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David M. Kent

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3 published item(s)

preprint2026arXiv

A Multi-Dataset Benchmark of Multiple Instance Learning for 3D Neuroimage Classification

Despite being resource-intensive to train, 3D convolutional neural networks (CNNs) have been the standard approach to classify CT and MRI scans. Recent work suggests that deep multiple instance learning (MIL) may be a more efficient alternative for 3D brain scans, especially when the pre-trained image encoder used to embed each 2D slice is frozen and only the pooling operation and classifier are trained. In this paper, we provide a systematic comparison of simple MIL, attention-based MIL, 3D CNNs, and 3D ViTs across three CT and four MRI datasets, including two large datasets of at least 10,000 scans. Our goal is to help resource-constrained practitioners understand which neural networks work well for 3D neuroimages and why. We further compare design choices for attention-based MIL, including different encoders, pooling operations, and architectural orderings. We find that simple mean pooling MIL, without any learnable attention, matches or outperforms recent MIL or 3D CNN alternatives on 4 of 6 moderate-sized tasks. This baseline remains competitive on two large datasets while being 25x faster to train. To explain mean pooling's success, we examine per-slice attention quality and a semi-synthetic dataset where we can derive the best possible classifier via a Bayes estimator. This analysis reveals the limits of existing MIL approaches and suggests routes for future improvements.

preprint2022arXiv

A standardized framework for risk-based assessment of treatment effect heterogeneity in observational healthcare databases

The Predictive Approaches to Treatment Effect Heterogeneity statement focused on baseline risk as a robust predictor of treatment effect and provided guidance on risk-based assessment of treatment effect heterogeneity in the RCT setting. The aim of this study was to extend this approach to the observational setting using a standardized scalable framework. The proposed framework consists of five steps: 1) definition of the research aim, i.e., the population, the treatment, the comparator and the outcome(s) of interest; 2) identification of relevant databases; 3) development of a prediction model for the outcome(s) of interest; 4) estimation of relative and absolute treatment effect within strata of predicted risk, after adjusting for observed confounding; 5) presentation of the results. We demonstrate our framework by evaluating heterogeneity of the effect of angiotensin-converting enzyme (ACE) inhibitors versus beta blockers on three efficacy and six safety outcomes across three observational databases. The proposed framework can supplement any comparative effectiveness study. We provide a publicly available R software package for applying this framework to any database mapped to the Observational Medical Outcomes Partnership Common Data Model. In our demonstration, patients at low risk of acute myocardial infarction received negligible absolute benefits for all three efficacy outcomes, though they were more pronounced in the highest risk quarter, especially for hospitalization with heart failure. However, failing diagnostics showed evidence of residual imbalances even after adjustment for observed confounding. Our framework allows for the evaluation of differential treatment effects across risk strata, which offers the opportunity to consider the benefit-harm trade-off between alternative treatments.

preprint2022arXiv

Individualized treatment effect was predicted best by modeling baseline risk in interaction with treatment assignment

Objective: To compare different risk-based methods for optimal prediction of treatment effects. Methods: We simulated RCT data using diverse assumptions for the average treatment effect, a baseline prognostic index of risk (PI), the shape of its interaction with treatment (none, linear, quadratic or non-monotonic), and the magnitude of treatment-related harms (none or constant independent of the PI). We predicted absolute benefit using: models with a constant relative treatment effect; stratification in quarters of the PI; models including a linear interaction of treatment with the PI; models including an interaction of treatment with a restricted cubic spline (RCS) transformation of the PI; an adaptive approach using Akaike's Information Criterion. We evaluated predictive performance using root mean squared error and measures of discrimination and calibration for benefit. Results: The linear-interaction model displayed optimal or close-to-optimal performance across many simulation scenarios with moderate sample size (N=4,250 patients; ~ 785 events). The RCS-model was optimal for strong non-linear deviations from a constant treatment effect, particularly when sample size was larger (N=17,000). The adaptive approach also required larger sample sizes. These findings were illustrated in the GUSTO-I trial. Conclusion: An interaction between baseline risk and treatment assignment should be considered to improve treatment effect predictions.