title: Detection and measurement of clinically meaningful visual field progression in clinical trials for glaucoma.
abstract: Glaucomatous visual field progression has both personal and societal costs and therefore has a serious impact on quality of life. At the present time, intraocular pressure (IOP) is considered to be the most important modifiable risk factor for glaucoma onset and progression. Reduction of IOP has been repeatedly demonstrated to be an effective intervention across the spectrum of glaucoma, regardless of subtype or disease stage. In the setting of approval of IOP-lowering therapies, it is expected that effects on IOP will translate into benefits in long-term patient-reported outcomes. Nonetheless, the effect of these medications on IOP and their associated risks can be consistently and objectively measured. This helps to explain why regulatory approval of new therapies in glaucoma has historically used IOP as the outcome variable. Although all approved treatments for glaucoma involve IOP reduction, patients frequently continue to progress despite treatment. It would therefore be beneficial to develop treatments that preserve visual function through mechanisms other than lowering IOP. The United States Food and Drug Administration (FDA) has stated that they will accept a clinically meaningful definition of visual field progression using Glaucoma Change Probability criteria. Nonetheless, these criteria do not take into account the time (and hence, the speed) needed to reach significant change. In this paper we provide an analysis based on the existing literature to support the hypothesis that decreasing the rate of visual field progression by 30% in a trial lasting 12-18 months is clinically meaningful. We demonstrate that a 30% decrease in rate of visual field progression can be reliably projected to have a significant effect on health-related quality of life, as defined by validated instruments designed to measure that endpoint.
authors: Bernard and Shirlee Brown Glaucoma Research Laboratory, Edward S. Harkness Eye Institute, Columbia University Medical Center, 635 W. 165th Street, New York, NY 10032, USA.
authors: C Gustavo
authors: CG
authors: De Moraes
authors: Bernard and Shirlee Brown Glaucoma Research Laboratory, Edward S. Harkness Eye Institute, Columbia University Medical Center, 635 W. 165th Street, New York, NY 10032, USA.
authors: Jeffrey M
authors: JM
authors: Liebmann
authors: Department of Ophthalmology, McGill University, McGill Academic Eye Centre, 5252 Boul de Maisonneuve West, 4th Floor, Montreal, Quebec H4A 3S5, Canada; Department of Ophthalmology and Visual Sciences, University of Wisconsin, 2880 University Avenue, Madison, WI, USA. Electronic address: leonard.levin@mcgill.ca.
authors: Leonard A
authors: LA
authors: Levin
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods*; D019468:Disease Management; D018450:Disease Progression; D005901:Glaucoma / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D058609:Visual Field Tests / Q000379:methods*; D014794:Visual Fields / Q000502:physiology*
chemical_list: D018696:Neuroprotective Agents
keywords: Clinical trials; Glaucoma; Intraocular pressure; Neuroprotection; Perimetry; Progression