Auditable Hierarchical Inference with Multimodal Evidence and Bayesian Active Inquiry

Alpha-TCM makes two contributions under a central thesis: auditable systems should separate domain knowledge, case evidence, probabilistic inference, and downstream authority. First, it proposes a nine-layer TCM-oriented architecture covering semantic definitions, multimodal acquisition, quality control, provenance-bearing knowledge, probabilistic inference, longitudinal updating, constrained decisions, language interaction, and human governance. Each layer specifies its information contract, failure boundary, dependencies, and validation status. This is a system-design proposal, not a claim of complete clinical implementation. Second, a controlled synthetic prototype instantiates Layers 1-5 to audit the knowledge-evidence interface. Four conditional-Gaussian encoders process synthetic tongue images, pulse waveforms, inquiry fields, and text, while a frozen bridge predicts a five-dimensional synthetic outcome. A versioned contextual prior is compiled independently of the renderer. Fusion removes duplicated reference-prior information before adding context. Equal-information controls, prior regularization, graded contamination, and structural corruption test contextual benefits, Bayesian specificity, and conflict detection. Across ten paired seeds and four training sizes, contextual knowledge improved mean absolute error over marginal committee fusion at 600 and 1,200 cases, but not over equal-information neural controls. Fully incorrect context harmed performance at every size, while prior effects were inconsistent and conflict scores did not track case-level damage. The results support contextual structure in low-data synthetic settings, not a specifically Bayesian advantage. The prototype establishes no claims about TCM theory or clinical, diagnostic, therapeutic, causal, longitudinal, or transfer validity.

Multimodal large language models (MLLMs) have shown great potential in medical applications, yet existing benchmarks inadequately capture real-world clinical complexity. We introduce MEDSYN, a multilingual, multimodal benchmark of highly complex clinical cases with up to 7 distinct visual clinical evidence (CE) types per case. Mirroring clinical workflow, we evaluate 18 MLLMs on differential diagnosis (DDx) generation and final diagnosis (FDx) selection. While top models often match or even outperform human experts on DDx generation, all MLLMs exhibit a much larger DDx--FDx performance gap compared to expert clinicians, indicating a failure mode in synthesis of heterogeneous CE types. Ablations attribute this failure to (i) overreliance on less discriminative textual CE ($\it{e.g.}$, medical history) and (ii) a cross-modal CE utilization gap. We introduce Evidence Sensitivity to quantify the latter and show that a smaller gap correlates with higher diagnostic accuracy. Finally, we demonstrate how it can be used to guide interventions to improve model performance. We will open-source our benchmark and code.

Multimodal models in oncology can produce accurate predictions, but accurate prediction does not reveal whether the model has learned biology that is shared across modalities, biology confined to one modality, or spurious correlations that reflect confounders rather than genuine biology. We introduce DECAT, a model-agnostic post-hoc evaluation framework that classifies multimodal representations into four diagnostic scenarios for a given task and modality, using five null-referenced metrics and a rule-based decision procedure. The framework operates on learned representations, requires no knowledge of which specific confounder is present, and returns indeterminate when the evidence is insufficient. We validate DECAT on synthetic data across four multimodal model classes (over 2,500 trained representations) and on real data from 8,979 TCGA patients, evaluating both multimodal embeddings and five pretrained pathology foundation models. Entangled models (e.g., CLIP) achieve near-perfect shared biology detection but falsely claim shared biology in the majority of cases where it is absent on real foundation model embeddings. This false claim rate increases with confound strength so that larger cohorts and stronger representations produce more confident but still incorrect diagnoses. Applied to both multimodal TCGA embeddings and five pathology foundation models without paired RNA, DECAT detects confounding invisible to AUROC without requiring the confounder labels, as confirmed by post-hoc stratification.