Workshops
Monday, 9 November 2015
17:00 - 18:00
WORKSHOPS - SESSION I
Health Policy Development Using Outcomes Research

17:00 - 18:00
Room: Gold (L2)

W1: DEFINING AND VALUING INNOVATION IN ONCOLOGY

Discussion Leaders:

Michael Drummond, MCom, DPhil, Professor of Health Economics, Centre for Health Economics, University of York, Heslington, York, UK bio

Alistair Mcguire, PhD, Professor of Health Economics, LSE Health, London School of Economics, London, UK

Monique Martin, PharmD, MSc, MBA, Vice President & General Manager HEOR Europe, MAPI, Uxbridge, UK

Elizabeth Jones, MSc, Project Leader, HEOR Europe, MAPI, Uxbridge, UK

PURPOSE:

To compare and evaluate how regulators and payers define and reward innovation.

DESCRIPTION:

Rising drug costs and budgetary constraints have led decision makers to be restrictive in the acceptation of new drugs and are increasingly asking for a demonstration of innovation. In cancer care this is especially important as many of these treatments are expensive and often have limited data on which to base their economic value. In this workshop we will focus on how regulators define and reimburse innovative therapies. We will give examples of accelerated approval, fast-track, priority review and breakthrough therapy status. In addition, we will adopt a decision maker’s perspective, where we will distinguish between types of innovation in particular a novel innovation which relates to a new product that alters the existing market and will create a new demand, and an incremental innovation which is associated with the improvement of an existing class of treatments. Issues relating to surrogate endpoints and the demonstration of innovation, will also be addressed. Furthermore we will attempt to show whether innovative status as defined by different regulators has market impact. Finally we will link these issues to other disease areas where innovation costs are high and product value is difficult to define. We will ensure audience participation by providing the product profiles of two imaginary products, characterizing breakthrough therapy and incremental innovation, at the room entry and we will ask the audience to rank market impact based on these product profiles in terms of likely accepted reimbursed price, volume and clinical importance.


17:00 - 18:00
Room: Brown 1-2 (L2)

W2: THE PUB & THE P-SUB: A POTENTIAL FRAMEWORK DEVELOPED TO ASSESS THE NEED FOR AND DESIGN OF MANAGED ENTRY AGREEMENTS FOR NEW DRUGS

Discussion Leaders:

Sabine Grimm, MSc, PhD Candidate, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK

Alan Brennan, PhD, Professor of Health Economics and Decision Modelling, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK

Mark J. Sculpher, MSc, PhD, Professor of Health Economics, Centre for Health Economics, University of York, Heslington, York, UK

Johan L. Severens, PhD, Professor of Evaluation in Health Care, Institute of Health Policy and Management, Institute of Health Policy & Management, Erasmus University Rotterdam, Rotterdam, The Netherlands

PURPOSE:

To present and discuss a framework developed to assess the need for and design of managed entry agreements for new drugs.

DESCRIPTION:

Managed Entry Agreements (MEAs) can be used by reimbursement authorities and manufacturers to agree a process for recommending new drugs that can include agreed price reductions and/or further research to be conducted.  The NICE Decision Support Unit was commissioned to develop a framework that could potentially be used for assessing proposed MEAs within NICE technology appraisals. In this workshop the speakers in turn will: 1. Present the framework and its application to several exemplar case study results. The methods are simple extensions / representations of the results from a standard cost-effectiveness analysis with probabilistic sensitivity analysis.  They calculate the "Payer Uncertainty Burden (PUB)" for the decision and the "Payer Optimality Gain (POG)" for the option which is most cost-effective.  For options which are not the most cost-effective, they estimate the "Payer Sub-optimality Burden (PSB)" and the "Payer Sub-optimality AND Uncertainty Burden (PSUB)".  Quantities are estimated in terms of financial cost or in QALYs, and presented both per person and for the country jurisdiction per annum.  This enables comparisons of risks and benefits to payers both across appraisals and between MEA options.   2. Discuss the issues which are likely to arise and processes which could be put in place if this framework were to be utilised by stakeholders in the NICE technology appraisal process. 3. Reflect on the issues which would need to be addressed for this framework to be adopted in the Netherlands. 4. Consider the potential use of the approach in jurisdictions globally. Finally, the panel will invite comments from the audience on whether and how such a framework could be further developed or utilised to analyse the need for and design of MEAs.

