When to Use Discrete Event Simulation (DES) for the Economic Evaluation of Health Technologies? A Review and Critique of the Costs and Benefits of DES

Modelling in economic evaluation is an unavoidable fact of life. Cohort-based state transition models are most common, though discrete event simulation (DES) is increasingly being used to implement more complex model structures. The benefits of DES relate to the greater flexibility around the implementation and population of complex models, which may provide more accurate or valid estimates of the incremental costs and benefits of alternative health technologies. The costs of DES relate to the time and expertise required to implement and review complex models, when perhaps a simpler model would suffice. The costs are not borne solely by the analyst, but also by reviewers. In particular, modelled economic evaluations are often submitted to support reimbursement decisions for new technologies, for which detailed model reviews are generally undertaken on behalf of the funding body. This paper reports the results from a review of published DES-based economic evaluations. Factors underlying the use of DES were defined, and the characteristics of applied models were considered, to inform options for assessing the potential benefits of DES in relation to each factor. Four broad factors underlying the use of DES were identified: baseline heterogeneity, continuous disease markers, time varying event rates, and the influence of prior events on subsequent event rates. If relevant, individual-level data are available, representation of the four factors is likely to improve model validity, and it is possible to assess the importance of their representation in individual cases. A thorough model performance evaluation is required to overcome the costs of DES from the users’ perspective, but few of the reviewed DES models reported such a process. More generally, further direct, empirical comparisons of complex models with simpler models would better inform the benefits of DES to implement more complex models, and the circumstances in which such benefits are most likely.

[1]  J R Beck,et al.  Markov Models in Medical Decision Making , 1993, Medical decision making : an international journal of the Society for Medical Decision Making.

[2]  Denis Getsios,et al.  Cost Effectiveness of Donepezil in the Treatment of Mild to Moderate Alzheimer’s Disease , 2012, PharmacoEconomics.

[3]  J. Karnon,et al.  Cost analysis of a hospital-at-home initiative using discrete event simulation , 2001, Journal of health services research & policy.

[4]  J. Caro,et al.  Cost-benefit analysis of preventing sudden cardiac deaths with an implantable cardioverter defibrillator versus amiodarone. , 2007, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[5]  M. E. Nita,et al.  Custo-efetividade e impacto orçamentário da saxagliptina como terapia adicional à metformina para o tratamento do diabetes mellitus tipo 2 no sistema de saúde suplementar do Brasil , 2012 .

[6]  Murray Krahn,et al.  Conceptualizing a Model , 2012, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[7]  J. Karnon,et al.  The clinical effectiveness and cost-effectiveness of screening programmes for amblyopia and strabismus in children up to the age of 4-5 years: a systematic review and economic evaluation. , 2008, Health technology assessment.

[8]  Jonathan D. Campbell,et al.  Cost-effectiveness of continuous glucose monitoring and intensive insulin therapy for type 1 diabetes , 2011, Cost effectiveness and resource allocation : C/E.

[9]  G. Nocea,et al.  Cost‐effectiveness of sitagliptin‐based treatment regimens in European patients with type 2 diabetes and haemoglobin A1c above target on metformin monotherapy , 2008, Diabetes, obesity & metabolism.

[10]  A. Brennan,et al.  A cost-utility analysis of clopidogrel in patients with ST elevation acute coronary syndromes in the UK. , 2010, International journal of cardiology.

[11]  J. Möller,et al.  Cost-effectiveness of novel relapsed-refractory multiple myeloma therapies in Norway: lenalidomide plus dexamethasone vs bortezomib , 2011, Journal of medical economics.

[12]  E. Buskens,et al.  The cost-effectiveness of atypicals in the UK. , 2008, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[13]  M. Nita,et al.  Cost-effectiveness and budget impact of saxagliptine as additional therapy to metformin for the treatment of diabetes mellitus type 2 in the Brazilian private health system. , 2012, Revista da Associacao Medica Brasileira.

[14]  T. Psaltopoulou,et al.  Economic evaluation of therapies for patients suffering from relapsed-refractory multiple myeloma in Greece , 2013, Cancer management and research.

