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

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.

SUBMITTER: Brancati FL

PROVIDER: S-EPMC3790961 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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

Brancati Frederick L FL Evans Mary M Furberg Curt D CD Geller Nancy N Haffner Steven S Kahn Steven E SE Kaufmann Peter G PG Lewis Cora E CE Nathan David M DM Pitt Bertram B Safford Monika M MM

Clinical trials (London, England) 20120201 1

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 ...[more]

PMID: 22334468

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Project description:BackgroundLittle has been reported regarding food and nutrient intake in individuals diagnosed with type 2 diabetes, and most reports have been based on findings in select groups or individuals who self-reported having diabetes.ObjectiveTo describe the baseline food and nutrient intake of the Look AHEAD (Action for Health in Diabetes) trial participants, compare participant intake to national guidelines, and describe demographic and health characteristics associated with food group consumption.MethodsThe Look AHEAD trial is evaluating the effects of a lifestyle intervention (calorie control and increased physical activity for weight loss) compared with diabetes support and education on long-term cardiovascular and other health outcomes. Participants are 45 to 75 years old, overweight or obese (body mass index [BMI] > or = 25), and have type 2 diabetes. In this cross-sectional analysis, baseline food consumption was assessed by food frequency questionnaire from 2,757 participants between September 2000 and December 2003.Statistical analysisDescriptive statistics were used to summarize intake by demographic characteristics. Kruskal-Wallis tests assessed univariate effects of characteristics on consumption. Multiple linear regression models assessed factors predictive of intake. Least square estimates were based on final models, and logistic regression determined factors predictive of recommended intake.ResultsNinety-three percent of the participants exceeded the recommended percentage of calories from fat, 85% exceeded the saturated fat recommendation, and 92% consumed too much sodium. Also, fewer than half met the minimum recommended servings of fruit, vegetables, dairy, and grains.ConclusionsThese participants with pre-existing diabetes did not meet recommended food and nutrition guidelines. These overweight adults diagnosed with diabetes are exceeding recommended intake of fat, saturated fats, and sodium, which may contribute to increasing their risk of cardiovascular disease and other chronic diseases.

Project description:BackgroundEvidence has established obesity as a risk factor for total knee replacement (TKR) due to osteoarthritis. Obesity is a risk factor for TKR. Randomized trials such as Look AHEAD (Action for Health in Diabetes) have shown long-term successful weight loss with an intensive lifestyle intervention (ILI). It is unknown, however, if intentional weight loss can reduce the risk of TKR.MethodsLook AHEAD randomized persons aged 45-76 with type 2 diabetes who had overweight or obesity to either an ILI to achieve/maintain 7% weight loss or to standard diabetes support and education (DSE). Reported knee pain was assessed using the Visual Analog Scale and Western Ontario McMaster University Osteoarthritis Index questionnaire in 5125 participants without previous TKR. Cox proportional hazard regression was used to model differences in risk of TKR in relation to randomization group assignment (ILI vs DSE) along with baseline body mass index category and baseline knee pain as potential confounders from baseline through Look AHEAD-Extension.ResultsBaseline mean ± SD Western Ontario McMaster University Osteoarthritis Index knee pain scores did not differ by treatment assignment (ILI: 3.6 ± 2.9, DSE: 3.9 ± 3.0, P = .08); as expected due to randomization. During follow up, the 631 (12%) participants who reported having a TKR were more likely to have been heavier (P < .001) and older (P < .001) at enrollment, but risk of TKR did not differ by treatment group assignment (hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.91-1.25, P = .43). Heterogeneity of treatment effect was observed according to baseline knee pain (interaction P = .02). In persons without knee pain at baseline, there was a 29% reduced risk of TKR in ILI compared to DSE (HR 0.71, 95% CI 0.52-0.96). However, in persons with knee pain at baseline, there was no statistically significant association of treatment assignment with respect to subsequent TKR incidence (HR 1.11, 95% CI 0.92-1.33).ConclusionFindings suggest that intensive lifestyle change including physical activity, dietary restriction and behavioral changes to achieve weight loss for prevention of TKR may be most effective in preventing TKR prior to the development of knee pain.

Dataset Information

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

Publications

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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