(published in Statistics in Medicine, Volume 31, issue 18, p.1944-1960, 2012.)
Description
Whereas traditional phase II cancer trials are usually single-arm, with tumor response as end-point, and phase III trials are randomized and incorporate interim analyses with progression- free survival or other failure time as endpoint, this paper proposes a new approach that seamlessly expands a randomized phase II study of response rate into a randomized phase III study of time to failure. This approach is based on advances in group sequential designs and joint modeling of the response rate and time to event. The joint modeling is reflected in the primary and secondary objectives of the trial, and the sequential design allows the trial to adapt to increase in information on response and survival patterns during the course of the trial, and to stop early either for conclusive evidence on efficacy of the experimental treatment or for the futility in continuing the trial to demonstrate it, based on the data collected so far.
Research and Software reported here was supported in part by the U.S. National Science Foundation under grant number DMS-0805879 and in part by Stanford NIH/NCRR CTSA award number UL1 RR025744.
Software
Section 4.3 of the paper describes the implementation of the design and shows tables of the design characteristics against specific alternatives. The package sp23design below is a complete implementation that is meant to be used both in designing the trial and in executing it in the field.
Install the package as usual on R from your favorite CRAN repository by selecting the package sp23design. Or in an R session, type
install.packages(“sp23design”)
Once the package is installed, typing example(generateSP23Design) will run an example that simulates case C of Table 1 in the paper. Additional examples are located in the examples sub-folder of the package directory that replicate all the scenarios in tables 1 and 2. Answers should be in the ballpark.