[15]  P. McEwan,et al.  Cost Effectiveness of Saxagliptin and Metformin versus Sulfonylurea and Metformin in the Treatment of Type 2 Diabetes Mellitus in Germany , 2012, Clinical Drug Investigation.

[16]  R. Holman,et al.  A model to estimate the lifetime health outcomes of patients with Type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model (UKPDS no. 68) , 2004, Diabetologia.

[17]  A. Tsai Cost-Effectiveness of Herpes Zoster Vaccine , 2006 .

[18]  Alexandra Ward,et al.  Modelling the economic and health consequences of cardiac resynchronization therapy in the UK , 2006, Current medical research and opinion.

[19]  Irina Proskorovsky,et al.  Economic evaluation of atorvastatin for prevention of recurrent stroke based on the SPARCL trial. , 2009, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[20]  Maureen A Smith,et al.  Retrospective cost-effectiveness analysis of screening mammography. , 2006, Journal of the National Cancer Institute.

[21]  Mirjam Kretzschmar,et al.  Cost-Effectiveness of Adolescent Pertussis Vaccination for The Netherlands: Using an Individual-Based Dynamic Model , 2010, PloS one.

[22]  S. Brailsford,et al.  The evaluation of screening policies for diabetic retinopathy using simulation , 2002, Diabetic medicine : a journal of the British Diabetic Association.

[23]  D. Nathwani,et al.  Economic evaluation of doripenem for the treatment of nosocomial pneumonia in the US: discrete event simulation , 2010, Current medical research and opinion.

[24]  Murray Krahn,et al.  Conceptualizing a model: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force--2. , 2012, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[25]  Alexandra Ward,et al.  Modelling the health benefits and economic implications of implanting dual-chamber vs. single-chamber ventricular pacemakers in the UK. , 2006, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[26]  J. Staffurth,et al.  A model of the cost-effectiveness of intensity-modulated radiotherapy in comparison with three-dimensional conformal radiotherapy for the treatment of localised prostate cancer. , 2012, Clinical oncology (Royal College of Radiologists (Great Britain)).

[27]  Kelly Cho,et al.  Florbetaben PET in the Early Diagnosis of Alzheimer's Disease: A Discrete Event Simulation to Explore Its Potential Value and Key Data Gaps , 2012, International journal of Alzheimer's disease.

[28]  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.

[29]  P. Anaya,et al.  Economic Evaluation of Bariatric Surgery in Mexico Using Discrete Event Simulation. , 2012, Value in health regional issues.

[30]  J. Norrefalk,et al.  A cost-utility study of the use of pregabalin added to usual care in refractory neuropathic pain patients in a Swedish setting , 2012, Journal of medical economics.

[31]  J. Gagliardino,et al.  Treatment of type 2 diabetes with saxagliptin: a pharmacoeconomic evaluation in Argentina , 2013, Health Economics Review.

[32]  Jaime J Caro,et al.  NICE cost-effectiveness appraisal of cholinesterase inhibitors: was the right question posed? Were the best tools used? , 2007, PharmacoEconomics.

[33]  M. Ekman,et al.  Cost Effectiveness of Quetiapine in Patients with Acute Bipolar Depression and in Maintenance Treatment after an Acute Depressive Episode , 2012, PharmacoEconomics.

[34]  J. Karnon,et al.  Tamoxifen Plus Chemotherapy versus Tamoxifen Alone as Adjuvant Therapies for Node-Positive Postmenopausal Women with Early Breast Cancer , 2012, PharmacoEconomics.

[35]  Jonathan Karnon,et al.  Cost utility analysis of early adjuvant letrozole or anastrozole versus tamoxifen in postmenopausal women with early invasive breast cancer: the UK perspective , 2008, The European Journal of Health Economics.

[36]  J. Caro,et al.  A Discrete-Event Simulation of Smoking-Cessation Strategies Based on Varenicline Pivotal Trial Data , 2011, PharmacoEconomics.

[37]  C. Marra,et al.  Cost Effectiveness of Herpes Zoster Vaccine in Canada , 2012, PharmacoEconomics.

