Addressing Challenges of Economic Evaluation in Precision Medicine Using Dynamic Simulation Modeling.

OBJECTIVES The objective of this article is to describe the unique challenges and present potential solutions and approaches for economic evaluations of precision medicine (PM) interventions using simulation modeling methods. METHODS Given the large and growing number of PM interventions and applications, methods are needed for economic evaluation of PM that can handle the complexity of cascading decisions and patient-specific heterogeneity reflected in the myriad testing and treatment pathways. Traditional approaches (eg, Markov models) have limitations, and other modeling techniques may be required to overcome these challenges. Dynamic simulation models, such as discrete event simulation and agent-based models, are used to design and develop mathematical representations of complex systems and intervention scenarios to evaluate the consequence of interventions over time from a systems perspective. RESULTS Some of the methodological challenges of modeling PM can be addressed using dynamic simulation models. For example, issues regarding companion diagnostics, combining and sequencing of tests, and diagnostic performance of tests can be addressed by capturing patient-specific pathways in the context of care delivery. Issues regarding patient heterogeneity can be addressed by using patient-level simulation models. CONCLUSION The economic evaluation of PM interventions poses unique methodological challenges that might require new solutions. Simulation models are well suited for economic evaluation in PM because they enable patient-level analyses and can capture the dynamics of interventions in complex systems specific to the context of healthcare service delivery.

[1]  J P Kassirer,et al.  The journal's policy on cost-effectiveness analyses. , 1994, The New England journal of medicine.

[2]  S. Scholz,et al.  Modeling rheumatoid arthritis using different techniques - a review of model construction and results , 2014, Health Economics Review.

[3]  Nathaniel D Osgood,et al.  Selecting a dynamic simulation modeling method for health care delivery research-part 2: report of the ISPOR Dynamic Simulation Modeling Emerging Good Practices Task Force. , 2015, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[4]  Jonathan Karnon,et al.  Model Parameter Estimation and Uncertainty: a Report of the Ispor-smdm Modeling Good Research Practices Task Force-6 Background to the Task Forcemodel-parameter-estimation-and- Uncertainty-analysis.asp). a Summary of These Articles Was Pre- Sented at a Plenary Session at the Ispor 16th Annual Intern , 2022 .

[5]  Koen Degeling,et al.  Accounting for parameter uncertainty in the definition of parametric distributions used to describe individual patient variation in health economic models , 2017, BMC Medical Research Methodology.

[6]  Jagpreet Chhatwal,et al.  Economic Evaluations with Agent-Based Modelling: An Introduction , 2015, PharmacoEconomics.

[7]  M. Atkins,et al.  Sequential treatment approaches in  the management of BRAF wild-type advanced melanoma: a cost-effectiveness analysis. , 2018, Immunotherapy.

[8]  R. Eldessouki,et al.  Health Care System Information Sharing: A Step Toward Better Health Globally. , 2012, Value in health regional issues.

[9]  D. Owens,et al.  State-transition modeling: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force--3. , 2012, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[10]  Maarten J. IJzerman,et al.  Matching the model with the evidence: comparing discrete event simulation and state-transition modeling for time-to-event predictions in a cost-effectiveness analysis of treatment in metastatic colorectal cancer patients. , 2018, Cancer epidemiology.

[11]  M. Drummond,et al.  Health Care Technology: Effectiveness, Efficiency and Public Policy@@@Methods for the Economic Evaluation of Health Care Programmes , 1988 .

[12]  Hendrik Koffijberg,et al.  A systematic review and checklist presenting the main challenges for health economic modeling in personalized medicine: towards implementing patient-level models , 2017, Expert review of pharmacoeconomics & outcomes research.

[13]  A. Briggs,et al.  Patient Heterogeneity in Health Economic Decision Models for Chronic Obstructive Pulmonary Disease: Are Current Models Suitable to Evaluate Personalized Medicine? , 2016, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[14]  Beate Jahn,et al.  Resource Modelling: The Missing Piece of the HTA Jigsaw? , 2014, PharmacoEconomics.

[15]  G. Baynam,et al.  Optimizing Precision Medicine for Public Health , 2019, Front. Public Health.

[16]  Eric Bonabeau,et al.  Agent-based modeling: Methods and techniques for simulating human systems , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Manish K. Mishra,et al.  Integrating systems engineering practice with health-care delivery , 2014 .

[18]  C. Mitton,et al.  Breaking the addiction to technology adoption. , 2014, Health economics.

