Designing for Intent-to-Treat *

Abstract

The principle of analysis by intent-to-treat (ITT) serves as the standard basis for design decisions as well as choice of analysis in clinical trials. ITT correctly contrasts the pragmatic consequences of the treatments offered in a study, as long as the study protocol accurately reflects the realities of clinical practice. We identify the study of ongoing treatment for chronic disease as the clinical context that most strains the ITT principle. In a placebo-controlled trial of a new drug in patients with a condition for which there are standard treatments, the ethical requirement to “rescue”patients who do poorly, and who might be taking placebo, causes “drop-in” from placebo to a standard treatment. We propose that this problem reflects a lack of fit between the standard fixed design and clinical reality, rather than a weakness of ITT. We propose that the adaptive nature of clinical decision making should be captured in the design of trials, and we show how the ITT principle can be used in such designs.