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

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.

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.

Keywords: alteplase; bias; ischemic stroke; meta-analysis; missing outcome data.

FIGURE 1

Forest plots comparing early and late mortality in the chosen meta‐analysis (top) and a meta‐analysis of treatment based on neuroimaging guidance (bottom)., In the chosen meta‐analysis with imputation of survival, excess mortality decreases between Day 7 and Day 90. In the meta‐analysis of treatment based on neuroimaging guidance using complete case analysis, excess mortality increases between Day 7 and Day 90. Effect sizes are reported as risk differences (RD) and 95% confidence intervals. The vertical dotted line represents the null (RD = 0). *p value <.05