Cost‐Effectiveness Analyses for Sequential Multiple Assignment Randomized Trials

Sequential multiple assignment randomized trials (SMARTs) have grown in popularity in recent years, and many of their study protocols propose conducting a cost-effectiveness analysis of the adaptive strategies embedded within them. The cost-effectiveness of these regimes is often proposed to be assessed using incremental cost-effectiveness ratios (ICERs). In this paper, we present an estimation and inference procedure for such cost-effectiveness measures for the embedded dynamic treatment regimes within a SMART design. In particular, we describe a targeted maximum likelihood estimator for the ICER of a SMART's embedded regimes with influence curve-based inference. We illustrate the performance of these methods using simulations. Throughout, we use as illustration a cost-effectiveness analysis for the Adaptive Strategies for Preventing and Treating Lapses of Retention in HIV Care (ADAPT-R; NCT02338739) trial, presenting estimated ICERs (with inference) for embedded regimes aimed at increasing HIV care adherence. This manuscript is one of the first to present cost-effectiveness analysis results from a SMART.