Optimal group sequential designs constrained on both overall and stage one error rates

2019 ◽  
Vol 48 (20) ◽  
pp. 4959-4975
Author(s):  
Yanning Liu ◽  
Dayong Li
2021 ◽  
Author(s):  
Daniel Lakens ◽  
Friedrich Pahlke ◽  
Gernot Wassmer

This tutorial illustrates how to design, analyze, and report group sequential designs. In these designs, groups of observations are collected and repeatedly analyzed, while controlling error rates. Compared to a fixed sample size design, where data is analyzed only once, group sequential designs offer the possibility to stop the study at interim looks at the data either for efficacy or futility. Hence, they provide greater flexibility and are more efficient in the sense that due to early stopping the expected sample size is smaller as compared to the sample size in the design with no interim look. In this tutorial we illustrate how to use the R package 'rpact' and the associated Shiny app to design studies that control the Type I error rate when repeatedly analyzing data, even when neither the number of looks at the data, nor the exact timing of looks at the data, is specified. Specifically for *t*-tests, we illustrate how to perform an a-priori power analysis for group sequential designs, and explain how to stop the data collection for futility by rejecting the presence of an effect of interest based on a beta-spending function. Finally, we discuss how to report adjusted effect size estimates and confidence intervals. The recent availability of accessible software such as 'rpact' makes it possible for psychologists to benefit from the efficiency gains provided by group sequential designs.


2013 ◽  
Vol 32 (23) ◽  
pp. 3991-4005 ◽  
Author(s):  
Ping Gao ◽  
Lingyun Liu ◽  
Cyrus Mehta

2018 ◽  
Vol 28 (8) ◽  
pp. 2385-2403 ◽  
Author(s):  
Tobias Mütze ◽  
Ekkehard Glimm ◽  
Heinz Schmidli ◽  
Tim Friede

Robust semiparametric models for recurrent events have received increasing attention in the analysis of clinical trials in a variety of diseases including chronic heart failure. In comparison to parametric recurrent event models, robust semiparametric models are more flexible in that neither the baseline event rate nor the process inducing between-patient heterogeneity needs to be specified in terms of a specific parametric statistical model. However, implementing group sequential designs in the robust semiparametric model is complicated by the fact that the sequence of Wald statistics does not follow asymptotically the canonical joint distribution. In this manuscript, we propose two types of group sequential procedures for a robust semiparametric analysis of recurrent events. The first group sequential procedure is based on the asymptotic covariance of the sequence of Wald statistics and it guarantees asymptotic control of the type I error rate. The second procedure is based on the canonical joint distribution and does not guarantee asymptotic type I error rate control but is easy to implement and corresponds to the well-known standard approach for group sequential designs. Moreover, we describe how to determine the maximum information when planning a clinical trial with a group sequential design and a robust semiparametric analysis of recurrent events. We contrast the operating characteristics of the proposed group sequential procedures in a simulation study motivated by the ongoing phase 3 PARAGON-HF trial (ClinicalTrials.gov identifier: NCT01920711) in more than 4600 patients with chronic heart failure and a preserved ejection fraction. We found that both group sequential procedures have similar operating characteristics and that for some practically relevant scenarios, the group sequential procedure based on the canonical joint distribution has advantages with respect to the control of the type I error rate. The proposed method for calculating the maximum information results in appropriately powered trials for both procedures.


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