A Practical Guide Towards Interpreting Time-Series Deep Clinical Predictive Models: A Reproducibility Study

We introduce Retrieval-Augmented Interpretable Learning (RAIL), a probabilistic meta-learning framework for zero-shot generation of task-specific interpretable models that synthesizes coefficient-space structure from natural-language task descriptions and a memory of previously learned task-specific predictors. RAIL retrieves related source tasks, transfers structure through coefficient space, and generates a new predictor in the original diagnostic-feature space, enabling zero-shot and few-shot clinical procedure prediction with feature-level explanations. Its probabilistic formulation provides uncertainty over retrieval, model coefficients, and predictions, supporting uncertainty-aware deployment: uncertain predictions or unstable explanations can be flagged for additional clinical review rather than treated as automatic decisions. This makes RAIL particularly suited for healthcare settings, where prediction tasks are highly long-tailed, new clinical targets arise frequently, and models must remain inspectable, uncertainty-aware, and compatible with human oversight. Across long-tailed clinical procedure prediction tasks, RAIL improves low-data model generation, benefits from clinically informed task representations, and yields retrieval, uncertainty, and coefficient-level diagnostics that make model behavior more transparent. These results suggest a path toward scalable clinical prediction systems that can adapt to new tasks while preserving interpretability and reliability.

Predictive models over structured electronic health records (EHRs) remain central to machine learning for healthcare, but few have jointly emphasized quantitative laboratory information and interpretability with respect to input medical events. We present BERT-LER, a BERT-style model for coded EHR timelines pretrained and fine-tuned from a de-identified EHR dataset of 75 million patients, that encodes laboratory test results as discrete tokens while retaining graded information through percentile-based binning, paired with Integrated Gradients for token-level attributions grounded in the input EHR sequence. We benchmark our approach on the public EHRShot benchmark suite and on an asthma severity progression study based on real-world data. This addresses a methodological gap in EHR foundation-style modeling by unifying laboratory value representation and explainability in a single framework, while assessing whether both predictive performance and explanations generalize beyond standard clinical prediction tasks. Across EHRShot and asthma tasks, BERT-LER achieves predictive performance that is competitive with, and on laboratory-related tasks often exceeds, publicly available benchmark models, and provides attributions that align with clinically known risk factors. Our architecture and explainability approach can be applied to many therapeutic areas and prediction tasks using language models trained on structured EHRs.

Predictive modelling is important for health data analysis and data-driven clinical decision-making. However, predictive studies are challenging to design optimally by hand when tens or even hundreds of features require selection, transformation, or interaction modelling. While complex machine learning models offer high performance, their "black-box" nature limits the clinical trust, transparency, and interpretability required for decision-making. We developed and evaluated an Exploratory AI Recommender that provides data-driven recommendations to improve predictive performance of existing interpretable statistical models. The developed framework uses flexible AI modelling to capture complex data patterns and explainable AI techniques to translate the patterns into three recommendation types: feature exclusion, non-linear terms, and feature interactions. We evaluated the framework by comparing predictive performance of a baseline (i.e., no interactions or non-linear terms) Cox Proportional Hazards (CPH) model against an augmented CPH incorporating recommendations suggested by our method. The primary analysis predicts the time to the first occurrence of a fall or related injury in 245,614 patients. Our method recommended excluding 23 features, including non-linear terms for two features, and including 221 suggested feature interactions. The C-index improved from 0.805 (95% CI 0.798-0.812) to 0.815 (95% CI 0.809-0.822), and so did calibration (intercept: -0.006 to 0.003; slope: 1.063 to 0.950). All recommendations were supported by existing literature. The method also proved effective on two additional public datasets, demonstrating wider applicability. The proposed Exploratory AI Recommender demonstrates the potential of explainable AI and data-driven study design to improve the process of developing, and the performance of high-dimensional transparent predictive models.