Incorporating Intermediate Endpoint in Two-Stage Design Decision Making

Abstract

This article proposes a new strategy that used intermediate endpoint from “pipeline” patients and observed final endpoint in interim decision-making to the two-stage 2-in-1 design. We demonstrate that the advantage of using purely intermediate endpoint at interim analysis highly depends on assumptions about the relationship between the intermediate and final endpoint. Those assumptions should be critically evaluated before adopting such a design, otherwise, the benefit of adaptation would be jeopardized, or even counter-productive. On the other hand, the approach that combines intermediate and final endpoint usually leads to a less dramatic yet more robust improvement.

Keywords:

• Clinical trial
• “Go/NoGo” decision
• Intermediate endpoint
• Two-stage design

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Funding

The author(s) reported there is no funding associated with the work featured in this article.