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C.A. Applegate, B.S. Hawkins, N.M. Bressler, E. Margalit, D. Gupta, J.S. Sunness; Designing Clinical Trials for Age–Related Geographic Atrophy of the Macula . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2123.
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To describe factors important for designing clinical trials for geographic atrophy (GA) from AMD.
Data from a large NIH–funded natural history study of GA were analyzed for the rate of and risk factors for enlargement of GA, and sample sizes required to detect a treatment effect. Recruitment data were analyzed to determine the percentage of patients who would be eligible for a clinical study of GA, based on specific eligibility criteria.
The median enlargement rate (ER) was 2.1 sq mm/year (0.83 MPS disc areas/year). Eyes with larger baseline atrophic areas tended to have larger ER, but the prior ER was the most significant factor in predicting subsequent ER. There is high concordance between eyes for ER in bilateral GA (r=0.76). To detect a 30% reduction in ER for a systemic treatment (alpha 0.05, power 0.9), 122 patients each in a control and treatment group would be required. For a uniocular treatment, 32 bilateral GA patients would be required, with the untreated eye serving as a control. For a clinical trial, one might select only patients with bilateral GA. 60% of the patients with GA in the natural history study were in the bilateral GA group. Baseline eligibility criteria of visual acuity 20/25–20/100 and GA area between 1.3 and 17.8 sq mm (0.5 and 7 MPS DA) would optimize the ability to measure changes in visual acuity and area over time. 60% of the bilateral GA patients met both these criteria, and 76% met the area criterion if there is no visual acuity exclusion. Thus, 36% of all patients with GA in the natural history study would meet the baseline eligibility criteria.
Clinical trials for GA are feasible, and data are available for estimating sample size and for defining eligibility criteria and recruitment needs.
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