A Multiple Testing Procedure for Clinical Trials

O'Brien, Peter C.; Fleming, Thomas R.

doi:10.2307/2530245

Cited by 3,311Statistical Methods in Clinical TrialsProbability and Statistical ResearchStatistical Methods and Bayesian Inference

A Multiple Testing Procedure for Clinical Trials

O'Brien, Peter C., Fleming, Thomas R.·1979·Biometrics

DOI 10.2307/2530245

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Abstract

A multiple testing procedure is proposed for comparing two treatments when response to treatment is both dichotomous (i.e., success or failure) and immediate. The proposed test statistic for each test is the usual (Pearson) chi-square statistic based on all data collected to that point. The maximum number (N) of tests and the number (m1 + m2) of observations collected between successive tests is fixed in advance. The overall size of the procedure is shown to be controlled with virtually the same accuracy as the single sample chi-square test based on N(m1 + m2) observations. The power is also found to be virtually the same. However, by affording the opportunity to terminate early when one treatment performs markedly better than the other, the multiple testing procedure may eliminate the ethical dilemmas that often accompany clinical trials.

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Because one interim analysis used a stopping boundary based on an alpha spending function of the O'Brien-Fleming type, a critical P value of 0.048 was required for the primary hypothesis.
“Because one interim analysis used a stopping boundary that was based on an alpha spending function of the O'Brien-Fleming type, 10 a critical P value of 0.048 was required for the primary hypothesis.”
From Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy (2001) · cites this paper as [10]

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Authors: O'Brien, P. C., & Fleming, T. R.
Affiliations: Mayo Clinic (US)
ORCID: Fleming, Thomas R.
Venue: Biometrics
Publisher: JSTOR
Published: 1979-09
Volume: 35
Issue: 3
Pages: 549
ISSN: 0006-341X (ISSN-L)
DOI: 10.2307/2530245
OpenAlex: W2059707463
Cited by: 3,311
References: 0
Citations by year: 2026: 64 · 2025: 91 · 2024: 126 · 2023: 117 · 2022: 107 · 2021: 131 · 2020: 114 · 2019: 108 · 2018: 105 · 2017: 94 · 2016: 100 · 2015: 107 · 2014: 153 · 2013: 98 · 2012: 130
FWCI: 8.11
Type: journal article
Language: en
Open access: closed
Locations: Biometrics (publishedVersion)
PubMed (publishedVersion)
Topics: Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
Physical Sciences › Mathematics › Statistics and Probability › Probability and Statistical Research
Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods and Bayesian Inference
Keywords: multiple comparisons, early stopping, clinical trials, binary outcomes, sequential testing, chi-square test, treatment comparison, type I error control, statistical power
MeSH terms: Clinical Trials as Topic, Humans, Statistics as Topic

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A Multiple Testing Procedure for Clinical Trials

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