Division of Neurocritical Care, Department of Neurology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, USA.
Acta Neurol Scand. 2022 Sep;146(3):252-257. doi: 10.1111/ane.13656. Epub 2022 Jun 2.
Recent national guidelines recommend alteplase treatment for ischemic stroke within 4.5 h of symptom-onset based on meta-analyses of randomized controlled clinical trials (RCT). A detailed description of missing outcome data (MOD) due to participant loss to follow-up has never been published. The objective of this study was to perform a methodlogical survey on missing outcome data in an alteplase for ischemic stroke meta-analysis.
A methodological survey was performed on a chosen meta-analysis of alteplase for ischemic stroke RCTs that most closely aligns with recent national guideline recommendations. Data were collected to assess the number of participants lost to follow-up; differential lost to follow-up between allocation groups; baseline characteristics of those lost to follow-up; and the imputation methods used by individual trials and the chosen meta-analysis. The number of participants lost to follow-up was compared with the fragility index; and repeated for individually positive RCTs in the meta-analysis.
The methodological survey revealed a substantial degree of missing information regarding MOD in the chosen meta-analysis and in individual RCTs. Single imputation was exclusively used in all RCTs and in the meta-analysis. The number of participants lost to follow-up was greater than the fragility index in the chosen meta-analysis and individually positive component RCTs suggesting that MOD may impact the direction of the reported effect or effect size.
This methodological survey of an alteplase for ischemic stroke meta-analysis revealed MOD may be an important source of unrecognized bias. This survey highlights the need for sensitivity analyses using more robust methods of imputation.
最近的国家指南建议根据随机对照临床试验（RCT）的荟萃分析，对症状发作后 4.5 小时内的缺血性脑卒中使用阿替普酶进行治疗。关于因参与者失访而导致的缺失结局数据（MOD），从未有过详细描述。本研究的目的是对阿替普酶治疗缺血性脑卒中荟萃分析中的缺失结局数据进行方法学调查。
对与最近的国家指南建议最一致的阿替普酶治疗缺血性脑卒中 RCT 的荟萃分析进行了方法学调查。收集的数据用于评估失访参与者的数量；分配组之间的差异失访；失访者的基线特征；以及各个试验和选定荟萃分析中使用的插补方法。将失访参与者的数量与脆弱指数进行比较；并对荟萃分析中的阳性个体 RCT 进行重复。
方法学调查显示，选定的荟萃分析和个别 RCT 中存在大量关于 MOD 的缺失信息。所有 RCT 和荟萃分析中均仅使用单一插补。失访参与者的数量大于选定荟萃分析和阳性个体 RCT 的脆弱指数，这表明 MOD 可能会影响报告的效果或效果大小的方向。
对阿替普酶治疗缺血性脑卒中荟萃分析的方法学调查显示，MOD 可能是未被识别的偏倚的重要来源。本调查强调需要使用更稳健的插补方法进行敏感性分析。
