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 .