A review of Bayesian perspectives on sample size derivation for confirmatory trials

TL;DR

This paper reviews Bayesian-inspired methods for determining sample sizes in confirmatory trials, addressing the uncertainty in effect size estimates and proposing consistent definitions for hybrid approaches to improve trial planning.

Contribution

It provides a unified framework for defining and applying Bayesian-inspired sample size calculations, connecting traditional and hybrid methods in clinical trial design.

Findings

Clarifies definitions of assurance, success probability, and expected power.

Demonstrates how Bayesian perspectives can reconcile effect size uncertainties.

Offers practical guidance for implementing hybrid sample size methods.

Abstract

Sample size derivation is a crucial element of the planning phase of any confirmatory trial. A sample size is typically derived based on constraints on the maximal acceptable type I error rate and a minimal desired power. Here, power depends on the unknown true effect size. In practice, power is typically calculated either for the smallest relevant effect size or a likely point alternative. The former might be problematic if the minimal relevant effect is close to the null, thus requiring an excessively large sample size. The latter is dubious since it does not account for the a priori uncertainty about the likely alternative effect size. A Bayesian perspective on the sample size derivation for a frequentist trial naturally emerges as a way of reconciling arguments about the relative a priori plausibility of alternative effect sizes with ideas based on the relevance of effect sizes. Many suggestions as to how such `hybrid' approaches could be implemented in practice have been put forward in the literature. However, key quantities such as assurance, probability of success, or expected power are often defined in subtly different ways in the literature. Starting from the traditional and entirely frequentist approach to sample size derivation, we derive consistent definitions for the most commonly used `hybrid' quantities and highlight connections, before discussing and demonstrating their use in the context of sample size derivation for clinical trials.