Early stopping of randomized clinical trials for overt efficacy is problematic

Dirk Bassler, Victor M. Montori, Matthias Briel, Paul Glasziou, Gordon Guyatt

Research output: Contribution to journalReview articleResearchpeer-review

81 Citations (Scopus)

Abstract

Objective: To illustrate controversial issues associated with stopping randomized controlled trials (RCTs) early for apparent benefit.

Study Design and Setting: The article presents our review of prior relevant work and our research group's reflections on early stopping.

Results: Compelling evidence suggests that trials stopped early for benefit systematically overestimate treatment effects, sometimes by a large amount. Unresolved controversies in trials stopped early for benefit include ethical and statistical problems in the interpretation of results.

Conclusions: The best strategy to minimize the problems associated with early stopping of RCTs for benefit is not to stop early. As an alternative, we suggest a threefold approach: a low P-value as the threshold for stopping at the time of interim analyses, not to look before a sufficiently large number of events has accrued and continuation of enrollment and follow-up for a further period. (C) 2008 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)241-246
Number of pages6
JournalJournal of Clinical Epidemiology
Volume61
Issue number3
DOIs
Publication statusPublished - Mar 2008
Externally publishedYes

Cite this

Bassler, Dirk ; Montori, Victor M. ; Briel, Matthias ; Glasziou, Paul ; Guyatt, Gordon. / Early stopping of randomized clinical trials for overt efficacy is problematic. In: Journal of Clinical Epidemiology. 2008 ; Vol. 61, No. 3. pp. 241-246.
@article{d468f3e0e776416c8aea2ffcc6440785,
title = "Early stopping of randomized clinical trials for overt efficacy is problematic",
abstract = "Objective: To illustrate controversial issues associated with stopping randomized controlled trials (RCTs) early for apparent benefit.Study Design and Setting: The article presents our review of prior relevant work and our research group's reflections on early stopping.Results: Compelling evidence suggests that trials stopped early for benefit systematically overestimate treatment effects, sometimes by a large amount. Unresolved controversies in trials stopped early for benefit include ethical and statistical problems in the interpretation of results.Conclusions: The best strategy to minimize the problems associated with early stopping of RCTs for benefit is not to stop early. As an alternative, we suggest a threefold approach: a low P-value as the threshold for stopping at the time of interim analyses, not to look before a sufficiently large number of events has accrued and continuation of enrollment and follow-up for a further period. (C) 2008 Elsevier Inc. All rights reserved.",
author = "Dirk Bassler and Montori, {Victor M.} and Matthias Briel and Paul Glasziou and Gordon Guyatt",
year = "2008",
month = "3",
doi = "10.1016/j.jclinepi.2007.07.016",
language = "English",
volume = "61",
pages = "241--246",
journal = "Journal of Chronic Diseases",
issn = "0895-4356",
publisher = "Elsevier",
number = "3",

}

Early stopping of randomized clinical trials for overt efficacy is problematic. / Bassler, Dirk; Montori, Victor M.; Briel, Matthias; Glasziou, Paul; Guyatt, Gordon.

In: Journal of Clinical Epidemiology, Vol. 61, No. 3, 03.2008, p. 241-246.

Research output: Contribution to journalReview articleResearchpeer-review

TY - JOUR

T1 - Early stopping of randomized clinical trials for overt efficacy is problematic

AU - Bassler, Dirk

AU - Montori, Victor M.

AU - Briel, Matthias

AU - Glasziou, Paul

AU - Guyatt, Gordon

PY - 2008/3

Y1 - 2008/3

N2 - Objective: To illustrate controversial issues associated with stopping randomized controlled trials (RCTs) early for apparent benefit.Study Design and Setting: The article presents our review of prior relevant work and our research group's reflections on early stopping.Results: Compelling evidence suggests that trials stopped early for benefit systematically overestimate treatment effects, sometimes by a large amount. Unresolved controversies in trials stopped early for benefit include ethical and statistical problems in the interpretation of results.Conclusions: The best strategy to minimize the problems associated with early stopping of RCTs for benefit is not to stop early. As an alternative, we suggest a threefold approach: a low P-value as the threshold for stopping at the time of interim analyses, not to look before a sufficiently large number of events has accrued and continuation of enrollment and follow-up for a further period. (C) 2008 Elsevier Inc. All rights reserved.

AB - Objective: To illustrate controversial issues associated with stopping randomized controlled trials (RCTs) early for apparent benefit.Study Design and Setting: The article presents our review of prior relevant work and our research group's reflections on early stopping.Results: Compelling evidence suggests that trials stopped early for benefit systematically overestimate treatment effects, sometimes by a large amount. Unresolved controversies in trials stopped early for benefit include ethical and statistical problems in the interpretation of results.Conclusions: The best strategy to minimize the problems associated with early stopping of RCTs for benefit is not to stop early. As an alternative, we suggest a threefold approach: a low P-value as the threshold for stopping at the time of interim analyses, not to look before a sufficiently large number of events has accrued and continuation of enrollment and follow-up for a further period. (C) 2008 Elsevier Inc. All rights reserved.

U2 - 10.1016/j.jclinepi.2007.07.016

DO - 10.1016/j.jclinepi.2007.07.016

M3 - Review article

VL - 61

SP - 241

EP - 246

JO - Journal of Chronic Diseases

JF - Journal of Chronic Diseases

SN - 0895-4356

IS - 3

ER -