Sangam: A Confluence of Knowledge Streams

A data-driven approach to optimized medication dosing: a focus on heparin

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dc.contributor Massachusetts Institute of Technology. Institute for Medical Engineering & Science
dc.contributor Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
dc.contributor Ghassemi, Mohammad Mahdi
dc.contributor Celi, Leo Anthony G.
dc.creator Danziger, John
dc.creator Richter, Stefan E.
dc.creator Eche, Ifeoma M.
dc.creator Chen, Tszyi W.
dc.creator Ghassemi, Mohammad Mahdi
dc.creator Celi, Leo Anthony G.
dc.date 2016-07-29T20:43:22Z
dc.date 2016-07-29T20:43:22Z
dc.date 2014-08
dc.date 2014-04
dc.date 2016-05-23T12:08:54Z
dc.date.accessioned 2023-03-01T18:10:59Z
dc.date.available 2023-03-01T18:10:59Z
dc.identifier 0342-4642
dc.identifier 1432-1238
dc.identifier http://hdl.handle.net/1721.1/103811
dc.identifier Ghassemi, Mohammad M., Stefan E. Richter, Ifeoma M. Eche, Tszyi W. Chen, John Danziger, and Leo A. Celi. “A Data-Driven Approach to Optimized Medication Dosing: a Focus on Heparin.” Intensive Care Medicine 40, no. 9 (August 5, 2014): 1332–1339.
dc.identifier https://orcid.org/0000-0001-5135-8588
dc.identifier.uri http://localhost:8080/xmlui/handle/CUHPOERS/279062
dc.description Purpose To demonstrate a novel method that utilizes retrospective data to develop statistically optimal dosing strategies for medications with sensitive therapeutic windows. We illustrate our approach on intravenous unfractionated heparin, a medication which typically considers only patient weight and is frequently misdosed. Methods We identified available clinical features which impact patient response to heparin and extracted 1,511 patients from the multi-parameter intelligent monitoring in intensive care II database which met our inclusion criteria. These were used to develop two multivariate logistic regressions, modeling sub- and supra-therapeutic activated partial thromboplastin time (aPTT) as a function of clinical features. We combined information from these models to estimate an initial heparin dose that would, on a per-patient basis, maximize the probability of a therapeutic aPTT within 4–8 h of the initial infusion. We tested our model’s ability to classifying therapeutic outcomes on a withheld dataset and compared performance to a weight-alone alternative using volume under surface (VUS) (a multiclass version of AUC). Results We observed statistically significant associations between sub- and supra-therapeutic aPTT, race, ICU type, gender, heparin dose, age and Sequential Organ Failure Assessment scores with mean validation AUC of 0.78 and 0.79 respectively. Our final model improved outcome classification over the weight-alone alternative, with VUS values of 0.48 vs. 0.42. Conclusions This work represents an important step in the secondary use of health data in developing models to optimize drug dosing. The next step would be evaluating whether this approach indeed achieves target aPTT more reliably than the current weight-based heparin dosing in a randomized controlled trial.
dc.description National Institutes of Health. National Institute for Biomedical Imaging and Bioengineering (Grant R01 EB001659)
dc.format application/pdf
dc.language en
dc.publisher Springer Berlin Heidelberg
dc.relation http://dx.doi.org/10.1007/s00134-014-3406-5
dc.relation Intensive Care Medicine
dc.rights Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
dc.rights Springer-Verlag Berlin Heidelberg and ESICM
dc.source Springer Berlin Heidelberg
dc.title A data-driven approach to optimized medication dosing: a focus on heparin
dc.type Article
dc.type http://purl.org/eprint/type/JournalArticle


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