Document Type

Article

Publication Date

4-3-2019

Publication Title

BMC Medical Research Methodology

Publisher

BMC

Volume

19

Issue

1

First page number:

1

Last page number:

12

Abstract

Background: Survival endpoint is frequently used in early phase clinical trials as the primary endpoint to assess the activity of a new treatment. Existing two-stage optimal designs with survival endpoint either over estimate the sample size or compute power outside the alternative hypothesis space. Methods: We propose a new single-arm two-stage optimal design with survival endpoint by using the one-sample log rank test based on exact variance estimates. This proposed design with survival endpoint is analogous to Simon’s two-stage design with binary endpoint, having restricted follow-up. Results: We compare the proposed design with the existing two-stage designs, including the two-stage design with survival endpoint based on the nonparametric Nelson-Aalen estimate, and Simon’s two-stage designs with or without interim accrual. The new design always performs better than these competitors with regards to the expected total study length, and requires a smaller expected sample size than Simon’s design with interim accrual. Conclusions: The proposed two-stage minimax and optimal designs with survival endpoint are recommended for use in practice to shorten the study length of clinical trials.

Keywords

Clinical trials; Exact variance; One-sample logrank test; Restricted follow-up; Simon's two-stage design

Disciplines

Public Health

File Format

pdf

File Size

2,477 KB

Language

English

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Download

UNLV article access

Search your library

Included in

Public Health Commons

Share

COinS