Migraine management consists of acute treatments, used in the moment of an attack for symptomatic relief, and preventive treatments, used to reduce the frequency, severity, and disability of attacks over time. Migraine treatment must be individualized. Thus, the treatment decision-making process is complex and requires considering multiple factors including efficacy and safety data, treatment characteristics, patient characteristics, and personal preferences.Given the numerous subjective variables factored into treatment decisions, one would hope that the objective variables, such as comparative efficacy data, would be clear. However, rather than comparing apples with apples when looking at trial outcomes, we are often left comparing apples with oranges because of heterogeneity in the trial endpoints. The lack of comparative effectiveness data results in less informed decision-making for patients, clinicians, guideline developers, pharmacists, and payers about the relative benefits of migraine medications. This potentially lengthens the time to improved patient outcomes, increases cycling from one medication to another and exposure to side effects, and reduces informed utilization of health care resources.In this issue of Neurology ® , Sharpless et al. 1 report on a study evaluating the characteristics and variation of endpoints used in trials supporting Food and Drug Administration (FDA) approvals of acute and preventive migraine medications. Using the Drugs@FDA online database, all prescription and over-the-counter acute and preventive medications approved by the FDA between January 1, 2001, and September 1, 2022, for migraine with or without aura and for episodic or chronic migraine were identified. The most recent FDA-approved labeling was used to describe indication, mechanism of action, mode of administration, manufacturer, approval year, number of pivotal trials, trial design, and primary endpoints. Endpoints were classified based on type and timing. Based on 45 pivotal trials, 16 medications were approved for migraine treatment between 2001 and 2022 based on 5 single primary and 3 coprimary groups of endpoints (Table ). Compared with older preventive trials, those published in the past 5 years were generally adherent to the applicable iteration of International Headache Society (IHS) trial design guidelines regarding the primary endpoint selection, except for the fremanezumab chronic migraine trial. 2-4 Among acute trials, many triptan trials were not adherent with the applicable iteration of IHS trial design guidelines (i.e., using pain relief rather than pain freedom), while the newer acute intervention trials were all adherent. 2,3,5 Regarding the timing of primary endpoints, all acute treatment trials used 2-hour endpoints. However, preventive trials had wide variability, including the entire treatment period, portions of the treatment period, or the final month of treatment.In addition to the differences in endpoint types and timing, variability was further compounded by inconsistencies in language. ...