Use of Real World Data

17:00 - 18:00
Room: Brown 3 (L2)

W3: ADJUSTING FOR TIME-DEPENDING CONFOUNDING AND CROSSOVER BIAS IN OBSERVATIONAL STUDIES AND CLINICAL TRIALS: PURPOSE, METHODS, AND ACCEPTANCE IN HTA

Discussion Leaders:

Felicitas Kuehne, MSc, Senior Scientist, Public Health and Health Technology Assessment, UMIT, Hall i.T., Austria

Uwe Siebert, MD, MPH, MSc, ScD, Professor, Department of Public Health & HTA/ONCTYROL, Area 4 HTA & Bioinformatics/Harvard T.H. Chan School of Public Health, Center for Health Decision Science, Department of Health Policy & Management, Harvard Medical School, Institute for Technology Assessment & Department of Radiology, Hall i.T., Austria

Nicholas Latimer, PhD, Senior Research Fellow in Health Economics, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK

Lars Beckmann, PhD, Research Fellow, Institute for Quality and Efficiency in Healthcare (IQWIG), Cologne, Germany

PURPOSE:

In this workshop, three invited speakers will provide an overview of causal methods. We present the purpose and methods of adjusting for time-depending confounding in observational studies and adjustment for crossover in randomized clinical trials (RCTs) in the context of health technology assessment (HTA). We discuss the indications and data requirements for applying these methods and discuss how well they are accepted in science and for approval from regulatory and reimbursement agencies.

DESCRIPTION:

Observational studies and RCTs need causal methods to estimate a valid causal effect. Causal methods are needed if there is confounding-by-indication in observational studies or when ITT analyses lead to biased effect estimates in RCTs with noncompliance or treatment switching. Since first HTA agencies have accepted and requested the use of causal methods, a paradigm shift is taking place, and the selection of the appropriate method has become crucial to yield patient access to innovative treatments. The workshop has three parts: 1. Prof. Uwe Siebert will take the educational perspective, introducing the concepts and methods of causal analysis and presenting case examples demonstrating how inadequate analysis can yield inappropriate results, impacting recommendations made by HTA agencies (e.g. NICE). 2. Dr. Nicholas Latimer will take the scientific perspective, explaining the theoretical background and comparing different methods (e.g., rank preserving structural failure time models, marginal structural models, two stage approach), and discussing recommendations regarding when to use which methods. 3. Dr. Lars Beckmann will take an agency-perspective, discussing the acceptance and barriers of statistical methods to approach treatment switching in RCTs in the process of drug approval and how treatment switching can influence study design, analytic strategy, approval, and the HTA process. We will provide an outlook to what should be done to move the field forward and will invite the audience to participate in this discussion.

Clinical Outcomes Research

17:00 - 18:00
Room: Space 1 (L0)

W4: MAKING SENSE OF NOVEL APPROACHES FOR INDIRECT COMPARISON: SIMILARITIES AND DIFFERENCES OF SIMULATION AND MATCHING BASED APPROACHES

Discussion Leaders:

K. Jack Ishak, PhD, MSc, Senior Research Leader, Evidera, Montreal, QC, Canada

Hemant Phatak, PhD, Group Director, Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ, USA

Cristina Masseria, PhD, Director Outcomes & Evidence, Global Health & Value, Pfizer Inc., New York, NY, USA

PURPOSE:

To assist researchers and decision makers in gaining a better understanding of simulated treatment comparison (STC) and matching-adjusted indirect comparison (MAIC) as alternative and complimentary approaches to traditional network meta-analysis (NMA). An example based on treatments for non-valvular atrial fibrillation (NVAF) where all three approaches have been applied will be used to highlight the similarities and differences between the methods and their underlying assumptions. The audience will be engaged to provide their impressions and experiences with the various methods.

DESCRIPTION:

STC and MAIC can overcome incomplete evidence networks where lack of comparative trials or common comparators prohibit comparisons between some of the treatments with an NMA.  Even with a complete network, heterogeneity between studies may compromise reliability NMA. STC and MAIC can address such heterogeneity, especially when it is attributable to differences in study populations. While conceptually similar, the two approaches differ in the methodology they use to balance the populations. STC uses predictive equations to generate adjusted outcomes in the comparator population, while MAIC achieves this by reweighting patients in one trial to match the profile of the other’s population. An example in cardiovascular disease will be used to illustrate the analytical steps of each approach, highlighting the assumptions being invoked. A notable feature of the example is the studies do have common comparator arms; this offers an opportunity to assess whether there is any heterogeneity due to factors beyond the population profiles, and how this may be leveraged in the analyses. Furthermore, common comparator arms also allow a contrasting of results from STC and MAIC with an NMA. The concepts will be generalized beyond the example to help address questions such as, when STC or MAIC should be considered, whether both approaches are always appropriate, when one should be favored over the other, etc.

