ECONOMIC OUTCOMES RESEARCH ISSUES
IP1: DISCRETE EVENT SIMULATION OR MARKOV MODEL: WAR OF THE WORLDS OR EXPANDING THE GALAXY?
Moderator: Bengt Jönsson PhD, Professor of Health Economics, Stockholm School of Economics, Stockholm, Sweden
Panelist(s): J. Jaime Caro MDCM, FRCPC, FAC, Senior Vice President Health Economics, United BioSource Corporation, Lexington, MA, USA; Mark J. Sculpher PhD, Professor, University of York, York, UK
ISSUE: Markov models have dominated the pharmacoeconomics field but discrete event simulation is making inroads. Which technique should be used? When? Should Agencies consider both?
OVERVIEW: For more than 20 years, the predominant modeling technique for health economic models has been one based on depicting the problem in terms of the states the population can be in and the transitions among those states (i.e. the ‘Markov' approach). By combining this structure with estimates of the value of the states weighted average net value(s) can be derived and these can be used to guide resource allocation decisions. The state-based concept implies various methodological choices and feasibility of implementation requires several assumptions but this approach is well-tested and the data demands are well within what most health economic problems pose. An alternative approach based on depiction of the problem in terms of the events that can occur has been proposed, borrowing heavily from the fields of engineering and operations research. Discrete-event simulations consider what can happen in a disease process and its management and what the consequences of these events might be. This approach requires fewer technique-driven assumptions but poses greater data demands and computational time. Orthogonal to the choice of state vs. event-based modeling is the decision to model a population as a cohort in the aggregate or rather as individuals. This panel will present the pro, con and neutral positions and stoke the audience into discussion of the merits of each approach.

PATIENT-REPORTED OUTCOMES RESEARCH ISSUES
IP2: PATIENT-REPORTED OUTCOME (PRO) AND UTILITY DATA IN MARKET ACCESS DECISION-MAKING
Moderator: Anne Heyes MBA, Research Manager, Mapi Values, Cheshire, UK
Panelist(s): Jan J. Busschbach PhD, Senior Research Associate, Erasmus Medical Center, Rotterdam, The Netherlands; Chloë Brown PhD, Director, Mapi Values, Lyon, France
ISSUE: To demonstrate and discuss the ways PROs, including utilities, are taken into account in appraisal of new pharmaceuticals seeking market access in Europe and Asia.
OVERVIEW: PRO is an umbrella term for a measurement of any aspect of a patient's health status derived directly from the patient without interpretation by a third party. It includes a variety of concepts from disease-related symptoms, functioning and satisfaction to multi-dimensional measures such as Health Related Quality of Life. Utilities, needed to calculate Quality Adjusted Life Years (QALYs), can be patient-derived in a variety of ways, often from instruments such as EQ-5D. Utility data are used by some national level market access decision-makers in those countries (e.g. UK, NL) where there are formal requirements for a cost-effectiveness assessment in the form of cost per QALY, although there may be no clear guidance on interpretation. However market access decision-makers in other countries, with their variety of health care systems and processes, have different perspectives on the role and importance of PRO data in determination of pricing and reimbursement.
In this issue panel we will discuss the position of market access decision-makers regarding the use of PRO assessments; the importance of these relative to core clinical information and their use in assessing cost-effectiveness. We will use evidence to provide insights into decisions that have been taken in Japan, UK, NL and France, and will present and contrast how utility and non-utility data have been evaluated in reaching pricing/reimbursement decisions for recent products, using examples in iron chelation therapy, sleep disorders, allergy, anemia and diabetes. We will then discuss with the audience options for how the data can be derived and presented optimally to show the added value of new products and support the payer in the decision-making process.

