The first Health Technology Assessment for the Acute Treatment of Migraine Attacks and Prevention has been published in Cephalalgia by the Clinical Trials Subcommittee of the International Headache Society.
Migraine is a leading cause for disability worldwide, with over 1 billion individuals, mostly women, living with it. It is defined as moderate to severe headache lasting between 4 and 72 hours and may include nausea, photophobia, and phonophobia. Large disparities in access to care exist and many people remain undiagnosed or receive subpar treatment.
Current therapeutics available for the treatment of migraine include established technologies such as analgesics, nonsteroidal anti-inflammatory drugs, serotonin agonists, ergots, and beta-blockers and newer technologies such as small molecules, monoclonal antibodies, and neuromodulatory devices.
The Clinical Trials Subcommittee recommends that studies of new technologies for acute migraine relief should target populations specified by the most recent International Classification of Headache Disorders, especially those with prior treatment failure, intolerance, contraindications, or those who are unable to ingest oral therapeutics. It is important that these patients are stratified into unique populations, randomly assigned into treatment and control cohorts, and compared with their counterparts in order to accurately assess therapies for these populations’ specific needs.
Studies of migraine prevention have been particularly lacking among pregnant or breastfeeding women, children, adolescents, and men. The Clinical Trials Subcommittee recommends that assessments be weighted to account for such gaps in evidence. Additionally, randomized controlled trials should recruit more participants from these underrepresented populations.
For studies which stratify patients by migraine frequency, the Clinical Trials Subcommittee states that that studies should assess monthly headache days (MHDs) or monthly migraine days (MMDs) on the basis of study motivation. Studies of patients with chronic migraine should use MHDs over MMDs as these phenotypes can change over time and not all headaches meet migraine diagnostic criteria. Studies of preventative migraine treatment should use MMDs over MHDs because they remove any need to account for pain disruption due sleep or for acute medication use.
In order to assess efficacy of new technologies, a traditional placebo should not be dispensed to patients, as placebos are not given in clinical practice. Instead, the Clinical Trials Subcommittee recommends that the current standard-of-care to be used as comparator. For example, appropriate comparators for acute treatment include 50 or 100 mg sumatriptan, 40 or 80 mg eletriptan, or 10 mg rizatriptan.
The specified endpoints for studies of migraine can be difficult to properly design as they are subjective and vary among concerned parties (ie, patient, clinician, caregivers, health care systems, and employers). In general, all domains of the European Network for Health Technology Assessment’s Core Model should be considered when designing study endpoints. Additionally, data collection should only occur when sufficient power has been established, accounting for primary outcomes, secondary outcomes, and anticipated patient drop-out.
For studies of health technologies which involve acute migraine, the Clinical Trials Subcommittee recommends the primary outcome to be pain relief or freedom at 2 hours whereas assessment of migraine prevention should measure MMD reduction over a time period of 3 to 6 months.
The Clinical Trials Subcommittee recommends the use of use generic instruments to evaluate secondary endpoints, including the Headache Impact Test, Migraine-Specific Quality of Life questionnaire, Migraine Disability Assessment scale, Migraine Functional Impact Questionnaire, and the Migraine Physical Function Impact Diary among others.
Given the complexity of assessing health technologies among patients with this chronic, intermittent disease, both direct and indirect costs should be assessed. Direct costs may include cost of treatment, management of adverse events, and physician visits. Indirect costs can be more nuanced and should involve at least 3 domains, such as monetizing the lost time at work or school, inability to complete household duties, and missed social or leisure activities.
The Clinical Trials Subcommittee concluded that the overall objective of assessing health technologies is to both determine whether individuals with migraine have improved symptoms from novel technologies. Additionally, the goal is to provide policymakers with comprehensive, evidence-based research on the technology in question. Authors stated that “additional elements of HTAs [health technology assessments] should examine migraine’s impact on healthcare systems and communities and consider the potential benefits of professional training and extending access to care for individuals in high-risk populations.”
Disclosure: Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.
Diener HC, Ashina M, Durand-Zaleski I, et al. Health technology assessment for the acute and preventive treatment of migraine: A position statement of the International Headache Society. Cephalalgia. Published online, January 20, 2021. doi:10.1177/0333102421989247