A Proposed S.C.O.R.E. Evaluation Framework for Large Language Models : Safety, Consensus, Objectivity, Reproducibility and Explainability

A comprehensive qualitative evaluation framework for large language models (LLM) in healthcare that expands beyond traditional accuracy and quantitative metrics needed. We propose 5 key aspects for evaluation of LLMs: Safety, Consensus, Objectivity, Reproducibility and Explainability (S.C.O.R.E.). We suggest that S.C.O.R.E. may form the basis for an evaluation framework for future LLM-based models that are safe, reliable, trustworthy, and ethical for healthcare and clinical applications.

A Multi-Center Study on the Adaptability of a Shared Foundation Model for Electronic Health Records

Foundation models hold promise for transforming AI in healthcare by providing modular components that are easily adaptable to downstream healthcare tasks, making AI development more scalable and cost-effective. Structured EHR foundation models, trained on coded medical records from millions of patients, demonstrated benefits including increased performance with fewer training labels, and improved robustness to distribution shifts. However, questions remain on the feasibility of sharing these models across different hospitals and their performance for local task adaptation. This multi-center study examined the adaptability of a recently released structured EHR foundation model ($FM_{SM}$), trained on longitudinal medical record data from 2.57M Stanford Medicine patients. Experiments were conducted using EHR data at The Hospital for Sick Children and MIMIC-IV. We assessed both adaptability via continued pretraining on local data, and task adaptability compared to baselines of training models from scratch at each site, including a local foundation model. We evaluated the performance of these models on 8 clinical prediction tasks. In both datasets, adapting the off-the-shelf $FM_{SM}$ matched the performance of GBM models locally trained on all data while providing a 13% improvement in settings with few task-specific training labels. With continued pretraining on local data, label efficiency substantially improved, such that $FM_{SM}$ required fewer than 1% of training examples to match the fully trained GBM's performance. Continued pretraining was also 60 to 90% more sample-efficient than training local foundation models from scratch. Our findings show that adapting shared EHR foundation models across hospitals provides improved prediction performance at less cost, underscoring the utility of base foundation models as modular components to streamline the development of healthcare AI.

Clinfo.ai: An Open-Source Retrieval-Augmented Large Language Model System for Answering Medical Questions using Scientific Literature

The quickly-expanding nature of published medical literature makes it challenging for clinicians and researchers to keep up with and summarize recent, relevant findings in a timely manner. While several closed-source summarization tools based on large language models (LLMs) now exist, rigorous and systematic evaluations of their outputs are lacking. Furthermore, there is a paucity of high-quality datasets and appropriate benchmark tasks with which to evaluate these tools. We address these issues with four contributions: we release Clinfo.ai, an open-source WebApp that answers clinical questions based on dynamically retrieved scientific literature; we specify an information retrieval and abstractive summarization task to evaluate the performance of such retrieval-augmented LLM systems; we release a dataset of 200 questions and corresponding answers derived from published systematic reviews, which we name PubMed Retrieval and Synthesis (PubMedRS-200); and report benchmark results for Clinfo.ai and other publicly available OpenQA systems on PubMedRS-200.

EHRSHOT: An EHR Benchmark for Few-Shot Evaluation of Foundation Models

While the general machine learning (ML) community has benefited from public datasets, tasks, and models, the progress of ML in healthcare has been hampered by a lack of such shared assets. The success of foundation models creates new challenges for healthcare ML by requiring access to shared pretrained models to validate performance benefits. We help address these challenges through three contributions. First, we publish a new dataset, EHRSHOT, containing de-identified structured data from the electronic health records (EHRs) of 6,712 patients from Stanford Medicine. Unlike MIMIC-III/IV and other popular EHR datasets, EHRSHOT is longitudinal and not restricted to ICU/ED patients. Second, we publish the weights of a 141M parameter clinical foundation model pretrained on the structured EHR data of 2.57M patients. We are one of the first to fully release such a model for coded EHR data; in contrast, most prior models released for clinical data (e.g. GatorTron, ClinicalBERT) only work with unstructured text and cannot process the rich, structured data within an EHR. We provide an end-to-end pipeline for the community to validate and build upon its performance. Third, we define 15 few-shot clinical prediction tasks, enabling evaluation of foundation models on benefits such as sample efficiency and task adaption. The code to reproduce our results, as well as the model and dataset (via a research data use agreement), are available at our Github repo here: https://github.com/som-shahlab/ehrshot-benchmark

Self-Supervised Time-to-Event Modeling with Structured Medical Records

Time-to-event models (also known as survival models) are used in medicine and other fields for estimating the probability distribution of the time until a particular event occurs. While providing many advantages over traditional classification models, such as naturally handling censoring, time-to-event models require more parameters and are challenging to learn in settings with limited labeled training data. High censoring rates, common in events with long time horizons, further limit available training data and exacerbate the risk of overfitting. Existing methods, such as proportional hazard or accelerated failure time-based approaches, employ distributional assumptions to reduce parameter size, but they are vulnerable to model misspecification. In this work, we address these challenges with MOTOR, a self-supervised model that leverages temporal structure found in large-scale collections of timestamped, but largely unlabeled events, typical of electronic health record data. MOTOR defines a time-to-event pretraining task that naturally captures the probability distribution of event times, making it well-suited to applications in medicine. After pretraining on 8,192 tasks auto-generated from 2.7M patients (2.4B clinical events), we evaluate the performance of our pretrained model after fine-tuning to unseen time-to-event tasks. MOTOR-derived models improve upon current state-of-the-art C statistic performance by 6.6% and decrease training time (in wall time) by up to 8.2 times. We further improve sample efficiency, with adapted models matching current state-of-the-art performance using 95% less training data.

