Standardizing emergency department-based migraine research: an analysis of commonly used clinical trial outcome measures.

OBJECTIVES

Although many high-quality migraine clinical trials have been performed in the emergency department (ED) setting, almost as many different primary outcome measures have been used, making data aggregation and meta-analysis difficult. The authors assessed commonly used migraine trial outcomes in two ways. First, the authors examined the association of each commonly used outcome versus the following patient-centered variable: the research subject's wish, when asked 24 hours after investigational medication administration, to receive the same medication the next time they presented to an ED with migraine ("would take again"). This variable was chosen as the criterion standard because it provides a simple, dichotomous, clinically sensible outcome, which allows migraineurs to factor important intangibles of efficacy and adverse effects of treatment into an overall assessment of care. The second part of the analysis assessed how sensitive to true efficacy each outcome measure was by calculating sample size requirements based on results observed in previously conducted clinical trials.

METHODS

This was a secondary analysis of data previously collected in four ED-based migraine randomized trials performed between 2003 and 2007. In each of these trials, subjects were asked 24 hours after administration of an investigational medication whether or not they would want to receive the same medication the next time they came to the ED with a migraine. Odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for sex and medication received, were calculated as measures of association between the most commonly used outcome measures and "would take again." The sensitivity of each outcome measure to treatment efficacy was determined by calculating the sample size that would be required to detect a statistically significant result using estimates of that outcome obtained in two clinical trials.

RESULTS

Data from 378 subjects were used for this analysis. Adjusted ORs for association of "would take again" and other commonly used primary headache outcomes are as follows: achieving a pain-free state by 2 hours, OR = 3.1 (95% CI = 1.8 to 5.4); sustained pain-free status, OR = 4.5 (95% CI = 1.9 to 11.0); and no need for rescue medication, OR = 3.7 (95% CI = 2.1 to 6.6). An improvement on a standardized 11-point pain scale of > or =33% had an adjusted OR = 5.2 (95% CI = 2.2 to 12.4). The best performing alternate outcome, > or =33% improvement, correctly classified 288 subjects and misclassified 77 subjects when compared to "would take again." At least 33% improvement and pain-free by 2 hours required the smallest sample sizes, while sustained pain-free and "would take again" required many more subjects.

CONCLUSIONS

"Would take again" was associated with all migraine outcome measures we examined. No individual outcome was more closely associated with "would take again" than any other. Even the best-performing alternate outcome misclassified more than 20% of subjects. However, sample sizes based on "would take again" tended to be larger than other outcome measures. On the basis of these findings and this outcome measure's inherent patient-centered focus, "would take again," included as a secondary outcome in all ED migraine trials, is proposed.