Economic Outcomes Research

17:00 - 18:00
Room: Space 2 (L0)

W5: GUIDANCE FOR EVIDENCE SYNTHESIS OF SURVIVAL OUTCOMES FOR COST-EFFECTIVENESS MODELING

Discussion Leaders:

Jeroen P Jansen, PhD, Director, Redwood Outcomes, San Francisco, CA, USA

Andrew Briggs, DPhil, MSc, William R. Lindsay Chair of Health Economics, Health Economics & Health Technology Assessment, Institute of Health & Wellbeing, University of Glasgow, Glasgow, UK

Nicky J. Welton, MSc, PhD, Reader in Evidence Synthesis, School of Social and Community Medicine, University of Bristol, Bristol, UK

PURPOSE:

This workshop will provide guidance regarding the selection of meta-analysis models for the synthesis of progression free survival and overall survival to create cost-effectiveness models. 

DESCRIPTION:

Cost-effectiveness analysis of oncology treatments are often based on progression free survival (PFS) and overall survival (OS). The proportional hazards assumption that underlies current approaches of meta-analysis of PFS and OS is not only often implausible, but can have a huge impact on decisions based on cost-effectiveness analysis. Common practice is to assume a parametric survival function for the baseline intervention (e.g. Weibull) and apply the treatment specific constant hazard ratio obtained with meta-analysis to calculate a corresponding survival function enabling comparisons of expected PFS and OS. Since the tail of the survival function has a major impact on the expected survival, violations of the constant hazard ratio can lead to severely biased estimates of cost-effectiveness. Alternative meta-analysis methods have been proposed that do not rely on the proportional hazards assumption, and the parametric nature of these meta-analysis models facilitate extrapolation of PFS and OS curves as commonly needed for cost-effectiveness analysis. Although these new meta-analysis models are very powerful in creating cost-effectiveness models that fit the clinical trial data better, their flexibility requires careful consideration to obtain a cost-effectiveness analysis that is plausible. The workshop starts with an introduction of the recently published meta-analysis models followed by outlining the requirements for valid extrapolation of PFS and OS over time using appropriate constraints. Next we will present an algorithm for the selection of a meta-analysis model for PFS and OS that provides a compromise between statistical criteria of model fit and epidemiological plausibility. The workshop will be concluded with an interactive session in the form of a multiple choice quiz where the proposed guidance needs to be applied to realistic examples.

Patient-Reported Outcomes & Patient Preference Research

17:00 - 18:00
Room: Space 3 (L0)

W6: ASSESSING MEDICATION ADHERENCE: PATIENT-REPORTED, CLINICAL, PHARMACOEPIDEMIOLOGIC, AND ECONOMIC APPROACHES

Discussion Leaders:

Sarah Clifford, PhD, Director, ICON Commercialisation and Outcomes, ICON Clinical Research, LLC, San Francisco, CA, USA

Lina Eliasson, PhD, Lead Outcomes Researcher, ICON PRO, Oxford, UK

RA Elliott, PhD, Lord Trent Professor of Medicines and Health, Social Research in Medicines and Health School of Pharmacy, University of Nottingham, Nottingham, UK

Shelagh Szabo, MSc, Director & Head of Evidence Generation, Redwood Outcomes, Vancouver, BC, Canada

PURPOSE:

The purpose of this workshop is to describe barriers to accurately estimating adherence; discuss approaches to assessing and evaluating adherence from the clinical, patient-reported, pharmacoepidemiologic, and economic perspectives; and develop study designs to robustly measure adherence using real-world examples.  

DESCRIPTION:

Although adherence to appropriately prescribed medications is a key contributor to effectiveness, non-adherence remains common. It is estimated that approximately 50% of patients may not take their medications as prescribed, which can impact the success of treatment and relevant clinical and patient-reported outcomes, and increase the economic burden. Understanding adherence is important not only for individual patient disease management, but also for accurately evaluating the benefits and risks of new vs. existing therapies.  However, accurately estimating medication adherence is challenging because of selection and reporting biases that impact study findings, in addition to inaccuracies in the adherence measures themselves. In many diseases there is little good quality evidence linking adherence to patient outcomes and associated economic impact, required for assessing the cost effectiveness of adherence-enhancing interventions. This workshop will provide a background for participants on adherence assessment and evaluation methods from a number of disciplines, including state-of-the-art approaches or the novel use of existing data sources. The strengths and limitations of the approaches will be reviewed.  While working within small groups, workshop participants will review, critique, and appraise existing study designs, and propose novel strategies to address adherence-related study questions. Researchers interested in understanding data and methods available to assess and evaluate adherence would benefit from participating in this workshop.

Tuesday, 10 November 2015
8:45 - 9:45
WORKSHOPS - SESSION II
Health Policy Development Using Outcomes Research

8:45 - 9:45
Room: Gold (L2)

W7: MARKET ACCESS 2020: WHAT ARE THE NEXT CHALLENGES?

