The Challenge of Early Crossover in Oncology Trials

This paper provides preparatory reading, to facilitate discussion during the meeting on “The Challenge of Early Crossover in Oncology Trials” to be held in Adelaide, Australia, in October 2014. The paper is not exhaustive, and does not cover every issue associated with treatment crossover (also called treatment switching) in detail. However it aims to provide an overview of the key issues associated with treatment crossover in the context of oncology randomised controlled trials (RCTs). In Section 2 of this paper we will define what we mean by treatment switching. In Section 3 we will describe why treatment switching causes a problem for the analysis of trials, from the perspective of a range of stakeholders. This will take into account clinical development programmes and the challenges of designing these in the face of international variations in clinical, regulatory and coverage practice with respect to evidence requirements and expectations. In Section 4 we will introduce approaches that may be taken to adjust for treatment switching and in Section 5 we will summarise the performance of these methods in simulation studies. This paper is supplemented by five additional papers: Background Paper 2 provides details on case studies submitted by Workshop participants; Background Papers 3-5 provide relevant guidance and recommendations on the use of switching adjustment methods made by regulatory and reimbursement agencies from around the world. Brief background and introduction to these papers are provided in Sections 6 and 7 of this paper. Background Paper 6 presents the proposed confidentiality rules for the Workshop. In the final section of the current paper, we highlight areas that have not been addressed by currently available guidance documents.