● Evaluation of Results
o Attack report form (diary): participants should use an easy-to-use electronic diary that records predefined endpoints. Investigator-initiated trials can use paper diaries.
o Primary endpoint: The percentage of participants who are pain-free 2 hours after treatment should be the primary measure of efficacy.
o Co-primary endpoints: Absence of the most bothersome migraine-associated symptom 2 hours after treatment can be used as a co-primary endpoint.
o Secondary endpoints
▪ Relapse: Relapse is defined as the occurrence of headache of any severity within 48 hours after administering an investigational treatment in participants who were pain-free 2 hours after treatment administration. If the treatment has a short half-life, a period of 24 hours may be used.
▪ Sustained pain freedom: Sustained pain freedom is defined as the percentage of participants who are pain-free at 2 hours and do not use rescue medication or relapse within 24 or 48 hours of initial treatment. This is a recommended secondary endpoint and is a primary endpoint for early intervention trials.
▪ Total freedom from migraine: Defined as the absence of pain, nausea, vomiting, photophobia, and phonophobia at the primary efficacy time point.
▪ Headache intensity: Participants should record the intensity of headache immediately before using the investigative treatment and at each specific time point. Headache intensity should be measured on a 4-point scale, a 100-mm Visual Analogue Scale (VAS), or an 11-point numerical rating scale (NRS).
▪ Headache relief: Defined as the decrease in headache pain from moderate or severe at baseline to mild or none at 2 hours after treatment.
▪ Time to meaningful relief: Time to meaningful relief can be used as a secondary efficacy measure.
▪ Time to pain freedom: A survival analysis of pain freedom can evaluate speed of onset of therapeutic effect. Time to pain freedom is a recommended secondary efficacy outcome measure.
▪ Duration of attacks: Duration of attacks should not be used as an efficacy measure.
▪ Rescue medication: The percentage of participants taking rescue medication 2 hours after intake of test treatment can be used as a secondary efficacy measure.
▪ Global evaluation: A simple Likert-type verbal scale can be used to assess participants’ global impression of acute treatment effect. This can be used as a secondary outcome measure.
▪ Global impact: Functional disability and health-related quality of life (HRQoL) are important secondary global measures.
▪ Associated symptoms:
● Nausea and vomiting: The presence or absence of nausea should be recorded at the time of treatment administration and at the primary efficacy endpoint.
● Photophobia: The presence or absence of photophobia should be recorded at the time of treatment administration and at the primary efficacy endpoint.
● Phonophobia: The presence or absence of phonophobia should be recorded at the time of treatment administration and at the primary efficacy endpoint.
▪ Time between onset of headache and intake of treatment: Both should be recorded.
▪ Treatment preference: Participants’ treatment preference is a useful exploratory global assessment method best suited for crossover trials.
▪ Blinding assessment: Determining how well a trial is blinded is important.
▪ Treatment of relapse: The efficacy of treatment of relapse should be measured by the percentage of participants with pain freedom 2 hours after administering medication for headache relapse.
▪ Adverse events: Participants should record adverse events that occur during the trial in the trial diary. These should be supplemented with responses to open questions when appropriate. Participants should record event severity, event seriousness, time of onset, and time of resolution.
● Hierarchy of endpoints: Trials assessing the efficacy, tolerability, and safety of interventions for the acute treatment of migraines should use the following hierarchy of endpoints:
● Pain-free after 2 hours
● Freedom from the most bothersome symptom at 2 hours
● Supporting the primary endpoints
● Headache relief at 2 hours
● Sustained pain-free to 24 hours
● Total freedom from migraine
● Freedom from nausea and vomiting, photophobia, or phonophobia
● Time to pain freedom
All other endpoints (tertiary or exploratory endpoints)
● Intensity of headache
● Headache relapse
● Time to meaningful relief
● Time to pain freedom
● Rescue medication
● Global evaluation
● Global impact (disability and HRQoL)
● Time between headache onset and treatment intake
● Preference of treatment
● Blinding assessment
● Treatment of recurrence
“It is therefore hoped that this edition of the Guidelines continues the tradition of its predecessors by providing investigators with a contemporary, standardized, and evidence-based approach to the conduct and reporting of clinical trials for the acute treatment of migraine attacks,” the researchers wrote.
Diener H, Tassorelli C, Dodick DW, et al. Guidelines of the International Headache Society for controlled trials of acute treatment of migraine attacks in adults: fourth edition [published online February 26, 2019]. Cephalagia. doi:10.1177/0333102419828967
This article originally appeared on Neurology Advisor