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BMC Medical Research Methodology

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Open Access 01-12-2019 | Research article

Two-stage optimal designs with survival endpoint when the follow-up time is restricted

Authors: Guogen Shan, Hua Zhang

Published in: BMC Medical Research Methodology | Issue 1/2019

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.

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Title: Two-stage optimal designs with survival endpoint when the follow-up time is restricted
Authors: Guogen Shan
Hua Zhang
Publication date: 01-12-2019
Publisher: BioMed Central
Published in: BMC Medical Research Methodology / Issue 1/2019
Electronic ISSN: 1471-2288
DOI: https://doi.org/10.1186/s12874-019-0696-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Two-stage optimal designs with survival endpoint when the follow-up time is restricted

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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