Development and Internal Validation of a Discrete Event Simulation Model of Diabetic Kidney Disease Using CREDENCE Trial
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ORIGINAL RESEARCH
Development and Internal Validation of a Discrete Event Simulation Model of Diabetic Kidney Disease Using CREDENCE Trial Data Michael Willis . Christian Asseburg . April Slee . Andreas Nilsson . Cheryl Neslusan
Received: July 22, 2020 / Accepted: August 29, 2020 Ó The Author(s) 2020
ABSTRACT Introduction: The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study showed that compared with placebo, canagliflozin 100 mg significantly reduced the risk of major cardiovascular events and adverse renal outcomes in patients with diabetic kidney disease (DKD). We developed a simulation model that can be used to estimate the long-
Digital Features To view digital features for this article go to https://doi.org/10.6084/m9.figshare.12888458. Electronic Supplementary Material The online version of this article (https://doi.org/10.1007/s13300020-00923-w) contains supplementary material, which is available to authorized users. M. Willis (&) A. Nilsson The Swedish Institute for Health Economics, Lund, Sweden e-mail: [email protected] C. Asseburg ESiOR Oy, Kuopio, Finland A. Slee Axio Research Inc, Seattle, WA, USA C. Neslusan Janssen Scientific Affairs, LLC, Titusville, NJ, USA
term health and economic consequences of DKD treatment interventions for patients matching the CREDENCE study population. Methods: The CREDENCE Economic Model of DKD (CREDEM-DKD) was developed using patient-level data from CREDENCE (which recruited patients with estimated glomerular filtration rate 30 to \ 90 mL/min/1.73 m2, urinary albumin to creatinine ratio [ 300–5000 mg/g, and taking the maximum tolerated dose of a renin–angiotensin–aldosterone system inhibitor). Risk prediction equations were fit for start of maintenance dialysis, doubling of serum creatinine, hospitalization for heart failure, nonfatal myocardial infarction, nonfatal stroke, and all-cause mortality. A micro-simulation model was constructed using these risk equations combined with user-definable kidney transplant event risks. Internal validation was performed by loading the model to replicate the CREDENCE study and comparing predictions with trial Kaplan–Meier estimate curves. External validation was performed by loading the model to replicate a subgroup of the CANagliflozin cardioVascular Assessment Study (CANVAS) Program with patient characteristics that would have qualified for inclusion in CREDENCE.
Diabetes Ther
Results: Risk prediction equations generally fit well and exhibited good concordance, especially for the placebo arm. In the canagliflozin arm, modest underprediction was observed for myocardial infarction, along with overprediction of dialysis, doubling of serum creatinine, and all-cause mortality. Discrimination was strong (0.85) for the renal outcomes, but weaker for the macrovascular outcomes and all-cause mortality (0.60–0.68). The model performed well in internal and external validation exercises. Conclusion: CREDEM-DKD is an important new tool in the evaluation of treatment interventions i
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