This post originally appeared on Bill of Health, the blog of the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School.

---

By Beatrice Brown

Human subjects research has long been plagued by racial inequality. While flagrant abuses have been curtailed, disparities have, unfortunately, persisted.

One area ripe for scrutiny is clinical trial enrollment. A 2018 study by William Feldman, Spencer Hey, and Aaron Kesselheim in Health Affairs documents racial disparities in trials that are exempt from typical requirements for informed consent from study participants.

Informed consent is a cornerstone of the ethical conduct of medical research, as affirmed by the Belmont Report in 1976. However, emergency conditions, such as cardiac arrest, are not conducive to obtaining informed consent. Patients may be incapacitated, and often there is simply not enough time to discuss the trial in a meaningful way with surrogates. Nevertheless, research on emergency conditions is important for improving clinical practice.

To respond to this issue, the FDA created the “exception from informed consent” (EFIC) process in 1996 to allow for the study of drugs and medical devices used to treat emergency conditions. The rationale for this process lies in weighing the ethical principle of beneficence with the ethical principle of respect for persons—if the clinical benefit to be derived for the population is sufficient, then exceptions from informed consent may be warranted.

However, even if there is an ethical justification for EFIC trials, for the practice to be just, the burdens and benefits of these trials ought to be fairly distributed.

Feldman, Hey, and Kesselheim’s findings raise questions about the fairness of EFIC trials. Although Black people represent only 13 percent of the US population, they made up 29 percent of participants at U.S. sites for EFIC trials.

This overrepresentation of Black people in EFIC trials stands in sharp contrast to their underrepresentation in clinical trials requiring informed consent.

Black people only make up 5 percent of clinical trial participants overall. Participation in clinical trials may afford patients better outcomes through access to cutting-edge treatments. Diversity and inclusivity in clinical trials are also important to understanding and analyzing research findings. Although efforts in various medical fields, such as in oncology, are underway to make clinical trials more inclusive, enrollment among Black people remains low.

This underrepresentation and overrepresentation both represent concerns for research ethics.

The underrepresentation of Black people in clinical trials that require informed consent may partially result from distrust fueled by past historical abuses in medical research. And overrepresentation of Black people in trials that bypass informed consent might exacerbate this distrust. The overrepresentation of Black people in EFIC trials, while not fully understood, may be due in part to the possibility that these trials are conducted in communities with higher proportions of Black people. The data raise questions about whether Black participants in EFIC trials (or their surrogates) would willingly consent if given the chance or if they would otherwise decline to enroll.

More must be done to ensure that EFIC trials do not perpetuate racial disparities. Though extensive work is needed, Feldman, Hey, and Kesselheim provide a few preliminary suggestions.

First, better community engagement may be helpful. The FDA requires that EFIC trial investigators engage in a community consultation process before initiation of trials, which includes providing information about the risks and benefits of the intervention and soliciting feedback on research plans. But a follow-up study demonstrated that Black people are underrepresented in this consultation process relative to their enrollment, and that groups with higher proportions of Black people support EFIC trials at lower rates. Deeper, targeted consultation in Black communities may help to improve the EFIC process and mitigate racial disparities by ensuring that these communities have a voice in shaping the conduct of these studies.

Second, Feldman, Hey, and Kesselheim propose that recruitment should be conducted in a wide variety of communities to ensure racial and ethnic parity. Many EFIC trials provide interventions in the field (i.e., before arrival to the emergency room) and enroll patients across wide catchment areas. It is important, the authors argue, that clinical investigators perform these trials in diverse communities and not only in areas with high proportions of Black people.

Finally, Feldman, Hey, and Kesselheim suggest that the FDA implement reporting requirements to ensure that better data are available on consent and race in these trials. Having better data would allow policy makers to improve the EFIC process, ensuring that it remains ethical and does not exacerbate already-existing racial disparities.

As COVID-19 continues to reveal deep racial disparities in our health care system, we must think carefully about how to resolve these disparities in all realms of medicine, including clinical trials and particularly those trials that bypass consent. Researchers conducting trials without informed consent must be cognizant of systemic racial injustices and ensure that they are not contributing to the persistence or worsening of disparities.

Beatrice (Bea) Brown received her Master of Bioethics (MBE) from Harvard Medical School in 2020 and her BA in Ethics, Politics, & Economics from Yale University in 2019. During the 2019-2020 academic year, she was a Petrie-Flom Student Fellow. As a Student Fellow, she wrote a research paper proposing a new argument for a constitutional right to physician-assisted death by redefining what it means to heal.