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arXiv 2103.04175stat.MEstat.AP
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以治疗后中间应答为条件识别主要分层因果效应

Identifying Principal Stratum Causal Effects Conditional on a Post-treatment Intermediate Response

Xiaoqing Tan, Judah Abberbock, Priya Rastogi, Gong Tang

摘要:

在早期乳腺癌的新辅助治疗试验中,患者通常被随机分配到对照组和具有额外靶向治疗的治疗组。通过二元病理学完全缓解(pCR)评估新方案的早期疗效,并通过长期临床结局(如生存期)评估最终疗效。尽管pCR与生存率密切相关,但尚未证实其为替代终点。为了充分理解其临床意义,重要的是建立因果被估量,例如在新方案下将实现pCR的患者的生存率的因果效应。在主分层框架下,以往的研究主要集中在通过改变模型参数对反事实结果进行敏感性分析。在温和的假设下,我们提出了一种方法来估计这些模型参数,使用经验数据,随后的因果估计的兴趣。我们还扩展了我们的方法来处理删失的结果数据。该方法适用于最近的临床试验,其性能通过模拟研究进行评估。

英文摘要:

In neoadjuvant trials on early-stage breast cancer, patients are usually randomized into a control group and a treatment group with an additional target therapy. Early efficacy of the new regimen is assessed via the binary pathological complete response (pCR) and the eventual efficacy is assessed via long-term clinical outcomes such as survival. Although pCR is strongly associated with survival, it has not been confirmed as a surrogate endpoint. To fully understand its clinical implication, it is important to establish causal estimands such as the causal effect in survival for patients who would achieve pCR under the new regimen. Under the principal stratification framework, previous studies focus on sensitivity analyses by varying model parameters in an imposed model on counterfactual outcomes. Under mild assumptions, we propose an approach to estimate those model parameters using empirical data and subsequently the causal estimand of interest. We also extend our approach to address censored outcome data. The proposed method is applied to a recent clinical trial and its performance is evaluated via simulation studies.

机构、总结、中文摘要均由AI分析而来,可能存在错误,请以论文正文为准。

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