Can We Improve the Statistical Analysis of Stroke Trials?: Statistical Reanalysis of Functional Outcomes in Stroke Trials

The statistical assumptions underlying the t test were not met for most of the acute data sets.

“However, the statistical assumptions underlying the t test were not met for most of the acute data sets. 9”

Continuous analyses based on the t test had comparable power to ordinal analyses when compared with ordinal and dichotomous analyses of existing acute stroke trial data.

“When compared with ordinal and dichotomous analyses of existing acute stroke trial data, continuous analyses (based on the t test) had comparable power to ordinal analyses. 9”

Using individual patient data from acute stroke trials, the OAST Collaboration found the ordering of approaches, best first, was: ordinal logistic regression, t test, robust ranks test, bootstrap, Mann-Whitney U/Wilcoxon test, Cochran-Armitage ranks test, 2 x 2 chi-square test, and median test.

“Using individual patient data from acute stroke trials, the OAST Collaboration compared several approaches and found that their ordering ('best' first) was: ordinal logistic regression, t test, robust ranks test, bootstrap, Mann-Whitney U /Wilcoxon test, Cochran-Armitage ranks test, 2 × 2 𝛘 2 test, and median test. 9”

The International Stroke Trial was neutral with a dichotomous analysis but positive using a variety of different ordinal analyses.

“(3) International Stroke Trial (IST; aspirin for acute ischemic stroke, Phase III megatrial) was neutral with a dichotomous analysis (primary analysis) 8 but positive using a variety of different ordinal analyses (data from 9 )”

Alteplase reduced the mRS by a median 1 point in the National Institute of Neurological Disorders and Stroke study of alteplase, analyzed by Mann-Whitney U test or robust ranks test.

“Second, the reduction of death or dependency may be described by the difference in medians, for example, alteplase reduced the mRS by a median 1 point in the National Institute of Neurological Disorders and Stroke study of alteplase (analysis by Mann-Whitney U test or robust ranks test; Table 1). 9”

Alteplase reduced the mRS by a mean 0.53 mRS points in the National Institute of Neurological Disorders and Stroke study of alteplase, analyzed by t test.

“When performing a continuous analysis, the reduction of death or dependency may be described by the difference in means, for example, alteplase reduced the mRS by a mean 0.53 mRS points in the National Institute of Neurological Disorders and Stroke study of alteplase (analysis by t test; Table 1). 9”

Most (85%) data sets from previous acute trials did not depart significantly from the proportionality assumption.

“Nevertheless, when examining individual data from previous acute trials, most (85%) data sets did not depart significantly from the proportionality assumption. 9”

STIPAS was neutral with a dichotomous analysis but negative on ordinal analysis.

“(4) Safety study of tirilazad mesylate in patients with acute ischemic stroke (STIPAS; tirilazad for acute ischemic stroke, Phase II trial) was neutral with a dichotomous analysis 10 but negative on ordinal analysis (data from the Optimising Analysis of Stroke Trials [OAST] Collaboration 9 )”