Hidden Data Challenges in Clinical Machine Learning

Machine learning (ML) studies using clinical data often rely on preprocessing and filtering pipelines before model development. The filtering decisions made in these pipelines can alter the dataset's statistical structure and may artificially reduce or increase the complexity of the prediction task. We argue that filtering choices should be treated as part of the scientific method rather than as a routine preprocessing step. We further discuss the need for explainable and transparent preprocessing pipelines that allow researchers to understand why specific filtering choices are made and how these choices affect the resulting data distribution and model performance. All of the source code for this work is available on GitHub.

Autoregressive electronic health record (EHR) foundation models predict the next event token in patient trajectories: sequences of structured medical events. A typical pretraining strategy is to concatenate all trajectories into a global stream and sample token windows from it. This gives patients with longer sequences more training exposure and allows tokens to attend across patient boundaries. We argue that these choices create a misalignment between pretraining and downstream clinical tasks. To explore this, we investigate how the composition of pretraining sequences affects clinical prediction performance. Using the global-stream approach as a baseline, we propose alternative sequence composition methods that control how patient trajectories contribute to pretraining sequences. Across four MIMIC-IV v2.2 tasks, our best method improves macro AUROC, AUPRC, F1, and balanced accuracy, with relative gains of 9.3% in F1 and 2.7% in AUPRC under a fixed training recipe. We find that these gains generalize across four additional evaluation settings, including the INSPIRE and eICU-CRD datasets, with improvements in macro AUROC, AUPRC, and F1 score. Our results show that simply changing how EHR data are presented to the model during pretraining can improve downstream performance, without changing the model or collecting additional data.

Learning from Electronic Health Records (EHRs) has gained significant attention due to its potential to improve clinical prediction. However, effective learning remains challenging because EHRs encode heterogeneous, temporally ordered clinical interactions. In particular, EHRs contain: (i) heterogeneous clinical entities, including patients, visits, diagnoses, prescriptions, and procedures, together with their heterogeneous interactions, (ii) longitudinal patient trajectories across hospital visits and (iii) shared statistical dependencies across related clinical prediction tasks. Existing EHR learning methods capture only a subset of these properties. To bridge this gap, we propose Multi-task Graph transformer for Heterogeneous Temporal EHRs (MiGHT-EHR), which jointly models all three within a unified representation learning method. MiGHT-EHR constructs a heterogeneous graph from EHRs in which nodes represent clinical entities and edges connect statistically associated entities identified via normalized point-wise mutual information. Across MIMIC-III and MIMIC-IV datasets, MiGHT-EHR outperforms state-of-the-art methods on average across four tasks: drug recommendation, prediction of length-of-stay, mortality, and readmission, with particularly strong improvements in mortality and readmission prediction. Furthermore, a post-hoc analysis of the learned representations reveals that patient neighborhoods are organized by clinical outcomes, salient medical concepts are recoverable as linear directions in the representation space, and task probabilities are well calibrated. Collectively, these findings demonstrate that MiGHT-EHR representations support diverse prediction tasks while preserving clinically interpretable structure.