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Clin Trials. 2012 Feb;9(1):113-24. doi: 10.1177/1740774511432726.

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

Collaborators (385)

Brancati FL, Swartz L, Cheskin L, Clark JM, Stewart K, Rubin R, Arceci J, Ball S, Charleston J, Diggins D, Johnson M, Lambert J, Michalski K, Jiggetts D, Sapun C, Bray GA, Rau K, Strate A, Greenway FL, Ryan DH, Williamson D, Armand B, Arceneaux J, Bachand A, Begnaud M, Berhard B, Caderette E, Cerniauskas B, Creel D, Crow D, Duncan C, Guay H, Johnson C, Jones L, Kora N, LaFleur K, Landry K, Lingle M, Perault J, Puckett C, Shipp M, Smith M, Tucker E, Lewis CE, Thomas S, Safford M, DiLillo V, Bragg C, Dobelstein A, Gilbert S, Glasser S, Hannum S, Hubbell A, Jones J, Lee D, Luketic R, Oden L, Raines J, Roche C, Truman J, Webb N, Azuero C, King J, Morgan A, Nathan DM, Cagliero E, Hayward K, Turgeon H, Delahanty L, Anderson E, Bissett L, Goldman V, Harlan V, Michel T, Larkin M, Stevens C, Miller K, Chen J, Blumenthal K, Winning G, Tsay R, Cyr H, Pinto M, Horton ES, Jackson SD, Hamdy O, Caballero AE, Bain S, Bovaird E, Fargnoli B, Spellman J, Goebel-Fabbri A, Lambert L, Ledbury S, Malloy M, Ovalle K, Blackburn G, Mantzoros C, McNamara A, Spellman K, Hill JO, Miller M, Van Dorsten B, Regensteiner J, Coelho L, Cohrs P, Green S, Hamilton A, Hamilton J, Leshchinskiy E, Munkwitz L, Rome L, Worley T, Craul K, Smith S, Foreyt JP, Reeves RS, Pownall H, Balasubramanyam A, Jones P, Burrington M, Chen CH, Gardner AC, Gee M, Griggs S, Hamilton M, Holley V, Joseph J, Palencia J, Schmidt J, White C, Johnson KC, Gresham C, Connelly S, Brewer A, Coday M, Jones L, Lichtermann L, Vosburg S, Taylor JL, Kitabchi AE, Nyenwe E, Lambeth H, Brewer A, Clark D, Crisler A, Force D, Green D, Kores R, Jeffery RW, Thorson C, Bantle JP, Redmon JB, Crow RS, Crow S, Raatz SK, Brelje K, Campbell C, Carls J, Carmean-Mihm T, Devonish J, Finch E, Fox A, Hoelscher E, James LD, Maddy VA, Ockenden T, Rice BI, Skarphol T, Tucker AD, Voeller MS, Walcheck C, Pi-Sunyer X, Patricio J, Heshka S, Pal C, Allen L, Chong L, Gluck M, Hirsch D, Holowaty MA, Horowitz M, Rau N, Steinberg DB, Wadden TA, Maschak BJ, Berkowitz RI, Braunstein S, Foster G, Glick H, Kumanyika S, Schwartz SS, Allen M, Bell Y, Brock J, Brozena S, Carvajal R, Chomentowski H, Crerand C, Davenport R, Diamond A, Fabricatore A, Goldberg L, Hesson L, Hudak T, Iqbal N, Jones-Corneille L, Kao A, Kuehnel R, Lipschutz P, Mullen M, Jakicic JM, Kelley DE, Wesche-Thobaben J, Kuller LH, Kriska A, Otto AD, Ewing L, Korytkowski M, Edmundowicz D, Yamamoto ME, Danchenko R, Elnyczky B, Garcia DO, Grove GA, Harper PH, Harrier S, Helbling NL, Ives D, Mancino J, Mathews A, Murray TY, Ritchea JR, Urda S, Wolf DL, Wing RR, Bright R, Pera V, Jakicic J, Gallagher K, Bach A, Bancroft B, Bertorelli A, Carey R, Charron T, Chenot H, Chula-Maguire K, Coward P, Cronkite L, Currin J, Daly M, Egan C, Ferguson E, Foss L, Gauvin J, Kieffer D, Lessard L, Maier D, Massaro JP, Monk T, Nicholson R, Patterson E, Phelan S, Raynor H, Raynor D, Robinson N, Robles D, Tavares J, Haffner SM, Hazuda HP, Montez MG, Lorenzo C, Coleman CF, Granado D, Hathaway K, Isaac JC, Ramirez N, Saenz R, Kahn S, Montgomery B, Knopp R, Lipkin E, Trence D, Barrett T, Bartell J, Greenberg D, Murillo A, Richmond BA, Socha J, Thomas A, Wesley A, Knowler WC, Bolin P, Killean T, Manus C, Krakoff J, Curtis JM, Glass J, Michaels S, Bennett PH, Morgan T, Begay S, Bloomquist P, Fallis B, Hermes J, Hollowbreast DF, Johnson R, Meacham M, Nelson J, Percy C, Poorthunder P, Sangster S, Scurlock N, Shovestull LA, Smiley J, Toledo K, Tomchee C, Tonemah D, Peters A, Ruelas V, Sengardi SG, Hillstrom KM, Konersman K, Serafin-Dokhan S, Espeland MA, Bahnson JL, Wagenknecht LE, Reboussin D, Rejeski WJ, Bertoni AG, Lang W, Lawlor MS, Lefkowitz D, Miller GD, Reynolds PS, Ribisl PM, Vitolins M, Chen H, West DS, Friedman LM, Craven BL, Dotson KM, Hodges A, Williams CC, Anderson A, Barnes JM, Barr M, Beavers DP, Beckner T, Davis C, Del Valle-Fagan T, Feeney PA, Goode C, Griffin J, Harvin L, Hogan P, Gaussoin SA, King M, Lane K, Neiberg RH, Walkup MP, Wall K, Windham T, Nevitt M, Schwartz A, Shepherd J, Rahorst M, Palermo L, Ewing S, Hayashi C, Maeda J, Marcovina SM, Chmielewski J, Gaur V, Soliman EZ, Prineas RJ, Campbell C, Zhang ZM, Alexander T, Keasler L, Hensley S, Li Y, Moran R, Foushee R, Hall NJ.

Author information

1
The Johns Hopkins University, Baltimore, MD 21205, USA. fbrancat@jhmi.edu

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00017953.

PMID:
22334468
PMCID:
PMC3790961
DOI:
10.1177/1740774511432726
[Indexed for MEDLINE]
Free PMC Article

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