Priors and decision thresholds in phase 2 and phase 3 randomized controlled trials evaluating drug efficacy using Bayesian methods: a systematic review

Abstract

Objective: To describe the priors and decision thresholds in phase 2 and 3 RCTs evaluating drug efficacy using Bayesian methods.

Study design and setting: A systematic review of phase 2 and 3 RCTs evaluating drug efficacy through Bayesian inference was conducted across the MEDLINE, EMBASE and Cochrane databases, with no date restrictions until September 2022. The type of prior used for the analysis of the primary endpoint and its characteristics (type and parameters of the distribution, justification, sensitivity analysis), the use of a posterior probability decision threshold defined a priori, and its value, were extracted.

Results: From 1161 articles screened, 69 articles were ultimately included, encompassing a total of 91 comparisons, as some trials assessed multiple primary endpoints or treatments. The prior was assigned to treatment effect in 51% of cases (n=46), to each arm in 37% (n=34), and was not explicitly defined in 12% (n=11). Prior distribution was described (with its parameters) in 59% of cases (n=54). A decision threshold was set a priori in 68% of results (n=62), and its value ranged from 70% to 99% (median 95%).

Conclusion: The inconsistent description of priors, along with the wide variation and occasional absence of decision thresholds, underscore the need for clear guidelines on the use and reporting of Bayesian methods.

Keywords: Bayesian methods; decision thresholds; drug efficacy; priors; randomized controlled trials.