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

Abstract

The use of response adaptive randomization (RAR) is becoming more common in clinical trials (Journal of Clinical Oncology. 2011;29(6):606-609). Such designs will change the randomization ratio based on information on treatment effect that accumulates within the trial (this is done in the background and not by unblinding the investigators). This has the effect of increasing the number of patients who are assigned to the better performing treatment arm. Acute care research represents an area where this may be of particular benefit, since few effective treatments exist for many emergency conditions such as stroke. Within such high stakes diseases, it may be advantageous to have a trial designed to improve the overall outcomes (on the average) of the population enrolled by tilting randomization towards the better treatment (which could be the placebo/standard treatment or the experimental treatment) (JAMA. 2012;307(22):2377-2378). Previous work by this research team focused on the impact of surrogate consent on acute care research. (BMC Emergency Medicine 2013, 13:18) In the summer of 2011, 400 emergency department patients and their family members at the University of Michigan were interviewed and rated their willingness to participate in 5 treatment and research options in the event of a future, hypothetical stroke. Two of the scenarios described an acute stroke trial with or without response adaptive randomization. While not the primary focus of that research study, 58% of the subjects agreed to the trial with response adaptive randomization, and 21% agreed to the standard clinical trial with fixed randomization. From this previous work, we learned that it would be ideal to more comprehensively describe the research trial to hypothetical patients and simulate the process that is used in actual acute trial enrollments as much as possible. This informed our follow up study that occurred in the summer of 2012. We presented a hypothetical stroke scenario to 418 subjects presenting to the emergency department for other, non-critical complaints. Half the subjects were presented a hypothetical clinical trial with standard 1:1 randomization, and half the subjects were presented a trial with RAR. 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%). Interestingly, only 62% of the RAR group versus 85% of the standard randomization group were able to accurately identify the allocation procedure when queried at the end of the scenario. The overarching goal of this investigation is to adjust the brief trial description procedure to improve understanding of the trial allocation procedure for the RAR. Improving the communication of the trial procedures within a simulated situation that mimics the rapid discussion regarding an emergency research trial would be beneficial for future interventional research studies in acute stroke and other serious emergent conditions.