Our study has some strengths, including its use of an active comparator, which is associated with partial control for unobserved confounding. We further adjusted for observed confounding using propensity score weighting. Taken together, these methods adjust for many health behaviors and comorbidities that may be associated with increased benzodiazepine-associated mortality. This is particularly useful given concern that benzodiazepine-opioid cotreatment and all-cause mortality may share common antecedents or outcomes, potentially associated with confounding by indication and collider bias.17 Another study strength is the generalizability of NHANES data, which contain demographic groups that are frequently not included in Veterans Affairs data, as well as older individuals with a higher burden of medical and psychiatric comorbidities not included in insurance claims data.16,20 Finally, our analysis spans a longer follow-up period, with a median of nearly 7 years, than similar analyses,16,20 which may explain the elevated death rates observed in our study (26.5 per 1000 person-years) for benzodiazepines without opioids in comparison with the mortality rates found by Patorno et al37 (12 per 1000 person-years), whose mean follow-up period was 145 to 160 days.
