Methods and Applications of Statistics in Clinical Trials, Volume 1: Concepts, Principles, Trials, and Designs

Chapter 48

N-of-1 Randomized Trials

Andrew L. Avins and John Neuhaus

48.1 Introduction

Comparative clinical trials in individual patients, commonly known as “N-of-1” trials, have been used for many years in the field of psychology and have found increasing applications for biomedical problems. Such trials can be structured to provide information generalizable to large groups of patients, but the primary application of N-of-1 trials is to help individual patients make more evidence-based decisions about specific aspects of their medical care [1]. In clinical practice, patients frequently undergo “therapeutic trials” in which a healthcare provider recommends a course of action that the patient tries and decides whether to continue, modify, or terminate. An N-of-1 study has the same goal as a therapeutic trial but brings a more structured and less biased approach to evaluating a therapeutic response [1–3]. Such trials are also known as “single-patient trials,” “individualized medication effectiveness trials,” and “individual patient trials” [4–6].

An N-of-1 trial is generally structured as a randomized, double-blind, controlled, multiple-period crossover trial in a single patient, often of a pharmacologic agent [1,3,6,7]. In these studies, a patient is assigned to different periods on the active and the comparator treatments, with outcome measurements obtained during each of these periods. At the end of the trial, the patient’s responses during each of the treatment conditions are ...