Abstract:
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Nowadays, when evaluating the anti-tumor activity of a new treatment, clinicians are interested not only in overall response rate, but also in other types of measurements indicating clinical benefit(s). Taking two primary efficacy endpoints as an example, if the new treatment can improve on either endpoint(s), it may be promising for further evaluation. Previously, we’ve proposed a single-arm two-stage phase II cancer clinical trial design with two dichotomous alternative primary efficacy endpoints. Because of unknown correlation between two endpoints at the design stage, minimax rule is used to determine the optimal design. The statistical inferences of such a design are discussed here. The MLE point estimators as well as confidence regions for the true event rates for the two efficacy endpoints are derived. Three types of confidence regions are obtained by inverting likelihood based test statistics: Wald, Score, and Likelihood ratio statistics. Among the three, the likelihood ratio-type confidence region performs the best in terms of good coverage probability and comparable expected area, and thus is recommended for this two-endpoint two-stage design.
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