Implementing Interventions with Varying Marginal Cost-Effectiveness: An Application in Precision Medicine

Purpose. A range of barriers may constrain the effective implementation of strategies to deliver precision medicine. If the marginal costs and consequences of precision medicine vary at different levels of implementation, then such variation will have an impact on relative cost-effectiveness. This study aimed to illustrate the importance and quantify the impact of varying marginal costs and benefits on the value of implementation for a case study in precision medicine. Methods. An existing method to calculate the value of implementation was adapted to allow marginal costs and consequences of introducing precision medicine into practice to vary across differing levels of implementation. This illustrative analysis used a case study based on a published decision-analytic model-based cost-effectiveness analysis of a 70-gene recurrence score (MammaPrint) for breast cancer. The impact of allowing for varying costs and benefits for the value of the precision medicine and of implementation strategies was illustrated graphically and numerically in both static and dynamic forms. Results. The increasing returns to scale exhibited by introducing this specific example of precision medicine mean that a minimum level of implementation (51%) is required for using the 70-gene recurrence score to be cost-effective at a defined threshold of €20,000 per quality-adjusted life year. The observed variation in net monetary benefit implies that the value of implementation strategies was dependent on the initial and ending levels of implementation in addition to the magnitude of the increase in patients receiving the 70-gene recurrence score. In dynamic models, incremental losses caused by low implementation accrue over time unless implementation is improved. Conclusions. Poor implementation of approaches to deliver precision medicine, identified to be cost-effective using decision-analytic model-based cost-effectiveness analysis, can have a significant economic impact on health systems. Developing and evaluating the economic impact of strategies to improve the implementation of precision medicine will potentially realize the more cost-effective use of health care budgets.

[1]  S. Dixon,et al.  Estimating the Cost-Effectiveness of Implementation: Is Sufficient Evidence Available? , 2016, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[2]  G. Aithal,et al.  Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications , 1999, The Lancet.

[3]  Karl Claxton,et al.  The NICE cost-effectiveness threshold: what it is and what that means. , 2008, PharmacoEconomics.

[4]  S. Dixon,et al.  How to Invest in Getting Cost-effective Technologies into Practice? A Framework for Value of Implementation Analysis Applied to Novel Oral Anticoagulants , 2017, Medical decision making : an international journal of the Society for Medical Decision Making.

[5]  Katherine Payne,et al.  Accounting for Capacity Constraints in Economic Evaluations of Precision Medicine: A Systematic Review , 2019, PharmacoEconomics.

[6]  D. Street,et al.  Efficiency and equity: a stated preference approach. , 2013, Health economics.

[7]  A Gafni,et al.  Cost effectiveness/utility analyses. Do current decision rules lead us to where we want to be? , 1992, Journal of health economics.

[8]  Karl Claxton,et al.  Unrelated Future Costs and Unrelated Future Benefits: Reflections on NICE Guide to the Methods of Technology Appraisal. , 2016, Health economics.

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

[10]  Valesca P Retèl,et al.  Scenario drafting to anticipate future developments in technology assessment , 2012, BMC Research Notes.

[11]  J. Kuijpens.  [Breast cancer in The Netherlands]. , 1990, Nederlands tijdschrift voor geneeskunde.

[12]  N Freemantle,et al.  When is it cost-effective to change the behavior of health professionals? , 2001, JAMA.

[13]  I. König,et al.  What is precision medicine? , 2017, European Respiratory Journal.

[14]  W. Gradishar,et al.  Barriers to the use of personalized medicine in breast cancer. , 2012, Journal of oncology practice.

[15]  Expected Value of Sample Information with Imperfect Implementation , 2016, Medical decision making : an international journal of the Society for Medical Decision Making.

[16]  E. Adang,et al.  Economic evaluation of innovative technologies in health care should include a short-run perspective , 2008, The European Journal of Health Economics.

[17]  O. Norheim,et al.  Using Cost-Effectiveness Analysis to Address Health Equity Concerns , 2017, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[18]  Lazaros Andronis,et al.  Adjusting Estimates of the Expected Value of Information for Implementation , 2016, Medical decision making : an international journal of the Society for Medical Decision Making.

[19]  E. Pearson.  Personalized medicine in diabetes: the role of ‘omics’ and biomarkers , 2016, Diabetic medicine : a journal of the British Diabetic Association.

