Using the Bayesian credible subgroups method to identify populations benefiting from treatment: An application to the Look AHEAD trial

Traditionally, subgroup analyses are used to assess whether patient characteristics moderate treatment effectiveness with general disregard for issues of multiplicity. Using data from The Action for Health in Diabetes (Look AHEAD) trial in the United States, we aim to identify a subgroup where all of its types of members experience a treatment benefit defined as reducing the likelihood of a major cardiovascular event under an intensive lifestyle and weight-loss intervention. We apply the credible subgroups method to a Bayesian logistic model with a conservative prior that is sceptical of large treatment effect heterogeneity. The covariate profiles for which there is sufficient evidence of treatment benefit are, coarsely, middle-aged women, in poor subjective general health and with moderately to poorly controlled diabetes. There is at least 80% posterior probability that the conditional average treatment effect is positive for all covariate profiles fitting this description, which account for 0.5% of trial participants. Conversely, the covariate profiles that are likely to be associated with no benefit are middle aged and older men in excellent subjective general health, with well-controlled diabetes. These profiles apply to less than 2% of trial participants. More information is required to determine treatment benefit or no benefit for the remainder of the trial population

Additional file 1: Table S1. of Efficacy and safety of palbociclib in combination with letrozole as first-line treatment of ER-positive, HER2-negative, advanced breast cancer: expanded analyses of subgroups from the randomized pivotal trial PALOMA-1/TRIO-18

Palbociclib dose modification scheme used in the PALOMA-1/TRIO-18 trial for managing neutropenia. Table S2. Baseline characteristics of the subgroup with visceral metastases (intention-to-treat population). Table S3. Most common all-cause adverse events that occurred in at least 10 % of patients <65 years of age in the palbociclib + letrozole arm of the safety population. Table S4. Most common all-cause adverse events that occurred in at least 10 % of patients ≥65 years of age in the palbociclib + letrozole arm of the safety population. Table S5. Most common all-cause adverse events that occurred in at least 10 % of patients with ductal carcinoma in the palbociclib + letrozole arm of the safety population. Table S6. Most common all-cause adverse events that occurred in at least 10 % of patients with lobular carcinoma in the palbociclib + letrozole arm of the safety population. Table S7. Most common all-cause adverse events that occurred in at least 10 % of patients with no prior neo-adjuvant/adjuvant systemic treatment in the palbociclib + letrozole arm of the safety population. Table S8. Most common all-cause adverse events that occurred in at least 10 % of patients with prior neo-adjuvant/adjuvant systemic treatment in the palbociclib + letrozole arm of the safety population. Table S9. Most common all-cause adverse events that occurred in at least 10 % of patients with bone-only metastases at baseline in the palbociclib + letrozole arm of the safety population. Table S10. Most common all-cause adverse events that occurred in at least 10 % of patients with visceral metastases in the palbociclib + letrozole arm of the safety population. Table S11. Most common all-cause adverse events that occurred in at least 10 % of patients with other metastases (bone with other non-visceral sites or other disease sites alone) in the palbociclib + letrozole arm of the safety population. (DOCX 74 kb