RadFusion: Benchmarking Performance and Fairness for Multimodal Pulmonary Embolism Detection from CT and EHR

Despite the routine use of electronic health record (EHR) data by radiologists to contextualize clinical history and inform image interpretation, the majority of deep learning architectures for medical imaging are unimodal, i.e., they only learn features from pixel-level information. Recent research revealing how race can be recovered from pixel data alone highlights the potential for serious biases in models which fail to account for demographics and other key patient attributes. Yet the lack of imaging datasets which capture clinical context, inclusive of demographics and longitudinal medical history, has left multimodal medical imaging underexplored. To better assess these challenges, we present RadFusion, a multimodal, benchmark dataset of 1794 patients with corresponding EHR data and high-resolution computed tomography (CT) scans labeled for pulmonary embolism. We evaluate several representative multimodal fusion models and benchmark their fairness properties across protected subgroups, e.g., gender, race/ethnicity, age. Our results suggest that integrating imaging and EHR data can improve classification performance and robustness without introducing large disparities in the true positive rate between population groups.

Evaluating Treatment Prioritization Rules via Rank-Weighted Average Treatment Effects

There are a number of available methods that can be used for choosing whom to prioritize treatment, including ones based on treatment effect estimation, risk scoring, and hand-crafted rules. We propose rank-weighted average treatment effect (RATE) metrics as a simple and general family of metrics for comparing treatment prioritization rules on a level playing field. RATEs are agnostic as to how the prioritization rules were derived, and only assesses them based on how well they succeed in identifying units that benefit the most from treatment. We define a family of RATE estimators and prove a central limit theorem that enables asymptotically exact inference in a wide variety of randomized and observational study settings. We provide justification for the use of bootstrapped confidence intervals and a framework for testing hypotheses about heterogeneity in treatment effectiveness correlated with the prioritization rule. Our definition of the RATE nests a number of existing metrics, including the Qini coefficient, and our analysis directly yields inference methods for these metrics. We demonstrate our approach in examples drawn from both personalized medicine and marketing. In the medical setting, using data from the SPRINT and ACCORD-BP randomized control trials, we find no significant evidence of heterogeneous treatment effects. On the other hand, in a large marketing trial, we find robust evidence of heterogeneity in the treatment effects of some digital advertising campaigns and demonstrate how RATEs can be used to compare targeting rules that prioritize estimated risk vs. those that prioritize estimated treatment benefit.

The accuracy vs. coverage trade-off in patient-facing diagnosis models

A third of adults in America use the Internet to diagnose medical concerns, and online symptom checkers are increasingly part of this process. These tools are powered by diagnosis models similar to clinical decision support systems, with the primary difference being the coverage of symptoms and diagnoses. To be useful to patients and physicians, these models must have high accuracy while covering a meaningful space of symptoms and diagnoses. To the best of our knowledge, this paper is the first in studying the trade-off between the coverage of the model and its performance for diagnosis. To this end, we learn diagnosis models with different coverage from EHR data. We find a 1\% drop in top-3 accuracy for every 10 diseases added to the coverage. We also observe that complexity for these models does not affect performance, with linear models performing as well as neural networks.

Missingness as Stability: Understanding the Structure of Missingness in Longitudinal EHR data and its Impact on Reinforcement Learning in Healthcare

There is an emerging trend in the reinforcement learning for healthcare literature. In order to prepare longitudinal, irregularly sampled, clinical datasets for reinforcement learning algorithms, many researchers will resample the time series data to short, regular intervals and use last-observation-carried-forward (LOCF) imputation to fill in these gaps. Typically, they will not maintain any explicit information about which values were imputed. In this work, we (1) call attention to this practice and discuss its potential implications; (2) propose an alternative representation of the patient state that addresses some of these issues; and (3) demonstrate in a novel but representative clinical dataset that our alternative representation yields consistently better results for achieving optimal control, as measured by off-policy policy evaluation, compared to representations that do not incorporate missingness information.

Effective Representations of Clinical Notes

Clinical notes are a rich source of information about patient state. However, using them to predict clinical events with machine learning models is challenging. They are very high dimensional, sparse and have complex structure. Furthermore, training data is often scarce because it is expensive to obtain reliable labels for many clinical events. These difficulties have traditionally been addressed by manual feature engineering encoding task specific domain knowledge. We explored the use of neural networks and transfer learning to learn representations of clinical notes that are useful for predicting future clinical events of interest, such as all causes mortality, inpatient admissions, and emergency room visits. Our data comprised 2.7 million notes and 115 thousand patients at Stanford Hospital. We used the learned representations, along with commonly used bag of words and topic model representations, as features for predictive models of clinical events. We evaluated the effectiveness of these representations with respect to the performance of the models trained on small datasets. Models using the neural network derived representations performed significantly better than models using the baseline representations with small ($N < 1000$) training datasets. The learned representations offer significant performance gains over commonly used baseline representations for a range of predictive modeling tasks and cohort sizes, offering an effective alternative to task specific feature engineering when plentiful labeled training data is not available.