Development of a prognostic prediction model to estimate the risk of multiple chronic diseases: constructing a copula-based model using Canadian primary care electronic medical record data

INTRODUCTION: The ability to estimate risk of multimorbidity will provide valuable information to patients and primary care practitioners in their preventative efforts. Current methods for prognostic prediction modelling are insufficient for the estimation of risk for multiple outcomes, as they do not properly capture the dependence that exists between outcomes. OBJECTIVES: We developed a multivariate prognostic prediction model for the 5-year risk of diabetes, hypertension, and osteoarthritis that quantifies and accounts for the dependence between each disease using a copula-based model. METHODS: We used data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) from 2009 onwards, a collection of electronic medical records submitted by participating primary care practitioners across Canada. We identified patients 18 years and older without all three outcome diseases and observed any incident diabetes, osteoarthritis, or hypertension within 5-years, resulting in a large retrospective cohort for model development and internal validation (n=425,228). First, we quantified the dependence between outcomes using unadjusted and adjusted Ø coefficients. We then estimated a copula-based model to quantify the non-linear dependence between outcomes that can be used to derive risk estimates for each outcome, accounting for the observed dependence. Copula-based models are defined by univariate models for each outcome and a dependence function, specified by the parameter θ. Logistic regression was used for the univariate models and the Frank copula was selected as the dependence function. RESULTS: All outcome pairs demonstrated statistically significant dependence that was reduced after adjusting for covariates. The copula-based model yielded statistically significant θ parameters in agreement with the adjusted and unadjusted Ø coefficients. Our copula-based model can effectively be used to estimate trivariate probabilities. DISCUSSION: Quantitative estimates of multimorbidity risk inform discussions between patients and their primary care practitioners around prevention in an effort to reduce the incidence of multimorbidity.