A Hybrid Machine Learning Approach for Synthetic Data Generation with Post Hoc Calibration for Clinical Tabular Datasets

Healthcare research and development face significant obstacles due to data scarcity and stringent privacy regulations, such as HIPAA and the GDPR, restricting access to essential real-world medical data. These limitations impede innovation, delay robust AI model creation, and hinder advancements in patient-centered care. Synthetic data generation offers a transformative solution by producing artificial datasets that emulate real data statistics while safeguarding patient privacy. We introduce a novel hybrid framework for high-fidelity healthcare data synthesis integrating five augmentation methods: noise injection, interpolation, Gaussian Mixture Model (GMM) sampling, Conditional Variational Autoencoder (CVAE) sampling, and SMOTE, combined via a reinforcement learning-based dynamic weight selection mechanism. Its key innovations include advanced calibration techniques -- moment matching, full histogram matching, soft and adaptive soft histogram matching, and iterative refinement -- that align marginal distributions and preserve joint feature dependencies. Evaluated on the Breast Cancer Wisconsin (UCI Repository) and Khulna Medical College cardiology datasets, our calibrated hybrid achieves Wasserstein distances as low as 0.001 and Kolmogorov-Smirnov statistics around 0.01, demonstrating near-zero marginal discrepancy. Pairwise trend scores surpass 90%, and Nearest Neighbor Adversarial Accuracy approaches 50%, confirming robust privacy protection. Downstream classifiers trained on synthetic data achieve up to 94% accuracy and F1 scores above 93%, comparable to models trained on real data. This scalable, privacy-preserving approach matches state-of-the-art methods, sets new benchmarks for joint-distribution fidelity in healthcare, and supports sensitive AI applications.