Defining post-stroke recovery: implications for design and interpretation of drug trials.

Measurement of stroke recovery is complex because definition of successful recovery is highly variable across measures and cut-off points for defining successful outcomes vary. The purpose of this paper is to describe patterns of recovery in stroke patients of varying severity when different measures are used and when different cut-off points are selected. 459 individuals enrolled in a prospective cohort study were assessed within 14 days post stroke and re-evaluated at 1, 3, and 6 months. Recovery was assessed using the NIH Stroke Scale, the Fugl-Meyer Assessment of Motor Recovery, the Barthel Index of Activities of Daily Living, the Physical Function Index of the SF-36, and the Modified Rankin Outcome Scale. Subjects also defined their preference (utility) for their current health state with a time-trade off question. We compared patterns of recovery using the different measures and varying the cut-off points for defining successful recovery. The percentage of patients who are believed to have recovered depends on how recovery is defined. If recovery is defined at the disability level (Barthel > 90), the majority 57.3% of stroke survivors experience a full recovery. Fewer individuals are considered to be fully recovered if impairments are measured (NIH </= 1, 44.9% and Fugl-Meyer > 90, 36.8%. Less than 25% of stroke survivors are considered recovered if recovery is defined relative to reported prior function in higher levels of physical activity. Shifting the definition of recovery on the modified Rankin scale from </= 1 to </= 2 shifts the percentage of those deemed recovered from </= 25% to 53.8%. In designing drug trials the methods for defining stroke recovery should be carefully considered. If recovery is defined in terms of disability, a higher proportion of the placebo group will achieve the outcome than if impairments are used to define recovery. The benchmarks for recovery in minor strokes must include measures of higher functioning (e.g. the SF-36 physical functioning index or a Rankin 0 (no symptoms).