the required system. The necessary information will need to be identified, disclosed, collected, evaluated, and managed.

Fourth, consideration should be given to those who will need to be educated.

Finally, the concerned interests must address who will run the system and examine both the individual and institutional relationships and interests. It is one thing, of course, to declare that there will be a Conflict of Interest (COI) committee. It is quite another to populate it, typically without compensation, and empower it to take action.

To assist groups in evaluating whether and how conflicts may arise, a series of questions is suggested. First, the draft guidance asks, "Does the research involve financial relationships that could create conflicts of interest?" This analysis should involve a review of:

  • How the research is supported?
  • Where and by whom was the study designed?
  • Where and by whom will the resulting data be analyzed?

A second issue is, "What interests are created by the financial relationships involved in the situation?" To answer this question will require a dissection of each aspect of the relationship to understand all the potential interests involved whether purely cash or other elements of monetary value.

Third, the question to be addressed is whether given the financial relationships, the institution is the appropriate site for research. Although no clarifying questions are asked, or potential standard given, the question is apparently designed to ask whether the financial interests are so pervasive that the conflict could never be adequately resolved.

Finally, "Would the rights and welfare of human subjects be better protected by taking a series of mitigating steps?" Potential steps include elimination or reduction of the financial interest or independent monitoring.

Everyone can do their part

The draft guidance identifies specific issues for consideration by each group addressed:

  • Institutions. The draft guidance addresses Institutions separately from their IRBs and does not distinguish between Institutions that might operate their own IRB, as opposed to contracting out for this function. To address financial conflicts of interest, a laundry list of potential actions are suggested. They include:
    • Separate responsibilities for financial decisions and research decisions. Notably a "financial decision" is not deferred. Presumably it means any decision that affects the receipt of value, including recruitment fees. Separating decisions about recruitment fees, for example, from those making research decisions may prove difficult in some situations.
    • Use of independent organizations to hold or administer the institution’s financial interest. Given the illiquid nature of some of the interests and their ad hoc nature, complete independence may also be problematic or not cost justified.
    • Extend the role of the COI committee to address institutional conflicts of interest, perhaps independently from individual conflicts of interest.
    • Include outside individuals to review and oversee financial interests. These individuals should presumably not be drawn from the Institution’s Board or significant financial supporters.

  • Investigators. The draft guidance is noteworthy in addressing the investigators themselves, suggesting that consideration be given to what "a financial relationship of any kind" might have on a clinical trial. It is also suggested that included information in the consent document might be information about a financial arrangement of the institution or an investigator and how it is being managed. This category often is not disclosed to trial participants.

The draft guidance suggests using special measures when conflicts exist such as nonbiased persons obtaining consents (presumably other than those participating in the trials directly, which could put a strain on resources) or the independent monitoring of research.

The draft guidance hopefully will be read and carefully considered by at least IRBs. Investigators will present a greater challenge, including how to involve them in a real discussion process.

Institutions will need to consider how, beyond the IRB process, to address the issues raised. If, however, each element of the process does devote the resources to reviewing and resolving the issues raised and addressing the processes suggested, undoubtedly the overall system will be improved.

[Editor’s note: Public comment is being accepted and can be accessed by going to (Docket 02N-0475). The draft guidance can be accessed at]

Clarification: Since last month’s Spotlight on Compliance article, "FDA issues guidance on use of electronic records," was authored, the FDA has moved forward to withdraw much of the Draft Guidance effort it has made with respect to Part 11. At this point, reliance must be placed primarily on the existing guidelines as the governing authority.