Understanding the Intention-to-treat Principle in Randomized Controlled Trials

Clinicians, institutions, and policy makers use results from randomized controlled trials to make decisions regarding therapeutic interventions for their patients and populations. Knowing the effect the intervention has on patients in clinical trials is critical for making both individual patient as well as population-based decisions. However, patients in clinical trials do not always adhere to the protocol. Excluding patients from the analysis who violated the research protocol (did not get their intended treatment) can have significant implications that impact the results and analysis of a study. Intention-to-treat analysis is a method for analyzing results in a prospective randomized study where all participants who are randomized are included in the statistical analysis and analyzed according to the group they were originally assigned, regardless of what treatment (if any) they received. This method allows the investigator (or consumer of the medical literature) to draw accurate (unbiased) conclusions regarding the effectiveness of an intervention. This method preserves the benefits of randomization, which cannot be assumed when using other methods of analysis. The risk of bias is increased whenever treatment groups are not analyzed according to the group to which they were originally assigned. If an intervention is truly effective (truth), an intention-to-treat analysis will provide an unbiased estimate of the efficacy of the intervention at the level of adherence in the study. This article will review the “intention-to-treat” principle and its converse, “per-protocol” analysis, and illustrate how using the wrong method of analysis can lead to a significantly biased assessment of the effectiveness of an intervention.