An examination of the efficiency of the sequential parallel design in psychiatric clinical trials.
BACKGROUND
Psychiatric 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.


OBJECTIVE
The 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.


METHODS
The 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.


RESULTS
The novel design reduces the sample size 20-25% compared to the standard design under a wide range of parameters.


CONCLUSIONS
There are no actual trials with the novel design therefore assumptions of the effect size across two periods for actual psychiatric agents is unknown.


CONCLUSIONS
The 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.
Tamura
Roy N
RN
Lilly Corporate Center, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. Tamura_Roy_N@lilly.com
Huang
Xiaohong
X
D002986:Clinical Trials as Topic / Q000191:economics / Q000379:methods*; D004526:Efficiency; D023381:Endpoint Determination; D006801:Humans; D001523:Mental Disorders / Q000628:therapy*; D015233:Models, Statistical; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D012107:Research Design; D018401:Sample Size
D010919:Placebos