Making the Ethical Oversight of All Clinical Trials Fit for Purpose

Abstract

ImportanceWith the increase in trials assessing comparative effectiveness of approved products and alternative care strategies, guidance is needed to ensure ethical oversight is fit for purpose for the risks, burdens, and constraints on choice this research presents.ObservationsUS regulations governing human research emerged in response to horrific research abuses, reinforcing the view that research holds greater risks, uncertainties, and potential for abuse than clinical care, and thus protections and oversight are required for research, but not for care. The research oversight system established by these regulations has been effective, with most clinical research reviewed in advance for possible risk and burdens and for threats to autonomy and justice. For clinical research, however, it has become too much of a one-size-fits-all mechanism. As more comparative effectiveness and other research on widely used clinical interventions are conducted, research oversight should be fit for purpose for these kinds of trials, with the degree of oversight based on 2 morally relevant features of a trial. The first of these features is the degree to which risks and burdens increase or change when research is integrated into clinical care compared with what patient-participants would have experienced in care absent the research. The second is whether the activity restricts meaningful patient decision-making about care in morally important ways: (1) does the research restrict a choice or decision that patients ordinarily are or should be involved in and (2) does research participation remove from patients the ability to make a decision that may be meaningful to them, one based, at least in part, on their values, priorities, logistical or practical considerations, and the like? Whether clinical trials add risk or burden to what patients would otherwise have experienced, and whether studies restrict meaningful decisions patients would or should have had the opportunity to make, should help to determine whether clinical studies are designated as greater than vs minimal risk. Further, it is recommended that investigators and oversight bodies consider streamlined consent procedures for research presenting minimal additional risk or burden and that does not constrain meaningful patient decisions, rather than assuming that waiving all consent requirements is the only alternative.Conclusions and RelevanceEthical oversight of clinical research must be fit for purpose—with greater oversight for studies with greater risks, uncertainties, and impacts on meaningful patient decisions—and more streamlined oversight for other types of research.