N of 1 randomized trials for investigating new drugs

doi:10.1016/0197-2456(90)90003-K

Controlled Clinical Trials

Volume 11, Issue 2, April 1990, Pages 88-100

https://doi.org/10.1016/0197-2456(90)90003-K Get rights and content

Abstract

Presently, in the process of new drug development, large sample parallel group randomized trials are often begun without the detailed knowledge of optimal dose, most responsive patient group, and optimal outcomes which would be desirable. We propose that randomized trials in individual subjects (N of 1 RCTs) could be used to elucidate these issues at an early stage of drug development. In appropriate conditions N of 1 RCTs can be used to define the rapidity with which a drug begins and ceases its clinical action, the likely range of the optimal drug dose, and the optimal outcomes on which subsequent trials should focus. N of 1 RCTs can also generate initial estimates of the proportion of patients who respond to a new agent and for determining sample size, inclusion criteria, and dosage regimen(s) for subsequent parallel group trials. We provide an example of 14N of 1 RCTs of amitryptyline in fibrositis that illustrate the ways in which N of 1 RCTs can elucidate these issues. The multiple uses of N of 1 RCTs suggest that the method has immense potential for use in the early phases of drug development programs.

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N of 1 randomized trials for investigating new drugs

Abstract

Prog Behav Mod

Single-Case Research Designs: Methods for Clinical and Applied Settings

Determining optimal therapy: randomized trials in individual patients

N Engl J Med