Statistical Methods for a Phase II Oncology Trial with a GMI Endpoint

• Activity Number: 583
• Type: Contributed
• Date/Time: Wednesday, August 4, 2010 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Stephanie Ann Kovalchik*+ and William Leonard Mietlowski
• Companies: University of California, Los Angeles and Novartis Oncology
• Keywords: phase II design ; progression-free survival ; growth modulation index ; cytostatic agent ; time to progression ; paired failure times

Abstract

For cytostatic cancer therapies, alternatives to traditional phase II end points are needed. Von Hoff (1998) proposed an intrapatient progression-free survival (PFS) ratio, the growth modulation index (GMI). Current practice in estimation of the GMI success rate is conservative and omits a measure of uncertainty.

We investigated methods for estimating the GMI success rate, including maximum-likelihood strategies and an approach using midranks for paired survival outcomes (Hudgens and Satten (2002)). Estimators were applied to a phase II GMI data set (Bonetti et al. (2001)). With simulation studies, a rank-based estimator had the most favorable properties. Its point estimate bias was consistently within 1.5%; its bias and precision were robust over a range of effect and censoring scenarios. Future GMI reporting should consider adopting the midrank methodology.