IRB review may include financial connections

IOM report says ethics demand IRB involvement

The Research Revitalization Act of 2001 introduced by Sen. Edward Kennedy (D-MA) in October addresses among other things financial conflicts of interest involving researchers. Though there are no federal laws that mandate that IRBs collect and evaluate the potential impact that financial conflicts of interests may have, the bill Sen. Kennedy introduced and a recent Institute of Medicine (IOM) report recommend that such an evaluation become a critical element in ethics and human subject protection.

"A central tenet in the protection of research participants is the independent review of research protocols to assess their scientific merit and ethical acceptability. It is also critical to consider whether conflicts of interest on the part of the investigator, the Research ERB [Research Ethics Review Board — IOM’s proposed new name for IRBs], or the institution place research participants at undue risk," the report states.

Specifically, the IOM report advocates that IRBs be aware of financial connections between principal investigators and sponsors or institutions and sponsors so that they can evaluate: 1) whether the connection has the potential to impact participants; and 2) whether the connection should be disclosed to participants. According to the U.S. Public Health Service (PHS), "a conflict of interest exists when a significant financial interest could directly and indirectly affect the design, conduct, or reporting of research."

Not everyone is anxious to take on this role, as some IRB members believe they are already overextended. Says Erica Heath, MBA, CIP, president of IRC, an independent IRB in San Anselmo, CA, "As the IOM noted in its lengthy report, many jobs have been given to IRBs, many of which the parent institution is better equipped to handle. "Most institutions have organizationwide policies and protections in place and separate committees to review potential conflicts," she points out.

Given the two bills introduced in Congress this year — Kennedy’s bill and the Human Research Subject Protections Act of 2002 (HR 4697), introduced in May by Rep. Diana DeGette (D-CO), IRBs may want to go ahead and develop a protocol for assessing financial conflicts of interest. To ensure that financial connections do not impact how a study is conducted or results reported, PHS recommends that IRBs do the following:

Obtain information on financial interests held by the institution and/or investigators involved in the study. (See questions, below.) "Under current regulations, research institutions are formally responsible for developing and communicating a process for reviewing, authorizing and monitoring arrangements that prevent conflicts of interest," Robin N. Fiore, PhD, assistant professor of philosophy at Florida Atlantic University in Boca Raton, points out. "However, the specifics have been left up to each institution, and vary widely."

Questions to assist in evaluating financial conflicts of interest

  • Who is the sponsor?
  • Who designed the clinical trial?
  • Who will analyze the safety and efficacy data?
  • Is there a Data Safety Monitoring Board?
  • What are the financial relationships between the clinical investigator and the commercial sponsor?
  • Is there any compensation that is affected by the study outcome?
  • Does the investigator have equity interest in the company — publicly held company or nonpublicly held company?
  • Does the investigator receive significant payments of other sorts (e.g., grants, compensation in the form of equipment, retainers for ongoing consultation, and honoraria)?
  • What are the specific arrangements for payment?
  • Where does the payment go? To the institution? To the investigator?
  • What is the payment per participant? Are there other arrangements?

Source: Office of Human Research Protections, Washington, DC.

Fiore cites a 2001 General Accounting Office (GAO) review of conflict-of-interest disclosure and management policies and procedures at major universities receiving substantial funding from NIH [National Institutes of Health] for biomedical research and having a high degree of technology transfer activity. "The GAO was critical of the degree of variation and laxity permitted by the current discretionary approach, finding that the ability of institutions to perform the requisite oversight is subverted by institutions own commercial relationships," she says. "Under the new HHS [U.S. Department of Health and Human Services] guidance, such information is to be formally shared with the IRB, and the IRB is now responsible for evaluating its relevance for the protection of human subject-participants and for considering changes to protocols and consent documents."

• Disclose financial interests held by IRB members. "In addition to disclosing financial conflicts of interests, IRBs should have written policies regarding recusal and the IRB chair, members and staff should recuse themselves accordingly," Fiore says. "The most effective means of protecting the integrity of the IRB process is to have the broadest possible participation of members from outside the institution to assure its independence."

• Make financial conflicts of interest part of any educational programs that exist to train participants in human research protections. "Education on how to assess and to mitigate the impact of financial interests is ess ential responsible conduct of research training for all who are involved in the research enterprise: investigators, staff, institutional officials, IRB members, vendors and contractors," says Fiore. "There are a number of initiatives aimed at making the training available at major academic research centers available to others on a cost-effective cooperative basis." (Editor’s note: CITI, the University of Miami’s Collaborative IRB Training Initiative, is one such program. See IRB Advisor, June 2002, p. 67.)

• Ensure that financial interests are disclosed in the informed consent document. "Without complete information about the risks of participation, including the possibility that financial interests of the investigator might influence their clinical judgment, robustly ethical consent is unobtainable," Fiore says. "Some argue that disclosure merely confuses or disturbs subject-participants and that efforts ought to be aimed at reducing or eliminating the conflicts themselves."