Abstract
The motivation for proposing sequential methods for cancer clinical trials is presented, and the methodology examined by re-analysing two completed phase III cancer trials of the Lung Cancer Working Party of the British Medical Research Council. The reanalysis proceeds as if the trials had been designed with a planned series of interim analyses governing stopping. Specifically, the triangular and double-triangular tests were applied. The sequential reanalysis gave a substantial reduction in the number of patient required, and deaths observed, for conclusions to be reached in comparison with the completed studies. In each case, the sequential analysis was stratified for baseline prognostic factors which were seen to be important at the first interim analysis.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- O'Brien P. C., Fleming T. R. A multiple testing procedure for clinical trials. Biometrics. 1979 Sep;35(3):549–556. [PubMed] [Google Scholar]
- Peto R., Pike M. C., Armitage P., Breslow N. E., Cox D. R., Howard S. V., Mantel N., McPherson K., Peto J., Smith P. G. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design. Br J Cancer. 1976 Dec;34(6):585–612. doi: 10.1038/bjc.1976.220. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosner G. L., Tsiatis A. A. The impact that group sequential tests would have made on ECOG clinical trials. Stat Med. 1989 Apr;8(4):505–516. doi: 10.1002/sim.4780080413. [DOI] [PubMed] [Google Scholar]
- Whitehead J. Interim analyses and stopping rules in cancer clinical trials. Br J Cancer. 1993 Dec;68(6):1179–1185. doi: 10.1038/bjc.1993.500. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whitehead J. Overrunning and underrunning in sequential clinical trials. Control Clin Trials. 1992 Apr;13(2):106–121. doi: 10.1016/0197-2456(92)90017-t. [DOI] [PubMed] [Google Scholar]