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Reinforcement learning and Bayesian data assimilation for model-informed precision dosing in oncology.
Maier, Corinna; Hartung, Niklas; Kloft, Charlotte; Huisinga, Wilhelm; de Wiljes, Jana.
Afiliación
  • Maier C; Institute of Mathematics, University of Potsdam, Potsdam, Germany.
  • Hartung N; Graduate Research Training Program PharMetrX: Pharmacometrics & Computational Disease Modelling, Freie Universität Berlin and University of Potsdam, Potsdam, Germany.
  • Kloft C; Institute of Mathematics, University of Potsdam, Potsdam, Germany.
  • Huisinga W; Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany.
  • de Wiljes J; Institute of Mathematics, University of Potsdam, Potsdam, Germany.
CPT Pharmacometrics Syst Pharmacol ; 10(3): 241-254, 2021 03.
Article en En | MEDLINE | ID: mdl-33470053
Model-informed precision dosing (MIPD) using therapeutic drug/biomarker monitoring offers the opportunity to significantly improve the efficacy and safety of drug therapies. Current strategies comprise model-informed dosing tables or are based on maximum a posteriori estimates. These approaches, however, lack a quantification of uncertainty and/or consider only part of the available patient-specific information. We propose three novel approaches for MIPD using Bayesian data assimilation (DA) and/or reinforcement learning (RL) to control neutropenia, the major dose-limiting side effect in anticancer chemotherapy. These approaches have the potential to substantially reduce the incidence of life-threatening grade 4 and subtherapeutic grade 0 neutropenia compared with existing approaches. We further show that RL allows to gain further insights by identifying patient factors that drive dose decisions. Due to its flexibility, the proposed combined DA-RL approach can easily be extended to integrate multiple end points or patient-reported outcomes, thereby promising important benefits for future personalized therapies.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Paclitaxel / Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos / Biomarcadores Farmacológicos / Aprendizaje / Neutropenia Tipo de estudio: Prognostic_studies Aspecto: Patient_preference Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: CPT Pharmacometrics Syst Pharmacol Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Paclitaxel / Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos / Biomarcadores Farmacológicos / Aprendizaje / Neutropenia Tipo de estudio: Prognostic_studies Aspecto: Patient_preference Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: CPT Pharmacometrics Syst Pharmacol Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos