Work

Control of Unconditional Type I Error in Clinical Trials With External Control Borrowing—A Two‐Stage Adaptive Design Perspective

Year: 2025

Type: article

Abstract: Patient enrollment can be a substantial burden in rare disease trials. One potential approach is to incorporate external control (EC) into concurrent randomized trials, or EC borrowing, to reduce such burden. Extensive research has been conducted to explore statistical methodologies. As in all designs, type I error control is essential. Conditional type I error rate has been used in the literature as the de facto metrics for type I error rate. However, research has shown that controlling the conditional type I error rate at the alpha level will disallow EC borrowing. Therefore, EC borrowing is practically at an impasse. Kopp-Schneider et al. concluded that a more appropriate metrics for type I error is necessary. We show that a trial with EC borrowing can be considered as a two-stage adaptive design. With this perspective, we propose to define type I error as the weighted averages of conditional type I error rate in trials with EC borrowing. Dynamic borrowing methods for controlling type I error are proposed.

Source: Pharmaceutical Statistics

DOI: 10.1002/pst.70011

Authors: Ping Gao, Xiao Ni, Jing Li, Rachel Chu

Institutions: Sarepta Therapeutics (United States), C4 Therapeutics (United States)

Language: English

Topic: Statistical Methods in Clinical Trials

Subfield: Statistics and Probability

Field: Mathematics

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,880