Comparative Effectiveness of Novel Pharmacologic and Evidence-Based Nonpharmacologic Treatments for Migraine Prevention -- Cycle 3 2021

This Targeted PCORI Funding Announcement seeks to fund rigorous, large-scale pragmatic trials that compare newly available pharmacologic and/or evidence-based nonpharmacologic treatments for the prevention of migraine.

Research Initiative Highlights 

Migraine is a highly prevalent chronic neurological disorder characterized by recurrent attacks and associated with symptoms that include nausea, pain, vomiting, and sensitivity to light and sound. Approximately 40 million Americans experience migraines and in 2016, the Global Burden of Disease ranked migraine as the second leading cause of disability worldwide.

Preventive treatments include both pharmacological and nonpharmacological options, with the goal to reduce the frequency, severity, and duration of attacks. Although there are many pharmacological options used for migraine prevention, most options were originally developed for the treatment of other conditions. Newly approved treatments such as calcitonin gene-related peptide (CGRP) antagonists have been developed specifically for migraine prevention and have been shown to be efficacious. However, there are uncertainties regarding the long-term comparative effectiveness of CGRP inhibitors compared with commonly prescribed preventives. Further, there is growing interest in the use of nonpharmacological therapies and additional research is needed to understand the role of such options in the prevention of migraine.

PCORI’s Targeted PFA is soliciting applications that respond to the following question:

What is the comparative effectiveness of novel pharmacologic and/or evidence-based nonpharmacologic treatments for the prevention of migraine?

PCORI is particularly interested in studies that compare emerging pharmacological options such as CGRP antagonists to standard prophylactic therapy or to each other. PCORI is also interested in studies that examine the comparative effectiveness of evidence-based nonpharmacological options for migraine prevention. As appropriate, studies may include nonpharmacological interventions as stand-alone therapy or as an adjunct to pharmacological options. 

Proposed studies should be large enough to enable precise estimates of effect sizes and to support evaluation of potential differences in treatment effectiveness in patient subgroups. Subgroups of particular interest include patients for whom prior preventive treatments have failed; patients with comorbidities including cardiovascular disease; migraine type (medication overuse, episodic/chronic migraine, migraine with aura); and menstrual-associated migraine. Applicants should clearly define criteria for the initiation of preventive therapy based on guideline recommendations. 

Applicants should consider a broad range of outcomes that are important to patients. Pharmacologic studies should be adequately powered to assess changes in the frequency of headache or migraine days consistent with and/or exceeding prior efficacy trials, while considering evidence gaps regarding long-term effectiveness.  Other important outcomes of interest include quality of life, headache-related disability, patient burden (i.e., time away from work or usual activities), functional impact, tolerability, adverse events, and use of abortive treatment.