Problems in design of stroke treatment trials.

Critical evaluation of the literature was use to identify remediable flaws in the design of clinical trials of stroke treatment. Trials of dexamethasone, dextran, and glycerol were reviewed. Available studies have in common major weaknesses in case selection (failure to exclude arteriolar strokes due to hemorrhage or lacunar infarction), and failure to estimate required sample size. Problems of case selection can be avoided with computerized tomography; the sample size required to show superiority of active treatment over placebo can be estimated using standard formulas. Prognostic stratification is suggested as a method of overcoming problems of unbalanced allocation. Further studies with improved design are required to evaluate the prospects for medical limitation of cerebral infarct size.