Intention-to-treat principle

Fig. 1: Per protocol analysis introduces bias into the estimate of intervention efficacy. For our analysis of this hypothetical randomized controlled trial of patients with cerebrovascular disease, it is assumed that the surgery is ineffective in preventing the adverse outcome of interest (stroke). Per protocol analysis of the treatment group (surgery + acetylsalicylic acid [ASA]) includes only those patients who adhered to the protocol (in this case, those who received surgery); “nonadherent” patients (those who died before having the opportunity to undergo surgery) are excluded. With this analysis, the event rate is 0.11 in the surgery + ASA arm and 0.20 in the control arm, which represents a relative risk reduction (RRR) of 0.45. The intention-to-treat analysis, which counts all events in all randomized patients, shows equal event rates (0.20) in both arms and no risk reduction. This analysis suggests the underlying truth, a treatment effect of zero. R = randomization.