Can Response-Adaptive Randomization Increase Participation in Acute Stroke Trials?

Abstract

Background and Purpose A response-adaptive randomization (RAR) trial design actively adjusts the ratio of participants assigned to each trial arm, favoring the better performing treatment by using outcome data from participants already in the trial. Compared to a standard clinical trial, a RAR study design has the potential to improve patient participation in acute stroke trials. Methods This cross-sectional randomized survey included adult emergency department patients, age 18 and over, without symptoms of stroke or other critical illness. A standardized protocol was used, and subjects were randomized to either an RAR or standard hypothetical acute stroke trial. After viewing the video describing the hypothetical trial (http://youtu.be/cKIWduCaPZc), reviewing the consent form, and having questions answered, subjects indicated whether they would consent to the trial. A multivariable logistic regression model was fitted to estimate the impact of RAR, while controlling for demographic factors and patient understanding of the design. Results A total of 418 subjects (210 standard 208 RAR) were enrolled. All baseline characteristics were balanced between groups. There was significantly higher participation in the RAR trial (67.3%) versus the standard trial (54.5%), absolute increase: 12.8% (95% CI: 3.7 to 22.2%). The RAR group had a higher odds ratio of agreeing to research (O.R. 1.89, 95% CI [1.2 – 2.9]), while adjusting for patient level factors. Trial designs were generally well understood by the participants. Conclusions The hypothetical RAR trial attracted more research participation than standard randomization. RAR has the potential to increase recruitment and offer benefit to future trial participants.

Clinical trialist perspectives on the ethics of adaptive clinical trials: a mixed-methods analysis

“…Clinical trials in the critically ill are particularly challenging [ 23 ]. Interesting, a hypothetical clinical trial scenario demonstrated greater participation when participants were offered a trial with response adaptive randomization [ 24 ].…”

Are outcome-adaptive allocation trials ethical?

“…Third, consent discussions should at least explain that adaptive allocation involves allocating some patients to treatments that accumulating evidence disfavors, and that at least in the case of studies using surrogate endpoints and small sample sizes, even if one arm performs better than another, there remains substantial uncertainty about its actual clinical utility. Indeed, were this disclosed to patients, one suspects purported recruitment advantages for adaptive allocation studies [23] would diminish.…”

Optimizing Communication of Emergency Response Adaptive Randomization Clinical Trials to Potential Participants

“…The two groups without additional comprehension questions were exposed to the same procedure as the 418 patients from the 2012 study. 3 These scenarios were presented to patients in video form on an iPad. Further details of the protocol are available in the supplemental material, including links to the videos.…”

“…If patients understand that they will have an increased chance of benefitting from a trial, then in the use of RAR should lead to an increase in patient participation when compared to standard fixed randomization. 3 However, with the increased complexity of RAR, properly conveying the necessary information about the trial to potential research subjects in a clear, concise, and comprehensible manner becomes even more challenging. In 2012, we presented hypothetical stroke scenarios to 418 emergency department patients at the University of Michigan, and asked them if they would be interested in signing up for the clinical trial based on our presentation.…”