HEALTH POLICY DEVELOPMENT USING OUTCOMES RESEARCH ISSUES

IP3: ADVANCING METHODS IN PERSONALIZED MEDICINE FOR CLINICAL DECISION MAKING (Speakers at this panel were invited)
Moderator: Uwe Siebert MD, MPH, MSc, ScD, Professor/Chair, Department of Public Health, Medical Decision Making and Health Technology Assessment at the University of Health Sciences, Medical Informatics and Technology, i.T, Austria
Panelists: M.J. Finley Austin PhD, Director, US External Science Policy, F. Hoffmann-La Roche Ltd., Basel, Switzerland; David L. Veenstra PharmD, PhD, Associate Professor, Department of Pharmacy, School of Pharmacy, University of Washington, Seattle, WA, USA; Adrian Towse MA, MPhil, Director, Office Health Economics, London, UK
ISSUE: Personalized medicine has the potential to revolutionize the practice of medicine, but despite significant scientific advances, very few genomics-based tests or treatments have reached consumers and – as with all new technologies – there may be some risk associated with this approach.
OVERVIEW: Personalized medicine is the use of a patient's genetic or clinical data to stratify a disease and select a preventive, diagnostic or therapeutic procedure, which is particularly suited to that patient. Personalized medicine makes it possible to give: "the appropriate drug, at the appropriate dose, to the appropriate patient, at the appropriate time".  David Veenstra will present “Risks and Benefits from Personalized Medicine for the Patient”.  M.J. Finley Austin will present “The Role of Personalized Medicine in Drug Development," and Adrian Towse will present “Value and Cost-Effectiveness of Personalized Medicine”.

IP4: ISPOR GREECE CHAPTER PANEL: IS ECONOMIC EVALUATION IN THE GREEK HEALTH CARE CONTEXT A FEASIBLE TARGET OR AN INTANGIBLE DREAM?
Moderator: Mary Geitona PhD, Assistant Professor, University of Thessaly, Volos, Greece
Panelist(s): Sotiria Papanicolaou MSc, MBA, Health Economics Manager, Janssen-Cilag Pharmaceutical SACI, Athens, Greece; Vassilis Kontozamanis MSc, MBA, President, National Organization for Medicines, Athens, Greece; Nikolaos Maniadakis PhD, Assistant Professor, University of Piraeus, Piraeus, Greece  
ISSUE: To investigate whether it is possible and feasible to incorporate cost-effectiveness analysis in the pharmaceutical decision making process in Greece and to determine the necessary steps in order to create the appropriate environment in which HTA can be performed efficiently.
OVERVIEW: Greece is one of the very few European countries which do not take into account economic evaluation criteria in the health care policy decision making. Therefore, pharmaceutical pricing and reimbursement decisions do not incorporate cost-effectiveness criteria but have traditionally been based on the daily cost of treatment, rather than on the relative cost per additional unit of benefit.
Based on other European countries' experience, we need to specify what is necessary to be done in order to ensure a credible and efficient method of health economic evaluation. We need to examine what other countries do and whether we can incorporate this in our framework and how. We need to evaluate the opportunities that currently exist, the weaknesses of our system and the hurdles that need to be tackled before implementing health economic evaluations in Greece.
We further need to answer to the following questions: Can HTA ensure a more effective allocation of resources in the Greek market, without restricting market access to the most innovative medicines? Is this even possible given the situation in Greece? What would the immediate benefits be?

