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Cited by 34Statistical Methods in Clinical TrialsStatistical Methods in EpidemiologyMeta-analysis and systematic reviews

Midcourse correction to a clinical trial when the event rate is underestimated: the Look AHEAD (Action for Health in Diabetes) Study

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Brancati, Frederick L, Evans, Mary, Furberg, Curt D, Geller, Nancy, Haffner, Steven, Kahn, Steven E, Kaufmann, Peter G, Lewis, Cora E +4 more·2012·Clinical Trials
DOI 10.1177/1740774511432726PMC PMC3790961
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Abstract

The Look AHEAD (Action for Health in Diabetes) Study is a long-term clinical trial that aims to determine the cardiovascular disease (CVD) benefits of an intensive lifestyle intervention (ILI) in obese adults with type 2 diabetes. The study was designed to have 90% statistical power to detect an 18% reduction in the CVD event rate in the ILI Group compared to the Diabetes Support and Education (DSE) Group over 10.5 years of follow-up. The original power calculations were based on an expected CVD rate of 3.125% per year in the DSE group; however, a much lower-than-expected rate in the first 2 years of follow-up prompted the Data and Safety Monitoring Board (DSMB) to recommend that the Steering Committee undertake a formal blinded evaluation of these design considerations. The Steering Committee created an Endpoint Working Group (EPWG) that consisted of individuals masked to study data to examine relevant issues. The EPWG considered two primary options: (1) expanding the definition of the primary endpoint and (2) extending follow-up of participants. Ultimately, the EPWG recommended that the Look AHEAD Steering Committee approve both strategies. The DSMB accepted these modifications, rather than recommending that the trial continue with inadequate statistical power. Trialists sometimes need to modify endpoints after launch. This decision should be well justified and should be made by individuals who are fully masked to interim results that could introduce bias. This article describes this process in the Look AHEAD study and places it in the context of recent articles on endpoint modification and recent trials that reported endpoint modification.

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Authors
Brancati, F. L., Evans, M., Furberg, C. D., Geller, N., Haffner, S., Kahn, S. E., Kaufmann, P. G., Lewis, C. E., Nathan, D. M., Pitt, B., Safford, M. M., & on behalf of the Look AHEAD Study Group
Affiliations
  • Johns Hopkins University (US)
  • National Institute of Diabetes and Digestive and Kidney Diseases (US)
  • Wake Forest University (US)
  • National Heart, Lung, and Blood Institute (US)
  • San Antonio, TX, USA
  • University of Washington (US)
  • University of Alabama at Birmingham (US)
  • Massachusetts General Hospital (US)
  • University of Michigan (US)
ORCID
Venue
Clinical Trials
Publisher
SAGE Publications
Published
2012-02
Volume
9
Issue
1
Pages
113-124
ISSN
  • 1740-7745 (ISSN-L)
  • 1740-7753
DOI
10.1177/1740774511432726
PMC
PMC3790961
OpenAlex
W2064153485
Cited by
34
References
3
Citations by year
2024: 2 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 5 · 2014: 8 · 2013: 4 · 2012: 1
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Trials (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5p30dk046204-15)
  • U.S. Public Health Service (P60KD079637)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-57171, DK 57136, DK57149, DK 57002, DK57182, DK56990, (DK 046204, DK57008, DK57177, DK 57078, DK57219, U01DK057149, DK-57178, U01DK057151, U01DK057135, U01DK057131, U01DK056990, DK-57135, U01DK057136, DK-56992, DK57154, U01DK057178, U01DK057182, U01DK057078, U01DK057154, U01DK057008, U01DK057171, DK57131, U01DK057002, U01DK057219, U01DK056992, U01DK057177, P30DK017047, P30DK048520, DK 57151, P30-DK046204, P30-DK 48520)
  • National Center for Research Resources (M01-RR-0021140, M01RR-00051, M01RR002719, M01RR000056, M01RR01346, M01RR000051, M01RR001066, M01RR001346, UL1RR024153, M0-1-RR-02719, M01-RR01066)
Topics
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
  • Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
Keywords
midcourse correction, statistical power, event rate, cardiovascular events, type 2 diabetes, intensive lifestyle intervention, obesity, data safety monitoring board
MeSH terms
Cardiovascular Diseases, Humans, Middle Aged, Randomized Controlled Trials as Topic, Single-Blind Method, Diabetes Complications

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