Accounting for between-study variation in incremental net benefit in value of information methodology.

Previous applications of value of information methods for determining optimal sample size in randomized clinical trials have assumed no between-study variation in mean incremental net benefit. By adopting a hierarchical model, we provide a solution for determining optimal sample size with this assumption relaxed. The solution is illustrated with two examples from the literature. Expected net gain increases with increasing between-study variation, reflecting the increased uncertainty in incremental net benefit and reduced extent to which data are borrowed from previous evidence. Hence, a trial can become optimal where current evidence is sufficient assuming no between-study variation. However, despite the expected net gain increasing, the optimal sample size in the illustrated examples is relatively insensitive to the amount of between-study variation. Further percentage losses in expected net gain were small even when choosing sample sizes that reflected widely different between-study variation.