IP5: WHAT IS THE ROLE OF HTA IN INTERNATIONAL DECISION MAKING?
Moderator: Mark JC Nuijten MD, PhD, MBA, Physician and Health Economist, Erasmus University, Rotterdam, The Netherlands
Panelist(s): Wolfgang Greiner PhD, Professor for Health Economics and Health Care Management, University of Bielefeld, Bielefeld, North Rhine-West, Germany; Peter J. Neumann ScD, Professor, Tufts-New England Medical Center, Boston, MA, USA; Gerry Oster PhD, Vice-President, PAI, Brookline, MA, USA
ISSUE: Information on the cost-effectiveness (CE) of medical interventions is becoming increasingly important in decision-making processes. Clinical innovations may not be reimbursed—and thus access to them effectively denied—because their CE ratio is deemed to exceed a pre-specified threshold. Economic data thus may have considerable consequences in terms of the range of medical interventions from which clinicians may choose and the quality of patient care. The uses of CE information therefore should be subjected to careful scrutiny.
OVERVIEW: The panel will discuss theoretical and practical issues regarding the use of CE data as a determining criterion in decisions regarding healthcare reimbursement decisions. Particular attention will be paid to methodological issues in the use of CE ratios and threshold values, and the extent to which the use of such criteria also reflect other potentially important decision-making criteria, such as equity and patient preferences. The panel also will address broader societal concerns that may conflict with the narrow application of CE criteria, including inequality and the value of innovation. Differences in the use of CE criteria in Europe and the United States of America also will be discussed.

PATIENT-REPORTED OUTCOMES RESEARCH ISSUES
IP6: PUBLIC-PRIVATE PARTNERSHIPS IN PRO INSTRUMENT DEVELOPMENT: AN IDEA WHOSE TIME HAS COME?
Moderator: Nancy Kline Leidy PhD, Senior Vice President Scientific Affairs, United BioSource Corporation, Bethesda, MD, USA
Panelist(s): Laurie B. Burke RPh, MPH, Director, FDA/CDER/OND-IO, Silver Spring, MD, USA; Asha Hareendran PhD, Senior Director, Global Outcomes Research, Pfizer, Ltd, UK & Chair, COPD PRO Working Group of the EFPIA Innovative Medicines Initiative (IMI) Respiratory calls, Sandwich, UK; Ingela Wiklund PhD, Director, Global Health Outcomes, GlaxoSmithKline, UK & Co-Chair, COPD PRO Working Group of the EFPIA Innovative Medicines Initiative (IMI) Respiratory calls, Uxbridge, Middlesex, UK
ISSUE: The development of different patient-reported outcome (PRO) instruments to measure the same concept across multiple products is expensive and inefficient. This panel will address independent versus collaborative instrument development, comparing and contrasting two new approaches to pre-competitive public-private collaboration.
OVERVIEW: Measuring the effects of treatments within clinical trials using endpoints that reflect patients' perspectives is a key component of successful drug evaluation programs. The development and validation of new PRO instruments can be expensive and time consuming. A collaborative approach for the development of instruments to capture endpoints that are common across products will save time and resources for industry and regulatory agencies and facilitate treatment decision making. This panel will address issues around independent versus collaborative efforts in the development of PRO instruments. Two approaches to public-private collaborative instrument development will be discussed: (1) A case-specific need-driven collaborative programs with multiple private sponsors and involvement of regulatory authorities; and (2) public-private partnerships with joint public-private funding. Each of these approaches will be discussed using examples from two currently active collaborative programs in the U.S. and Europe: (1) The EXACT-PRO Initiative, a program involving multiple pharmaceutical sponsors, international experts in clinical research and members of the U.S. Food & Drug Administration (FDA) to develop a single tool to evaluate exacerbation outcomes in international trials of COPD. This tool is currently undergoing translation for use in international trials; and (2) The Innovative Medicines Initiative (IMI), a partnership between the pharmaceutical industry represented by the European Federation of Pharmaceutical Industries and Associations (EEPIA) and the European Communities represented by the European Commission. The first call for proposals for the IMI is now underway, including a call for studies of PROs in COPD. These approaches will be compared and contrasted with an opportunity for the audience to ask questions and participate in discussion.

