Data Analysis Planning and Reporting for Confirmatory Multi-Lab Preclinical Trials: A Tutorial.

Confirmatory multi-lab preclinical trials are a powerful experimental strategy to enable decisions to transition from preclinical to clinical settings. With their complexity, such study designs pose several challenges in statistical planning, analysis, and reporting of experiments. To address these, we convened an expert group of biostatisticians and biomedical scientists currently involved in such trials to summarize in a tutorial the most common challenges and offer general guidance. Furthermore, we incorporated statistical advice from existing clinical trials' guidelines and adapted it into recommendations for preclinical trials. We describe strategies on key topics such as calculating sample sizes, handling differences between centers, and selecting relevant covariates. Additionally, we give guidance on statistical methods to account for lab effects and proper reporting of analyses. We embed this in a general discussion on remaining open questions to advance the analysis of preclinical confirmatory studies. The provided general, non-case-specific guidance serves as a conversation starter between biomedical scientists and statisticians to develop robust statistical analysis strategies for confirmatory multi-lab preclinical trials.