Statistical reporting of clinical trials with individual changes from allocated treatment.

We consider clinical trials in which information is available about subjects' treatment changes after randomization. To understand whether any difference between randomized groups in the intention-to-treat analysis can be explained by such treatment changes, we need analysis strategies which take account of treatment actually received. Selection bias is then a potentially serious problem. We relate risk in a time-dependent proportional hazards model to current treatment, with treatment combinations coded in two alternative ways. To reduce selection bias, treatment history (number of treatments dropped) and baseline covariates can be added to the model. Including current risk markers would also reduce selection bias but makes interpretation difficult. The methods are illustrated using data from the British Medical Research Council (MRC) elderly hypertension trial, with time to cardiovascular death as an outcome. Results for the comparison of diuretic and beta-blocker treatment are similar in all analyses, suggesting that selection bias is small and adding support to the hypothesis that the observed treatment differences are due to the randomized treatments themselves.

RCT Entities:   Population Interventions Outcomes