Abstract
In clinical development, a two-stage design combining two separate studies (e.g., a phase II dose finding study and a phase III confirmatory study) into a single trial is commonly considered. The purpose of a two-stage design is not only to reduce lead time between the two studies, but also to evaluate the treatment effect in a more efficient way. In practice, one of the difficulties in utilizing a two-stage design is that the study endpoints at different stages may be different. For example, a biomarker (or the same study endpoint with different duration) may be considered at the first stage, while a regular study endpoint is used at the second stage. As per the studies the case where both study endpoints are continuous variables with certain correlation structure. In this paper, our attention is on the case where the study endpoints are count data which are obtained at the two stages with different time intervals. Statistical procedure for combining data observed from the two different stages are proposed. Furthermore, results on hypotheses testing and sample size calculation are derived for the comparison of two treatments based on data observed from a two-stage design.
Highlights
In recent years, the use of a two-stage adaptive seamless design that combines a phase IIb study and a phase III study into a single study has received much attention [1,2,3,4]
A biomarker may be considered at the first stage and a regular study endpoint is used at the second stage provided that the biomarker is predictive of the regular study endpoint
Statistical analysis of count data collected from a twoβ2
Summary
The use of a two-stage adaptive seamless design that combines a phase IIb study and a phase III study into a single study has received much attention [1,2,3,4]. A biomarker may be considered at the first stage and a regular study endpoint is used at the second stage provided that the biomarker is predictive of the regular study endpoint In these cases, the validity of the standard test statistics for combining data collected from both phases is questionable. Study with biomarker or clinical endpoint with different durations at the two stages while the objective is for dose selection in the first stage but efficacy confirmation in the second stage would lead to the scenario described in case (iv). Mi and ni, both ( ) λi − E(λi ) σ λi d → N (0,1) and ( ) , βi − E(βi ) σ βi d → N (0,1)
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