The scope of this project is quite impressive, involving the analysis of more than 30 trials to examine whether there is heterogeneity in relative treatment efficacy by age, sex, socioeconomic status and comorbidity. I thought the proposal did a good job of justifying the focus on multimorbidity. However, the proposal could be strengthened by providing further justification for the focus on age, sex and socioeconomic status. And with respect to the latter, I am not sure how reliably information on educational attainment and income are available in the trial data requested; would also prefer to see more information on how socioeconomic status will be categorized (the description, “collapsing the reported categories into a three-level variable”, is not clear). One other point for consideration – the proposal explains, for purposes of selecting the main outcome measure, that “… within each indication we will select endpoints common to trials for that indication”. However, would it not be better to use the primary outcome measure as specified within each trial? Please clarify.