title: Repeated-measures analysis of the National Institute of Neurological Disorders and Stroke rt-PA stroke trial.
abstract: Previous analyses, including the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stoke Trial, have assessed the clinical treatment efficacy only at single study point, but did not assess efficacy using outcomes collected at multiple time points and incorporate within-patient correlation. The data from the NINDS rt-PA Stroke Trial was analyzed with repeated-measures analysis with generalized estimating equations (GEE) approach using dichotomized outcomes (modified Rankin Scale [mRS], National Institutes of Health Stroke Scale [NIHSS], Barthel Index [BI], and Glasgow Outcome Scale [GOS]). The results were compared with data from previous analyses. All of the outcome variables at different time points were significantly correlated. rt-PA was superior to placebo overall and at specific time points individually. The overall odds of having minimal or no disability (mRS score 0 or 1) for patients treated with rt-PA was higher than those treated with placebo (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.5-3.0). The ORs were 2.3 (95% CI, 1.5-3.4) times higher at 3 months, 1.9 (95% CI, 1.3-2.8) times higher at 6 months, and 2.0 (95% CI, 1.3-2.9) times higher at 12 months. A similar treatment effect also was observed with the NIHSS, BI, and GOS. Compared with previous analyses, an augmented treatment effect with larger ORs and smaller P values were observed. Repeated-measures analysis provides an alternative method for assessing treatment effect, as demonstrated in the analysis of data from the NINDS rt-PA Stroke Trial. This method could be used in future stroke trials in which outcomes of interest are collected at multiple time points.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425, USA. feng@musc.edu
authors.forename: Wuwei
authors.initials: W
authors.lastname: Feng
authors.forename: Gabriela
authors.initials: G
authors.lastname: Vasquez
authors.forename: M Fareed K
authors.initials: MF
authors.lastname: Suri
authors.forename: Kamakshi
authors.initials: K
authors.lastname: Lakshminarayan
authors.forename: Adnan I
authors.initials: AI
authors.lastname: Qureshi
mesh_terms: D003627:Data Interpretation, Statistical; D004185:Disability Evaluation; D004311:Double-Blind Method; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015600:Glasgow Coma Scale; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D055825:National Institute of Neurological Disorders and Stroke (U.S.); D016017:Odds Ratio; D011237:Predictive Value of Tests; D020127:Recovery of Function; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014481:United States
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator