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This research demonstrates that Large Language Models can effectively extract latent clinical confounders from unstructured EHR notes to significantly reduce bias in causal inference for sepsis treatment. The study identifies direct augmentation of propensity score models as the optimal integration strategy, outperforming traditional NLP methods and matching approaches on real-world data with 21k+ patients. These findings provide critical methodological guidance for leveraging LLMs to improve decision-making pipelines where unmeasured variables traditionally hinder accurate effect estimation.
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LLM-Extracted Covariates for Clinical Causal Inference: Rethinking Integration Strategies

arXiv3 min read

arXiv:2604.16763v3 Announce Type: replace Abstract: Causal inference from electronic health records (EHR) is fundamentally limited by unmeasured confounding: critical clinical states such as frailty, goals of care, and mental status are documented in free-text notes but absent from structured data. Large language models can extract these latent confounders as interpretable, structured covariates, yet how to effectively integrate them into causal estimation pipelines has not been systematically studied. Using the MIMIC-IV database with 21,859 sepsis patients, we compare seven covariate-integration strategies for estimating the effect of early vasopressor initiation on 28-day mortality, spanning tabular-only baselines, traditional NLP representations, and three LLM-augmented approaches. A central finding is that not all integration strategies are equally effective: directly augmenting the propensity score model with LLM covariates achieves the best performance, while dual-caliper matching on text-derived categorical distances restricts the donor pool and degrades estimation. In semi-synthetic experiments with known ground-truth effects, LLM-augmented propensity scores reduce estimation bias from 0.0143 to 0.0003 relative to tabular-only methods, and this advantage persists under substantial simulated extraction error. On real data, incorporating LLM-extracted covariates reduces the estimated treatment effect from 0.055 to 0.027, directionally consistent with the CLOVERS randomized trial, and a doubly robust estimator yielding 0.031 confirms the robustness of this finding. Our results offer practical guidance on when and how text-derived covariates improve causal estimation in critical care. Our code is available at https://github.com/fpxlei/LLM-Covariates-Causal.

Abstract:Causal inference from electronic health records (EHR) is fundamentally limited by unmeasured confounding: critical clinical states such as frailty, goals of care, and mental status are documented in free-text notes but absent from structured data. Large language models can extract these latent confounders as interpretable, structured covariates, yet how to effectively integrate them into causal estimation pipelines has not been systematically studied. Using the MIMIC-IV database with 21,859 sepsis patients, we compare seven covariate-integration strategies for estimating the effect of early vasopressor initiation on 28-day mortality, spanning tabular-only baselines, traditional NLP representations, and three LLM-augmented approaches. A central finding is that not all integration strategies are equally effective: directly augmenting the propensity score model with LLM covariates achieves the best performance, while dual-caliper matching on text-derived categorical distances restricts the donor pool and degrades estimation. In semi-synthetic experiments with known ground-truth effects, LLM-augmented propensity scores reduce estimation bias from 0.0143 to 0.0003 relative to tabular-only methods, and this advantage persists under substantial simulated extraction error. On real data, incorporating LLM-extracted covariates reduces the estimated treatment effect from 0.055 to 0.027, directionally consistent with the CLOVERS randomized trial, and a doubly robust estimator yielding 0.031 confirms the robustness of this finding. Our results offer practical guidance on when and how text-derived covariates improve causal estimation in critical care. Our code is available at this https URL.

Machine Learning (cs.LG)

arXiv:2604.16763 [cs.LG]

(or arXiv:2604.16763v3 [cs.LG] for this version)

Full text under the publisher's open licence · 236 words

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