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. 2020 Nov 1;30(6):1050-1059.
doi: 10.1080/10543406.2020.1818253. Epub 2020 Sep 14.

Futility stopping in clinical trials, optimality and practical considerations

Affiliations

Futility stopping in clinical trials, optimality and practical considerations

Yen Chang et al. J Biopharm Stat. .

Abstract

Stopping for futility is a useful tool in a clinical trial. It is widely used in single-arm trials in oncology and in many two-arm trials. We review three stopping rules for futility. We give recommendations for the optimal timing of futility looks in two-stage trials in terms of the information fraction and the probability of stopping under the alternative hypothesis. We discuss futility stopping in trials with substantial uncertainty about the variability of the outcome and in crossover trials.

Keywords: Simon’s design; crossover trial; futility stopping; phase 2 trial.

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Figures

Figure 1.
Figure 1.
Optimal two-stage designs with an interim analysis for futility to minimize EN0 or 0.5EN0 + 0.5ENA. Maximum sample size with futility over sample size without futility stopping (n/n0), information fraction (t) for the futility look, probability to stop for futility under HA (ξ) and probability to stop for futility under H0 (γ) for different combinations of one-sided type I error and power, (0.025, 90%) shown by solid lines, (0.05, 90%) by dashed lines, (0.025, 80%) by dotted lines and (0.05, 80%) by dot-dash lines).

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