Generalizability in real-world trials

Abstract

AbstractReal-world evidence (RWE) trials have a key advantage over conventional randomized controlled trials (RCTs) due to their possibly higher external validity. This allows for better generalizability of results to larger populations, which is essential for evidence-based decision making in clinical medicine, pharmacoepidemiology, and health policy. Random sampling of RWE trial participants is regarded the gold standard for generalizability. Additionally, the use of sample correction procedures can increase the generalizability of trial results, even when using non-randomly sampled real-world data (RWD). This study presents descriptive evidence on the extent to which the design of currently planned or already conducted RWD/E trials takes sampling into account. It also examines whether random sampling or procedures for correcting non-random samples are considered. Based on text-mining of publicly available metadata provided during registrations of RWD/E trials onclinicaltrials.gov, EU-PAS, and the OSF-RWE registry, it is shown that the share of RWD/E trial registrations with information on sampling increased from 65.27% in 2002 to 97.43% in 2022, with a corresponding increase from 14.79% to 28.30% for trials with random samples. For RWD/E trials with non-random samples, there is an increase from 0.00% to 0.22% of trials in which sample correction procedures are used. We conclude that the potential benefits of RWD in terms of generalizing trial results are not yet being fully realized.