A decision support tool to find the best cyclosporine dose when switching from intravenous to oral route in pediatric st
- PDF / 828,770 Bytes
- 8 Pages / 595.276 x 790.866 pts Page_size
- 46 Downloads / 159 Views
PHARMACOKINETICS AND DISPOSITION
A decision support tool to find the best cyclosporine dose when switching from intravenous to oral route in pediatric stem cell transplant patients Vincent Leclerc 1,2
&
Nathalie Bleyzac 1 & Antony Ceraulo 3 & Yves Bertrand 3 & Michel Ducher 1,2
Received: 9 September 2019 / Accepted: 25 May 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose Managing the pharmacokinetic variability of immunosuppressive drugs after pediatric hematopoietic stem cell transplantation (HSCT) is a clinical challenge. Thus, the aim of our study was to design and validate a decision support tool predicting the best first cyclosporine oral dose to give when switching from intravenous route. Methods We used 10-years pediatric HSCT patients’ dataset from 2008 to 2018. A tree-augmented naïve Bayesian network model (method belonging to artificial intelligence) was built with data from the first eight-years, and validated with data from the last two. Results The Bayesian network model obtained showed good prediction performances, both after a 10-fold cross-validation and external validation, with respectively an AUC-ROC of 0.89 and 0.86, a percentage of misclassified patients of 28.7% and 35.2%, a true positive rate of 0.71 and 0.65, and a false positive rate of 0.12 and 0.14 respectively. Conclusion The final model allows the prediction of the most likely cyclosporine oral dose to reach the therapeutic target specified by the clinician. The clinical impact of using this model needs to be prospectively warranted. Respecting the decision support tool terms of use is necessary as well as remaining critical about the prediction by confronting it with the clinical context. Keywords Cyclosporine . Artificial intelligence . Therapeutic targeting . Pediatrics . Hematopoietic Stem Cell Transplantation
Introduction Pediatric hematopoietic stem cell transplantation (HSCT) is a complex clinical situation, with the use of many narrow therapeutic index medications [1]. Numerous variability factors may influence pharmacokinetics, moreover when switching from a route of administration to another [2]. The high Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00228-020-02918-9) contains supplementary material, which is available to authorized users. * Vincent Leclerc [email protected] 1
EMR 3738, Ciblage Thérapeutique en Oncologie, Faculté de Médecine et de Maïeutique Lyon-Sud Charles Mérieux, Université Claude Bernard Lyon 1, 165 chemin du Grand Revoyet-BP 12, 69921 Oullins Cedex, Lyon, France
2
Pharmacy Department, Hôpital Pierre Garraud, Groupement Hospitalier Nord, Hospices Civils de Lyon, 136 rue du Commandant Charcot, 69005 Lyon, France
3
Institute of Pediatric Hematology and Oncology (IHOPe), Hematology Unit, Hospices Civils de Lyon and Claude Bernard University, Lyon, France
interindividual variability (due to the pediatric population and the wide range of diseases treated by HSCT) and the high intra-individual variability (
Data Loading...
