文章基本信息

标题：Impact of lack-of-benefit stopping rules on treatment effect estimates of two-arm multi-stage (TAMS) trials with time to event outcome
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作者：Babak Choodari-Oskooei ; Mahesh KB Parmar ; Patrick Royston 等
期刊名称：Trials
印刷版ISSN：1745-6215
电子版ISSN：1745-6215
出版年度：2013
卷号：14
期号：1
页码：23
DOI：10.1186/1745-6215-14-23
语种：English
出版社：BioMed Central
摘要：In 2011, Royston et al. described technical details of a two-arm, multi-stage (TAMS) design. The design enables a trial to be stopped part-way through recruitment if the accumulating data suggests a lack of benefit of the experimental arm. Such interim decisions can be made using data on an available ‘intermediate’ outcome. At the conclusion of the trial, the definitive outcome is analyzed. Typical intermediate and definitive outcomes in cancer might be progression-free and overall survival, respectively. In TAMS designs, the stopping rule applied at the interim stage(s) affects the sampling distribution of the treatment effect estimator, potentially inducing bias that needs addressing. We quantified the bias in the treatment effect estimator in TAMS trials according to the size of the treatment effect and for different designs. We also retrospectively ‘redesigned’ completed cancer trials as TAMS trials and used the bootstrap to quantify bias. In trials in which the experimental treatment is better than the control and which continue to their planned end, the bias in the estimate of treatment effect is small and of no practical importance. In trials stopped for lack of benefit at an interim stage, the treatment effect estimate is biased at the time of interim assessment. This bias is markedly reduced by further patient follow-up and reanalysis at the planned ‘end’ of the trial. Provided that all patients in a TAMS trial are followed up to the planned end of the trial, the bias in the estimated treatment effect is of no practical importance. Bias correction is then unnecessary.
关键词：Overall Survival ; Definitive Outcome ; Average Treatment Effect ; Treatment Effect Estimate ; Interim Stage