Experts say federal agencies must clarify rules permitting payment to research subjects.
The development of life-saving drugs and cutting-edge treatments depends on people participating in clinical research. But federal regulators restrict clinical researchers from using the exchange of payments for research participation—a powerful study recruitment strategy—because they worry that this practice leads to coercion or undue inducement.
Because of the regulatory limits on payments in clinical research, Institutional Review Boards (IRBs)—the committees in charge of evaluating the ethics of research proposals—often block researchers from paying prospective research participants, which inhibits their ability to move forward with projects. To speed the pace of research development and innovation, regulators must revisit their definitions of coercion and undue inducement, as well as encourage the use of financial incentives for research recruitment, assert Emily Largent and Holly Fernandez Lynch, professors at the Perelman School of Medicine at the University of Pennsylvania.
Under current U.S. Health and Human Services (HHS) regulations, IRBs cannot allow researchers to use risk-based payments—compensation designed to offset the risks of adverse health effects—to recruit human subjects for their studies because of their coercive and inducive effects. Although Largent and Fernandez Lynch recognize that federal regulations should police potential unethical payments for research participation, they argue that current rules offer very little guidance on what coercion and undue inducement mean.
Eighteen agencies, including HHS, have adopted the Common Rule, which requires IRBs to scrutinize whether researchers obtain informed consent from study participants. Although the Common Rule informs IRBs that coercive or inducive practices on the part of researchers make informed consent impossible, IRBs bear the burden of deciding when payments reach the level of coercion or undue influence, explain Largent and Fernandez Lynch.
Worse still, the Common Rule does not address the ethical reasons that payment of research participant raises concerns, write Largent and Fernandez Lynch. Such explanation of the ethical implications could provide some guidance for determining when a practice crosses over to coercive or unduly influential, making it unfortunate that the Common Rule remains silent—even though its scope covers almost all American clinical research, add Largent and Fernandez Lynch.
The HHS Office for Human Research Protections (OHRP), although squarely in charge of regulatory oversight on clinical research, also fails to provide operational definitions of coercion and undue inducement. Although their guidance documents frame payments for research participation more carefully than the Common Rule, OHRP’s pattern of regulatory enforcement is inconsistent and unpredictable, according to Largent and Fernandez Lynch.
The lack of clear regulatory guidance on payments for research participation has led to a longstanding trend of IRB decisions that disfavor offering financial incentives to people who participate in research studies. But Largent and Fernandez Lynch argue that scholars do not have a foundation for the reasons they offer to support this trend.
They explain that worries about financial payments stem in part from many historical research scandals, including the Nazi human experiments and the Tuskegee syphilis study. Although Largent and Fernandez Lynch recognize the pernicious nature of these events, they argue that excessive payments for research participation did not cause these scandals. Instead, other unethical research practices—in the words of Largent and Fernandez Lynch, “deception,” “researcher conflicts of interest,” and “outright torture”—produced these research travesties.
Critics of payment in exchange for participation argue that study participants should not bear the uncertain risks inherent to clinical studies in exchange for compensation. These critics, however, overestimate the risk of harm in clinical research, claim Largent and Fernandez Lynch. Before beginning clinical studies, researchers need to convince IRBs of the appropriateness of potential risks. Researchers do not have free rein over their research processes, and they must ensure safety at each stage of research.
According to Largent and Fernandez Lynch, OHRP should revise its guidance documents to address the misconceptions about the pervasive influence of money on the study participants’ judgment. Presently, researchers can—and commonly do—recruit participants with payments IRBs deem non-coercive. Largent and Fernandez Lynch urge OHRP to state clearly that “genuine offers of payment are never coercive” and to make clear that payments for research participation generally benefit the progress of clinical studies. If OHRP makes these updates, Largent and Fernandez Lynch predict that IRBs will worry less about the risk of regulatory enforcement actions.
Largent and Fernandez Lynch also argue that amendments to the Common Rule could help better guide IRB decision-making. The Obama Administration made progress on clarifying which research populations are most susceptible to coercion and undue influence—an effort that indicated the administration’s intention to revisit research policy and liberalize the standards on payments for research participation. But because of the Trump Administration’s reluctance to spearhead Obama-era research policy initiatives, IRBs should not expect an amended Common Rule to provide much needed regulatory guidance.
Largent and Fernandez Lynch’s paper appears in the Yale Journal of Health Policy, Law, and Ethics.
