Results and endpoints used in acute migraine clinical trials vary significantly. However, developing a core set of patient-centered outcomes and endpoints can improve individual studies and facilitate informed treatment decisions. This is evident from research published in Headache.
In order to provide an overview of the current literature on clinical studies in acute migraine, with the aim of supporting future endpoint selection and outcome assessment and facilitating the development of new therapies, the researchers conducted a systematic literature search that focused on the scope and the Frequency of specific concepts, endpoints and and results.
Acute migraine clinical trial results were grouped into one of four broad categories: pain-related outcomes (including pain relief and freedom, general pain, headache recurrence, medication use, and meaningful relief); symptoms not associated with pain (including the most bothersome symptoms, nausea, vomiting, photophobia, phonophobia, and aura); Disability and / or impairment; and patient reported outcome measures (PROMs, including headache and non-headache specific PROMs).
A total of 1567 publications were identified; 705 were included for final analysis. The publication dates of the articles were between 1972 and 2019, and the mean interrater agreement for descriptive variables – including age, gender, migraine characteristics, and study design – had a kappa estimate of 0.86.
To focus on more recent pharmacological and device-related literature on acute migraine, the researchers identified a subset of studies (n = 451) to evaluate.
Within this subgroup, the mean total sample size was 243 participants per study. The mean age was 39.1 (± 3.9) years, 82.9% of the participants were women and 85.1% were white. Most of these publications (90.1%) rated a general migraine population rather than a specific subgroup, such as those with menstrual, episodic, or chronic migraines.
The researchers found that 95.3% of the publications rated 1 or more pain-related outcomes, while 67.2% rated 1 or more associated symptoms or the most bothersome symptom. Just over 41% of the studies assessed disability and impairment outcomes, and 35.3% examined 1 or more PROMs.
The most commonly observed pain-related outcomes were pain relief, pain relief, general pain, headache recurrence, and rescue medication use (72.1%, 64.9%, 34%, 44.8% and 61.6%, respectively). A majority of the publications examining pain relief used an ordinal response scale (94.2%), while others used a continuous response scale such as the visual analogue scale (VAS) or the numerical rating scale (NRS; 4.5% overall; 71.4%) VAS) used. The endpoints varied widely and ranged from 10 minutes to 24 hours after treatment, with 2 hours being the most commonly used time point.
The majority of the studies that focused on freedom from pain used an order scale, while the majority of the studies that reported general pain used a 4-category response scale. In studies assessing headache recurrence, a 24 hour cutoff and the presence of at least one pain-related outcome was used, and in studies of rescue medication, at least one pain-related outcome was used as the primary endpoint.
In studies of disabilities and impairments, an ordinal response scale with 4 response categories was mainly used. The most common type of endpoint was fixed time point analysis. 44.6% of the publications examined assessed changes from the baseline, 2.7% assessed both fixed points in time and changes from the baseline, and 1.1% assessed other endpoints.
PROMs were combined across all studies, with 35.3% of publications rating 1 or more PROMs. Most of these studies (n = 159) rated 1 or more non-migraine or headache-specific patient-reported results.
Headache-related PROMs have rarely been used in acute migraine studies. Only 28 publications examined 1 or more migraine or headache-related outcomes reported by patients. Of these, more than half (60.7%) used the 24-hour questionnaire on migraine-specific quality of life and 17.9% used the revised questionnaire on the perception of migraine in patients. The most common non-headache-specific PROMs related to satisfaction, efficacy, and preference of treatment as measured by 4 or 7-category scales, 4 or 5-category scales, and a binary or 3-category scale. respectively.
Limitations of the study include the potential for publication bias and the inability, due to the size of the project, to investigate several relevant methodological and clinical topics.
“Current studies on the acute treatment of migraines show great variability in outcomes and in the way the results are used to define endpoints,” the researchers concluded. “Standardizing outcomes and endpoints … will facilitate comparisons between studies and facilitate communication with patients about the benefits of treatment alternatives.”
“Future work should rigorously evaluate existing PROMs against given criteria and examine other areas of criteria such as physical and cognitive function,” they added. “Based on ongoing quality work and feedback from the [US Food and Drug Administration]Developing measures to measure cognitive function can also be informative. “
Disclosure: Several authors of the study have stated that they are part of the pharmaceutical industry. For a full list of the authors’ information, see the original reference.
Houts CR, McGinley JS, Nishida TK et al. Systematic review of results and endpoints in clinical trials on acute migraines. A headache. 2021; 61 (2): 263-26; 275. doi: 10.1111 / head.14067
This article originally appeared on Clinical Pain Advisor