Article first published online: 19 DEC 2012
Copyright © 2012 John Wiley & Sons, Ltd.
Statistics in Medicine
Volume 32, Issue 15, pages 2544–2554, 10 July 2013
How to Cite
Jaki, T., André, V., Su, T.-L. and Whitehead, J. (2013), Designing exploratory cancer trials using change in tumour size as primary endpoint. Statist. Med., 32: 2544–2554. doi: 10.1002/sim.5716
- Issue published online: 11 JUN 2013
- Article first published online: 19 DEC 2012
- Manuscript Accepted: 3 DEC 2012
- Manuscript Received: 30 MAY 2012
- tumour size;
- phase II;
- score statistic
In phase III cancer clinical trials, overall survival is commonly used as the definitive endpoint. In phase II clinical trials, however, more immediate endpoints such as incidence of complete or partial response within 1 or 2 months or progression-free survival (PFS) are generally used. Because of the limited ability to detect change in overall survival with response, the inherent variability of PFS and the long wait for progression to be observed, more informative and immediate alternatives to overall survival are desirable in exploratory phase II trials. In this paper, we show how comparative trials can be designed and analysed using change in tumour size as the primary endpoint. The test developed is based on the framework of score statistics and will formally incorporate the information of whether patients survive until the time at which change in tumour size is assessed. Using an example in non-small cell lung cancer, we show that the sample size requirements for a trial based on change in tumour size are favourable compared with alternative randomized trials and demonstrate that these conclusions are robust to our assumptions. Copyright © 2012 John Wiley & Sons, Ltd.