[20]  Gijs van de Wetering,et al.  Quantifying short run cost-effectiveness during a gradual implementation process , 2013, The European Journal of Health Economics.

[21]  Michel Wensing,et al.  Economic barriers to implementation of innovations in health care: is the long run-short run efficiency discrepancy a paradox? , 2008, Health policy.

[22]  S. Eckermann.  The Value of Value of Information Methods to Decision-Making: What VOI Measures Enable Optimising Joint Research and Reimbursement Decisions Within a Jurisdiction? , 2017 .

[23]  Peter A. Richardson,et al.  Genomic-based targeted therapy and management of advanced non-small cell lung cancer: Protocol for a qualitative study of oncologists' perceptions and behaviors regarding genomic-based targeted therapy , 2015 .

[24]  Katherine Payne,et al.  Removing barriers to a clinical pharmacogenetics service. , 2008, Personalized medicine.

[25]  W C Black,et al.  The CE Plane , 1990, Medical decision making : an international journal of the Society for Medical Decision Making.

[26]  M Johannesson,et al.  On the decision rules of cost-effectiveness analysis. , 1993, Journal of health economics.

[27]  S. Dixon,et al.  When Future Change Matters: Modeling Future Price and Diffusion in Health Technology Assessments of Medical Devices. , 2016, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[28]  A. Gafni,et al.  Changing the problem to fit the solution: Johannesson and Weinstein's (mis) application of economics to real world problems. , 1993, Journal of health economics.

[29]  Eddy M. Adang,et al.  Time to incorporate time in cost-effectiveness analysis , 2012, The European Journal of Health Economics.

[30]  Rob Baltussen,et al.  Programme costs in the economic evaluation of health interventions , 2003, Cost effectiveness and resource allocation : C/E.

[31]  C Proudlove,et al.  Gefitinib for the first-line treatment of locally advanced or metastatic non-small cell lung cancer. , 2010, Health technology assessment.

[32]  J. Reis-Filho,et al.  The European Society for Medical Oncology (ESMO) Precision Medicine Glossary. , 2018, Annals of oncology : official journal of the European Society for Medical Oncology.

[33]  David W. Dowdy,et al.  Clinical Effectiveness and Cost-Effectiveness of HIV Pre-Exposure Prophylaxis in Men Who Have Sex with Men: Risk Calculators for Real-World Decision-Making , 2014, PloS one.

[34]  M Sculpher,et al.  Evaluating the cost-effectiveness of interventions designed to increase the utilization of evidence-based guidelines. , 2000, Family practice.

[35]  Karl Claxton,et al.  The Value of Implementation and the Value of Information: Combined and Uneven Development , 2008, Medical decision making : an international journal of the Society for Medical Decision Making.

[36]  J. Doctor,et al.  A nonparametric elicitation of the equity-efficiency trade-off in cost-utility analysis. , 2005, Journal of health economics.

[37]  Maarten J. IJzerman,et al.  Value of Implementation of Strategies to Increase the Adherence of Health Professionals and Cancer Survivors to Guideline-Based Physical Exercise. , 2017, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[38]  Maiwenn J Al,et al.  Revisiting the decision rule of cost-effectiveness analysis under certainty and uncertainty. , 2003, Social science & medicine.

[39]  Denis Horgan,et al.  An Index of Barriers for the Implementation of Personalised Medicine and Pharmacogenomics in Europe , 2014, Public Health Genomics.

[40]  Julie Sakowski,et al.  Economic Perspectives on Personalized Health Care and Prevention , 2013, Forum for health economics & policy.

[41]  Andrew R Willan,et al.  Optimal clinical trial design using value of information methods with imperfect implementation. , 2009, Health economics.

[42]  A F Monk,et al.  ASSESSMENT OF THE LEARNING CURVE IN HEALTH TECHNOLOGIES , 2000, International Journal of Technology Assessment in Health Care.

[43]  Alastair Fischer,et al.  Non-linearity in the cost-effectiveness frontier. , 2006, Health economics.

[44]  Mehdi Najafzadeh,et al.  Barriers for integrating personalized medicine into clinical practice: A qualitative analysis , 2013, American journal of medical genetics. Part A.

[45]  E. Rogers,et al.  Diffusion of innovations , 1964, Encyclopedia of Sport Management.