Issues Panels – Session I (4 panels)

FDA DRAFT GUIDANCE FOR THE INDUSTRY ON THE ASSESSMENT OF PATIENT REPORTED OUTCOMES – WHAT ARE THE IMPLICATIONS FOR GLOBAL CLINICAL RESEARCH?
 

Moderator: Patrick Marquis MBA, MD, Managing Director,  Mapi Values, Boston, MA, USA

Panelists: David W. Miller PhD, Vice President, Global Health Outcomes, GlaxoSmithKline, Research Triangle Park, NC, USA; Ingela Wiklund PhD, Professor, Senior Principal Scientist, Global Director Outcomes Research, Astra Zeneca, Molndal, Sweden

ISSUE: To discuss from the industry perspective and from the European regulatory perspective the interpretation and the implications of the draft guidance issued by the FDA regarding the assessment of treatment effect based on Patient Reported Outcome (PRO) measures. Panelists will be composed of two members from the industry (drug developer perspective), and one European regulator.

OVERVIEW: The new PRO paradigm has been introduced a few years ago in the US and is now broadly used by the FDA and by outcomes researchers. This was a very important step towards the integration of the patient’s perspective into the regulatory process. Indeed, PROs are used for label development and promotional claim. The second most important step is the release of a draft guidance regarding the development and validation of PRO questionnaires as well as their implementation in clinical trials, their analysis and interpretation. However, if most of the recommendations can be agreed upon by the different stakeholders, some points deserve more discussion particularly from a European regulatory perspective: acceptation of the concept of PRO as a general model for patient reported assessments, cross-cultural development and validation, determination of minimum important difference and interpretation of the clinical significance of findings... The implications on global clinical development programs should also be pictured and potential challenges for integrating the new FDA recommendations brought up.

PHARMACOECONOMIC STUDIES POST-LAUNCH: WHO NEEDS THEM?
 

Moderator: Adrian Towse MA, Office of Health Economics, London, UK

Panelists: Martin Buxton BA Soc Sci, Professor, Brunel University, Uxbridge, Middlesex, UK; Rosario Trindade, Infarmed, Lisbon, Portugal; Claude Le Pen PhD, Aremis Consultants and Paris Dauphine University, Paris, France; Michael Drummond PhD, Director, University of York, York, UK

ISSUE: To compare and contrast the different approaches to the requests for, and the conduct of, post-launch studies in different European countries.

OVERVIEW: There is increasing interest in conducting pharmacoeconomics and outcomes research studies post-launch. These include additional clinical studies, observational studies and research into the impact of new drugs on quality of life. In countries where a national agency evaluates the cost-effectiveness of new drugs, such as the United Kingdom and Portugal, the agency may make recommendations for further research. However, a recent survey indicates that these suggestions may not necessarily be followed by industry, because of the cost or complexity of studies, or doubts about their impact on decision making. In other countries, such as France, there appears to be substantial industry activity in conducting post-launch studies, even though they are not officially required. The panel will discuss the various needs for post-launch studies in Europe and the practical problems of carrying them out.

WHAT IS GOING ON IN GERMANY?
 

Moderators: Marianne Van Genugten, Project Director,  MAPI Values, Houten, The Netherlands; Jeanni Van Loon MSc, Development Director Europe, Mapi Values, Houten, The Netherlands

Panelists:  York Zoellner MS, PharmD, Health Economics Manager , Solvay, Hannover, Germany; Reiner Leidl PhD, Department of Health Economics, Ludwig-Maximilians-University, Munich, Germany

ISSUE: An increasing number of countries endorse HE guidelines and the pharmaceutical industries are these days busy with preparing dossiers for national authorities for obtaining targeted prices and maximizing the reimbursement level of their new drugs (e.g. in the UK, Finland, Norway, the Netherlands etc.). In some countries without official guidelines it is considered supportive for the pricing and reimbursement negotiations to submit dossiers (like France). In Germany, as one of the largest EU countries and pharmaceutical markets, the situation is not very clear for the different stakeholders. Although Germany is currently establishing a federal institute on quality and efficiency in medicine with some features resembling UK’s NICE, the impact for future coverage of drugs within the statutory health insurance system remain somewhat unclear. When will this new agency begin to work, how will it work and interact with other agencies contributing to coverage decisions, and what will be its role in a European perspective? Will experiences from other countries such as the UK and the Netherlands be taken into account? Should industry already start preparing for NICE like dossiers or will this not be required in the near future?