[38]  A. Burroughs,et al.  An economic evaluation of vasoactive agents used in the United Kingdom for acute bleeding oesophageal varices in patients with liver cirrhosis , 2007, Current medical research and opinion.

[39]  Cost-effectiveness of population screening for Helicobacter pylori in preventing gastric cancer and peptic ulcer disease, using simulation. , 2003, Journal of medical screening.

[40]  Walter J. Jones,et al.  Comparison of Markov Model and Discrete-Event Simulation Techniques for HIV , 2012, PharmacoEconomics.

[41]  Alexandra Ward,et al.  Modeling the economic and health consequences of managing chronic osteoarthritis pain with opioids in Germany: comparison of extended-release oxycodone and OROS hydromorphone , 2007, Current medical research and opinion.

[42]  Jonathan Karnon,et al.  Alternative decision modelling techniques for the evaluation of health care technologies: Markov processes versus discrete event simulation. , 2003, Health economics.

[43]  Rodolfo Saracci,et al.  Everything should be made as simple as possible but not simpler. , 2006, International journal of epidemiology.

[44]  D. Yin,et al.  Development of a diabetes treatment simulation model: with application to assessing alternative treatment intensification strategies on survival and diabetes‐related complications , 2008, Diabetes, obesity & metabolism.

[45]  J Karnon,et al.  Selecting a decision model for economic evaluation: a case study and review , 1998, Health care management science.

[46]  Jonathan Karnon,et al.  Modeling using discrete event simulation: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force--4. , 2012, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[47]  The cost-effectiveness of paliperidone extended release in Spain , 2012, Journal of medical economics.

[48]  J. Caro,et al.  Economic implications of extended-release metoprolol succinate for heart failure in the MERIT-HF trial: a US perspective of the MERIT-HF trial. , 2005, Journal of cardiac failure.

[49]  Peter Lindgren,et al.  Modeling the cost-effectiveness of treatment of rheumatoid arthritis with rituximab using registry data from Southern Sweden , 2009, International Journal of Technology Assessment in Health Care.

[50]  M. Löthgren,et al.  Cost effectiveness of long-acting risperidone in Sweden , 2010, Applied health economics and health policy.

[51]  Grazyna Adamiak,et al.  Methods for the economic evaluation of health care programmes, 3rd ed , 2006 .

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

[53]  P. Schädlich,et al.  Health economic evaluation of insulin glargine vs NPH insulin in intensified conventional therapy for type 1 diabetes in Germany , 2012, Journal of medical economics.

[54]  A. Boonen,et al.  A discrete event modelling framework for simulation of long-term outcomes of sequential treatment strategies for ankylosing spondylitis , 2011, Annals of the rheumatic diseases.

[55]  M. Neyt,et al.  Cost Effectiveness of Drug-Eluting Stents In Belgian Practice , 2012, PharmacoEconomics.

[56]  S. Wilson Methods for the economic evaluation of health care programmes , 1987 .

[57]  J. Caro,et al.  Pharmacoeconomics of quetiapine for the management of acute mania in bipolar I disorder , 2007, Expert review of pharmacoeconomics & outcomes research.

[58]  Jonathan Karnon,et al.  Model Performance Evaluation (Validation and Calibration) in Model-based Studies of Therapeutic Interventions for Cardiovascular Diseases , 2013, Applied Health Economics and Health Policy.

[59]  Johan L Severens,et al.  Modeling complex treatment strategies: construction and validation of a discrete event simulation model for glaucoma. , 2010, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[60]  G. Laux,et al.  Costs and effects of long-acting risperidone compared with oral atypical and conventional depot formulations in Germany , 2012, PharmacoEconomics.

[61]  J. Barendregt,et al.  Cost-Effectiveness of Total Hip and Knee Replacements for the Australian Population with Osteoarthritis: Discrete-Event Simulation Model , 2011, PloS one.

[62]  R. Wasiak,et al.  Modelling the clinical and economic implications of galantamine in the treatment of mild-to-moderate Alzheimer's disease in Germany , 2010, Journal of medical economics.