dose finding at the first stage and efficacy confirmation at the second stage) and when there is a shift in patient population caused by protocol amendments, the derived test statistics and formulas for sample size calculation and allocation are necessarily modified for controlling the overall type I error at the prespecified level. ![]() In cases in which the study objectives at different stages are different (e.g. binary responses), and contain time-to-event data assuming that there is a well-established relationship between the study endpoints at different stages, and that the study objectives at different stages are the same. In this article, formulas for sample size calculation/allocation are derived for cases in which the study endpoints are continuous, discrete (e.g. Adaptive seamless designs have been considered as one possible way to shorten the time and patient exposure necessary to discover, develop, and demonstrate the benefits of a new drug. It is also of interest to know how the sample size calculation/allocation should be done for achieving the study objectives originally set for the two stages (separate studies). In this case, it is important to determine how the data collected from both stages should be combined for the final analysis. design.7 This is often true, for example, of group sequential designs (section V.A.) and designs with adaptive modifications to the sample size (section V.B.). a biomarker versus a regular clinical endpoint or the same study endpoint with different treatment durations). ![]() In many cases, study endpoints considered in a two-stage seamless adaptive design may be similar but different (e.g. One of the most commonly considered adaptive designs is probably a two-stage seamless adaptive trial design that combines two separate studies into one single study. They can be used for backgrounds, wallpapers, textiles. Simulations are conducted to confirm the control of the familywise Type I error and the adaptive seamless Phase 2-3 design is illustrated with an example.Īdaptive seamless designs adaptive decision familywise type I error intermediate endpoint multiple test procedure.In recent years, the use of adaptive design methods in clinical research and development based on accrued data has become very popular because of its efficiency and flexibility in modifying trial and/or statistical procedures of ongoing clinical trials. Seamless patterns are images that can be tiled or repeated infinitely without any visible seams or gaps. We illustrate our proposed design with an example trial design for oncology. Seamless designs are one approach, aiming to combine different study types in a single study, which traditionally are performed sequentially with often. It is proved that the proposed design can preserve the familywise Type I error under a mild assumption that is expected to hold in practical considerations. Here we propose an adaptive seamless Phase 2-3 design with multiple endpoints which can expand an ongoing Phase 2 trial into a Phase 3 trial based on an intermediate endpoint for adaptive decision and test the endpoints with a powerful multiple test procedure. Multiple endpoints are often tested when a regulatory approval is pursued. ![]() Adaptive seamless Phase 2-3 design has been considered as one possible way to expedite development time for a drug program by allowing the expansion from an ongoing Phase 2 trial into a Phase 3 trial.
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