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进行荟萃分析时处理结局数据缺失的试验参与者:对提议方法的系统调查

Handling trial participants with missing outcome data when conducting a meta-analysis: a systematic survey of proposed approaches.

作者信息

Akl Elie A, Kahale Lara A, Agoritsas Thomas, Brignardello-Petersen Romina, Busse Jason W, Carrasco-Labra Alonso, Ebrahim Shanil, Johnston Bradley C, Neumann Ignacio, Sola Ivan, Sun Xin, Vandvik Per, Zhang Yuqing, Alonso-Coello Pablo, Guyatt Gordon

机构信息

Department of Internal Medicine, Clinical Epidemiology Unit, American University of Beirut Medical Center, P.O. Box: 11-0236, Riad-El-Solh, Beirut, 1107, 2020, Beirut, Lebanon.

Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.

出版信息

Syst Rev. 2015 Jul 23;4:98. doi: 10.1186/s13643-015-0083-6.

Abstract

BACKGROUND

When potentially associated with the likelihood of outcome, missing participant data represents a serious potential source of bias in randomized trials. Authors of systematic reviews frequently face this problem when conducting meta-analyses. The objective of this study is to conduct a systematic survey of the relevant literature to identify proposed approaches for how systematic review authors should handle missing participant data when conducting a meta-analysis.

METHODS

We searched MEDLINE and the Cochrane Methodology register from inception to August 2014. We included papers that devoted at least two paragraphs to discuss a relevant approach for missing data. Five pairs of reviewers, working independently and in duplicate, selected relevant papers. One reviewer abstracted data from included papers and a second reviewer verified them. We summarized the results narratively.

RESULTS

Of 9,138 identified citations, we included 11 eligible papers. Four proposed general approaches for handling dichotomous outcomes, and all recommended a complete case analysis as the primary analysis and additional sensitivity analyses using the following imputation methods: based on reasons for missingness (n = 3), relative to risk among followed up (n = 3), best-case scenario (n = 2), and worst-case scenario (n = 3). Three of these approaches suggested taking uncertainty into account. Two papers proposed general approaches for handling continuous outcomes, and both proposed a complete case analysis as the reference analysis and the following imputation methods as sensitivity analyses: based on reasons for missingness (n = 2), based on the mean observed in the same trial or other trials (n = 1), and based on informative missingness differences in means (n = 1). The remaining eligible papers did not propose general approaches but addressed specific statistical issues.

CONCLUSIONS

All proposed approaches for handling missing participant data recommend conducting a complete case analysis for the primary analysis and some form of sensitivity analysis to evaluate robustness of results. Although these approaches require further testing, they may guide review authors in addressing missing participant data.

摘要

背景

当与结果的可能性相关时,缺失的参与者数据是随机试验中一个严重的潜在偏倚来源。系统评价的作者在进行荟萃分析时经常面临这个问题。本研究的目的是对相关文献进行系统调查,以确定系统评价作者在进行荟萃分析时应如何处理缺失参与者数据的建议方法。

方法

我们检索了从创刊至2014年8月的MEDLINE和Cochrane方法学注册库。我们纳入了至少用两段篇幅讨论缺失数据相关方法的论文。五对评审员独立且重复地挑选相关论文。一名评审员从纳入的论文中提取数据,另一名评审员进行核实。我们对结果进行了叙述性总结。

结果

在9138条检索到的文献中,我们纳入了11篇符合条件的论文。四篇论文提出了处理二分结局的一般方法,均推荐将完全病例分析作为主要分析,并使用以下插补方法进行额外的敏感性分析:基于缺失原因(n = 3)、相对于随访中的风险(n = 3)、最佳情况(n = 2)和最差情况(n = 3)。其中三种方法建议考虑不确定性。两篇论文提出了处理连续结局的一般方法,均建议将完全病例分析作为参考分析,并使用以下插补方法进行敏感性分析:基于缺失原因(n = 2)、基于同一试验或其他试验中观察到的均值(n = 1)以及基于均值中信息性缺失差异(n = 1)。其余符合条件的论文未提出一般方法,而是探讨了特定的统计问题。

结论

所有提出的处理缺失参与者数据的方法都建议将完全病例分析作为主要分析,并进行某种形式的敏感性分析以评估结果的稳健性。虽然这些方法需要进一步检验,但它们可能会指导综述作者处理缺失的参与者数据。

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