Migraine is a neurological disorder that compromises quality of life and is disabling for a large, predominantly female population. It affects 18.2% of women and 6.5% of men annually in the United States. Although the mechanism involved is unclear, different hormone profiles have been observed for women who experience migraines. Migraine can be impacted by women’s menstrual cycles, thus many women seek treatment from OB/GYNs. However, it is treated in a variety of clinical settings. Primary care physicians, neurologists, headache specialists and OB/GYNs may all treat migraine patients.
This is an exciting time in migraine research. The understanding that the calcitonin gene-related peptide (CGRP) plays a role in the transmission of pain signals in the brain has led to the introduction of a new generation of migraine therapies targeting CGRP or CGRP receptors. The first, a monoclonal antibody, received approval in 2018. Other investigational candidates include both monoclonal antibodies and small molecules. In addition, investigational products with new delivery mechanisms intend to accelerate delivery of previously approved migraine drugs such as triptans.
Operational and Methodological Considerations in Migraine Trials
Clinical trials of migraine drugs may involve treatment of acute migraine or prophylaxis. Inclusion/exclusion criteria must consider the severity, duration and frequency of migraines and the presence or absence of symptoms such as throbbing, nausea, sensitivity to light (photophobia) and sound (phonophobia), and aura. FDA guidance for acute treatment recommends testing multiple doses in patients with and without aura.
Approval of drugs for acute treatment has been based on four co-primary endpoints: pain, nausea, photophobia, and phonophobia. Patient-reported outcomes data is critical as studies rely on patients’ self-reported symptoms using a four-point scale for headache and binary scale (present or absent) for other symptoms. Important considerations in migraine studies include:
Key Risks and Mitigations in Migraine Studies
Risk 1: A high screen-failure rate
There can be a high screen-failure rate in migraine studies because of the extensive and highly specific requirements as to medical history, frequency of migraines, severity of headache pain and distribution of aura and other symptoms.
Risk 2: Inconsistency in completion of e-diary data on headache and other symptoms
While electronic and paper diaries each have advantages, e-diaries are increasingly preferred as they allow for the collection of patient-reported data in closer proximity to reported events. However, use of e-diaries is not intuitive for all patients, and limitations regarding allowable time for data entry can sometimes prevent patients from entering data.
For Assistance With Your Migraine Program
As a CRO committed to improving healthcare outcomes for women, Health Decisions is determined to advance and accelerate clinical development of improved treatments for migraine. The Health Decisions clinical team has experience in central nervous system studies and understands how to address key operational issues and mitigate risks in migraine trials. Please contact us to explore how a partnership with Health Decisions can support the efficient, timely development of your investigational migraine product.
The Leading Full-Service Women’s Health CRO from Pre-IND or -IDE to Regulatory Approval and Beyond
Health Decisions is a full-service CRO specializing in the clinical development of drugs, diagnostics, medical devices and combination drug/devices in all areas of women’s health as well development of diagnostics for all therapeutic areas. Our experience, expertise, site network, and KOL and investigator relationships enable us to address the challenges of developing women’s health products in areas including general gynecology indications, contraception, sexual health, infertility, obstetrics, menopause and osteoporosis and other indications that affect women disproportionately and profoundly, including autoimmune disorders and malefactor infertility. Health Decisions is headquartered in Durham, NC.