Risks, Benefits, and Taking Participants’ Values Seriously: The Case of HIV Cure Research

By Robert Steel

The introduction and refinement of highly effective antiretroviral treatments has transformed HIV into a manageable chronic condition. Nonetheless, treatment is lifelong, burdening people living with HIV and health systems. So there is interest in a cure. But cure trials can be risky and the medical benefit of potentially being cured is limited against a baseline of antiretroviral access. Hence, participation in HIV cure research may involve substantial net risks: it may be a “bad deal,” medically speaking, for the participants. This is the source of a challenge to the ethics of HIV cure trials: perhaps they fail to have a “favorable risk-benefit ratio,” which is widely understood to be an ethical requirement on clinical trials.

Determining whether this is so requires taking up some view on what makes a risk-benefit ratio favorable. That, in turn, requires some view on the purpose of risk-benefit review: why do we have review committees prospectively evaluate, and potentially reject, studies on the basis of their risks and benefits? Of course, this process may serve multiple purposes simultaneously. Nonetheless, I contend that one of the most central is to protect participants from mistakenly entering into research that doesn’t actually make sense for them given their values and priorities. Research is complex and difficult to understand, so it makes sense to supplement participants’ individual attempts to navigate the research process with third-party review by experts.

But this helpful assistance should not extend to attempting to correct the participant’s values or priorities. Many people living with HIV express high degrees of altruism and solidarity. For people who centrally value the discovery of a cure, it can make sense to be willing to accept serious levels of personal risk in research. If a person has such values and priorities, ethics reviewers should not get in the way: they should not attempt to “correct” the “mistake” of being so altruistic. Indeed, something has gone very wrong if the ethics community finds itself committed to denying noble people the opportunity to do noble things.

Of course, not all people living with HIV think or feel the same way. Many are interested in participating in research, but many are not. Some may be willing to accept substantial risks and others will certainly not be. For very risky research, it makes sense to be extremely sensitive to the possibility of participants enrolling by mistake. But instead of flatly rejecting a very risky proposed trial, I recommend that a review committee could require that the protocol include special measures to ensure it really does recruit eyes-wide-open altruists—for instance, by recruiting from populations they expect to be especially committed, using extended and enhanced consent processes, having explicit values conversations, and even, if necessary, using comprehension tests. Only when reviewers deem that no combination of such measures could be feasibly effective should they outright reject a study on risk-benefit grounds.

Values are important not just because they control how much people are willing to sacrifice, but also for what. Consider two very altruistic potential participants. But for one, the existence of a cure for HIV is of large symbolic importance, even if it is infeasible for widespread use, whereas the other cares more about having a large impact on populations burdened by HIV. They are both altruistic, and both care about fighting HIV, but they care in importantly different ways. Different trials make sense for each. Indeed, in some cases the second may be more appropriately directed to volunteer with HIV-related services rather than being in research at all. The goal of prior review of risks and benefits should not be to discover what makes a trial “worth it” in some objective sense that would apply across both these hypothetical participants. Rather, it should be to enable each to enroll in those trials (and only those trials) which genuinely make sense for them. Or, that’s what we should care about if we take their values seriously.

 

Paper title: Reconceptualizing Risk-Benefit Analyses: the Case of HIV Cure Research

Author: Robert Steel

Affiliations:

Center for Population-Level Bioethics, Rutgers University

Clinical Center Department of Bioethics, National Institutes of Health

Competing interests: The opinions in this paper are solely the author’s own, and do not represent any position or policy of the NIH, the US Public Health Service, or the US Department of Health and Human Services. I have no competing interests to declare.

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