Do Bayesian adaptive trials offer advantages for comparative effectiveness research? Protocol for the RE-ADAPT study

BACKGROUND Randomized clinical trials, particularly for comparative effectiveness research (CER), are frequently criticized for being overly restrictive or untimely for health-care decision making. PURPOSE Our prospectively designed REsearch in ADAptive methods for Pragmatic Trials (RE-ADAPT) study is a 'proof of concept' to stimulate investment in Bayesian adaptive designs for future CER trials. METHODS We will assess whether Bayesian adaptive designs offer potential efficiencies in CER by simulating a re-execution of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study using actual data from ALLHAT. RESULTS We prospectively define seven alternate designs consisting of various combinations of arm dropping, adaptive randomization, and early stopping and describe how these designs will be compared to the original ALLHAT design. We identify the one particular design that would have been executed, which incorporates early stopping and information-based adaptive randomization. LIMITATIONS While the simulation realistically emulates patient enrollment, interim analyses, and adaptive changes to design, it cannot incorporate key features like the involvement of data monitoring committee in making decisions about adaptive changes. CONCLUSION This article describes our analytic approach for RE-ADAPT. The next stage of the project is to conduct the re-execution analyses using the seven prespecified designs and the original ALLHAT data.