E.C. Faulkner

Challenges in the Development and Reimbursement of Personalized Medicine—Payer and Manufacturer Perspectives and Implications for Health Economics and Outcomes Research: A Report of the ISPOR Personalized Medicine Special Interest Group

BACKGROUND Personalized medicine technologies can improve individual health by delivering the right dose of the right drug to the right patient at the right time but create challenges in deciding which technologies offer sufficient value to justify widespread diffusion. Personalized medicine technologies, however, do not neatly fit into existing health technology assessment and reimbursement processes. OBJECTIVES In this article, the Personalized Medicine Special Interest Group of the International Society for Pharmacoeconomics and Outcomes Research evaluated key development and reimbursement considerations from the payer and manufacturer perspectives. METHODS Five key areas in which health economics and outcomes research best practices could be developed to improve value assessment, reimbursement, and patient access decisions for personalized medicine have been identified. RESULTS These areas are as follows: 1 research prioritization and early value assessment, 2 best practices for clinical evidence development, 3 best practices for health economic assessment, 4 addressing health technology assessment challenges, and 5 new incentive and reimbursement approaches for personalized medicine. CONCLUSIONS Key gaps in health economics and outcomes research best practices, decision standards, and value assessment processes are also discussed, along with next steps for evolving health economics and outcomes research practices in personalized medicine.

Health Technology Assessment for Molecular Diagnostics: Practices, Challenges, and Recommendations from the Medical Devices and Diagnostics Special Interest Group

BACKGROUND Health technology assessments (HTAs) are increasingly used to inform coverage, access, and utilization of medical technologies including molecular diagnostics (MDx). Although MDx are used to screen patients and inform disease management and treatment decisions, there is no uniform approach to their evaluation by HTA organizations. OBJECTIVES The International Society for Pharmacoeconomics and Outcomes Research Devices and Diagnostics Special Interest Group reviewed diagnostic-specific HTA programs and identified elements representing common and best practices. METHODS MDx-specific HTA programs in Europe, Australia, and North America were characterized by methodology, evaluation framework, and impact. Published MDx HTAs were reviewed, and five representative case studies of test evaluations were developed: United Kingdom (National Institute for Health and Care Excellences Diagnostics Assessment Programme, epidermal growth factor receptor tyrosine kinase mutation), United States (Palmettos Molecular Diagnostic Services Program, OncotypeDx prostate cancer test), Germany (Institute for Quality and Efficiency in Healthcare, human papillomavirus testing), Australia (Medical Services Advisory Committee, anaplastic lymphoma kinase testing for non-small cell lung cancer), and Canada (Canadian Agency for Drugs and Technologies in Health, Rapid Response: Non-invasive Prenatal Testing). RESULTS Overall, the few HTA programs that have MDx-specific methods do not provide clear parameters of acceptability related to clinical and analytic performance, clinical utility, and economic impact. The case studies highlight similarities and differences in evaluation approaches across HTAs in the performance metrics used (analytic and clinical validity, clinical utility), evidence requirements, and how value is measured. Not all HTAs are directly linked to reimbursement outcomes. CONCLUSIONS To improve MDx HTAs, organizations should provide greater transparency, better communication and collaboration between industry and HTA stakeholders, clearer links between HTA and funding decisions, explicit recognition of and rationale for differential approaches to laboratory-developed versus regulatory-approved test, and clear evidence requirements.

The application of economics concepts to stratified medicine—use of health economics data to support market access for stratified medicine interventions

Abstract Stratified medicine (SM), as opposed to empirical medicine, is the practice of using biomarkers or diagnostic tests to guide the choice of therapeutic treatments. The link between the diagnostic test and the therapy provides new opportunities for value creation and may strengthen the value proposition to pricing and reimbursement authorities. However, SM provides new challenges for the value assessment process, in particular health technology assessment (HTA) and pricing and reimbursement (P&R) decisions. Although health economics (HE) should be relevant for all stakeholders, not all stakeholders are comfortable with analysis/interpretation of economic data relevant to SM interventions as this approach is still in an early/emergent stage in most markets. This article addresses how different stakeholders are using health economic data in the overall value of information analysis to inform prioritization and reimbursement of SM interventions. Findings of an expert discussion outlines key challenges affecting various stakeholders when applying health economic data in the healthcare decision-making process for SM interventions.

Developing the Value Proposition for Personalized Medicine

Standard methodological approaches have successfully been applied to evaluate the cost-effectiveness of numerous personalized medicine tests, particularly for companion diagnostics developed in the context of a clinical trial. However, disagreement has emerged about the extent to which existing methods can characterize the value of personalized medicine. This chapter provides an overview of cost-effectiveness analysis and the factors determining the value of personalized medicine. The authors identify limitations of the traditional cost-effectiveness analysis framework and methodological issues that will arise with increasing use of multiple “omics” profiles to guide individualized selection of treatments.

