Two-stage phase II oncology designs using short-term endpoints for early stopping

Kunz, Cornelia and Wason, James M. S. and Kieser, Meinhard (2017) Two-stage phase II oncology designs using short-term endpoints for early stopping. Statistical Methods in Medical Research, 26 (4). pp. 1671-1683. ISSN 0962-2802

[thumbnail of article]
PDF (article)
article.pdf - Accepted Version
Available under License Creative Commons Attribution-NonCommercial.

Download (553kB)


Phase II oncology trials are conducted to evaluate whether the tumour activity of a new treatment is promising enough to warrant further investigation. The most commonly used approach in this context is a two-stage single-arm design with binary endpoint. As for all designs with interim analysis, its efficiency strongly depends on the relation between recruitment rate and follow-up time required to measure the patients’ outcomes. Usually, recruitment is postponed after the sample size of the first stage is achieved up until the outcomes of all patients are available. This may lead to a considerable increase of the trial length and with it to a delay in the drug development process. We propose a design where an intermediate endpoint is used in the interim analysis to decide whether or not the study is continued with a second stage. Optimal and minimax versions of this design are derived. The characteristics of the proposed design in terms of type I error rate, power, maximum and expected sample size as well as trial duration are investigated. Guidance is given on how to select the most appropriate design. Application is illustrated by a phase II oncology trial in patients with advanced angiosarcoma, which motivated this research.

Item Type:
Journal Article
Journal or Publication Title:
Statistical Methods in Medical Research
Additional Information:
The final, definitive version of this article has been published in the Journal, Statistical Methods in Medical Research, 26 (4), 2017, © SAGE Publications Ltd, 2017 by SAGE Publications Ltd at the Statistical Methods in Medical Research page: on SAGE Journals Online:
Uncontrolled Keywords:
?? two-stage designsoncologyshort-term endpointearly stoppinghealth information managementepidemiologystatistics and probability ??
ID Code:
Deposited By:
Deposited On:
26 Apr 2016 10:56
Last Modified:
31 Dec 2023 00:34