A methodological assessment of randomization integrity in alteplase for acute ischemic stroke individual patient data meta-analyses

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dc.contributor.authorMickenautsch, Steffen
dc.contributor.authorGarg, Ravi
dc.contributor.authorTorrealba-Acosta, Gabriel
dc.date.accessioned2025-07-25T09:33:36Z
dc.date.available2025-07-25T09:33:36Z
dc.date.issued2025
dc.description.abstractObjectives Little is known about the integrity of randomization for randomized controlled trials (RCT) included in alteplase for stroke meta-analyses. If the RCTs were not properly randomized, the results could not be accepted at face value. The objective was to assess the integrity of randomization in individual patient data (IPD) meta-analyses supporting alteplase for acute ischemic stroke. Methods We assessed randomization reporting, performed qualitative risk of bias assessments arising from the randomization process, and performed fixed effects meta-analyses of baseline variables for which zero heterogeneity is expected if all included RCTs have unbiased randomization. Fixed-effects meta-analyses of baseline age, weight, and National Institute of Health Stroke Scale (NIHSS) score were performed. If heterogeneity was present (I2 > 0%), trials were systematically removed, starting with the RCT with the largest t-statistic until the I2 value was 0%. Results The NINDS rt-PA Stroke Study had a high risk of bias, the ECASS-3 RCT had some concerns, and all other trials were graded as low risk according to the Cochrane Risk of Bias (ROB-2) tool. The NINDS rt-PA Stroke Study contributed to heterogeneity in age and weight meta-analyses, and the ECASS-3 RCT contributed to heterogeneity in the NIHSS score meta-analysis. Removal of suspect trials resulted in the expected I2 value of 0%. Conclusions: The NINDS rt-PA Stroke Study and ECASS-3 trials contributed to heterogeneity in fixed effects meta-analyses of baseline variables while there should have been none. These RCTs are likely a source of selection bias in IPD meta-analyses due to suspect randomization.
dc.identifier.citationGarg, R., Torrealba-Acosta, G., Mickenautsch, S. and Berger, V.W., 2025. A methodological assessment of randomization integrity in alteplase for acute ischemic stroke individual patient data meta-analyses. PloS one, 20(3), p.e0315342.
dc.identifier.urihttps://doi.org/10.1371/journal.pone.0315342
dc.identifier.urihttps://hdl.handle.net/10566/20613
dc.language.isoen
dc.publisherPublic Library of Science
dc.subjectECASS-3 RCT
dc.subjectObjectives
dc.subjectRCTs
dc.subjectNational Institute of Health Stroke Scale (NIHSS)
dc.subjectFixed-effects
dc.titleA methodological assessment of randomization integrity in alteplase for acute ischemic stroke individual patient data meta-analyses
dc.typeArticle

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