Type I error rate control in adaptive designs for confirmatory clinical trials with treatment selection at interim

Pharmaceutical Statistics
M PoschFrank Bretz

Abstract

Interest in confirmatory adaptive combined phase II/III studies with treatment selection has increased in the past few years. These studies start comparing several treatments with a control. One (or more) treatment(s) is then selected after the first stage based on the available information at an interim analysis, including interim data from the ongoing trial, external information and expert knowledge. Recruitment continues, but now only for the selected treatment(s) and the control, possibly in combination with a sample size reassessment. The final analysis of the selected treatment(s) includes the patients from both stages and is performed such that the overall Type I error rate is strictly controlled, thus providing confirmatory evidence of efficacy at the final analysis. In this paper we describe two approaches to control the Type I error rate in adaptive designs with sample size reassessment and/or treatment selection. The first method adjusts the critical value using a simulation-based approach, which incorporates the number of patients at an interim analysis, the true response rates, the treatment selection rule, etc. We discuss the underlying assumptions of simulation-based procedures and give several examples where the...Continue Reading

References

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Citations

Apr 26, 2011·Journal of Biopharmaceutical Statistics·Gernot Wassmer
Jan 23, 2016·Pharmaceutical Statistics·Andrew P Grieve
Mar 18, 2015·Statistics in Medicine·Peter BauerGernot Wassmer
Apr 12, 2013·Biometrical Journal. Biometrische Zeitschrift·Toshifumi SugitaniChikuma Hamada
Apr 23, 2014·Biometrical Journal. Biometrische Zeitschrift·Alexandra C GrafFranz Koenig
Oct 17, 2014·Pharmaceutical Statistics·Florian KlinglmuellerFranz Koenig
Oct 22, 2014·Journal of Biopharmaceutical Statistics·Mark Chang, Jing Wang
Jun 11, 2014·Journal of Biopharmaceutical Statistics·H M James HungPeiling Yang
Apr 26, 2011·Journal of Biopharmaceutical Statistics·Sue-Jane WangRobert O'Neill
Jun 2, 2012·Journal of Biopharmaceutical Statistics·William F RosenbergerFeifang Hu
Nov 28, 2019·Statistics in Medicine·Antonia ZapfTim Friede
Feb 16, 2020·Pharmaceutical Statistics·Haolun ShiGuosheng Yin
Aug 8, 2021·Journal of Medical Ethics·Michael Os Afolabi, Lauren E Kelly

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