Turner N L, Dias S, Ades A E, Welton N J
School of Social and Community Medicine, University of Bristol, Bristol, U.K.
Stat Med. 2015 May 30;34(12):2062-80. doi: 10.1002/sim.6475. Epub 2015 Mar 24.
Missing outcome data are a common threat to the validity of the results from randomised controlled trials (RCTs), which, if not analysed appropriately, can lead to misleading treatment effect estimates. Studies with missing outcome data also threaten the validity of any meta-analysis that includes them. A conceptually simple Bayesian framework is proposed, to account for uncertainty due to missing binary outcome data in meta-analysis. A pattern-mixture model is fitted, which allows the incorporation of prior information on a parameter describing the missingness mechanism. We describe several alternative parameterisations, with the simplest being a prior on the probability of an event in the missing individuals. We describe a series of structural assumptions that can be made concerning the missingness parameters. We use some artificial data scenarios to demonstrate the ability of the model to produce a bias-adjusted estimate of treatment effect that accounts for uncertainty. A meta-analysis of haloperidol versus placebo for schizophrenia is used to illustrate the model. We end with a discussion of elicitation of priors, issues with poor reporting and potential extensions of the framework. Our framework allows one to make the best use of evidence produced from RCTs with missing outcome data in a meta-analysis, accounts for any uncertainty induced by missing data and fits easily into a wider evidence synthesis framework for medical decision making.
缺失的结局数据是随机对照试验(RCT)结果有效性的常见威胁,若未进行适当分析,可能导致治疗效果估计产生误导。有缺失结局数据的研究也会威胁到纳入这些数据的任何荟萃分析的有效性。本文提出了一个概念上简单的贝叶斯框架,用于在荟萃分析中考虑因二元结局数据缺失而产生的不确定性。拟合了一个模式混合模型,该模型允许纳入关于描述缺失机制的参数的先验信息。我们描述了几种替代参数化方法,最简单的是对缺失个体中事件发生概率的先验。我们描述了一系列关于缺失参数可以做出的结构假设。我们使用一些人工数据场景来证明该模型产生考虑不确定性的治疗效果偏差调整估计的能力。对氟哌啶醇与安慰剂治疗精神分裂症的荟萃分析用于说明该模型。最后,我们讨论了先验的引出、报告不佳的问题以及该框架的潜在扩展。我们的框架允许在荟萃分析中充分利用有缺失结局数据的随机对照试验产生的证据,考虑由缺失数据引起的任何不确定性,并轻松融入更广泛的医学决策证据综合框架。