Discussion Leaders:

Meriem Bouslouk, PhD, MSc, Officer, Pharmaceuticals Department, Federal Joint Committee (G-BA), Berlin, Germany

Jan Mueller-Berghaus, MD, Paul-Ehrlich- Institute (PEI), Langen, Germany

Antoni Gilabert-Perramon, PhD, Managing Director of Pharmacy and Medicines, Catalan Health Service, Government of Catalonia, Barcelona, Spain

Mondher Toumi, MD, MSc, PhD, Professor of Public Health, Department of Public Health, Aix-Marseille University, Marseille, France

PURPOSE:

In this workshop, the speakers propose to confront different perspectives: an academic professor, a national HTA from the G-BA (Germany), a regional payer from Spain (Catalonia) and a regulator from Paul-Ehrlich-Institut (Germany) in order to share vision on future market access models in place or in discussion to cope with the evolving pharmaceuticals environment. Challenges will include: (1)Pressure on health budgets; (2) Technological and scientific advances, i.e. advanced therapeutic medicinal products, personalized medicines, digital medicine; (3) Joint regulators/payers initiatives, multi-HTA collaboration; (4) Increased payer risk-aversion and increasingly limited information at launch; (5) Development of integrated healthcare (IH); (6) Growing prevalence of chronic conditions; (7) Increased access inequity between European Union (EU) Member States (MS).

DESCRIPTION:

Adaptive pathways and limited evidence at time of launch may enhance coverage with evidence development. More pragmatic clinical trial designs may be considered to cope with concomitant development of companion diagnostics, segmentation of patients, targeted therapies. Adaptive pathways may become standard approach. Cost-containment measures will fall under MS parliaments’ supervision. Fast development of electronic communication will allow online monitoring of drug utilisation patterns. Post-launch observational studies will become unavoidable to meet regulators and payers’ expectations. Pan-European HTA coordination could lead to one single European HTA body assessing drugs prior to national HTA. Managed entry agreements, ambulatory DRG, and bundled payments will be frequent. IH will expand shifting payer’s role to healthcare providers. Differential pricing will address inequity across EU MS. Based on their long experience, the contributors will explain how extended collaborations and interactions between key stakeholders will become a critical issue to maintain the sustainability of healthcare systems, in a fast evolving environment. Contributors will involve the audience by encouraging them to provide input and real life experience to enlarge the contribution to this debate.


8:45 - 9:45
Room: Brown 3 (L2)

W8: EVIDENCE SYNTHESIS BASED ON AGGREGATE AND INDIVIDUAL-LEVEL DATA: CONSIDERATIONS FOR USE IN HTA DECISION MAKING

Discussion Leaders:

Timothy Reason, MSc, Senior Consultant, Real-World Evidence Solutions, IMS Health, London, UK

Pedro Saramago Goncalves, MSc, PhD, Research Fellow, Centre of Health Economics, University of York, Heslington, York, UK

Yumi Asukai, MSc, Director, R&D Value Evidence Analytics, GSK, Uxbridge, UK

Keith R Abrams, PhD, Professor of Medical Statistics, Department of Health Sciences, University of Leicester, Leicester, UK

PURPOSE:

This workshop will discuss potential dangers of relying on evidence synthesis from network meta-analysis (NMA) based solely on aggregate data in informing comparative effectiveness, and the impact of such use on decision-making. We will highlight potential solutions and current barriers to resolution to initiate a dialogue among the community for responsible evidence generation.

DESCRIPTION:

Lack of head-to-head trials between relevant comparators has led to increased use of NMA techniques for establishing comparative effectiveness. These techniques have become especially relevant in economic evaluation and HTA to inform resource allocation at the national level. Realistically, most NMAs are conducted using aggregate data; while key steps can be taken to address potential bias, such as adjustment for effect modifiers and selecting appropriate studies or sub-populations to minimise heterogeneity, there are still several issues that cannot be adequately addressed without individual patient data (IPD). Tim Reason will review current standards of NMAs and how to correct for potential bias, as well as the advantages of using IPD in place of aggregate data in addressing ecological bias and study-level confounding, Pedro Saramago will discuss how the use of IPD can increase power for sub-group analyses and allow richer stratification of patients for decision making, potentially allowing appropriate judgements to be made for particular subgroups. Yumi Asukai will discuss the impact of using results of evidence syntheses in economic models and the pros and cons of having IPD-based NMAs, including decreased uncertainty, both structural and parameter. Lastly, Keith Abrams will summarise the issues raised in the wider context of policy decisions. The audience will be asked to comment on hypothetical case studies and how the use of IPD could improve the ultimate decision; discussion will centre around advantages of having access to IPD in establishing comparative effectiveness for the purposes of health care policy decision making.

