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This paper argues that standard uncertainty scores in selective prediction can track class membership rather than clinical ambiguity when the outcome is a rare minority, which can systematically defer or misclassify minority patients. The authors propose threshold-aligned uncertainty measures and class-stratified evaluation, and report results on synthetic data and three neurodegenerative cohorts. Readers should note that the evidence is limited to the evaluated conditions and that the fix addresses a specific failure mode, not clinical deployment safety in general.
When uncertainty quantification fails: structural vulnerabilities and corrections for selective prediction under clinical class imbalance
arXiv:2610.37561v1 Announce Type: cross Abstract: Background. Selective prediction systems improve the safety of clinical artificial intelligence by deferring ambiguous cases to human experts while automating high-confidence decisions. However, this safety mechanism relies entirely on the premise that uncertainty scores accurately reflect clinical ambiguity. In prognostic tasks characterized by severe class imbalance, where the clinical outcome of interest is a minority, this assumption breaks down. Standard uncertainty measures cease to capture clinically aligned ambiguity; instead, they become a proxy for class membership, systematically penalizing minority patients regardless of their individual predictive clarity. Results. Across 56 synthetic conditions and three neurodegenerative cohorts spanning severe class imbalance to near-balanced conditions (multiple sclerosis, Parkinson's Disease, Alzheimer's Disease), our framework consistently maintained bounded, balanced risk across trajectories. In contrast, global metrics either collapsed minority Sensitivity or protected the minority at the expense of majority patients. Applying CCR with standard entropy fails to protect the minority because it breaks within-class monotonicity when tau=0.5. Combining CCR with threshold-aware metrics restores strict monotonicity, correctly identifies ambiguous patients, and safely mitigates minority exclusion. Conclusions. Under clinical class imbalance, standard uncertainty quantification measures dataset sparsity rather than clinical ambiguity, creating a systemic illusion of safety. This bias is a correctable structural flaw. Clinical pipelines deploying selective prediction under imbalance should adopt threshold-aligned uncertainty measures and class-stratified evaluation. This reduces class-specific risk imbalance, supporting safer selective prediction under the evaluated conditions without silently excluding the most vulnerable patients.
Abstract:Background. Selective prediction systems improve the safety of clinical artificial intelligence by deferring ambiguous cases to human experts while automating high-confidence decisions. However, this safety mechanism relies entirely on the premise that uncertainty scores accurately reflect clinical ambiguity. In prognostic tasks characterized by severe class imbalance, where the clinical outcome of interest is a minority, this assumption breaks down. Standard uncertainty measures cease to capture clinically aligned ambiguity; instead, they become a proxy for class membership, systematically penalizing minority patients regardless of their individual predictive clarity. Results. Across 56 synthetic conditions and three neurodegenerative cohorts spanning severe class imbalance to near-balanced conditions (multiple sclerosis, Parkinson's Disease, Alzheimer's Disease), our framework consistently maintained bounded, balanced risk across trajectories. In contrast, global metrics either collapsed minority Sensitivity or protected the minority at the expense of majority patients. Applying CCR with standard entropy fails to protect the minority because it breaks within-class monotonicity when tau=0.5. Combining CCR with threshold-aware metrics restores strict monotonicity, correctly identifies ambiguous patients, and safely mitigates minority exclusion. Conclusions. Under clinical class imbalance, standard uncertainty quantification measures dataset sparsity rather than clinical ambiguity, creating a systemic illusion of safety. This bias is a correctable structural flaw. Clinical pipelines deploying selective prediction under imbalance should adopt threshold-aligned uncertainty measures and class-stratified evaluation. This reduces class-specific risk imbalance, supporting safer selective prediction under the evaluated conditions without silently excluding the most vulnerable patients.
Machine Learning (cs.LG); Artificial Intelligence (cs.AI)
arXiv:2610.37561 [cs.LG]
(or arXiv:2610.37561v1 [cs.LG] for this version)
https://doi.org/10.48550/arXiv.2610.37561 Focus to learn more arXiv-issued DOI via DataCite (pending registration)
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