Comparative Effectiveness Clinical Trials in Psychiatry: Superiority, Noninferiority, and the Role of Active Comparators
J Clin Psychiatry 2011;72(10):1344-1349
© Copyright 2016 Physicians Postgraduate Press, Inc.
Purchase This PDF for $40.00
If you are not a paid subscriber, you may purchase the PDF.
(You'll need the free Adobe Acrobat Reader.)
Receive immediate full-text access to JCP. You can subscribe to JCP online-only ($86) or print + online ($156 individual).
With your subscription, receive a free PDF collection of the NCDEU Festschrift articles. Hurry! This offer ends December 31, 2011.
If you are a paid subscriber to JCP and do not yet have a username and password, activate your subscription now.
As a paid subscriber who has activated your subscription, you have access to the HTML and PDF versions of this item.
Click here to login.
Did you forget your password?
Still can't log in? Contact the Circulation Department at 1-800-489-1001 x4 or send email
The Agency for Healthcare Research and Quality, part of the US Department of Health and Human Services, has issued several Requests for Applications to conduct comparative effectiveness research (CER). Many of the applications will involve randomized controlled clinical trials that include an active comparator. The inclusion of an active comparator has implications for clinical trial design.
Despite a common misperception, a clinical trial result of no significant difference between active treatment groups does not imply equivalence or noninferiority. A noninferiority trial, on the other hand, can directly test whether one active treatment group is noninferior to the other. For example, noninferiority of an inexpensive generic could be tested in comparison with a novel, more costly intervention. Although seldom used in psychiatry, noninferiority clinical trials could play a fundamental role in CER. Features of noninferiority and the nearly ubiquitous superiority designs are contrasted. The noninferiority margin is defined and its application and interpretation are discussed.
Evidence of noninferiority can only come from well-designed and conducted noninferiority CER. Sample sizes needed in noninferiority trials and in superiority trials that include an active comparator are substantially larger than those needed in trials that can utilize a placebo control in their scientific design. As a result, trials with active comparators are more costly, require longer recruitment duration, and expose more participants to the risks of an experiment than do trials in which the only comparator is placebo.
J Clin Psychiatry
Submitted: March 3, 2010; accepted May 10, 2010.
Online ahead of print: February 8, 2011 (doi:10.4088/JCP.10m06089whi).
Corresponding author: Andrew C. Leon, PhD, Weill Cornell Medical College, Departments of Psychiatry and Public Health, Box 140, 525 East 68th St, New York, NY 10065 (email@example.com).