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 Sep 17:15:364.
doi: 10.1186/1745-6215-15-364.

Correcting for multiple-testing in multi-arm trials: is it necessary and is it done?

James M S Wason  1 , Lynne Stecher, Adrian P Mander
Affiliations
Review

Correcting for multiple-testing in multi-arm trials: is it necessary and is it done?

James M S Wason et al. Trials. .

Abstract

Background: Multi-arm trials enable the evaluation of multiple treatments within a single trial. They provide a way of substantially increasing the efficiency of the clinical development process. However, since multi-arm trials test multiple hypotheses, some regulators require that a statistical correction be made to control the chance of making a type-1 error (false-positive). Several conflicting viewpoints are expressed in the literature regarding the circumstances in which a multiple-testing correction should be used. In this article we discuss these conflicting viewpoints and review the frequency with which correction methods are currently used in practice.

Methods: We identified all multi-arm clinical trials published in 2012 by four major medical journals. Summary data on several aspects of the trial design were extracted, including whether the trial was exploratory or confirmatory, whether a multiple-testing correction was applied and, if one was used, what type it was.

Results: We found that almost half (49%) of published multi-arm trials report using a multiple-testing correction. The percentage that corrected was higher for trials in which the experimental arms included multiple doses or regimens of the same treatments (67%). The percentage that corrected was higher in exploratory than confirmatory trials, although this is explained by a greater proportion of exploratory trials testing multiple doses and regimens of the same treatment.

Conclusions: A sizeable proportion of published multi-arm trials do not correct for multiple-testing. Clearer guidance about whether multiple-testing correction is needed for multi-arm trials that test separate treatments against a common control group is required.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Illustration of a multi-arm trial and the benefit of a shared control group. Separate controlled trials will require a greater number of control patients compared to a multi-arm trial with shared control group.
Figure 2
Figure 2
Flowchart representing consensus from literature on under what circumstances multiple-testing adjustment is necessary.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Reed JC. Toward a New Era in cancer treatment: message from the new editor-in-chief. Mol Cancer Ther. 2012;11:1621–1622. doi: 10.1158/1535-7163.MCT-12-0703. - DOI
    1. Parmar MK, Carpenter J, Sydes MR. More multiarm randomised trials of superiority are needed. Lancet. 2014;384:283–284. doi: 10.1016/S0140-6736(14)61122-3. - DOI - PubMed
    1. Stucke K, Kieser M. A general approach for sample size calculation for the three-arm ‘gold standard’ non-inferiority design. Statist Med. 2012;31:3579–3596. doi: 10.1002/sim.5461. - DOI - PubMed
    1. Baron G, Perrodeau E, Boutron I, Ravaud P. Reporting of analyses from randomized controlled trials with multiple arms: a systematic review. BMC Med. 2013;11:84. doi: 10.1186/1741-7015-11-84. - DOI - PMC - PubMed
    1. Dudoit S, Van Der Laan MJ. Multiple Testing Procedures with Applications to Genomics. 494. New York, NY: Springer; 2008.

Publication types

MeSH terms

LinkOut - more resources