44% and 60% cost savings was achieved relative to the corresponding one-stage designs that included only study controls, only public controls and both public and study controls, respectively. The total cost of our proposed replication-based two-stage design was consistently less than the joint-analysis two-stage design that included both public and study controls, though the latter design maintained greater power. The joint-analysis two-stage design with only public controls was the least expensive design and had modestly greater power than the replication-based two-stage design for most follow-up platforms. In addition to having the lowest power among two-stage designs, the joint-analysis two-stage design that included only study controls was substantially more expensive than any other two-stage sampling design.