OVERVIEW: Views on what is going on in Germany according to industry and the academic world will be shortly presented and will be put in perspective by the consultancy with regard to the various existing systems in other European countries. In the last 20 minutes the floor will be opened for general discussion, focusing on the yet unclear German situation.

INDUSTRY’S VS. STATUTORY HEALTH INSURANCE’S VS. UNIVERSITY’S RESEARCH INTERESTS – IS THERE MUTUAL BENEFIT IN EPIDEMIOLOGICAL AND OUTCOMES RESEARCH?
 

Moderator: Bernd Brüggenjürgen MD, MPH, Alpha Care GmbH, Celle, Germany

Panelists:   Wolfgang Meyer-Sabellek Prof, PhD, AstraZeneca, Wedel, Germany; Christoph Straub, Techniker Krankenkasse, Hamburg, Germany; Stefan N. Willich Prof, PhD  University Medicine Berlin, Charité, Berlin, Germany
 

ISSUE: Three perspectives (industry, health insurance and research) will be presented to compare and differentiate where objectives of the different perspectives overlap and what is jointly feasible for epidemiologic and outcomes studies in the context of changing agencies' and institutional requests.

OVERVIEW: Pharmacoeconomics and outcomes research performed in the development phase and increasingly in post-launch are often performed in cooperation between industry and university and only quite recently also with paymasters. Depending on the development status of the product the corresponding research interests are changing over time. However, cooperation can be observed over the full development cycle from mere epidemiologic research, over clinical research to producing cost-effectiveness data in real life clinical practice. In addition, objectives of research are increasingly driven by statutory agencies determining the framework of reimbursement or use of drugs (e.g. NICE in the UK) which drives further research, comprising both epidemiologic, clinical and observational studies and health service research. The panel will discuss the types of studies where cooperation deserves further support, where interesting potential for cooperation exists and where potential pitfalls might occur.

Issue Panels – Session II (4 panels) 

ECONOMIC ISSUES IN RISK MANAGEMENT
 

Moderator: Adrian Towse MA, Director, Office of Health Economics, London, UK  

Panelists: Lou Garrison PhD, Professor, University of Washington, Seattle, WA, USA ; Thomas Lonngren, Director, European Medicines Agency, EMEA, Canary Wharf, London, UK

ISSUE: An improved risk management process is currently a major initiative at the FDA and has received increasing attention at the EMEA. This initiative has focused on patient safety and pharmacovigilance programs to accompany the launch of new products and to identify areas where the regulator and the company can work better together in the pre-authorisation period. The economic and policy implications of these changes have not been fully addressed. In particular the need to use more formal approaches to calculating the health gains and losses associated with decisions to delay or withdraw the authorization of products.

OVERVIEW: It has been generally recognized that risk management programs and approaches that focus on drug safety alone run the risk of insufficient attention to the benefits side of the equation. These are likely to impose additional costs on drug development, including larger study sizes and a longer time to product launch. The downside maybe that fewer patients will receive the benefits that the product provides. This panel will discuss whether economic implications of these risk management requirements in terms of how they are likely to affect development time and costs, patient access to innovation, and aggregate health outcomes. In addition, potential methodologies and procedures to measure and assess these impacts will be discussed, including the possibility of using cost-utility analyses to project the trade-offs and the use of value of information approaches to assess whether additional risk management investments represent value for money to society. This raises the policy question of whether regulatory authorities should explicitly use models to project these trade-offs in the course of their deliberations. The pros and cons of this will be discussed.

CHALLENGES TO ATTAIN THE TARGETED PRICE AND MAXIMUM REIMBURSEMENT IN ALL EUROPEAN COUNTRIES
 

Moderator: Jeanni Van Loon MSc, Development Director Europe, Mapi Values, Houten, The Netherlands

Panelists: Guido Van den Boom PhD, Health Outcomes Manager, Novartis Pharma BV, Arnhem, The Netherlands; Jens Grueger PhD,  Head of Pricing and Health Economics Department, Novartis Pharma AG, Basel, Switzerland; H. Van Dieten MSc, Policy Advisor Pharmacoeconomics, Health Care Insurance Board  (CVZ), Diemen, The Netherlands

ISSUE: Attaining the targeted price and maximum reimbursement of a new product in all EU member states is more and more a time consuming challenge for health economics (HE) managers. Headquarters develop core models adaptable to key countries. But who are the key countries these days, of course the big five EU countries, although? Preparing dossiers in which the cost-effectiveness of the new drug has to be proven and -preferably published results around the time of submission- is required in an increasing number of countries. Does this impact the sequence of launching? The decision makers require sound economic evaluations, but are data on the right comparator available, how have they modeled from efficacy to effectiveness? What have colleague decision makers in other countries decided? etc. The problems encountered by all parties will be enlightened.

