Designing and analysing clinical trials in mental health: an evidence synthesis approach.

Objective: When planning a clinical study, evidence on the treatment effect is often available from previous studies. However, this evidence is mostly ignored for the analysis of the new study. This is unfortunate, since using it could lead to a smaller study without compromising power. We describe a design that addresses this issue.

Methods: We use a Bayesian meta-analytic model to incorporate the available evidence in the analysis of the new study. The shrinkage estimate for the new study integrates the evidence from the other studies. At the planning phase of the study, it allows a statistically justified reduction of the sample size.

Results: The design is illustrated using data from an Food and Drug Administration (FDA) review of lurasidone for the treatment of schizophrenia. Three studies inform the meta-analysis before the new study is conducted. Results from an additional phase III study, which were not available at the time of the FDA review, are then used for the actual analysis.

Conclusions: In the presence of reliable and relevant evidence, the design offers a way to conduct a smaller study without compromising power. It therefore fills a gap between the assessment of evidence and its actual use in the design and analysis of studies.