Transportability from Randomized Trials to Clinical Care: On Initial HIV Treatment with Efavirenz and Suicidal Thoughts or Behaviors.

Efavirenz was associated with increased suicidal thoughts/behaviors in an analysis of randomized trials. However, analyses of observational data have found no evidence of increased hazard. To assess whether population differences explain this divergence we transported the effect of efavirenz from these trials to a specific target population. Using inverse odds weights and multiple imputation, the effect of efavirenz on suicidal thoughts/behaviors in these randomized trials (enrolled 2001-2007) was transported to a trials-eligible cohort of adults in the United States initiating antiretroviral therapy while receiving HIV clinical care at medical centers between 1999-2015. Overall, 8,291 cohort and 3,949 trial participants were eligible. Antidepressant prescription (19% vs. 13%) and injection drug history (16% vs. 10%) were more frequent in the cohort versus trials. Compared to the effect in trials, the estimated hazard ratio for efavirenz on suicidal thoughts/behaviors was attenuated in our target population (trials=2.3, 95%CI: 1.2, 4.4; transported=1.8, 95%CI: 0.90, 4.4), whereas the incidence rate difference was similar (trials=5.1, 95%CI: 1.6, 8.7; transported=5.4, 95%CI: -0.4, 11.4). In our target population, there was over 20% attenuation of the hazard ratio estimate compared to the trials-only estimate. Transporting results from trials to a target population is informative for addressing external validity.