For instance, an interesting research question upon which to design a comparative effectiveness research trial would be the following: among adults at risk for an opioid use disorder who are already using mu-opioid agonists to treat chronic non-cancer pain, what are comparative benefits versus harms of continuing such opioids versus switching to partial mu-opioid receptor agonist buprenorphine, either (a) alone or (b) combined with an alpha-2 adrenergic receptor agonist (e.g., clonidine, lofexidine, or guanfacine)? The gene discussed is OPRM1; the disease is cancer.