Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Jan 7;82(1):77-9.
doi: 10.1212/01.wnl.0000438226.10353.1c. Epub 2013 Dec 4.

The questionable use of unequal allocation in confirmatory trials

Spencer Phillips Hey  1 , Jonathan Kimmelman
Affiliations
Review

The questionable use of unequal allocation in confirmatory trials

Spencer Phillips Hey et al. Neurology. .

Abstract

Randomization is the standard means for addressing known and unknown confounders within the patient population in clinical trials. Although random assignment to treatment arms on a 1:1 basis has long been the norm, many 2-armed confirmatory trials now use unequal allocation schemes where the number of patients receiving investigational interventions exceeds those in the comparator arm. In what follows, we offer 3 arguments for why investigators, institutional review boards, and data and safety monitoring boards should exercise caution when planning or reviewing 2-armed confirmatory trials involving unequal allocation ratios. We close by laying out some of the conditions where uneven allocation can be justified ethically.

PubMed Disclaimer

References

    1. Broderick JP, Palesch YY, Demchuck AM. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med 2013;368:893–903 - PMC - PubMed
    1. Hawker K, O'Connor P, Freedman MS, et al. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol 2009;66:460–471 - PubMed
    1. Wolinsky JS, Narayana PA, O'Connor P, et al. Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol 2007;61:14–24 - PubMed
    1. LeWitt PA, Guttman M, Tetrud JW, et al. Adenosine A2A receptor antagonist istradefylline (KW-6002) reduces “off” time in Parkinson's disease: a double-blind, randomized, multicenter clinical trial. Ann Neurol 2008;63:295–302 - PubMed
    1. Cudkowicz ME, Shefner JM, Schoenfeld DA, et al. Trial of celecoxib in amyotrophic lateral sclerosis. Ann Neurol 2006;60:22–31 - PubMed

Publication types

MeSH terms

LinkOut - more resources