Measuring outcomes as a function of baseline severity of ischemic stroke.

BACKGROUND

The spectrum of neurological impairments following acute ischemic stroke is broad. The initial stroke severity predicts responses to treatment and outcomes after ischemic stroke. While clinical trials are using baseline severity as an enrollment criterion or a stratified variable, adjustment of outcome measures as a function of initial impairments has not been done.

METHODS

We developed a responder analysis that defines favorable outcomes at 90 days as influenced by the baseline National Institutes of Health Stroke Scale (NIHSS). Favorable outcome was defined as a modified Rankin Scale (mRS) score of 0 if the baseline NIHSS score was <8, mRS score of 0-1 if the NIHSS score was 8-14, and mRS score of 0-2 if the NIHSS score was >14. The concept stemmed from the data of two European rtPA trials. The analysis is a predefined secondary endpoint in a trial testing abciximab. We also used the analysis to reexamine the Trial of Org 10172 in Acute Stroke Treatment data.

RESULTS

The responder analysis did not change the overall results of any of the 3 previous trials, but it did give information about differences in responses among subgroups of patients. Evidence about the potential utility of tPA for treatment of patients with mild stroke appeared from the analysis of the second European trial of rtPA. The analysis also provided a hint of efficacy of abciximab.

CONCLUSIONS

The responder analysis appears to be a potentially useful way to evaluate outcomes of patients enrolled in clinical trials in stroke. The results of the analysis have clinical relevance and can further explain differences in responses to therapies. In addition, the analysis allows for improved comparisons of results among clinical trials.