A sequential, multiple assignment, randomized trial design with a tailoring function.

ABSTRACT

We present a trial design for sequential multiple assignment randomized trials (SMARTs) that use a tailoring function instead of a binary tailoring variable allowing for simultaneous development of the tailoring variable and estimation of dynamic treatment regimens (DTRs). We apply methods for developing DTRs from observational data tree-based regression learning and Q-learning. We compare this to a balanced randomized SMART with equal re-randomization probabilities and a typical SMART design where re-randomization depends on a binary tailoring variable and DTRs are analyzed with weighted and replicated regression. This project addresses a gap in clinical trial methodology by presenting SMARTs where second stage treatment is based on a continuous outcome removing the need for a binary tailoring variable. We demonstrate that data from a SMART using a tailoring function can be used to efficiently estimate DTRs and is more flexible under varying scenarios than a SMART using a tailoring variable.