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Abstract:
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Regulatory guidance suggests controlling the family-wise error rate (FWER) in confirmatory clinical trials. The two-trial paradigm represents a further requirement to demonstrate efficacy in a clinical submission: A statistically significant outcome in at least two adequate and well-controlled clinical trials. Within each trial, different endpoints may require different sample size to achieve the adequacy of power. Sometimes the sample size driven by one endpoint could be twice as large as that required by other endpoints. These unbalanced requirements of resources in a single trial are amplified under the two-trial convention and may lead to financial and logistical challenges for the trial sponsor. It is, therefore, often of interest to pool the data from the two trials for an endpoint to make a confirmatory claim without doubling the sample size. However, it remains unclear what approaches could be used to manage multiplicity adjustments for the pooled analysis using data from two identically designed trials. In this talk, we provide principles of controlling the submission-wise error rate (SWER) and examples of multiplicity adjustments for the pooled analysis.
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