The proposed Migraine Clinical Outcome Assessment System (MiCOAS) aims to improve and standardize endpoints and the assessment of those endpoints in migraine clinical trials. Such standardized clinical outcome assessments (COAs), developed to incorporate the patient voice and empirically supported by gold-standard instrument development techniques, will aid in the interpretability of results from and across migraine clinical trials and, by extension, advance the development and approval of migraine treatments. The UG3 phase of the grant will first assemble a group of stakeholders (substantive research experts, patient advocates, clinicians, psychometricians, regulators, and payers) to guide the project (AIM 1). Comprehensive systematic review of the migraine literature will be undertaken to fully understand current migraine outcomes, in both acute and preventative migraine trials (AIM 2). Results from qualitative research using patient-centered interviews (AIM 3) will ensure that endpoints identified during AIM 1 and AIM 2 as targets for development/refinement are meaningful to patients. The UH3 grant stage will use additional patient-centered qualitative research to fully understand the patient experience with respect to the target endpoints identified in UG3 and what aspects are most important to them, patient language in discussing said endpoints, and any possible areas of study that were not previously identified (AIM 4). Using the patient-interview results, outcome measures will be developed using gold- standard techniques. In the expected case of developing/refining a preventative quality-of- life/impact/disability-type measure, a new data collection of migraine patients will be designed and executed and gold-standard psychometric techniques will be employed to empirically evaluate and refine candidate items, finalize the items selected to the final assessment, and evaluate the initial validity and fit-for-purpose of the outcome assessment. A separate data collection will also be designed, executed, and analyzed for the draft outcome assessments intended for acute migraine trials (AIM 5). The overarching purpose of this grant is to develop a publicly available core set of migraine endpoints and their related COAs for migraine. Given this, proper dissemination of findings through scientific outlets in the form of presentations and manuscripts is essential (AIM 6). Successful completion of the overall goal of the proposed project will result in standardized and empirically-supported migraine COAs for clinical trials that are meaningful to patients and statistically robust.
For long-term sustainability of the drug development and approval process, the FDA has identified ?a need for a more collaborative, multi-stakeholder approach to the development, modification and/or selection of clinical outcome assessment (COAs) within specific disease area(s) that incorporates input from patients and care partners, drug developers, researchers, regulators, payers, and other decision makers.? Migraine, a severely debilitating, chronic, and under-researched complex of neurological and related symptoms, is one such area where a standard set of rigorously defined and psychometrically verified outcomes, developed to more fully capture the patient experience and voice, could result in large strides in the assessment and treatment of migraine. The proposed Migraine Clinical Outcome Assessment System (MiCOAS), which will be developed with input from relevant stakeholders and with a focus on incorporating the patient experience and feedback regarding endpoints and outcomes most meaningful to them, seeks to provide a standard set of migraine COAs; standardizing an optimized set of COAs in migraine clinical trials could lead to more accurate assessments of outcomes and, ultimately, a better understanding of treatments to address the symptoms identified as most important to patients suffering from migraine.