Dimitrakopoulou Vasiliki, Efthimiou Orestis, Leucht Stefan, Salanti Georgia
Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece.
Stat Med. 2015 Feb 28;34(5):742-52. doi: 10.1002/sim.6364. Epub 2014 Dec 10.
Missing outcome data are a problem commonly observed in randomized control trials that occurs as a result of participants leaving the study before its end. Missing such important information can bias the study estimates of the relative treatment effect and consequently affect the meta-analytic results. Therefore, methods on manipulating data sets with missing participants, with regard to incorporating the missing information in the analysis so as to avoid the loss of power and minimize the bias, are of interest. We propose a meta-analytic model that accounts for possible error in the effect sizes estimated in studies with last observation carried forward (LOCF) imputed patients. Assuming a dichotomous outcome, we decompose the probability of a successful unobserved outcome taking into account the sensitivity and specificity of the LOCF imputation process for the missing participants. We fit the proposed model within a Bayesian framework, exploring different prior formulations for sensitivity and specificity. We illustrate our methods by performing a meta-analysis of five studies comparing the efficacy of amisulpride versus conventional drugs (flupenthixol and haloperidol) on patients diagnosed with schizophrenia. Our meta-analytic models yield estimates similar to meta-analysis with LOCF-imputed patients. Allowing for uncertainty in the imputation process, precision is decreased depending on the priors used for sensitivity and specificity. Results on the significance of amisulpride versus conventional drugs differ between the standard LOCF approach and our model depending on prior beliefs on the imputation process. Our method can be regarded as a useful sensitivity analysis that can be used in the presence of concerns about the LOCF process.
缺失结局数据是随机对照试验中常见的问题,它是由于参与者在研究结束前退出而产生的。缺少此类重要信息可能会使研究对相对治疗效果的估计产生偏差,从而影响荟萃分析结果。因此,处理存在缺失参与者的数据集的方法备受关注,这些方法旨在将缺失信息纳入分析,以避免功效损失并将偏差降至最低。我们提出了一种荟萃分析模型,该模型考虑了在采用末次观察结转(LOCF)法估算患者的研究中效应量估计可能存在的误差。假设结局为二分变量,我们在考虑LOCF估算过程对缺失参与者的敏感性和特异性的情况下,分解未观察到的成功结局的概率。我们在贝叶斯框架内拟合所提出的模型,探索敏感性和特异性的不同先验设定。我们通过对五项比较氨磺必利与传统药物(氟哌噻吨和氟哌啶醇)对精神分裂症患者疗效的研究进行荟萃分析来说明我们的方法。我们的荟萃分析模型得出的估计结果与对采用LOCF法估算患者的荟萃分析结果相似。考虑到估算过程中的不确定性,精度会根据用于敏感性和特异性的先验设定而降低。根据对估算过程的先验信念,标准LOCF方法与我们的模型在氨磺必利与传统药物疗效差异的结果上有所不同。我们的方法可被视为一种有用的敏感性分析,可在对LOCF过程存在担忧的情况下使用。
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