Semi-supervised Double Deep Learning Temporal Risk Prediction (SeDDLeR) with Electronic Health Records

Abstract

Background:Risk prediction plays a crucial role in planning for prevention, monitoring, and treatment. Electronic Health Records (EHRs) offer an expansive repository of temporal medical data encompassing both risk factors and outcome indicators essential for effective risk prediction. However, challenges emerge due to the lack of readily available gold-standard outcomes and the complex effects of various risk factors. Compounding these challenges are the false positives in diagnosis codes, and formidable task of pinpointing the onset timing in annotations. Objective:We develop a Semi-supervised Double Deep Learning Temporal Risk Prediction (SeDDLeR) algorithm based on extensive unlabeled longitudinal Electronic Health Records (EHR) data augmented by a limited set of gold standard labels on the binary status information indicating whether the clinical event of interest occurred during the follow-up period. Methods:The SeDDLeR algorithm calculates an individualized risk of developing future clinical events over time using each patient’s baseline EHR features via the following steps: (1) construction of an initial EHR-derived surrogate as a proxy for the onset status; (2) deep learning calibration of the surrogate along gold-standard onset status; and (3) semi-supervised deep learning for risk prediction combining calibrated surrogates and gold-standard onset status. To account for missing onset time and heterogeneous follow-up, we introduce temporal kernel weighting. We devise a Gated Recurrent Units (GRUs) module to capture temporal characteristics. We subsequently assess our proposed SeDDLeR method in simulation studies and apply the method to the Massachusetts General Brigham (MGB) Biobank to predict type 2 diabetes (T2D) risk. Results:SeDDLeR outperforms benchmark risk prediction methods, including Semi-parametric Transformation Model (STM) and DeepHit, with consistently best accuracy across experiments. SeDDLeR achieved the best C-statistics ( 0.815, SE 0.023; vs STM +.084, SE 0.030, P-value .004; vs DeepHit +.055, SE 0.027, P-value .024) and best average time-specific AUC (0.778, SE 0.022; vs STM + 0.059, SE 0.039, P-value .067; vs DeepHit + 0.168, SE 0.032, P-value <0.001) in the MGB T2D study. Conclusion:SeDDLeR can train robust risk prediction models in both real-world EHR and synthetic datasets with minimal requirements of labeling event times. It holds the potential to be incorporated for future clinical trial recruitment or clinical decision-making.