Clinical value claims in multimodal AI outpace supporting evidence

As artificial intelligence systems move toward clinical deployment, ensuring reliable prediction behavior is fundamental for safety-critical decision-making tasks. One proposed safeguard is selective prediction, where models can defer uncertain predictions to human experts for review. In this work, we empirically evaluate the reliability of uncertainty-based selective prediction in multilabel clinical condition classification using multimodal ICU data. Across a range of state-of-the-art unimodal and multimodal models, we find that selective prediction can substantially degrade performance despite strong standard evaluation metrics. This failure is driven by severe class-dependent miscalibration, whereby models assign high uncertainty to correct predictions and low uncertainty to incorrect ones, particularly for underrepresented clinical conditions. Our results show that commonly used aggregate metrics can obscure these effects, limiting their ability to assess selective prediction behavior in this setting. Taken together, our findings characterize a task-specific failure mode of selective prediction in multimodal clinical condition classification and highlight the need for calibration-aware evaluation to provide strong guarantees of safety and robustness in clinical AI.

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.

Electronic health record (EHR) data are inherently multimodal, and leveraging multiple modalities can improve predictive performance. However, most existing approaches rely on deep fusion, which obscures how individual modalities contribute to predictions and limits the interpretability of multimodal reasoning. We propose an explicit multimodal routing framework for clinical prediction that enables interpretable, robust, and auditable reasoning across three EHR modalities: structured longitudinal variables (L), clinical notes (N), and chest X-rays (I). Our model constructs discrete unimodal, directional bimodal, and trimodal routes to capture both individual modality signals and asymmetric cross-modal interactions. To audit multimodal reasoning and assess robustness, we introduce inference-time route masking, which simulates missing modalities and reweights the remaining routes without retraining. We analyze changes in performance and routing weights under these scenarios to understand model decision-making. We evaluate our framework on multi-label phenotype prediction (K = 25) and binary ICU mortality prediction using trimodal patient stays from MIMIC-IV, revealing systematic differences in modality reliance across clinical condition groups. Overall, our framework offers a transparent, auditable, and practical approach to multimodal clinical prediction, providing interpretability, robustness, and insights into how different data sources drive model decisions.