TY - JOUR T1 - Explainable machine learning models for predicting long-term clinical outcomes in chronic disease management A1 - Leonid Alemán-Gonzales A1 - Benita Maritza Choque-Quispe A1 - William Harold Mamani-Zapana A1 - Charles Ignacio Mendoza-Mollocondo A1 - Elsa Gabriela Maquera-Bernedo A1 - Edwin Wilber Chambi-Mamani A1 - Juan Reynaldo Paredes-Quispe JF - Journal of Advanced Pharmacy Education and Research JO - J Adv Pharm Educ Res SN - 2249-3379 Y1 - 2026 VL - 16 IS - 2 DO - 10.51847/oAm3W008H7 SP - 176 EP - 183 N2 - Chronic disease management increasingly requires tools that can identify patients at elevated long-term risk before irreversible complications occur. This study aimed to develop and validate explainable machine learning models for predicting 5-year major adverse clinical events among patients with coexisting type 2 diabetes and hypertension. The central objective was to evaluate whether high predictive performance could be combined with transparent explanations suitable for clinical decision support. A retrospective longitudinal electronic health record dataset was analyzed for 15,000 adult patients followed over 5 years. The dataset included 50 predictor variables covering demographics, laboratory trajectories, medication use, comorbidity burden, healthcare utilization, and neighborhood-level socioeconomic deprivation. XGBoost, random forest, and penalized logistic regression models were trained and evaluated using 5-fold cross-validation. The primary outcome was a composite 5-year major adverse event endpoint comprising myocardial infarction, ischemic stroke, end-stage renal disease, or all-cause mortality. XGBoost achieved the highest discrimination, with an area under the receiver operating characteristic curve of 0.83, followed by random forest and logistic regression. Calibration results showed acceptable agreement between predicted and observed risk after probability recalibration. SHAP analysis identified HbA1c variability, medication adherence, estimated glomerular filtration rate decline, systolic blood pressure variability, prior cardiovascular disease, and socioeconomic deprivation index as the most influential predictors. Local explanations demonstrated how individual-level risk scores were driven by both modifiable clinical factors and structural risk indicators. Decision curve analysis indicated that the XGBoost model provided greater net clinical benefit than treat-all or treat-none strategies across clinically plausible risk thresholds. The study is limited by its fabricated dataset, retrospective simulation design, and restriction to two chronic conditions. Nevertheless, it demonstrates an empirically coherent framework for combining predictive accuracy, calibration, explainability, and clinical utility assessment. The findings support the feasibility of transparent long-term risk prediction models for chronic disease management‎. UR - https://japer.in/article/explainable-machine-learning-models-for-predicting-long-term-clinical-outcomes-in-chronic-disease-ma-tehs19iaibtbk0d ER -