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Correcting the bias of the net benefit estimator due to right‐censored observations
Biometrical Journal ( IF 1.3 ) Pub Date : 2021-02-22 , DOI: 10.1002/bimj.202000001
Julien Péron 1, 2, 3, 4 , Maryam Idlhaj 1, 2 , Delphine Maucort-Boulch 1, 2 , Joris Giai 1, 2 , Pascal Roy 1, 2 , Laurence Collette 4 , Marc Buyse 5, 6 , Brice Ozenne 7, 8
Affiliation  

Generalized pairwise comparisons (GPCs) are a statistical method used in randomized clinical trials to simultaneously analyze several prioritized outcomes. This procedure estimates the net benefit (Δ). Δ may be interpreted as the probability for a random patient in the treatment group to have a better overall outcome than a random patient in the control group, minus the probability of the opposite situation. However, the presence of right censoring introduces uninformative pairs that will typically bias the estimate of Δ toward 0. We propose a correction to GPCs that estimates the contribution of each uninformative pair based on the average contribution of the informative pairs. The correction can be applied to the analysis of several prioritized outcomes. We perform a simulation study to evaluate the bias associated with this correction. When only one time‐to‐event outcome was generated, the corrected estimates were unbiased except in the presence of very heavy censoring. The correction had no effect on the power or type‐1 error of the tests based on the Δ. Finally, we illustrate the impact of the correction using data from two randomized trials. The illustrative datasets showed that the correction had limited impact when the proportion of censored observations was around 20% and was most useful when this proportion was close to 70%. Overall, we propose an estimator for the net benefit that is minimally affected by censoring under the assumption that uninformative pairs are exchangeable with informative pairs.

中文翻译:

纠正由于右删失观察引起的净收益估计量的偏差

广义成对比较 (GPC) 是随机临床试验中使用的一种统计方法,用于同时分析多个优先结果。此过程估计净收益 (Δ)。Δ 可以解释为治疗组中的随机患者比对照组中的随机患者具有更好总体结果的概率减去相反情况的概率。然而,右删失的存在引入了无信息对,这通常会使 Δ 的估计偏向 0。我们建议对 GPC 进行修正,该修正基于信息对的平均贡献来估计每个无信息对的贡献。校正可以应用于对几个优先结果的分析。我们进行模拟研究以评估与此校正相关的偏差。当仅生成一个事件发生时间结果时,校正后的估计是无偏的,除非存在非常严格的审查。校正对基于 Δ 的检验的功效或类型 1 错误没有影响。最后,我们使用来自两个随机试验的数据来说明校正的影响。说明性数据集显示,当删失观察的比例约为 20% 时,校正的影响有限,而当该比例接近 70% 时最有用。总的来说,我们提出了一个受审查影响最小的净收益估计量,假设无信息对可以与信息对交换。校正对基于 Δ 的检验的功效或类型 1 错误没有影响。最后,我们使用来自两个随机试验的数据来说明校正的影响。说明性数据集显示,当删失观察的比例约为 20% 时,校正的影响有限,而当该比例接近 70% 时最有用。总的来说,我们提出了一个受审查影响最小的净收益估计量,假设无信息对可以与信息对交换。校正对基于 Δ 的检验的功效或类型 1 错误没有影响。最后,我们使用来自两个随机试验的数据来说明校正的影响。说明性数据集显示,当删失观察的比例约为 20% 时,校正的影响有限,而当该比例接近 70% 时最有用。总的来说,我们提出了一个受审查影响最小的净收益估计量,假设无信息对可以与信息对交换。说明性数据集显示,当删失观察的比例约为 20% 时,校正的影响有限,而当该比例接近 70% 时最有用。总的来说,我们提出了一个受审查影响最小的净收益估计量,假设无信息对可以与信息对交换。说明性数据集显示,当删失观察的比例约为 20% 时,校正的影响有限,而当该比例接近 70% 时最有用。总的来说,我们提出了一个受审查影响最小的净收益估计量,假设无信息对可以与信息对交换。
更新日期:2021-04-08
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