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 surrogate outcome




Salvaging Forbidden Treasure in Medical Data: Utilizing Surrogate Outcomes and Single Records for Rare Event Modeling

Yin, Xiaohui, Sacco, Shane, Aseltine, Robert H., Wang, Fei, Chen, Kun

arXiv.org Machine Learning

The vast repositories of Electronic Health Records (EHR) and medical claims hold untapped potential for studying rare but critical events, such as suicide attempt. Conventional setups often model suicide attempt as a univariate outcome and also exclude any ``single-record'' patients with a single documented encounter due to a lack of historical information. However, patients who were diagnosed with suicide attempts at the only encounter could, to some surprise, represent a substantial proportion of all attempt cases in the data, as high as 70--80%. We innovate a hybrid and integrative learning framework to leverage concurrent outcomes as surrogates and harness the forbidden yet precious information from single-record data. Our approach employs a supervised learning component to learn the latent variables that connect primary (e.g., suicide) and surrogate outcomes (e.g., mental disorders) to historical information. It simultaneously employs an unsupervised learning component to utilize the single-record data, through the shared latent variables. As such, our approach offers a general strategy for information integration that is crucial to modeling rare conditions and events. With hospital inpatient data from Connecticut, we demonstrate that single-record data and concurrent diagnoses indeed carry valuable information, and utilizing them can substantially improve suicide risk modeling.


On the Role of Surrogates in Conformal Inference of Individual Causal Effects

Gao, Chenyin, Gilbert, Peter B., Han, Larry

arXiv.org Machine Learning

Learning the Individual Treatment Effect (ITE) is essential for personalized decision making, yet causal inference has traditionally focused on aggregated treatment effects. While integrating conformal prediction with causal inference can provide valid uncertainty quantification for ITEs, the resulting prediction intervals are often excessively wide, limiting their practical utility. To address this limitation, we introduce \underline{S}urrogate-assisted \underline{C}onformal \underline{I}nference for \underline{E}fficient I\underline{N}dividual \underline{C}ausal \underline{E}ffects (SCIENCE), a framework designed to construct more efficient prediction intervals for ITEs. SCIENCE applies to various data configurations, including semi-supervised and surrogate-assisted semi-supervised learning. It accommodates covariate shifts between source data, which contain primary outcomes, and target data, which may include only surrogate outcomes or covariates. Leveraging semi-parametric efficiency theory, SCIENCE produces rate double-robust prediction intervals under mild rate convergence conditions, permitting the use of flexible non-parametric models to estimate nuisance functions. We quantify efficiency gains by comparing semi-parametric efficiency bounds with and without the incorporation of surrogates. Simulation studies demonstrate that our surrogate-assisted intervals offer substantial efficiency improvements over existing methods while maintaining valid group-conditional coverage. Applied to the phase 3 Moderna COVE COVID-19 vaccine trial, SCIENCE illustrates how multiple surrogate markers can be leveraged to generate more efficient prediction intervals.