At what level of collective equipoise does a randomized clinical trial become ethical for the members of institutional review board/ethical committees?

Source

Clinical Translational Science Institute, Center for Evidence-based Medicine and Health Outcomes Research, Tampa, FLorida, USA ; Department of Internal Medicine, Division of Evidence-based Medicine and Health Outcomes Research University of South Florida, Tampa, FLorida, USA.

Abstract

BACKGROUND:

The conduct of a randomized controlled trial (RCT) is deemed ethical only if we are in state of "equipoise" as to which treatment would be most beneficial for the patients. Individual equipoise applies to an individual clinician or a member of ethical, institutional review board (IRB), whilst collective equipoise refers to the profession as a whole. It is argued that physicians are not bound by the equipoise but their actions are directed by the confines of the expert opinion. Experts can agree or disagree in various proportions on the merit of a given treatment. Hence, the collective equipoise will be often incomplete. In turn, the opinions of content expert in the field of the proposed trial influence the IRB members' decision regarding trial approval.

METHODS:

We conducted a survey of IRB members at University of South Florida and the IRB members attending the bioethics conference organized in Clearwater, Florida, USA. The survey was made available as hard copy (paper based) and included six hypothetical scenarios outlining clinical trials targeted at measuring the collective equipoise. We defined the collective equipoise as the situation when survey participants were equally split (50:50) in their decision regarding whether a proposed clinical trial would be ethical to conduct. The opinion of 100 experts in the field expressed as proportion of experts favoring treatment A vs. B in each of the five scenarios was made available to the participants.

RESULTS:

The response rate of our survey was 33% (71/218). Fifty percent of the IRB members would approve an RCT addressing the efficacy of two drugs for the management of headache even if 80% of experts favor one treatment over another (median: 80%; third quartile: 80%). Similarly, half of participating IRB members would approve the study when the median distribution of equipoise among experts was 70% (70 in favor of treatment A vs. 30 in favor of treatment B) for treatment of leukemia, 60% for treatment of geriatric patients and 70% for treatment of newborns. Half of IRB members would approve the study when the median distribution of equipoise among experts was 70% for treatment for leukemia in dogs and 85% for leukemia in rats (and 25% of IRB members would approve such a study even if 100% of experts favors one treatment over another). None of the demographic features of respondents affected collective equipoise.

CONCLUSIONS:

This is the first study assessing collective equipoise among ethical committee/IRB members. Our study findings show that IRB members perceived that conduct of a trial enrolling humans is unethical when the equipoise level is beyond 80% (80:20 distribution of uncertainty). IRB members require a higher level of equipoise when it comes to testing a new drug in humans than in animals. A relatively high level of equipoise is needed for IRB members to be comfortable to approve trials involving life-threatening situations, children and elderly patients.

TimAllenMDJD

Wednesday, October 30, 2013