Bayesian Sample Size Calculations for Comparing Two Strategies in SMART Studies

Abstract

In the management of most chronic conditions characterized by the lack of universally effective treatments, adaptive treatment strategies (ATSs) have grown in popularity as they offer a more individualized approach. As a result, sequential multiple assignment randomized trials (SMARTs) have gained attention as the most suitable clinical trial design to formalize the study of these strategies. While the number of SMARTs has increased in recent years, sample size and design considerations have generally been carried out in frequentist settings. However, standard frequentist formulae require assumptions on interim response rates and variance components. Misspecifying these can lead to incorrect sample size calculations and correspondingly inadequate levels of power. The Bayesian framework offers a straightforward path to alleviate some of these concerns. In this paper, we provide calculations in a Bayesian setting to allow more realistic and robust estimates that account for uncertainty in inputs through the ‘two priors’ approach. Additionally, compared to the standard frequentist formulae, this methodology allows us to rely on fewer assumptions, integrate pre‐trial knowledge, and switch the focus from the standardized effect size to the MDD. The proposed methodology is evaluated in a thorough simulation study and is implemented to estimate the sample size for a full‐scale SMART of an internet‐based adaptive stress management intervention on cardiovascular disease patients using data from its pilot study conducted in two Canadian provinces.

Frequentist and Bayesian Sample Size Determination for Single-Arm Clinical Trials Based on a Binary Response Variable: A Shiny App to Implement Exact Methods

“…This methodology, based on the introduction of two distinct prior distributions and thus based on the so-called two-priors approach, has been initially formalized by Wang and Gelfand [2]. It is now well known with many implementations presented in the literature (see, among others, [3]- [10]).…”