Translation of Black-Box Clinical Prediction Models into Standalone Transparent Nomograms: Temporal External Validation in Heart Transplantation

Objective: To propose and retrospectively validate an integrated framework addressing three barriers to clinical translation of readmission prediction: lack of explainability, absence of deployment reliability infrastructure, and inadequate demographic fairness evaluation. Materials and Methods: We constructed a cohort of 415231 adult admissions from the MIMIC-IV database (30-day readmission prevalence 18.0%), split 70/15/15. Logistic regression, XGBoost, and LightGBM models were trained on 26 features. SHAP provided per-patient explanations. Fairness was evaluated across 16 subgroups using AUC-ROC, false negative rate (FNR), and positive predictive value (PPV). Calibration was assessed using Brier scores and calibration curves. Results: XGBoost achieved AUC-ROC 0.696 (95% CI 0.691-0.701), outperforming or matching the LACE baseline (AUC 0.60-0.68). LightGBM achieved best calibration (Brier 0.146). Prior admissions were the dominant predictor. All subgroups met equity thresholds (delta AUC <= 0.05, delta FNR <= 0.10). Conclusion: This framework delivers competitive performance, clinically actionable explanations, and strong demographic equity. Code is publicly available at https://github.com/Tomisin92/readmission-prediction.

Deploying clinical prediction models across healthcare systems often fails when key training covariates are unavailable at deployment and labeled outcomes are limited in the target domain. For example, high-performing models for out-of-hospital cardiac arrest (OHCA) rely on detailed prehospital measurements routinely collected in high-resource settings but unavailable in many international registries. Existing methods either discard missing covariates, sacrificing predictive information, or rely on untestable assumptions about their target distribution. We propose DRUM (\underline{D}istributionally \underline{R}obust \underline{U}nsupervised transfer learning with structurally \underline{M}issing covariates), a framework that transfers prediction models to target populations where certain covariates are structurally absent and outcome labels are unavailable. DRUM partitions covariates into shared components ($X$), observed across all settings, and missing components ($A$), observed only in the source. Rather than imputing missing covariates, DRUM optimizes worst-case predictive performance over the unknown target distribution of $A \mid X$ using a neural network generator, with a robustness parameter controlling allowable deviation from the source conditional. We further develop a bias correction procedure that reduces sensitivity to nuisance estimation error. Simulations show substantial improvements in both mean and worst-case prediction error under distribution shift. Applied to cross-national OHCA prediction, transferring models from a US registry to multiple Asian registries where prehospital variables are unrecorded, DRUM yields better-calibrated predictions and improved clinical classification performance across sites.

Black-box models limit the adoption of artificial intelligence in medicine because their predictions are difficult to interpret and reproduce. We present a statistically grounded framework for interpretable, rule-based clinical classification using the Bernoulli Naïve Bayes (BNB) model. Supervised chi-square-guided binarization converts continuous variables into binary indicators by selecting thresholds that maximize association with the clinical outcome within the training folds, which allows BNB to operate on continuous medical data without sacrificing transparency. On three benchmark datasets, Pima Indians Diabetes, Wisconsin Breast Cancer, and Heart Failure Prediction, the framework reached areas under the receiver operating characteristic curve of 0.800, 0.984, and 0.919, respectively. Probabilistic reliability was assessed with a leakage-safe cross-validated calibration analysis reporting Brier score and calibration intercept and slope, and post-hoc beta calibration improved probability calibration across datasets. These results indicate that an interpretable, statistically motivated framework can perform comparably to more complex models while providing explicit decision rules expressed in clinical units and calibrated risk estimates. A complete worked example further shows that model inference can be reproduced from a printed reference table using only basic arithmetic, without software or proprietary tools, supporting trustworthy and auditable use of artificial intelligence in clinical settings.