Medical side effects of treatment are listed as a potential key outcome. Does this mean side effects of the comparators being evaluated or does it mean side effects of opioid therapy?

This depends on the nature of the study’s clinical interventions. For example, if the study looks at a direct treatment approach that may supplement or replace opioids and there are possible harms associated with those alternative non-opioid treatments, then PCORI would be interested in the harms associated both with those non-opioid interventions as well as the opioid component of the study.