Reimbursement Trends and Evidence Requirements for Ultra-Orphan Therapies Across Europe: Optimising Market Access in Increasingly Challenging Markets.

Total Morawski JH1, Paul A2, Spinner DS2, Doyle JJ3, Faulkner EC4, Ransom JF1 1 Quintiles Consulting, Hawthorne, NY, USA; 2 Quintiles Consulting, Durham, NC, USA; 3 Department of Epidemiology and the Department of Healthcare Policy & Management at the Mailman School of Public Health, Columbia University, NY, USA; 4 Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, NC, USA Reimbursement Trends and Evidence Requirements for Ultra-Orphan Disease Therapies Across Europe: Optimising Market Access in Increasingly Challenging Markets

Next Generation Sequencing Technology: Health Technology Assessment, Market Access Trends and Potential Impacts on The Future of Companion Diagnostic Testing.

PCN215 Next GeNeratioN SequeNCiNG teChNoloGy: health teChNoloGy aSSeSSmeNt, market aCCeSS treNdS aNd PoteNtial imPaCtS oN the Future oF ComPaNioN diaGNoStiC teStiNG Faulkner E.C.1, Spinner D.S.2, Ransom J.F.3, Paul A.4, Chawla A.S.5, Doyle J.J.6, Shaw W.H.2, Fitzgerald J.T.2 1Institute for Pharmacogenomics and Individualized Therapy, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA, 2Quintiles, Durham, NC, USA, 3Quintiles Global Consulting, Hawthorne, NY, USA, 4Quintiles Global Consulting, Durham, NC, USA, 5Quintiles Consulting, Durham, NC, USA, 6Quintiles, Hawthorne, NY, USA Objectives: Next Generation Sequencing (NGS) offers a potentially powerful platform for extremely sensitive, high-throughput, multiplex, quantitative detection of nucleic acid biomarkers. While NGS currently represents a small portion of global clinical molecular diagnostic testing, new funding and reimbursement initiatives promise to accelerate its clinical utilization. Given increasing numbers of predictive/ prognostic biomarkers but limited tissue and need for less invasive sample acuisition, NGS has the potential to transform personalized medicine (PM) and companion diagnostics. The current study characterized global NGS availability and reimbursement trends. Health technology assessments (HTAs) for NGS and other relevant multiplex/ gene panel tests were also studied for evolving evidence requirements. MethOds: Key health care provision, HTA agency, and payer websites in the EU, US, Australia and Canada were reviewed to identify NGS funding and reimbursement initiatives, and relevant HTAs. In addition, a limited number of stakeholder interviews were conducted to help further characterize the evolving global NGS landscape. Results: A number of NGS funding and reimbursement initiatives were identified, especially France, Germany, UK, US and Australia. Initiatives have been mainly centered on funding of pilot clinical utility demonstrations through research and clinical use. In Germany and US, specific initiatives are underway to develop specific NGS reimbursement codes and payment rates. A number of HTAs for NGS and other multiplex/ gene panel test platforms were identified, primarily for oncology, cardiovascular, infectious disease, inherited disease, and neuropsychiatry applications. Key HTA concerns include test clinical utility, cost-effectiveness, realworld reproducibility and equity of access given potential cost. cOnclusiOns: Payers and providers increasingly recognize NGS as enabling expanded adoption of PM approaches. As PM expands with increasing numbers of clinically actionable biomarkers, ensuring that test evidence development is aligned with expectations, and expectations with reality are key steps. Further, developing reimbursement/ funding mechanisms to support testing uptake will be critical in all markets.

The Case For Early Payer Engagement.

Global healthcare expenditure is increasing [1], creating budget pressures and challenging market access for an increasing number of drugs [2]. For instance, from 1998-2008, NICE granted restricted or no access to ~60% of drugs from the top 10 Pharma and since 2004, IQWiG classified 70% of reviewed drugs as “benefit not proven” [3]. Payers are often bewildered by decisions made by pharmaceutical manufacturers when designing their clinical trials, choosing their comparators, or making certain safety and efficacy claims with mismatched evidence. This misalignment may be the result of clinical development plans focused on regulatory compliance that do not fully consider the real-world patient populations that reflect Payer’s chief concerns. Not engaging Payers as early as possible during the asset development process could result in delay of approval and/or rejection of reimbursement. Knowledge of payer priorities and the level of evidence they seek are crucial to characterization of real value of assets and competitive differentiation. The objective of this study was to illustrate the case for early payer engagement to ensure optimal patient access to differentiated assets. We here present the relative merits of various approaches to engage with Payers as well as case studies exemplifying the positive impact of early engagement.