A methodological assessment of randomization integrity in alteplase for acute ischemic stroke individual patient data meta-analyses.
<h4>Objectives</h4>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 integr...
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2025-01-01
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| Online Access: | https://doi.org/10.1371/journal.pone.0315342 |
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| author | Ravi Garg Gabriel Torrealba-Acosta Steffen Mickenautsch Vance W Berger |
| author_facet | Ravi Garg Gabriel Torrealba-Acosta Steffen Mickenautsch Vance W Berger |
| author_sort | Ravi Garg |
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| description | <h4>Objectives</h4>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.<h4>Methods</h4>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%.<h4>Results</h4>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%.<h4>Conclusions</h4>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. |
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| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-d2ae78a2aa1e46f6a772b2d91445cbe82025-08-20T02:22:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01203e031534210.1371/journal.pone.0315342A methodological assessment of randomization integrity in alteplase for acute ischemic stroke individual patient data meta-analyses.Ravi GargGabriel Torrealba-AcostaSteffen MickenautschVance W Berger<h4>Objectives</h4>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.<h4>Methods</h4>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%.<h4>Results</h4>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%.<h4>Conclusions</h4>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.https://doi.org/10.1371/journal.pone.0315342 |
| spellingShingle | Ravi Garg Gabriel Torrealba-Acosta Steffen Mickenautsch Vance W Berger A methodological assessment of randomization integrity in alteplase for acute ischemic stroke individual patient data meta-analyses. PLoS ONE |
| title | A methodological assessment of randomization integrity in alteplase for acute ischemic stroke individual patient data meta-analyses. |
| title_full | A methodological assessment of randomization integrity in alteplase for acute ischemic stroke individual patient data meta-analyses. |
| title_fullStr | A methodological assessment of randomization integrity in alteplase for acute ischemic stroke individual patient data meta-analyses. |
| title_full_unstemmed | A methodological assessment of randomization integrity in alteplase for acute ischemic stroke individual patient data meta-analyses. |
| title_short | A methodological assessment of randomization integrity in alteplase for acute ischemic stroke individual patient data meta-analyses. |
| title_sort | methodological assessment of randomization integrity in alteplase for acute ischemic stroke individual patient data meta analyses |
| url | https://doi.org/10.1371/journal.pone.0315342 |
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