New thinking: reducing the sample size by selecting fast progressors • Eyes with faster progression are much more likely to develop a clinical endpoint: 98% versus only 14% over 3 years. • Sample size can be reduced from 495 to 182 per arm when the progression rate increases from 0.54 dB/year to 1.56 dB/year (30% treatment effect assumed) 11 Curr Opin Ophthalmol . 2012 Mar;23(2):144 - 54. Ophthalmology. 2023 May;130(5):469 - 477. Ophthalmology. 2024 Jun;131(6):645 - 657. Fast progressors have a higher likelihood of meeting FDA event criteria Six - month run - in predicts future progression — feasible for clinical trials