{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T10:19:50Z","timestamp":1777544390586,"version":"3.51.4"},"reference-count":24,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2008,8,1]],"date-time":"2008-08-01T00:00:00Z","timestamp":1217548800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Trials"],"published-print":{"date-parts":[[2008,8]]},"abstract":"<jats:p>Background Treatment group imbalances in baseline stroke severity in the NINDS intravenous t-PA for acute stroke treatment trial led to controversy regarding the efficacy of tissue plasminogen activator (t-PA) in the treatment of acute ischemic stroke.<\/jats:p>\n                  <jats:p>Purpose Describe the steps used to independently re-evaluate this trial.<\/jats:p>\n                  <jats:p>Methods NIH appointed an independent multidisciplinary committee that gained access to the original data. We undertook analyses of t-PA efficacy accounting for this imbalance, as well as analyses to identify subgroups that experienced additional harm or benefit from t-PA. Analyses of time from stroke onset to treatment (OTT), blood pressure, and intracerebral hemorrhage are given as illustrations.<\/jats:p>\n                  <jats:p>Results Despite subgroup imbalances in baseline stroke severity, when t-PA was administered to acute ischemic stroke patients according to study protocol, there was a statistically significant and clinically important benefit of t-PA treatment resulting in a higher likelihood of having a favorable clinical outcome at 3 months. Moreover, we were unable to identify subgroups of patients between which t-PA treatment effect differed, albeit these analyses had low power. These data failed to support the NINDS investigators' conclusion that effect of t-PA therapy diminished with increasing values of OTT within the protocol-specified 3 h time limit. In addition, the blood pressure measurements were highly variable and inconsistently determined so as to be too unreliable for inclusion in analysis.<\/jats:p>\n                  <jats:p>Conclusion With new NIH requirements for data-sharing, the frequency of re-analysis of clinical trial data may increase substantially. This re-evaluation provides a blueprint for future re-evaluations of other trials. These best practices include re-analysis of the study data, after suitable replication, by an independent multidisciplinary committee, including a skilled statistical programmer analyst. Primary investigators should address significant errors determined in such re-analyses. Clinical Trials 2008; 5: 308\u2014315. http:\/\/ctj.sagepub.com<\/jats:p>","DOI":"10.1177\/1740774508094404","type":"journal-article","created":{"date-parts":[[2008,8,12]],"date-time":"2008-08-12T09:48:11Z","timestamp":1218534491000},"page":"308-315","source":"Crossref","is-referenced-by-count":9,"title":["Methods and processes for the reanalysis of the NINDS tissue plasminogen activator for acute ischemic stroke treatment trial"],"prefix":"10.1177","volume":"5","author":[{"given":"Vicki","family":"Hertzberg","sequence":"first","affiliation":[{"name":"Department of Biostatistics, Emory University,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Ingall","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"O'Fallon","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Mayo 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