Why ML-based cough models do not generalize: a systematic cross-dataset evaluation for tuberculosis screening

Cough acoustics are promising for non-invasive tuberculosis (TB) screening, yet whether machine learning (ML) models capture disease-related acoustics or artifacts of data collection remains unresolved. We evaluated the cross-dataset generalizability of classical ML and deep learning (DL) cough-based TB classifiers across three independent datasets. Despite moderate within-dataset performance (ROC-AUC up to 0.755 ± 0.056), both pipelines fail to generalize, with external performance frequently below 0.6, indicating a possible limitation of the data. We further observed audio representations are organized by recording device and dataset rather than TB status, predicted TB probability tracks country-level prevalence in CODA, and device mismatch degrades transfer while device-diverse training improves it. Additionally, a clinical-variable baseline generalizes more consistently (ROC-AUC 0.655 - 0.711), indicating acquisition-specific variability is a stronger driver of poor generalizability than population shift. High within-dataset performance is not enough. External validation is essential before cough-based TB models are clinically ready.