Integration of mathematical model predictions into routine workflows to support clinical decision making in haematology

Background Individualization and patient-specific optimization of treatment is a major goal of modern health care. One way to achieve this goal is the application of high-resolution diagnostics together with the application of targeted therapies. However, the rising number of different treatment modalities also induces new challenges: Whereas randomized clinical trials focus on proving average treatment effects in specific groups of patients, direct conclusions at the individual patient level are problematic. Thus, the identification of the best patient-specific treatment options remains an open question. Systems medicine, specifically mechanistic mathematical models, can substantially support individual treatment optimization. In addition to providing a better general understanding of disease mechanisms and treatment effects, these models allow for an identification of patient-specific parameterizations and, therefore, provide individualized predictions for the effect of different treatment modalities. Results In the following we describe a software framework that facilitates the integration of mathematical models and computer simulations into routine clinical processes to support decision-making. This is achieved by combining standard data management and data exploration tools, with the generation and visualization of mathematical model predictions for treatment options at an individual patient level. Conclusions By integrating model results in an audit trail compatible manner into established clinical workflows, our framework has the potential to foster the use of systems-medical approaches in clinical practice. We illustrate the framework application by two use cases from the field of haematological oncology.

[1]  Markus Scholz,et al.  Modeling individual time courses of thrombopoiesis during multi-cyclic chemotherapy , 2019, PLoS Comput. Biol..

[2]  Hilde van der Togt,et al.  Publisher's Note , 2003, J. Netw. Comput. Appl..

[3]  Fabian Prasser,et al.  A generic solution for web-based management of pseudonymized data , 2015, BMC Medical Informatics and Decision Making.

[4]  Michael Schroeder,et al.  MAGPIE: Simplifying access and execution of computational models in the life sciences , 2017, PLoS Comput. Biol..

[5]  Markus Scholz,et al.  A biomathematical model of human thrombopoiesis under chemotherapy. , 2010, Journal of theoretical biology.

[6]  Markus Löffler,et al.  Modelling chemotherapy effects on granulopoiesis , 2014, BMC Systems Biology.

[7]  I. Glauche,et al.  Reduced tyrosine kinase inhibitor dose is predicted to be as effective as standard dose in chronic myeloid leukemia: a simulation study based on phase III trial data , 2018, Haematologica.

[8]  M. Baccarani,et al.  Chronic myeloid leukaemia , 2007, The Lancet.

[9]  Dirk Hasenclever,et al.  Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. , 2004, Blood.

[10]  I. Glauche,et al.  Quantitative prediction of long-term molecular response in TKI-treated CML – Lessons from an imatinib versus dasatinib comparison , 2018, Scientific Reports.

[11]  M. Pfreundschuh,et al.  Practicability and acute haematological toxicity of 2- and 3-weekly CHOP and CHOEP chemotherapy for aggressive non-Hodgkin's lymphoma: results from the NHL-B trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). , 2003, Annals of oncology : official journal of the European Society for Medical Oncology.

[12]  Anna-Karin Hamberg,et al.  A Bayesian decision support tool for efficient dose individualization of warfarin in adults and children , 2015, BMC Medical Informatics and Decision Making.

[13]  Anca I. D. Bucur,et al.  Workflow-driven clinical decision support for personalized oncology , 2016, BMC Medical Informatics and Decision Making.

[14]  Markus Scholz,et al.  A Biomathematical Model of Human Erythropoiesis under Erythropoietin and Chemotherapy Administration , 2013, PloS one.

[15]  Markus Scholz,et al.  Model-based optimization of G-CSF treatment during cytotoxic chemotherapy , 2017, Journal of Cancer Research and Clinical Oncology.

[16]  M. Scholz,et al.  A combined model of human erythropoiesis and granulopoiesis under growth factor and chemotherapy treatment , 2014, Theoretical Biology and Medical Modelling.

[17]  Inigo Martincorena,et al.  Precision oncology for acute myeloid leukemia using a knowledge bank approach , 2017, Nature Genetics.

[18]  Nicola D. Roberts,et al.  Prognosis for patients with CML and >10% BCR-ABL1 after 3 months of imatinib depends on the rate of BCR-ABL1 decline. , 2014, Blood.

[19]  Jeffrey S. Barrett,et al.  Bmc Medical Informatics and Decision Making Integration of Modeling and Simulation into Hospital-based Decision Support Systems Guiding Pediatric Pharmacotherapy , 2008 .

[20]  Martin C. Müller,et al.  Model-based decision rules reduce the risk of molecular relapse after cessation of tyrosine kinase inhibitor therapy in chronic myeloid leukemia. , 2013, Blood.

[21]  Tsai-Chung Li,et al.  Development of a real-time clinical decision support system upon the web mvc-based architecture for prostate cancer treatment , 2011, BMC Medical Informatics Decis. Mak..

[22]  Dirk Hasenclever,et al.  Modeling combined chemo- and immunotherapy of high-grade non-Hodgkin lymphoma , 2016, Leukemia & lymphoma.

[23]  James Lyons-Weiler,et al.  Clinical decision modeling system , 2007, BMC Medical Informatics Decis. Mak..

[24]  Ingo Roeder,et al.  Dynamic modeling of imatinib-treated chronic myeloid leukemia: functional insights and clinical implications , 2006, Nature Medicine.