Use of Real World Data

8:45 - 9:45
Room: Space 1 (L0)

W9: DEVELOPMENT OF EVIDENCE PACKAGES FOR REGULATORY AND REIMBURSEMENT SUBMISSIONS IN RARE DISEASES: REAL-WORLD EXAMPLES

Discussion Leaders:

Nicola Bonner, MSc, Senior Research Manager, EDOA, Adelphi Values Ltd, Bollington, UK

Alexandra Bowden, PhD, Senior Manager, Ultragenyx Pharmaceutical Inc., Novato, CA, USA

Vasudha Bal, MSc, MBA, Director, Patient Reported Outcomes, Worldwide Health Outcomes, Value & Access, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

Anne Kilburg, MSc, Principal Consultant, Wellmera AG, Basel, Switzerland

PURPOSE:

This workshop will highlight the importance of, and challenges associated with development of evidence such as suitable endpoints, Clinical Outcome Assessments (COAs) and comparators in rare diseases using real-world examples.

DESCRIPTION:

Increasing numbers of rare diseases are being recognized and more medicines to treat them being developed. There are several unique challenges for developing evidence packages in rare diseases such as the paucity of information on patient populations, disease progression and appropriate COAs. As with all clinical development programs, disease specific COAs are an important part of assessing signs and symptoms of rare diseases and treatment response. The objectives will be achieved through four presentations of approximately 12 minutes and audience questions. Firstly, Vasudha Bal will present the overall challenges of collecting data to support registration and reimbursement. She will outline the key areas where collecting such evidence could be particularly difficult. Nicola Bonner will then discuss the challenges associated with developing COAs, and special considerations associated with clinical trials and regulatory approaches in rare diseases. This segment will involve audience members sharing examples of challenges associated with conducting research in rare diseases. Anne Kilburg will discuss the evidence needs and requirements for HTA/payer bodies for a positive value assessment and reimbursement. This section of the workshop will involve an interactive exercise with the audience to vote blinded case studies in terms of their value assessment/reimbursement outcomes. Alexandra Bowden will then share an example of a healthcare professional administered COA for assessment of physical functioning limitations associated with a rare genetic disease. This section of the workshop will involve audience members trying some of the activities assessed by the instrument and discussing the challenges associated with ensuring consistent assessment of the activities. The session will close with audience questions and sharing their own examples of work in rare diseases.

Clinical Outcomes Research

8:45 - 9:45
Room: Space 2 (L0)

W10: MOVING THE SCIENCE FORWARD: TACKLING KEY PSYCHOMETRIC AND METHODOLOGICAL ISSUES FACING THE FIELD OF CLINICAL OUTCOME ASSESSMENT

Discussion Leaders:

Tara Symonds, PhD, COA Strategy Lead & Partner, Clinical Outcomes Solutions Ltd., Folkestone, Kent, UK

Kathleen W. Wyrwich, PhD, Executive Director, Center of Excellence, Outcomes Research, Evidera, Bethesda, MD, USA

Antoine Regnault, PhD, Research Director, HEOR & Strategic Market Access, Mapi, Lyon, France

Stephen Joel Coons, PhD, Executive Director, PRO Consortium, Critical Path Institute, Tucson, AZ, USA

PURPOSE:

The purpose of this workshop is to present several key unresolved methodological issues facing the regulatory and scientific community in the field of clinical outcome assessment (COA) and to discuss insight gained from initial deliberations aimed at achieving scientific consensus and resolution.   

DESCRIPTION:

A group of measurement specialists convened to discuss issues identified by academics, industry, and regulators as scientifically challenging in the context of developing, evaluating, and interpreting COAs.  The issues addressed by this panel included: 1) Methods for determining clinically meaningful change e.g.  What defines a good anchor?  Are distribution-based methods useful? What is the appropriate role for cumulative distribution functions? Are qualitative studies a more direct way of deriving meaningful change from patients’ and clinicians’ perspectives? 2) Quantitative assessment of cross-cultural differences e.g. If a COA is not quantitatively equivalent cross-culturally, what are the solutions?  When is absence of equivalence an important issue? 3) Use of mixed methods research in instrument development e.g. What is the value of mixed methods research in COA tool development?  Can it provide a more efficient way of developing content for new measures?  When is a qualitative sample sufficient for exploratory quantitative analysis? 4) Context effects and use of computer adaptive testing (CAT) e.g. Do context effects have the potential to introduce enough response bias to necessitate the time and expense of additional quantitative research?  How to address the perceived limitation regarding use of CAT e.g. heterogeneity, and concept coverage/content balance, and selected/non-selected response bias? The discussion leaders will outline the issues and describe the current consensus landscape, noting how future research will move the field towards resolution.  Discussion leaders will engage attendees to share their perspectives on the most relevant and effective approaches to addressing each of the issues, as well as to provide insight gained from their own research.

