Evaluating Performance of a Decision Support System to Improve Methotrexate Pharmacotherapy in Children and Young Adults With Cancer
- 1 February 2011
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Therapeutic Drug Monitoring
- Vol. 33 (1), 99-107
- https://doi.org/10.1097/ftd.0b013e318203b41e
Abstract
The management of high-dose methotrexate (MTX) therapy in patients with cancer depends on the routine monitoring of drug exposures in conjunction with leucovorin (LV), urine pH, patient hydration, and other clinical indices of patient well-being. A key factor in patient oversight is the facilitation of MTX clearance to minimize drug-related toxicity. The aim of this investigation was to evaluate the performance of a clinical decision support system and Bayesian forecasting algorithm in the prediction of MTX concentrations and assessment of LV dosing requirements in pediatric and young adult patients with cancer based on the current practice at the Children's Hospital of Philadelphia. Fifty patients ranging in age from 8 months to 21 years (weight range, 7.6-163.3 kg) contributing 80 total dosing events (183 MTX serum concentrations) were studied. The forecasting model was able to consistently predict future MTX concentrations with the knowledge of one prior concentration and continued to improve with additional concentration data made available through daily therapeutic drug monitoring. Precision was good at 12.9% with low bias at 2.2%. Comparison between the decision support system recommendations for LV rescue relative to the actual LV administration was also made. Sixteen patients would have initiated rescue therapy earlier, seven patients would have received a larger dose (42 smaller), and LV would have been given less often for 37 patients. The forecasting algorithm in the MTX dashboard was reasonably accurate in predicting MTX concentrations and should improve further as the underlying model and prediction algorithm evolves. This decision support system can be useful in helping physicians decide if a patient is clearing MTX as expected or if more aggressive rescue therapy is warranted.Keywords
This publication has 28 references indexed in Scilit:
- Integration of modeling and simulation into hospital-based decision support systems guiding pediatric pharmacotherapyBMC Medical Informatics and Decision Making, 2008
- Understanding and Managing Methotrexate NephrotoxicityThe Oncologist, 2006
- Population Pharmacokinetics of High-Dose Methotrexate in Children with Acute Lymphoblastic LeukaemiaClinical Pharmacokinetics, 2006
- High‐dose methotrexate‐induced nephrotoxicity in patients with osteosarcomaCancer, 2004
- Bayesian population model of methotrexate to guide dosage adjustments for folate rescue in patients with breast cancerJournal of Clinical Pharmacy & Therapeutics, 2002
- Bayesian Estimation of Methotrexate Pharmacokinetic Parameters and Area Under the Curve in Children and Young Adults with Localised OsteosarcomaClinical Pharmacokinetics, 2002
- Prediction of methotrexate elimination after high dose infusion in children with acute lymphoblastic leukaemia using a population pharmacokinetic approachFundamental & Clinical Pharmacology, 1999
- Clinical Pharmacodynamics of High-Dose Methotrexate in Acute Lymphocytic LeukemiaNew England Journal of Medicine, 1986
- METHOTREXATE SYSTEMIC CLEARANCE INFLUENCES PROBABILITY OF RELAPSE IN CHILDREN WITH STANDARD-RISK ACUTE LYMPHOCYTIC LEUKAEMIAThe Lancet, 1984
- Some suggestions for measuring predictive performanceJournal of Pharmacokinetics and Biopharmaceutics, 1981