Abstract WP108: What is Equipoise? Stroke Researchers and IRB Chairs Respond

Abstract

Background: The concept of “equipoise” is often cited as a prerequisite to the conduct of ethical randomized clinical trials (RCTs). However, significant difficulties persist in determining when it exists around a specific clinical question. This issue has arisen around recent stroke RCTs such as ESCAPE and SWIFT DIRECT. We sought to capture how stroke research principal investigators (PIs) and institutional review board (IRB) chairs understand the concept of equipoise. Methods: We invited stroke PIs and IRB chairs to complete a telephone interview consisting of 9 semi-structured questions surrounding equipoise and the ethics of RCTs. Interviewees provided written informed consent and results remained anonymous. The study was approved by our local IRB. Interviews were recorded and transcribed. Each interview was then analyzed for relevance to the concept of equipoise, with relevant sections coded and organized into themes. Results: We invited 59 PIs and 84 IRB chairs, with 13 PIs and 15 IRB chairs completing the standardized interview. Respondents defined equipoise in 5 different ways, with the most common definition being uncertainty based on any of individual opinion, group opinion, evidence, lack of evidence, regional variation, or trial design. PIs sought to determine equipoise through appeals to the literature, preliminary clinical data, surveys of expert opinion, and known disagreement. IRB chairs were more dependent upon expert opinion, including that of trial PIs themselves, and were more concerned with patient protections and specifics of study design. All (100%) PIs and 77% of IRB chairs felt that the concept was helpful, though 80% of both groups also found it to be problematic. Conclusion: Stroke PIs and IRB chairs differ in their understanding of how equipoise is defined and operationalized, which may directly impact the design and approval of current and future stroke trials.