Calculation of sample size for stroke trials assessing functional outcome: comparison of binary and ordinal approaches.

BACKGROUND: Many acute stroke trials have given neutral results. Sub-optimal statistical analyses may be failing to detect efficacy. Methods which take account of the ordinal nature of functional outcome data are more efficient. We compare sample size calculations for dichotomous and ordinal outcomes for use in stroke trials.
METHODS: Data from stroke trials studying the effects of interventions known to positively or negatively alter functional outcome--Rankin Scale and Barthel Index--were assessed. Sample size was calculated using comparisons of proportions, means, medians (according to Payne), and ordinal data (according to Whitehead). The sample sizes gained from each method were compared using Friedman 2 way ANOVA.
RESULTS: Fifty-five comparisons (54 173 patients) of active vs. control treatment were assessed. Estimated sample sizes differed significantly depending on the method of calculation (P<0.0001). The ordering of the methods showed that the ordinal method of Whitehead and comparison of means produced significantly lower sample sizes than the other methods. The ordinal data method on average reduced sample size by 28% (inter-quartile range 14-53%) compared with the comparison of proportions; however, a 22% increase in sample size was seen with the ordinal method for trials assessing thrombolysis. The comparison of medians method of Payne gave the largest sample sizes.
CONCLUSIONS: Choosing an ordinal rather than binary method of analysis allows most trials to be, on average, smaller by approximately 28% for a given statistical power. Smaller trial sample sizes may help by reducing time to completion, complexity, and financial expense. However, ordinal methods may not be optimal for interventions which both improve functional outcome and cause hazard in a subset of patients, e.g. thrombolysis.