Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目的：根据随机对照临床试验（RCT）的荟萃分析，最近的国家指南推荐阿替普酶治疗症状发作4.5h内的缺血性卒中。由于参与者失去随访而导致的缺失结果数据（MOD）的详细描述从未发表过。这项研究的目的是对阿替普酶中缺血性卒中meta分析的缺失结果数据进行方法学调查。
方法：对选择的阿替普酶用于缺血性卒中RCT的荟萃分析进行了方法学调查，该方法与最近的国家指南建议最接近。收集数据以评估失去随访的参与者数量；分配组之间失去随访的差异；那些失去随访的基线特征；以及个别试验和所选荟萃分析使用的填补方法。将失去随访的参与者人数与脆弱性指数进行比较；并在荟萃分析中重复进行个体阳性随机对照试验。
结果：方法学调查显示，在所选的荟萃分析和个体随机对照试验中，关于MOD的信息缺失程度很大。所有RCT和荟萃分析均仅使用单次填补。在选择的荟萃分析和单独的阳性成分RCT中，失去随访的参与者数量大于脆弱性指数，表明MOD可能会影响报告的效果或效果大小的方向。
结论：这项对阿替普酶用于缺血性卒中的meta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。这项调查强调了使用更可靠的插补方法进行敏感性分析的必要性。
方法：对选择的阿替普酶用于缺血性卒中RCT的荟萃分析进行了方法学调查，该方法与最近的国家指南建议最接近。收集数据以评估失去随访的参与者数量；分配组之间失去随访的差异；那些失去随访的基线特征；以及个别试验和所选荟萃分析使用的填补方法。将失去随访的参与者人数与脆弱性指数进行比较；并在荟萃分析中重复进行个体阳性随机对照试验。
结果：方法学调查显示，在所选的荟萃分析和个体随机对照试验中，关于MOD的信息缺失程度很大。所有RCT和荟萃分析均仅使用单次填补。在选择的荟萃分析和单独的阳性成分RCT中，失去随访的参与者数量大于脆弱性指数，表明MOD可能会影响报告的效果或效果大小的方向。
结论：这项对阿替普酶用于缺血性卒中的meta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。这项调查强调了使用更可靠的插补方法进行敏感性分析的必要性。
