title: 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.
authors.affiliation: The George Institute for Global Health, Sydney, Australia.|The Charles Perkins Centre, University of Sydney, Sydney, Australia.|Royal Prince Alfred Hospital, Sydney, Australia.|Imperial College London, London, UK.
authors.forename: Bruce
authors.identifier: 0000-0002-0490-7465
authors.initials: B
authors.lastname: Neal
authors.affiliation: The George Institute for Global Health, Sydney, Australia.|Royal North Shore Hospital and University of Sydney, Sydney, Australia.
authors.forename: Vlado
authors.initials: V
authors.lastname: Perkovic
authors.affiliation: Department of Medicine, Stanford Center for Clinical Research (SCCR), Stanford University, Stanford, California.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: Royal North Shore Hospital and University of Sydney, Sydney, Australia.
authors.forename: Greg
authors.initials: G
authors.lastname: Fulcher
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey.
authors.forename: Ngozi
authors.initials: N
authors.lastname: Erondu
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey.
authors.forename: Mehul
authors.identifier: 0000-0003-3489-1967
authors.initials: M
authors.lastname: Desai
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey.
authors.forename: Wayne
authors.initials: W
authors.lastname: Shaw
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey.
authors.forename: Gordon
authors.initials: G
authors.lastname: Law
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey.
authors.forename: Marc K
authors.initials: MK
authors.lastname: Walton
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey.
authors.forename: Norm
authors.initials: N
authors.lastname: Rosenthal
authors.affiliation: University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: de Zeeuw
authors.affiliation: University of Oxford, Oxford, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Matthews
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D000068896:Canagliflozin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000150:complications / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D058065:Diabetic Cardiomyopathies / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016903:Drug Monitoring; D000074099:Equivalence Trials as Topic; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009026:Mortality; D015203:Reproducibility of Results; D012307:Risk Factors; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D015415:Biomarkers; D007004:Hypoglycemic Agents; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000068896:Canagliflozin
keywords: SGLT2 inhibitor; cardiovascular disease; type 2 diabetes