Trustworthy Clinical Decision Support Using Meta-Predicates and Domain-Specific Languages
Authors: Michael Bouzinier, Sergey Trifonov, Michael Chumack, Eugenia Lvova, Dmitry Etin
Organizations: Harvard University, Cambridge, MA, USA · IDEXX Laboratories, Westbrook, ME, USA · Forome Association, Newton, MA, USA · Deggendorf Institute of Technology, Germany
\textbf{Background:} Regulatory frameworks for AI in healthcare, including the EU AI Act and FDA guidance on AI/ML-based medical devices, require clinical decision support to demonstrate not only accuracy but auditability. Existing formal languages for clinical logic validate syntactic and structural correctness but not whether decision rules use epistemologically appropriate evidence. \textbf{Methods:} Drawing on design-by-contract principles, we introduce meta-predicates -- predicates about predicates -- for asserting epistemological constraints on clinical decision rules expressed in a DSL. An epistemological type system classifies annotations along four dimensions: purpose, knowledge domain, scale, and method of acquisition. Meta-predicates assert which evidence types are permissible in any given rule. The framework is instantiated in AnFiSA, an open-source platform for genetic variant curation, and demonstrated using the Brigham Genomics Medicine protocol on 5.6 million variants from the Genome in a Bottle benchmark. \textbf{Results:} Decision trees used in variant interpretation can be reformulated as unate cascades, enabling per-variant audit trails that identify which rule classified each variant and why. Meta-predicate validation catches epistemological errors before deployment, whether rules are human-written or AI-generated. The approach complements post-hoc methods such as LIME and SHAP: where explanation reveals what evidence was used after the fact, meta-predicates constrain what evidence may be used before deployment, while preserving human readability. \textbf{Conclusions:} Meta-predicate validation is a step toward demonstrating not only that decisions are accurate but that they rest on appropriate evidence in ways that can be independently audited. While demonstrated in genomics, the approach generalises to any domain requiring auditable decision logic.
Large language models (LLMs) offer promising clinical decision support but remain vulnerable to hallucinated facts, unsupported recommendations, and citation errors. We present DIASENTINEL, a fully on-premise multi-agent system for one-year type 2 diabetes mellitus (T2DM) risk screening and guideline-grounded report generation from electronic health records (EHRs). The system integrates calibrated risk prediction, deterministic clinical signal extraction, Reciprocal Rank Fusion over American Diabetes Association (ADA) guidelines, and a hybrid verification layer combining rule-based checks with LLM entailment. The demonstration provides a real-time batch-screening dashboard and an interactive patient report interface with cited recommendations, verification results, and raw EHR comparison. DIASENTINEL demonstrates a practical framework for reliable, auditable, and privacy-preserving LLM-based clinical decision support.
Longitudinal electronic health records (EHRs) capture years of patient history across notes, codes, labs, and procedures, and contain evidence needed to reason about likely clinical outcomes. However, comprehensive clinician review of these records is impractical, and LLM-based processing is costly and often unreliable, missing some relevant observations while hallucinating others. We therefore propose EviGen, a three-layer framework for verifiable clinical rationale generation that addresses these challenges. The first layer is a patient-conditioned retriever that uses learnable queries to find evidence predictive of, not just textually relevant to, a clinical outcome and ranks it by prediction attribution scores. The second layer is an LLM generator that consumes this ranked evidence as a scaffold to produce a clinical rationale grounded in the retrieved spans. The third layer is a process-supervised verifier that checks the generated rationale at the reasoning-step level, flagging unreliable claims. Across three medical prediction datasets, EviGen improves prediction performance and rationale faithfulness over full-context LLM and RAG baselines, and is preferred by clinical reviewers in a usability evaluation.
Predictive modeling for clinical decision support requires both strong predictive performance and transparent, auditable, and human-reviewable decision logic. Although deep learning and tree-based ensemble methods can achieve high accuracy, their black-box nature remains a major obstacle to trustworthy clinical deployment. Moreover, clinical prediction often operates under practical constraints, including limited sample sizes, severe class imbalance, and feature evolution arising from changes in diagnostic criteria or clinical documentation practices. We propose Medical Heuristic Learning (MHL), a constrained paradigm for LLM-assisted rule learning. Rather than relying on updates to implicit model weights, MHL integrates statistical probes, medical knowledge probes, initial rule synthesis, and iterative rule optimization to construct an executable rule-based expert system. The resulting rule system is expressed entirely using the native logical and control-flow constructs of a programming language. Valid rule versions are recorded and retained along the search trajectory, making the decision logic explicit, interpretable, and auditable. MHL also supports continual learning by using previously validated rules as a starting point and iteratively revising them in response to updated feature information under data drift or feature evolution. MHL is not tied to any specific programming language. Comprehensive experiments on medical datasets show that MHL achieves predictive performance comparable to that of state-of-the-art methods, performs favorably in small-sample and highly imbalanced settings, and supports the transfer and adaptive revision of validated rules under feature evolution. Overall, these findings suggest that non-gradient-based heuristic systems offer an approach to balancing predictive performance and transparency in clinical decision support.