Limitations
There were several limitations associated with our analysis, based on both the available data and the methodology used for the meta-regression. The meta-regression was used to account for heterogeneity in trials due to differences in patient populations, but data on certain populations were limited. Differences in inclusion/exclusion criteria could also include unmeasured confounders for the placebo effect (see Table S4 ). The publication of subgroup analyses of patients who had failed ≥2 therapies also complicated the analysis, and we elected to include these alongside their ‘parent’ phase 3 data in the meta-regression that included type of migraine (episodic or chronic), percentage of patients with ≥2 prior treatment failures in each trial, and the route of administration for treatment (i.e., SC or IV) as covariates. Table S3 attempts to address this limitation but having access to the subgroup data for 0 or 1 treatment failures would have been preferable. Finally, we only included anti-CGRP monoclonal antibodies in this analysis, and it remains to be determined what impact oral, intranasal, or intramuscular routes of administration might have on placebo responses to other pharmacologic treatments, such as gepants or onabotulinumtoxinA .