HEALTH POLICY DEVELOPMENT USING OUTCOMES RESEARCH ISSUES
IP7: IS THE PURSUIT OF QALY MAXIMISATION A NOBLE CAUSE? (ISPOR Invited Issue Panel)
Moderator: Adrian Towse MA, MPhil, Director, Office Health Economics, London, UK
Panelist(s): Mark J. Sculpher PhD, Professor, University of York, York, UK; Erik Nord PhD, Senior Researcher, Norwegian Institute of Public Health, Oslo, Norway; Georg Marckmann MPH, MD, Professor, University of Tüebingen, Department of Medical Ethics, Tübingen, Germany
ISSUE: To discuss the merits of “QALY maximization” as a theoretical basis for the evaluation of healthcare technologies and to consider research opportunities associated with wider or alternative principles of health care decision making.
OVERVIEW: As NICE approaches its 10th anniversary, the application of such formal cost-utility methods to inform reimbursement and pricing decisions still represents the minority methodology within Europe. However a large proportion of current pharmacoeconomic research focuses upon the methods of evaluating new healthcare technologies assuming the principle of maximizing health gain from a fixed budget. Contrasting perspectives will be put forward from panelists on the advantages and disadvantages of utilising QALY maximization as the basis for healthcare decision making. Specific issues that will be discussed include whether maximizing health gain from a fixed budget should be the primary focus of payers and HTA agencies, if not what is the correct “maximand”? The panel will consider whether population preferences between equity of access, the rule of rescue and technical efficiency be accounted for within HTA systems and if so how can this be practically achieved? Also what are the possible longer term consequences for patient access and innovation of new technologies from the strict application of QALY maximization? Consideration of the role and weight formal quantitative methods should receive within the broader decision making framework will be discussed. The question of whether it is ethical to primarily focus on QALY maximization will also be considered by the panel. Finally if alternative principles for HTA assessment are identified, the panel will discuss whether current HTA methods are sufficiently capable to support such alternative principles or are new theories of health care decision making required?

IP8: FAST IS BEST! IS RAPID HEALTH TECHNOLOGY ASSESSMENT TO SUPPORT MARKET ACCESS DECISION-MAKING A GOOD THING?
Moderator: Jeanni Van Loon MSc, Development Director - Europe, Mapi Values, Houten, The Netherlands
Panelist(s): Keith H. Tolley MPhil, Director, Tolley Health Economics Limited, Buxton, Derbyshire, UK; Meindert Boysen MSc, Associate Director Single Technology Appraisals, National Institute for Health and Clinical Excellence (NICE), Manchester, UK; Andrew Walker, PhD, Senior Lecturer, University of Glasgow, Glasgow, UK
ISSUE: What are the advantages and limitations of rapid health technology assessment when used to support decisions on market access for new pharmaceuticals in Europe?
OVERVIEW: The use of health technology assessment (HTA) and formal cost-effectiveness analysis by bodies such as NICE and Scottish Medicines Consortium (SMC) has become well established in the UK to support market access decision making for new pharmaceuticals. Whilst SMC have always performed rapid HTA on single drugs based primarily on company submissions of clinical and cost-effectiveness evidence, NICE has traditionally conducted detailed technology appraisals of one or more drugs in a therapy area with clinical reviews and economic modelling conducted by independent academic institutions. However, under pressure to produce guidance faster and closer to drug launch, in the last two years NICE has also begun performing rapid single technology appraisals based on company submissions of evidence. The approaches of NICE and SMC to performing rapid HTA and pharmacoeconomics differ in important ways, in terms of process and methodology. The issues panel will explore the advantages and limitations of alternative England and Scotland approaches to rapid appraisal and investigate whether this is better in terms of granting access to cost-effective medicines than a slower ‘more rigorous' process of appraisal with independent assessment. The panelists from NICE and SMC will therefore present the advantages and limitations of the rapid appraisal processes and methods for their respective bodies. Before opening to audience debate the third panelist will explore (primarily from a pharma industry/consulting agency perspective) the rigour and value for decision making of the rapid approaches described and the transferability of key principles and methods from the UK model to other European countries to support pricing, reimbursement and market access decisions.

