The n-of-1 clinical trial: the ultimate strategy for individualizing medicine?

Abstract

N-of-1 or single subject clinical trials consider an individual patient as the sole unit of observation in a study investigating the efficacy or side-effect profiles of different interventions. The ultimate goal of an n-of-1 trial is to determine the optimal or best intervention for an individual patient using objective data-driven criteria. Such trials can leverage study design and statistical techniques associated with standard population-based clinical trials, including randomization, washout and crossover periods, as well as placebo controls. Despite their obvious appeal and wide use in educational settings, n-of-1 trials have been used sparingly in medical and general clinical settings. We briefly review the history, motivation and design of n-of-1 trials and emphasize the great utility of modern wireless medical monitoring devices in their execution. We ultimately argue that n-of-1 trials demand serious attention among the health research and clinical care communities given the contemporary focus on individualized medicine.

Figure 1. Hypothetical outcomes associated with two individual n-of-1 trials investigating the efficacy of two different antihypertensive medications

The wavy dark and light lines reflect the SBP levels for individuals 1 and 2, respectively, during the trial. The design included a baseline period followed by four alternating periods in which two drugs, A and B, were administered with a washout period between drug administrations. Note that individual 1 had better blood pressure control while on drug A, as indicated by the horizontal lines denoting ‘drug A’ and ‘drug B’, which reflect the average blood pressure achieved while on the drugs. Individual 2 had better blood pressure control on drug B. SBP: Systolic blood pressure.