To evaluate the impact of migraine trial designs on daily diary compliance in acute and preventive migraine trials.

Given the differences in treatment goals for acute versus preventive migraine drugs, different electronic patient-reported outcome (ePRO) diary designs are used to capture migraine data. Daily diary compliance is critical for data quality, and there is broad use of episodic diary designs, which ask participants to report each migraine in real time, and daily diary designs that ask participants once per day to report migraine occurrence. Importantly, different designs may impact compliance and ultimately data quality and trial success.

ePRO metadata from 17 trials with a mix of episodic and/or daily diaries (n=586,725) included 6 acute migraine trials and 11 preventive migraine trials.  Compliance was calculated for daily diaries only (n=501,112) based on whether there was a diary completed as expected that day. 

Of the 6 acute trials, one trial was a “daily only” design with 86.0% compliance, and five trials were “daily + episodic” designs with 66.9% compliance. In content review, the “daily only” diary did not collect migraine occurrence data and was excluded from further analyses.

Of the 11 preventive trials, compliance in “daily only” trials (n=5) was 89.1% and in “daily + episodic” trials (n=6) was 89.8%.  Adult-only preventive trials had higher compliance with “daily only” designs (92.2%) versus “daily + episodic” designs (90.0%) (p<.001). Similarly, in preventive trials of child/adolescent participants with caregiver roles for data entry, there was higher compliance in “daily only” trials (75.9%) versus “daily + episodic” trials (52.2%) (p<.001).

Daily diary compliance in acute migraine trials is lower than in preventive trials and deserves further investigation.  Trials with “daily + episodic” designs had lower compliance for daily diaries, which may reflect the increased participant burden associated with the added episodic diary on migraine days.