The survival difference between adherers and non-adherers to placebo in the Coronary Drug Project has been used to support the thesis that adherence adjustment in randomized trials is not generally possible and, therefore, that only intention-to-treat analyses should be trusted. We previously demonstrated that adherence adjustment can be validly conducted in the Coronary Drug Project using a simplistic approach. Here, we re-analyze the data using an approach that takes full advantage of recent methodological developments.
We used inverse-probability weighted hazards models to estimate the 5-year survival and mortality risk when individuals in the placebo arm of the Coronary Drug Project adhere to at least 80% of the drug continuously or never during the 5-year follow-up period.
Adjustment for post-randomization covariates resulted in 5-year mortality risk difference estimates ranging from − 0.7 (95% confidence intervals (CI), − 12.2, 10.7) to 4.5 (95% CI, − 6.3, 15.3) percentage points.
Our analysis confirms that appropriate adjustment for post-randomization predictors of adherence largely removes the association between adherence to placebo and mortality originally described in this trial.