Estimands and missing data in clinical trials of chronic pain treatments: advances in design and analysis.
Estimands and missing data in clinical trials of chronic pain treatments: advances in design and analysis.
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DOI：
10.1097/j.pain.0000000000001937
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发表时间：
2020-10
期刊：
影响因子：
7.4
通讯作者：
McDermott MP
中科院分区：
文献类型：
--
作者：
Cai X;Gewandter JS;He H;Turk DC;Dworkin RH;McDermott MP
在治疗慢性疼痛的临床试验中，提早退出的参与者比例可高达50%。在这些研究中，早期停药的主要原因包括感觉到的疗效不足和不良事件。常用的弥补缺失数据的策略包括最后一次观察、基线观察和更多原则性的方法，如混合模型重复测量和多重补偿。考虑到观察到的数据，所有这些方法都需要关于辍学后结果的条件分布的强有力且不可检验的假设。我们回顾了在临床试验中处理缺失数据的统计学方法的最新发展，包括更加强调精确地制定研究目标和估计感兴趣的治疗效果的含义。一种灵活的方法似乎很适合于慢性疼痛临床试验的分析，即基于对照的归因，它允许对退出后结果的条件分布做出各种假设，这些假设可以根据估计和感兴趣的情况进行定制。例如，这些假设可能取决于所陈述的辍学原因。我们使用普瑞巴林治疗糖尿病周围神经病变和带状疱疹后神经痛的4个临床试验的数据来说明这些方法。在规划慢性疼痛临床试验时，对试验目标的仔细考虑应确定试验估计的定义，这反过来又应为用于在统计分析中适应缺失数据的方法提供信息。
In clinical trials of treatments for chronic pain, the percentage of participants who withdraw early can be as high as 50%. Major reasons for early withdrawal in these studies include perceived lack of efficacy and adverse events. Commonly used strategies for accommodating missing data include last observation carried forward, baseline observation carried forward, and more principled methods such as mixed-model repeated-measures and multiple imputation. All these methods require strong and untestable assumptions concerning the conditional distribution of outcomes after dropout, given the observed data. We review recent developments in statistical methods for handling missing data in clinical trials, including implications of the increased emphasis being placed on precise formulation of the study objectives and the estimand (treatment effect to be estimated) of interest. A flexible method that seems to be well suited for the analysis of chronic pain clinical trials is control-based imputation, which allows a variety of assumptions to be made concerning the conditional distribution of postdropout outcomes that can be tailored to the estimand of interest. These assumptions can depend, for example, on the stated reasons for dropout. We illustrate these methods using data from 4 clinical trials of pregabalin for the treatment of painful diabetic peripheral neuropathy and postherpetic neuralgia. When planning chronic pain clinical trials, careful consideration of the trial objectives should determine the definition of the trial estimand, which in turn should inform methods used to accommodate missing data in the statistical analysis.
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影响因子：
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