Future Directions in Clinical Trials and Intention-To-Treat Analysis: Fulfilling Admirable Intentions Through the Right Questions.

Abstract

We call for clinical trials researchers to carefully consider questions about use of intention-to-treat (ITT) analysis and per protocol analysis. We discuss how questions about efficacy and mechanisms of efficacy are appropriately answered through the application of per protocol analysis. ITT analysis is well-suited and appropriate for addressing questions related to treatment effectiveness, typically adherence to the treatment with respect to an outcome. While guided by admirable intentions, ITT analysis is often not guided by the right questions, leading to ITT misapplication. We address additional misconceptions that often lead to ITT misapplication, including issues relating to treatment noncompletion and violation of random assignment. We further highlight future directions and implications, particularly that future clinical child and adolescent research trial designs will be increasingly characterized by hybrid trials that combine elements of efficacy, effectiveness, and implementation research, where ITT and per protocol analysis will be appropriately applied to answer the right questions.