Examining the Impact of Trial Length on Detecting Medication Effects for Alcohol Use Disorder: A Meta-Regression Study

Abstract

Background

The U.S. Food and Drug Administration (FDA) recommends a minimum duration of 6 months for randomized controlled trials (RCTs) evaluating pharmacotherapies for alcohol use disorder (AUD). The relationship between trial length and treatment effects is not well understood. The current study conducted meta-regression analyses of RCTs for AUD to examine the association between trial length and observed medication effect sizes in clinical trials.

Methods

This secondary data analysis utilized data from a systematic literature review that identified 139 pharmacotherapy RCTs for AUD conducted between 1985 and 2023. Meta-regressions were conducted using the metafor package in R to examine whether shorter (< 12 weeks) or longer (> 12 weeks) trials differed in observed medication effect sizes for abstinence- and drinking-based endpoints, relative to 12-week trials, which represented the median trial duration. Publication bias was addressed using a weight-function model.

Results

For abstinence-based endpoints, neither shorter (< 12 weeks; β = 0.13, SE = 0.21, p = 0.54) nor longer (> 12 weeks; β = 0.11, SE = 0.11, p = 0.30) trials differed significantly from the 12-week reference group in observed medication effect sizes. Similarly, for drinking-based endpoints, neither shorter (< 12 weeks; β = −0.07, SE = 0.09, p = 0.39) nor longer (> 12 weeks; β = 0.06, SE = 0.05, p = 0.26) trials differed significantly from 12-week trials in observed medication effect sizes. All results remained nonsignificant after adjusting for publication bias. In sensitivity analyses restricted to trials with statistically significant effect sizes, trials > 12 weeks showed smaller estimated treatment effects compared to trials ≤ 12 weeks.

Conclusions

Observed medication effect sizes did not differ significantly across trial lengths for abstinence and drinking-based endpoints, except for analyses restricted to trials with significant effect sizes, where there was an advantage for trials that were 12 weeks or shorter. These findings inform efforts to optimize AUD RCT design.