Treatment estimands in clinical trials of patients hospitalised for COVID-19: ensuring trials ask the right questions
Treatment estimands in clinical trials of patients hospitalised for COVID-19: ensuring trials ask the right questions
复制标题
DOI：
10.1186/s12916-020-01737-0
复制
发表时间：
2020-09-09
期刊：
影响因子：
9.3
通讯作者：
Carpenter, James R.
中科院分区：
文献类型：
--
作者：
Kahan, Brennan C.;Morris, Tim P.;Carpenter, James R.
在设计临床试验时，明确定义感兴趣的治疗估计（要估计的治疗估计）可以帮助阐明试验目标，并确保试验所解决的问题具有临床意义。在定义估算时存在几个挑战。在本文中，我们在COVID-19住院患者治疗试验的背景下讨论了其中一些问题，并就如何确定关键结果的估计值提出了建议。我们建议，治疗效果通常应以死亡率和通气需求等结果的比例差异（或风险或优势比）以及通气天数等结果的均值差异来衡量。我们进一步建议，应根据以患者为中心还是以资源为中心的观点，以不同的方式处理因死亡导致的截断；对于前者，应该使用复合方法，而对于后者，最好使用while-alive方法。最后，我们建议应该从治疗政策的角度来处理随机治疗的终止，在分析中忽略非依从性（即治疗意图）。
When designing a clinical trial, explicitly defining the treatment estimands of interest (that which is to be estimated) can help to clarify trial objectives and ensure the questions being addressed by the trial are clinically meaningful. There are several challenges when defining estimands. Here, we discuss a number of these in the context of trials of treatments for patients hospitalised with COVID-19 and make suggestions for how estimands should be defined for key outcomes. We suggest that treatment effects should usually be measured as differences in proportions (or risk or odds ratios) for outcomes such as death and requirement for ventilation, and differences in means for outcomes such as the number of days ventilated. We further recommend that truncation due to death should be handled differently depending on whether a patient- or resource-focused perspective is taken; for the former, a composite approach should be used, while for the latter, a while-alive approach is preferred. Finally, we suggest that discontinuation of randomised treatment should be handled from a treatment policy perspective, where non-adherence is ignored in the analysis (i.e. intention to treat).