Economic Outcomes Research

8:45 - 9:45
Room: Space 3 (L0)

W11: TRANSLATING PHARMACOMETRICS TO PHARMACOECONOMICS

Discussion Leaders:

Richard J. Willke, PhD, Vice President, Outcomes & Evidence Lead CV/Metabolic, Pain, Urology, Gender Health, Global Health & Value, Pfizer Inc., New York, NY, USA

Scott Marshall, PhD, Senior Director, Pharmacometrics, Global Clinical Pharmacology, Pfizer, Inc, Sandwich, UK

Julia F Slejko, PhD, Assistant Professor, Pharmaceutical Health Services Research, University of Maryland School of Pharmacy, Baltimore, MD, USA

PURPOSE:

A key aspect of any health economic model is the way that treatment outcomes are determined. The purpose of this workshop is to present a practical, step-by-step example of how pharmacometric findings may inform health economic model inputs.  We will: 1) Present an overview of pharmacoeconomic models, 2) illustrate how a health economic model structured to be consistent with pharmacometric findings can be a powerful tool to project the clinical and health economic results of a clinical trial or other health intervention on specific populations, and 3) engage the audience in a discussion about evaluations of potential cost-effectiveness and the probability of a drugs’ success in later-stage clinical trials.

DESCRIPTION:

Pharmacometrics is an analytic approach that draws upon pharmacokinetics, pharmacodynamics, statistics and clinical pharmacology to combine information about biomarkers and clinical studies to predict efficacy and safety outcomes. Presenter #1(SM) will present an overview of pharmacometrics and pharmacometric model-based meta-analysis (PMBMA), a type of meta-regression which employs non-linear models estimated on a trial/arm mean-level data to relate patient and trial characteristics, dosing/treatment, and biomarkers/surrogate endpoints to clinical outcomes.   Using modeling software, Presenter #2 (JS) will present a practical, step-by-step example of how a PMBMA can be used to create model inputs to inform early stage cost-effectiveness analysis of a potential COPD drug. Presenter #3 (RW) will discuss the potential findings that may result from such an analysis and how they may relate to trial patient selection. Presenter #4 (JP) will engage the audience with pre-defined discussion points about potential cost-effectiveness to inform later-stage clinical trials.

Patient-Reported Outcomes & Patient Preference Research

8:45 - 9:45
Room: Brown 1-2 (L2)

W12: OPTIMIZING PATIENT INVOLVEMENT IN PAYER HEALTH CARE DECISIONS TO ACCESS NEW THERAPIES

Discussion Leaders:

Nicola Bedlington, Director, European Patients' Forum, Brussels, Belgium

Michael Barry, MD, PhD, Clinical Director, National Centre for Pharmacoeconomics, Dublin, Ireland

Bettina Ryll, MD, PhD, Founder, Melanoma Patient Network Europe, Uppsala, Sweden

Veronica Foote, BA, Head of Patient Relations & External Communications, Novartis Oncology Europe, Surrey, UK

PURPOSE:

Patients are becoming increasingly involved with the use of evidence to support payer decisions for new therapies and technologies. This includes involvement in study designs and measures to produce evidence, as well as health technology assessment processes that synthesize and interpret evidence and engage with patient experts. With the continued evolution of HTA processes and patient representation, there is now considerable uncertainty as to the type and level of involvement of patients in payer decisions, the outcomes of these interactions and what can be learned from them. This workshop will provide insight into what is currently known and discuss shared experiences.

DESCRIPTION:

This workshop will explore experiences across different types of patients, HTA organizations and levels of involvement based on work conducted by the ISPOR European patient representatives roundtable. Nicola Bedlington will describe the ISPOR patient-led project intended to capture cases of patient interaction with HTA processes and highlight general themes that emerged. Patients and patient leaders will present specific experiences with HTA systems and describe the benefits and challenges of engagement. Representatives from an HTA agency, a patient organization, and industry will reflect on these findings and what more must be done to these processes. Audience members will be invited to share their own experiences with HTA processes and reflect on the case examples. Audience members will then be engaged in a priority setting exercise regarding where more research and action are required. The discussion is intended to identify specific areas for future work and potential solutions.

16:30 - 17:30
WORKSHOPS - SESSION III
Health Policy Development Using Outcomes Research

16:30 - 17:30
Room: Brown 3 (L2)

W13: THE ROLE OF VALUE OF INFORMATION IN HTA: ARE WE MISSING AN OPPORTUNITY?

Discussion Leaders:

Gianluca Baio, PhD, Reader in Statistics & Health Economics, Statistical Science, University College London, London, UK

Nicky J. Welton, MSc, PhD, Reader in Evidence Synthesis, School of Social and Community Medicine, University of Bristol, Bristol, UK

Mark Strong, PhD, Clinical Senior Lecturer in Public Health, School of Health and Related Research, University of Sheffield, Sheffield, UK

Anna Heath, BSc, PhD Student, Statistical Science, University College London, London, UK

PURPOSE:

The purpose of this workshop is to: (i) demonstrate, with examples, recent developments in the computation of Expected Value of Partial Perfect Information (EVPPI); and (ii) to discuss the potential role of Value of Information (VoI) in assessing key drivers of decision uncertainty and the need for further research.

