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Comparison of Cox Model Methods in A Low-dimensional Setting with Few Events.

ABSTRACT: Prognostic models based on survival data frequently make use of the Cox proportional hazards model. Developing reliable Cox models with few events relative to the number of predictors can be challenging, even in low-dimensional datasets, with a much larger number of observations than variables. In such a setting we examined the performance of methods used to estimate a Cox model, including (i) full model using all available predictors and estimated by standard techniques, (ii) backward elimination (BE), (iii) ridge regression, (iv) least absolute shrinkage and selection operator (lasso), and (v) elastic net. Based on a prospective cohort of patients with manifest coronary artery disease (CAD), we performed a simulation study to compare the predictive accuracy, calibration, and discrimination of these approaches. Candidate predictors for incident cardiovascular events we used included clinical variables, biomarkers, and a selection of genetic variants associated with CAD. The penalized methods, i.e., ridge, lasso, and elastic net, showed a comparable performance, in terms of predictive accuracy, calibration, and discrimination, and outperformed BE and the full model. Excessive shrinkage was observed in some cases for the penalized methods, mostly on the simulation scenarios having the lowest ratio of a number of events to the number of variables. We conclude that in similar settings, these three penalized methods can be used interchangeably. The full model and backward elimination are not recommended in rare event scenarios.

SUBMITTER: Ojeda FM

PROVIDER: S-EPMC4996851 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Comparison of Cox Model Methods in A Low-dimensional Setting with Few Events.

Ojeda Francisco M FM Müller Christian C Börnigen Daniela D Trégouët David-Alexandre DA Schillert Arne A Heinig Matthias M Zeller Tanja T Schnabel Renate B RB

Genomics, proteomics & bioinformatics 20160517 4

Prognostic models based on survival data frequently make use of the Cox proportional hazards model. Developing reliable Cox models with few events relative to the number of predictors can be challenging, even in low-dimensional datasets, with a much larger number of observations than variables. In such a setting we examined the performance of methods used to estimate a Cox model, including (i) full model using all available predictors and estimated by standard techniques, (ii) backward eliminati ...[more]

PMID: 27224515

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Project description:BackgroundCOVID-19 has led to an unprecedented strain on health care facilities across the United States. Accurately identifying patients at an increased risk of deterioration may help hospitals manage their resources while improving the quality of patient care. Here, we present the results of an analytical model, Predicting Intensive Care Transfers and Other Unforeseen Events (PICTURE), to identify patients at high risk for imminent intensive care unit transfer, respiratory failure, or death, with the intention to improve the prediction of deterioration due to COVID-19.ObjectiveThis study aims to validate the PICTURE model's ability to predict unexpected deterioration in general ward and COVID-19 patients, and to compare its performance with the Epic Deterioration Index (EDI), an existing model that has recently been assessed for use in patients with COVID-19.MethodsThe PICTURE model was trained and validated on a cohort of hospitalized non-COVID-19 patients using electronic health record data from 2014 to 2018. It was then applied to two holdout test sets: non-COVID-19 patients from 2019 and patients testing positive for COVID-19 in 2020. PICTURE results were aligned to EDI and NEWS scores for head-to-head comparison via area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve. We compared the models' ability to predict an adverse event (defined as intensive care unit transfer, mechanical ventilation use, or death). Shapley values were used to provide explanations for PICTURE predictions.ResultsIn non-COVID-19 general ward patients, PICTURE achieved an AUROC of 0.819 (95% CI 0.805-0.834) per observation, compared to the EDI's AUROC of 0.763 (95% CI 0.746-0.781; n=21,740; P<.001). In patients testing positive for COVID-19, PICTURE again outperformed the EDI with an AUROC of 0.849 (95% CI 0.820-0.878) compared to the EDI's AUROC of 0.803 (95% CI 0.772-0.838; n=607; P<.001). The most important variables influencing PICTURE predictions in the COVID-19 cohort were a rapid respiratory rate, a high level of oxygen support, low oxygen saturation, and impaired mental status (Glasgow Coma Scale).ConclusionsThe PICTURE model is more accurate in predicting adverse patient outcomes for both general ward patients and COVID-19 positive patients in our cohorts compared to the EDI. The ability to consistently anticipate these events may be especially valuable when considering potential incipient waves of COVID-19 infections. The generalizability of the model will require testing in other health care systems for validation.

Dataset Information

Comparison of Cox Model Methods in A Low-dimensional Setting with Few Events.

Publications

Comparison of Cox Model Methods in A Low-dimensional Setting with Few Events.

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