Methodological survey of missing outcome data in an alteplase for ischemic stroke meta‐analysis

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. MATERIALS AND 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. CONCLUSION: 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.