OVERVIEW: By means of a dramatization (role-play) in a fictitious country, the problems encountered by all parties (i.e. local HE manager, headquarters, the local decision maker) in Price and Reimbursement negotiations will be shortly presented. In the last 20 minutes the audience will be encouraged to participate in an interactive discussion, on how to overcome the pitfalls and how to deal with the increasing number of EU countries encountering the same problems. The program will be concluded with some solutions and guidance on how to avoid the pitfalls from a multi-party perspective

SCIENCE OR ADVERTISING: HOW EDITORS DRAW THE LINE
 

Moderator: C. Daniel Mullins PhD, Professor and Chair of Pharmaceutical Health Services Research, University of Maryland, Baltimore, MD, USA  

Panelists: Christopher Carswell, Editor, Pharmacoeconomics, Adis International, Auckland, New Zealand; Alan Lyles MPH, RPh, Professor,  University of Baltimore, Baltimore, MD, USA; Josephine Mauskopf PhD, Division Director, Global Health Economics, RTI Health Solutions, RTI International, Research Triangle Park, NC, USA
 

ISSUE: Editors from Value in Health (Mauskopf), Clinical Therapeutics (Lyles) and Pharmacoeconomics (Carswell) will discuss how the editorial and peer-review process for pharmacoeconomics and outcomes research papers is designed to ensure sound methodology and unbiased reporting of results.

OVERVIEW: The editorial and peer-review process for pharmacoeconomics and outcomes research articles is designed to assure that published papers use sound methodology and appropriate data, and present results and conclusions that are substantiated, unbiased and useful for decision-making. The editors of three journals that publish significant numbers of pharmacoeconomics and outcomes research papers will discuss ways to evaluate such papers to achieve these goals. A brief review of the editorial and peer-review process for each journal will be presented and then followed by an interactive session with the attendees discussing such topics as:  criteria for performing sensitivity analyses for modeling papers; how to utilize the ISPOR task force guidelines for database studies; how, when, and at what rate discounting should be performed; the use of accepted criteria for validating quality of life measures; incorporating the best evidence from clinical trials and other sources into modeling studies; presenting balanced conclusions rather than 'company value messages'; the process for determining authorship and acknowledgements; and disclosure of real and potential conflicts of interest. The discussion will provide guidance for both authors and reviewers of papers.

DO DECISION-MAKERS HAVE LESS CREDIBILITY WITH MODELING RESULTS?
 

Moderator: Uwe Siebert MD, MPH, MSc, Decision Scientist, Director of the Cardiovascular Research Program, Institute for Technology Assessment, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA and Director of the Program on Health Technology Assessment and Decision Sciences (HTA&DS), Institute for Medical Informatics, Biostatistics, and Epidemiology, University of Munich, Munich, Germany.

Panelists: Bernhard Gibis MD, MPH, Head of Department of Quality Assurance, National Association of Statutory Health Insurance Physicians (NASHIP), Berlin, Germany; Michael Drummond PhD, Director, Centre for Health Economics, University of York, York, UK. 

ISSUE: Over the last few years, the use of decision-analytic modeling techniques to optimize decisions in patient outcomes and to aid resource allocation has strongly increased. More and more sophisticated modeling techniques are available. A growing number of Health Technology Assessment Agencies require decision-analytic cost-effectiveness studies to extrapolate results from clinical trials to the long-term and routine health care context of a specific country or health care system. NICE and other organizations that are responsible for reviewing the cost-effectiveness of medical technologies are now requiring in their guidelines the use of probabilistic sensitivity analyses as part of virtually all modeling studies. Software to develop and evaluate models has strongly improved. However, the ultimate question has not been answered: "Do modeling studies have an impact on decisions in medicine and health care, and in particular, what are the concerns decision makers have with modeling results?  

OVERVIEW: The credibility of decision models for decision makers and the impact of modeling results will be judged from both the scientific view (Drummond) and the perspective of decision makers (Gibis). In particular, we will discuss which features (transparency, parsimony, methodologic approach, time horizon, validation etc.) influence the acceptability of modeling results. There are numerous applications of models such as cost-effectiveness analysis and resource allocation, forecasting and health care planning, and value-of-information analysis and future research prioritization. The panelists and the attendees will discuss in which areas modeling is most important. Finally, we will attempt to come to a conclusion about what needs to be changed to improve the credibility and the impact of modeling results in health-care decision making.