Publication

Evaluating the Ability of Economic Models of Diabetes to Simulate New Cardiovascular Outcomes Trials: A Report on the Ninth Mount Hood Diabetes Challenge

Si, L., Willis, M. S., Asseburg, C., Nilsson, A., Tew, M., Clarke, P. M., Lamotte, M., Ramos, M., Shao, H., Shi, L., Zhang, P., McEwan, P., Ye, W., Herman, W. H., Kuo, S., Isaman, D. J., Schramm, W., Sailer, F., Brennan, A., Pollard, D., Smolen, H. J., Leal, J., Gray, A., Patel, R., Feenstra, T. & Palmer, A. J., Sep-2020, In : Value in Health. 23, 9, p. 1163-1170 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Lei Si
  • Michael S Willis
  • Christian Asseburg
  • Andreas Nilsson
  • Michelle Tew
  • Philip M Clarke
  • Mark Lamotte
  • Mafalda Ramos
  • Hui Shao
  • Lizheng Shi
  • Ping Zhang
  • Phil McEwan
  • Wen Ye
  • William H Herman
  • Shihchen Kuo
  • Deanna J Isaman
  • Wendelin Schramm
  • Fabian Sailer
  • Alan Brennan
  • Daniel Pollard
  • Harry J Smolen
  • José Leal
  • Alastair Gray
  • Rishi Patel
  • Talitha Feenstra
  • Andrew J Palmer

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.

Original languageEnglish
Pages (from-to)1163-1170
Number of pages8
JournalValue in Health
Volume23
Issue number9
Publication statusPublished - Sep-2020

    Keywords

  • Benzhydryl Compounds/therapeutic use, Calibration, Canagliflozin/therapeutic use, Cardiovascular Diseases/complications, Diabetes Mellitus, Type 2/complications, Glucosides/therapeutic use, Humans, Models, Economic, Outcome Assessment, Health Care/methods, Risk Assessment, Sodium-Glucose Transporter 2 Inhibitors/therapeutic use

ID: 143469792