Design of cancer trials based on progression‐free survival with intermittent assessment. (26th March 2018)

• Record Type: Journal Article
• Authors: Zeng, Leilei; Cook, Richard J.; Lee, Ker‐Ai
• Is Part Of: Statistics in medicine. Volume 37:Number 12(2018)
• Page Start: 1947
• Page End: 1959
• Publication Date: 2018-03-26
• Subjects: cancer trials -- intermittent assessment of progression -- multistate model -- progression‐free survival -- sample size estimation; Medical statistics -- Periodicals; Statistique médicale -- Périodiques; Statistiques médicales -- Périodiques; 610.727
• DOI: 10.1002/sim.7641
• Languages: English
• ISSNs: 0277-6715

Abstract

Abstract : Therapeutic advances in cancer mean that it is now impractical to performed phase III randomized trials evaluating experimental treatments on the basis of overall survival. As a result, the composite endpoint of progression‐free survival has been routinely adopted in recent years as it is viewed as enabling a more timely and cost‐effective approach to assessing the clinical benefit of novel interventions. This article considers design of cancer trials directed at the evaluation of treatment effects on progression‐free survival. In particular, we derive sample size criteria based on an illness‐death model that considers cancer progression and death jointly while accounting for the fact that progression is assessed only intermittently. An alternative approach to design is also considered in which the sample size is derived based on a misspecified Cox model, which uses the documented time of progression as the progression time rather than dealing with the interval censoring. Simulation studies show the validity of the proposed methods.