Optimizing the analysis strategy for the CANVAS Program: A prespecified plan for the integrated analyses of the CANVAS and CANVAS-R trials

Abstract

Two large cardiovascular outcome trials of canagliflozin, comprising the CANVAS Program, will complete in early 2017: the CANagliflozin cardioVascular Assessment Study (CANVAS) and the CANagliflozin cardioVascular Assessment Study-Renal (CANVAS-R). Accruing data for the sodium glucose co-transporter 2 (SGLT2) inhibitor class has identified questions and opportunities that were not apparent when the trials were designed. Accordingly, a series of modifications have been made to the planned analyses. These updates will ensure that the data from the CANVAS Program will maximize advances in scientific knowledge and patient care. The specification of the analysis strategy prior to knowledge of the trial results, their design by the independent scientific trial Steering Committee, the detailed a priori definition of the analysis plans, and the external review provided by the US Food and Drug Administration all provide maximally efficient and robust utilization of the data. The CANVAS Program should significantly advance our understanding of the effects of canagliflozin, and the broader SGLT2 inhibitor class, on a range of important efficacy and safety outcomes.

Keywords: SGLT2 inhibitor; cardiovascular disease; type 2 diabetes.

Figure 1

Overview of canagliflozin trial timelines. ^*Planned; recruitment ongoing. ^†Note that the patient populations in CANVAS and CANVAS‐R are nearly identical to facilitate an integrated analysis of the data

Figure 2

Sequential hypothesis testing plan for the CANVAS Program. ACR, albumin:creatinine ratio; CANA, canagliflozin; CV, cardiovascular; HF, heart failure