Methods and Applications of Statistics in Clinical Trials, Volume 2: Planning, Analysis, and Inferential Methods

Chapter 16

Intention-to-Treat Analysis

John M. Lachin

16.1 Introduction

A clinical trial of a new therapy (agent, intervention, diagnostic procedure, etc.) has many objectives. One objective is to evaluate whether the therapy has the intended biological or physiological effect, which is often termed pharmacological efficacy in relation to a new pharmaceutical agent. Another is to evaluate the pragmatic use of the therapy in clinical practice, which is often termed simply effectiveness. The intention-to-treat principle refers to a strategy for the design, conduct, and analysis of a clinical trial aimed at assessing the latter, which is the pragmatic effectiveness of a therapy in clinical practice.

An analysis for the assessment of pharmacological efficacy generally excludes subjects who either did not comply with the assigned therapy or could not tolerate it because of adverse effects. Such analyses are often termed per-protocol, efficacy subset, or evaluable subset analyses and involve post hoc subset selection or post hoc exclusions of randomized subjects. Conversely, for the assessment of effectiveness in an intent-to-treat analysis, follow-up data for all randomized subjects should be obtained and included in the analysis. This design is the essence of the intention-to-treat principle.

16.2 Missing Information

16.2.1 Background

The intention-to-treat principle evolved from the evaluation by regulatory officials at the Food and Drug Administration (FDA) [1], as well as scientists ...