DESCRIPTION:

In health economic evaluations, the EVPPI is a measure of the sensitivity of a decision to uncertainty in individual model inputs. The EVPPI can therefore help decision makers focus on the key parameters driving decision uncertainty and point towards areas where there truly is a need for further research. Until recently, the EVPPI was computationally intensive to calculate and required a high level of technical expertise. However, recent statistical developments have allowed approximations of the EVPPI that are accurate, fast, efficient and straightforward to compute.  Now the technical barriers to computing VoI have been removed there is an opportunity to use the methods routinely in HTA. The workshop will begin with Dr Baio who will give an introduction to EVPPI and the need for efficient computational methods, by presenting some examples to illustrate how the EVPPI can be used within an HTA context. Next, Dr. Strong will present a novel non-parametric regression method for approximating the EVPPI. He will illustrate the method using the “SAVI” web app, a simple user interface for the non-parametric regression method which requires only the probabilistic sensitivity analysis sample. Miss Heath will present a further development to the non-parametric regression method and will demonstrate the ease with which the EVPPI can be computed using the R package BCEA. We finish the workshop with a discussion, led by Dr Welton, of the facilitators and barriers to the routine adoption of VoI calculation in HTA now that computational difficulties have largely been solved.


16:30 - 17:30
Room: Gold (L2)

W14: ORPHAN DRUG EVIDENCE REQUIREMENTS FOR POSITIVE HTA RECOMMENDATIONS

Discussion Leaders:

Josie Godfrey, MA, Associate Director, Highly Specialised Technologies, National Institute for Health and Care Excellence (NICE), London, UK

François Meyer, MD, Advisor to the President, International Affairs, French National Authority for Health (HAS), Paris, France

Mondher Toumi, MD, MSc, PhD, Professor of Public Health, Department of Public Health, Aix-Marseille University, Marseille, France

Meriem Bouslouk, PhD, MSc, Officer, Pharmaceuticals Department, Federal Joint Committee (G-BA), Berlin, Germany

PURPOSE:

In this workshop, the speakers explore how the available degree of evidence for orphan drugs influences health technology assessment (HTA) outcomes and decision-making in three different European orphan drug assessment procedures and critically discuss the results with the audience on the basis of concrete current examples to enable recommendations for future HTA.

DESCRIPTION:

With the introduction of the Regulation (EC) No 141/2000 on orphan medicinal products, specific criteria have been established to ensure a scientific designation of pharmaceuticals as orphan drugs within the European Union. These products undergo different market access procedures and incentives in the European countries, including different points in time for their patient's availability, different national policies for benefit assessment and different coverage. Because of the high prices and increasing budget impact of orphan drugs, health technology assessments, in their function as the basis for related reimbursement, are of crucial interest for access to these pharmaceuticals. A generic HTA decision framework happens to be inappropriate in some countries, especially when driven by incremental cost-effectiveness ratio. The contributors will give an overview of current approaches of evaluating orphan drugs by different HTA bodies with a focus on evidence requirements in specific countries like France, Germany and UK. Examples will be used to illustrate the heterogeneity of decisions across Europe and make recommendations to maximize chances to achieve positive HTA outcomes. The moderator Professor Toumi will stimulate the audience to contribute to the debate by discussing their experience with current orphan drug HTA outcomes.

Use of Real World Data

16:30 - 17:30
Room: Space 2 (L0)

W15: SAMPLE SIZE ESTIMATION AND POWER CALCULATION FOR PROSPECTIVE OBSERVATIONAL STUDIES

Discussion Leaders:

Eric Gemmen, MA, Senior Practice Leader, Epidemiology & Outcomes Research, Real-World & Late Phase Research, Quintiles, Inc., Rockville, MD, USA

Mark J Nixon, MSc, PhD, Director, Chilli Consultancy, Salisbury, UK

Jennifer Liu, PhD, Biostatistician, Chilli Consultancy, Salisbury, UK

PURPOSE:

To highlight challenges and offer solutions to sample size estimation and power calculation for observational studies and patient registries, through use of numerous case examples and live calculations.