IP9: MARKET ACCESS OF MEDICAL DEVICES IN EUROPE: HAVE METHODOLOGICAL APPROACHES BECOME A HINDRANCE OR HELP?
Moderator: Stacey J. Ackerman MSE, PhD, Vice President, Covance Market Access Services Inc, San Diego, CA, USA
Panelist(s): Uwe Siebert MD, MPH, MSc, ScD, Professor/Chair, Department of Public Health, Medical Decision Making and Health Technology Assessment at the University of Health Sciences, Medical Informatics and Technology, i.T, Austria; Arne Heissel PhD, Director Reimbursment & Health Economics, Spinal & Biologics, Medtronic International, Tolochenaz, Switzerland
ISSUE: Will European authorities and decision-making bodies routinely embrace methodological approaches, such as meta-analysis of diagnostic tests and adaptive clinical trials of therapeutic devices?
OVERVIEW: European authorities and decision-making bodies appraise diagnostic and therapeutic medical devices, in addition to drugs, to inform market access decisions. The distinguishing characteristics of medical devices and drugs explain the inherent differences in research approach, including study design and analysis. The Agency for Healthcare Research and Quality (AHRQ) is currently developing and discussing the frameworks, principles, and guidance for evaluation of diagnostic tests. In addition, the ISPOR book entitled, Medical Device and Diagnostics Outcomes Research: Issues and Good Research Practices is nearing completion. During this issue panel, several analytical approaches will be presented, such as meta-analysis of diagnostic tests, adaptive clinical trials of therapeutic devices, and decision modeling to link test performance (sensitivity and specificity) to patient-relevant outcomes. Methodologists and decision makers on the panel will present contrasting perspectives. There will be discussion about whether these methodological approaches are likely to be increasingly adopted for guideline development or reimbursement purposes in European countries. The role of medical device companies in generating evidence and influencing the regulatory and reimbursement environments will be a topic for audience debate.

IP10: FUTURE SCIENTIFIC AND POLICY CONSEQUENCES OF THE IQWIG APPROACH FOR EUROPE
Moderator: Mark JC Nuijten MD, PhD, MBA, Consultant, Ars Accessus Medica/Erasmus University Rotterdam, Amsterdam, The Netherlands
Panelist(s): Christoph Vauth MSc, Head Health Technology Unit, Leibniz University Hannover, Hannover, Germany; John Hutton PhD, Professor of Health Economics, University of York, York, UK  
ISSUE: Cost-effectiveness data is becoming increasingly a formal requirement for reimbursement submissions in Europe and the incremental cost-effectiveness ratio is becoming an essential decision criterion in health care reimbursement decisions. Most of the European countries have similar health economic guidelines. The recent IQWIG guidelines for Germany shows a substantial difference with the other guidelines in Europe, which may have important consequences for the development of health economics as a science and its relevance and role in health care decision making processes.
OVERVIEW: The panel will discuss theoretical and conceptual discrepancies between the German and other guidelines, especially the NICE guidelines, which can be considered the most influential guidance in Europe. An important discrepancy is the difference in outcomes assessment: cost-effectiveness vs. cost-utility. This and other conceptual differences will be explained from a legal and historical perspective in the respective countries. The scientific consequences of the current IQWIG guidelines will be addressed. In a broader view the current methodological debates on discounting, utilities and costing seem minor issues compared with substantial conceptual differences of the IQWIG guideline, illustrated by the concept of a cost-effectiveness frontier. On the other hand the cost-effectiveness approach seems more in line with AMCP guidelines in the US, justifying also the question, if the use of health economic data by decision makers in Germany will become comparable to the US. Panel members represent the relevant countries (Germany, UK, US). Key topics will include: will IQWiG guidelines lead to a split in different health economics schools? Will IQWIG guidelines prevent central European reimbursement decision and health economic standards? Will other countries, who currently have no formal requirement (e.g. France), follow NICE or IGWIG guidance?