Mae O Gordon1, Eve J Higginbotham2, Dale K Heuer3, Richard K Parrish4, Alan L Robin5, Patricia A Morris6, Deborah A Dunn6, Bradley S Wilson6, Michael A Kass6. 1. Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, Missouri, USA. Electronic address: mae@wustl.edu. 2. Office of Inclusion & Diversity, Perelman School of Medicine, Philadelphia, Pennsylvania, USA. 3. The Eye Institute, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. 4. Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Florida, USA. 5. Department of Ophthalmology Wilmer Institute and Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA. 6. Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, Missouri, USA.
Abstract
PURPOSE: To assess the impact of a masked Endpoint Committee on estimates of the incidence of primary open-angle glaucoma (POAG) treatment efficacy and statistical power of the Ocular Hypertension Treatment Study-Phase 1, 1994-2002 (OHTS-1). DESIGN: Retrospective interrater reliability analysis of endpoint attribution by the Endpoint Committee. METHODS: After study closeout, we recalculated estimates of endpoint incidence, treatment efficacy, and statistical power using all-cause endpoints and POAG endpoints. To avoid bias, only the first endpoint per participant is included in this report. RESULTS: The Endpoint Committee reviewed 267 first endpoints from 1636 participants. The Endpoint Committee attributed 58% (155 of 267) of the endpoints to POAG. The incidence of all-cause endpoints vs POAG endpoints was 19.5% and 13.2%, respectively, in the observation group and 13.1% and 5.8%, respectively, in the medication group. Treatment effect for all-cause endpoints was a 33% reduction in risk (relative risk = 0.67, 95% confidence interval [CI] of 0.54-0.84) and a 56% reduction in risk for POAG endpoints (relative risk = 0.44, 95% CI of 0.31-0.61). Post hoc statistical power for detecting treatment effect was 0.94 for all-cause endpoints and 0.99 for POAG endpoints. CONCLUSION: Endpoint Committee adjudication of endpoints improved POAG incidence estimates, increased statistical power, and increased calculated treatment effect by 23%. An Endpoint Committee should be considered in therapeutic trials when common ocular and systemic comorbidities, other than the target condition, could compromise study results.
RCT Entities:
PURPOSE: To assess the impact of a masked Endpoint Committee on estimates of the incidence of primary open-angle glaucoma (POAG) treatment efficacy and statistical power of the Ocular Hypertension Treatment Study-Phase 1, 1994-2002 (OHTS-1). DESIGN: Retrospective interrater reliability analysis of endpoint attribution by the Endpoint Committee. METHODS: After study closeout, we recalculated estimates of endpoint incidence, treatment efficacy, and statistical power using all-cause endpoints and POAG endpoints. To avoid bias, only the first endpoint per participant is included in this report. RESULTS: The Endpoint Committee reviewed 267 first endpoints from 1636 participants. The Endpoint Committee attributed 58% (155 of 267) of the endpoints to POAG. The incidence of all-cause endpoints vs POAG endpoints was 19.5% and 13.2%, respectively, in the observation group and 13.1% and 5.8%, respectively, in the medication group. Treatment effect for all-cause endpoints was a 33% reduction in risk (relative risk = 0.67, 95% confidence interval [CI] of 0.54-0.84) and a 56% reduction in risk for POAG endpoints (relative risk = 0.44, 95% CI of 0.31-0.61). Post hoc statistical power for detecting treatment effect was 0.94 for all-cause endpoints and 0.99 for POAG endpoints. CONCLUSION: Endpoint Committee adjudication of endpoints improved POAG incidence estimates, increased statistical power, and increased calculated treatment effect by 23%. An Endpoint Committee should be considered in therapeutic trials when common ocular and systemic comorbidities, other than the target condition, could compromise study results.
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Authors: Michael A Kass; Dale K Heuer; Eve J Higginbotham; Richard K Parrish; Cheryl L Khanna; James D Brandt; Joern B Soltau; Chris A Johnson; John L Keltner; Julia B Huecker; Bradley S Wilson; Lei Liu; J Phillip Miller; Harry A Quigley; Mae O Gordon Journal: JAMA Ophthalmol Date: 2021-04-15 Impact factor: 8.253
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