1. Evaluating the ability of economic models of diabetes to simulate new cardiovascular outcomes trials: A report on the ninth mount hood diabetes challenge
- Author
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Lei Si, Lizheng Shi, Wen Ye, Shihchen Kuo, Jose Leal, Philip Clarke, Andrew J. Palmer, Wendelin Schramm, Talitha L Feenstra, Mark Lamotte, Hui Shao, Michael Willis, M Ramos, Harry J. Smolen, Rishi A Patel, Deanna J. M. Isaman, Christian Asseburg, Michelle Tew, Phil McEwan, Daniel Pollard, Ping Zhang, William H. Herman, Alan Brennan, Alastair Gray, Fabian Sailer, Andreas Nilsson, PharmacoTherapy, -Epidemiology and -Economics, Value, Affordability and Sustainability (VALUE), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
- Subjects
medicine.medical_specialty ,Cardiovascular Diseases/complications ,Active Comparator ,Outcome Assessment ,Health Care/methods ,Canagliflozin/therapeutic use ,Economic ,Placebo ,Risk Assessment ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Glucosides ,Models ,Benzhydryl Compounds/therapeutic use ,Outcome Assessment, Health Care ,Empagliflozin ,Diabetes Mellitus ,Medicine ,Humans ,Generalizability theory ,030212 general & internal medicine ,Benzhydryl Compounds ,Canagliflozin ,Sodium-Glucose Transporter 2 Inhibitors ,Event (probability theory) ,business.industry ,Diabetes Mellitus, Type 2/complications ,030503 health policy & services ,Health Policy ,Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ,Hazard ratio ,Public Health, Environmental and Occupational Health ,Outcome Assessment, Health Care/methods ,Type 2/complications ,Glucosides/therapeutic use ,Models, Economic ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Calibration ,0305 other medical science ,business ,Risk assessment ,medicine.drug - Abstract
Objectives: The cardiovascular outcomes challenge examined the predictive accuracy of 10 diabetes models in estimating hard outcomes in 2 recent cardiovascular outcomes trials (CVOTs) and whether recalibration can be used to improve replication. Methods: Participating groups were asked to reproduce the results of the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) and the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program. Calibration was performed and additional analyses assessed model ability to replicate absolute event rates, hazard ratios (HRs), and the generalizability of calibration across CVOTs within a drug class. Results: Ten groups submitted results. Models underestimated treatment effects (ie, HRs) using uncalibrated models for both trials. Calibration to the placebo arm of EMPA-REG OUTCOME greatly improved the prediction of event rates in the placebo, but less so in the active comparator arm. Calibrating to both arms of EMPA-REG OUTCOME individually enabled replication of the observed outcomes. Using EMPA-REG OUTCOME–calibrated models to predict CANVAS Program outcomes was an improvement over uncalibrated models but failed to capture treatment effects adequately. Applying canagliflozin HRs directly provided the best fit. Conclusions: The Ninth Mount Hood Diabetes Challenge demonstrated that commonly used risk equations were generally unable to capture recent CVOT treatment effects but that calibration of the risk equations can improve predictive accuracy. Although calibration serves as a practical approach to improve predictive accuracy for CVOT outcomes, it does not extrapolate generally to other settings, time horizons, and comparators. New methods and/or new risk equations for capturing these CV benefits are needed.
- Published
- 2020