Data-driven prediction of fifteen-year all-cause mortality among 2.3 million individuals in the VA

ABSTRACT We present a data-driven framework to predict 15-year all-cause mortality using outpatient administrative records for 2.3 million Veterans in the largest integrated U.S. healthcare system. Rather than relying on predefined clinical phenotypes, we used the 1,000 most common outpatient medical codes from each of three data types/modalities – ICD-9 (Dx), Current Procedural Terminology (CPT), and prescription drugs (Rx), encoded as binary features. Using these features, we trained three machine learning (ML) algorithms (logistic regression with lasso, random forest, and a 3-layered feed-forward neural network) to predict 15-year mortality risk. The features were also mapped to variables for the widely used Charlson Comorbidity Index (CCI), Elixhauser, and Veterans Aging Cohort Study (VACS) indices, refitted for 15-year mortality prediction, for baseline comparison. All our models significantly outperformed the widely used CCI, Elixhauser, and VACS indices, with C-statistics ranging from 0.82 to 0.84 versus 0.739–0.804 for the baselines. Relative improvements in C-statistics of our approach over the baselines were consistent across different subgroups (age groups of <65 years, those 65+years, Blacks, Hispanics, etc.) Our approach enabled the identification of high-impact predictors with clinical grounding, without requiring hand-curated phenotypes. Cardiovascular diseases and mental health diagnoses/treatments emerged as leading long-term mortality indicators. Using unsupervised ML techniques including PCA and K-means clustering, we associated interpretable patterns and complex interactions between diagnoses and treatments, highlighting comorbidities, disease trajectories, and healthcare utilization patterns. The ability to achieve the predictive performance and algorithmically detect such relationships purely from outpatient data supports the scalability and broad applicability of our framework. This framework not only improves mortality risk stratification over existing clinical indices, but also enables better understanding of how medical codes, regardless of category, interact to predict long-term outcomes.