[19]  U. Siebert,et al.  Cost effectiveness of personalized treatment in women with early breast cancer: the application of OncotypeDX and Adjuvant! Online to guide adjuvant chemotherapy in Austria , 2015, SpringerPlus.

[20]  Stirling Bryan,et al.  Transparency in Decision Modelling: What, Why, Who and How? , 2019, PharmacoEconomics.

[21]  Rom Langerak,et al.  Comparison of Timed Automata with Discrete Event Simulation for Modeling of Biomarker-Based Treatment Decisions: An Illustration for Metastatic Castration-Resistant Prostate Cancer. , 2017, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[22]  Jörgen Möller,et al.  Discrete event simulation: the preferred technique for health economic evaluations? , 2010, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[23]  M. Dowsett,et al.  Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. , 2005, The New England journal of medicine.

[24]  D. Marshall,et al.  Do economic evaluations of targeted therapy provide support for decision makers? , 2011, The American journal of managed care.

[25]  Maarten J. IJzerman,et al.  Constrained Optimization Methods in Health Services Research-An Introduction: Report 1 of the ISPOR Optimization Methods Emerging Good Practices Task Force. , 2017, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[26]  Brian T. Denton,et al.  Improving Patient Access to Chemotherapy Treatment at Duke Cancer Institute , 2013, Interfaces.

[27]  Itai Ashlagi,et al.  Kidney Exchange and the Alliance for Paired Donation: Operations Research Changes the Way Kidneys Are Transplanted , 2015, Interfaces.

[28]  Jörgen Möller,et al.  Advantages and disadvantages of discrete-event simulation for health economic analyses , 2016, Expert review of pharmacoeconomics & outcomes research.

[29]  Xiange Zhang,et al.  Application of discrete event simulation in health care: a systematic review , 2018, BMC Health Services Research.

[30]  Deirdre Weymann,et al.  Valuation of Health and Nonhealth Outcomes from Next-Generation Sequencing: Approaches, Challenges, and Solutions. , 2018, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[31]  M J Buxton,et al.  Modelling in economic evaluation: an unavoidable fact of life. , 1997, Health economics.

[32]  Milton C. Weinstein,et al.  Recent Developments in Decision-Analytic Modelling for Economic Evaluation , 2012, PharmacoEconomics.

[33]  Kathryn A Phillips,et al.  Themed Section: Assesing the Value of Next-Generation Sequencing Methodological Issues in Assessing the Economic Value of Next-Generation Sequencing Tests: Many Challenges and Not Enough Solutions , 2018 .

[34]  Kathryn A Phillips,et al.  Precision Medicine: From Science To Value. , 2018, Health affairs.

[35]  David C. Lane,et al.  Invited Review and Reappraisal Industrial Dynamics. , 1997 .

[36]  Maarten J. IJzerman,et al.  Real-world data on discordance between estrogen, progesterone, and HER2 receptor expression on diagnostic tumor biopsy versus tumor resection material , 2019, Breast Cancer Research and Treatment.

[37]  Uwe Siebert,et al.  Personalized treatment of women with early breast cancer: a risk-group specific cost-effectiveness analysis of adjuvant chemotherapy accounting for companion prognostic tests OncotypeDX and Adjuvant!Online , 2017, BMC Cancer.

[38]  Maarten J. IJzerman,et al.  Applying dynamic simulation modeling methods in health care delivery research-the SIMULATE checklist: report of the ISPOR simulation modeling emerging good practices task force. , 2015, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[39]  A. Levy,et al.  HEALTH TECHNOLOGY ASSESSMENT AND PERSONALIZED MEDICINE: ARE ECONOMIC EVALUATION GUIDELINES SUFFICIENT TO SUPPORT DECISION MAKING? , 2014, International Journal of Technology Assessment in Health Care.

[40]  J. Blay,et al.  Molecular screening program to select molecular-based recommended therapies for metastatic cancer patients: analysis from the ProfiLER trial. , 2019, Annals of oncology : official journal of the European Society for Medical Oncology.

[41]  Jonathan Karnon,et al.  Modeling Using Discrete Event Simulation , 2012 .

[42]  M. Hoogendoorn,et al.  Broadening the Perspective of Cost-Effectiveness Modeling in Chronic Obstructive Pulmonary Disease: A New Patient-Level Simulation Model Suitable to Evaluate Stratified Medicine. , 2019, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[43]  T. Schelling Models of Segregation , 1969 .