Table 4.

Total sample size calculations for a hypothetical two-arm trial using a milestone-based composite endpoint

	2-Year Study		3-Year Study
Data Source	HR = 0.50	HR = 0.75	HR = 0.50	HR = 0.75
Annual Visits*	436	2078	292	1404
All Visits**	324	1552	236	1142

Hazard ratios of 0.50 and 0.75 denote an assumed reduction in the hazard ratio of 50% and 25%, respectively, among the experimental arm relative to the comparison arm. All calculations specified 80% target power for a two-sided log-rank test at α= 0.05 and all estimates reflect the total sample size required across two arms. ^*Control survival curve estimated based on progression milestone data collected at 12, 24, and 36 months. ^**Control survival curve estimated based on progression milestone data collected at 3, 6, 9, 12, 18, 24, 30, and 36 months. HR, hazard ratio.