• Roy N Tamura and Xiaohong Huang.
• Lilly Corporate Center, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. Tamura_Roy_N@lilly.com
• Clin Trials. 2007 Jan 1; 4 (4): 309-17.

BackgroundPsychiatric clinical trials have a high failure rate, even among agents which are known to be effective. Because of this high failure rate, a novel clinical trial design has been proposed which incorporates a second phase in which non-responders to placebo are randomly reassigned to drug or placebo.PurposeThe purpose of this research is to examine the efficiency of this new design compared to the conventional two arm clinical trial. We consider both binary and continuous endpoints.MethodsThe limiting distribution of a class of weighted average test statistics is obtained for the binary case which allows analytic calculation of the power for a given set of parameters. For the continuous case, we examine the efficiency of seemingly unrelated regression and a weighted average statistic via simulation.ResultsThe novel design reduces the sample size 20-25% compared to the standard design under a wide range of parameters.LimitationsThere are no actual trials with the novel design therefore assumptions of the effect size across two periods for actual psychiatric agents is unknown.ConclusionsThe new design reduces sample size which in turn should reduce the cost of clinical trials. Further refinements of the design are possible including alternative test statistics and incorporation of additional data from placebo responders.

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