Ethics of Informed Consent for Randomized Comparative Effectiveness Studies

By Stacey Kusterbeck

Randomized comparative effectiveness studies often compare treatments within the standard of care to determine which is better for patients. When research and clinical care are combined in this way, healthcare providers can be confused about what is required in terms of obtaining consent for enrollment in the research study.

“There is misunderstanding on the part of researchers and IRB [Institutional Review Board] members about the obligations to obtain consent in these contexts. Obtaining consent for the clinical intervention is not enough. Research consent is required,” asserts Lois Shepherd, JD, Wallenborn professor of biomedical ethics and professor of law at the University of Virginia.

Consent obligations have been bypassed in some major comparative effectiveness studies, including studies that randomly assigned interventions to premature newborns and that compare drugs given in ambulances to adults in a state of agitation.^1,2 “It is not known how often studies are taking place without consent. But some have involved thousands of patients,” notes Shepherd. “And we’re not talking here about studies that qualify for a waiver of consent requirements because of an emergency situation.”

Physicians have an ethical obligation to inform their patients that they are being placed in a research study that will choose their course of care, and to obtain consent. This is the case even when the two arms are within the standard of care and the comparative risks and potential for benefit are similar, says Donna T. Chen, MD, MPH, a professor at the Center for Health Humanities and Ethics at University of Virginia School of Medicine.

Breach of trust is a central ethical concern. “It feels like taking unfair advantage of the trust that patients have in their healthcare providers. It also has the potential to further erode trust in the clinical research enterprise, as well,” says Chen. Randomized comparative effectiveness research is no different from any other randomized clinical trials in terms of the requirement to obtain consent, argue Shepherd and Chen in a recent paper.³ “In normal clinical care, physicians do not choose their patients’ treatments by flipping a coin or another intentionally random process. Instead, they engage them in a shared decision-making process,” says Shepherd. Patients can ask questions and either consent to or decline an intervention. “Ethical and legal rights to bodily integrity and self-determination are also at stake, as well as transparency,” says Shepherd.

The authors support innovative study designs aimed to improve healthcare, but not by keeping patients in the dark about being placed into research. By placing patients in clinical trials without their knowledge, clinicians are failing to meet their ethical obligations for autonomy and bodily integrity and are breaching fiduciary duties, the authors underscore.

“We were interested in providing a strong counterpoint to the arguments some ethicists and researchers have been making that consent either is not, or should not, be required ethically or legally,” says Shepherd. The authors focus on the common law — the body of law created by courts to resolve disputes between parties, such as tort law. Participants unknowingly placed by providers into randomized interventional studies without their knowledge or consent could have legal claims against those providers that they might pursue in court. “We think the research regulations require consent for randomized comparative effectiveness research studies. But so does the common law, which is often unappreciated,” says Shepherd.

REFERENCES

1. Cole JB, Moore JC, Nystrom PC, et al. A prospective study of ketamine versus haloperidol for severe prehospital agitation. Clin Toxicol (Phila). 2016;54(7):556-562.
2. Katheria A, Reister F, Essers J, et al. Association of umbilical cord milking vs. delayed umbilical cord clamping with death or severe intraventricular hemorrhage among preterm infants. JAMA. 2019;322(19):1877-1886.
3. Shepherd L, Chen D. Medical research without consent? It’s like déjà vu all over again. Indiana Law Journal. 2024;99(3):1-80.