DESCRIPTION:

Unlike randomized controlled trials (RCTs), prospective observational studies and patient registries typically address objectives rather than test specific hypotheses. Nevertheless, estimation of sample size is an important part of the planning process for these studies.  A minimum sample size and power is required to allow for adequate exploration of the objectives and to ensure sufficient generalizability of the results.  Sample size estimation for observational studies is more complex than sample size calculation for RCTs; subgroup analyses and modeling are to be expected in observational studies, and these analysis methods require more assumptions and larger sample sizes. On the other hand, sample sizes must not be so large as to raise concern that the observational study includes an unnecessarily high number of sites and patients, which is particularly true where a specific commercial product is being observed. This workshop will provide examples/case studies of sample size estimations performed for a variety of prospective observational studies with an array of objectives, including burden of illness, comparative effectiveness, comparative safety and personalized medicine.  We will focus on sample size estimation methods for observational studies that take the following analysis techniques into account: 1.) Outcome comparisons against historical comparators and historical controls. 2.) Propensity score matching to support comparisons of cohorts. 3.)Investigation of factors that influence outcomes within subgroups. 4.) Multiple comparison adjustments to support comparisons between multiple study sites and multiple patient types over multiple time points. 5.) Time-to-event analyses including a) disease progression or remission, c) major adverse cardiac event, etc. 6.) Re-estimation of sample size based on interim results. Audience input based on experience will be encouraged throughout the session, which will include live use of sample size estimation software.


16:30 - 17:30
Room: Space 3 (L0)

W16: RETROSPECTIVE HEALTH OUTCOMES RESEARCH AND HEALTH-ECONOMIC EVALUATION BASED ON REAL-WORLD DATA ANALYSES IN EUROPE: DATA AVAILABILITY, STRENGTHS AND LIMITATIONS, AND DATABASE-SPECIFIC CONSIDERATIONS

Discussion Leaders:

Thomas Wilke, PhD, Partner, Ingress-Health, Wismar, Germany

Myrthe P. P. van Herk-Sukel, PhD, Manager, Research Department, Epidemiologist, PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands

Andreas Fuchs, PhD, Consulting Pharmacist, AOK PLUS, Dresden, Germany

Wilhelmine Meeraus, MSc, Research Scientist, Medicines and Healthcare Products Regulatory Agency, The Clinical Practice Research Datalink, London, UK

PURPOSE:

There is a growing need to obtain real-world evidence/outcomes data in numerous indications. Retrospective database studies seem to be a fast and rather cost-effective option to collect these data. However, there may be disadvantages of database studies as well, i.e. because of limited availability of clinical data (in some databases), the mostly retrospective nature of data, non-representativeness of some databases and difficulty in assessing confounders. In this workshop, we will discuss these issues in four sessions based on a general overview of available retrospective health databases across Europe.

DESCRIPTION:

In the first panel presentation, Thomas presents results of a benchmarking of available non-disease specific health care databases (both claims and GP-/specialist databases) across Europe. He also discusses strength/limitations of retrospective database analyses with respect to different disease areas and different study objectives. Andreas will discuss specifics of German claims data (available variables, strengths and weaknesses). Specifically, he will describe how to access German claims data and will discuss reliability of German claims information based on an example study in diabetes mellitus 2 patients. Wilhelmine will discuss specifics of the UK GP-based CPRD database which can also be linked to specific other databases, e.g. the HES hospital database. They will also discuss strengths and weaknesses of this widely used retrospective health database for health outcomes research, with a focus on diabetes recording and treatment. Finally, Myrthe van Herk-Sukel will discuss specifics of the PHARMO Database Network which is a population-based network of healthcare databases and combines data from different healthcare settings in the Netherlands. She will also present a case example in the area of Oncology. Interactive element: The discussion between participants will be about the value of combining data of different datasets in different countries for observational research, but also for HTA purposes.

Economic Outcomes Research

16:30 - 17:30
Room: Space 1 (L0)

W17: CHALLENGES AND SOLUTIONS TO SUCCESSFULLY DETERMINE REAL-WORLD COST-EFFECTIVENESS

Discussion Leaders:

Saskia de Groot, MSc, Researcher, Institute of Health Policy & Management, Institute for Medical Technology Assessment (iMTA), Erasmus University Rotterdam, Rotterdam, The Netherlands

Hedwig M. Blommestein, MSc, Researcher, Institute of Health Policy & Management, Erasmus University Rotterdam, Rotterdam; Comprehensive Cancer Organisation, Utrecht; Institute for Medical Technology Assessment, Erasmus University Rotterdam, Rotterdam, The Netherlands

Margreet G. Franken, PhD, Researcher, Institute for Medical Technology Assessment (iMTA), Erasmus University Rotterdam, Rotterdam, The Netherlands

Annet F.M. van Abeelen, PhD, Pharmaco Economics & Access Manager, Health Economics and Business Development, Roche Pharmaceuticals Netherlands, Woerden, The Netherlands

PURPOSE:

Real-world cost-effectiveness analysis (RW-CEA) is often complicated by great heterogeneity and non-randomised treatment. The aim of this workshop is to share insight into methods to appropriately deal with incomparability issues including propensity score matching (PSM), discrete event simulation (DES), and data synthesis. Strengths and limitations of these methods will be discussed from a theoretical and empirical point of view.

DESCRIPTION:

As opposed to trial patients, real-world patients generally have a worse prognosis, more comorbidities, and are older. Therefore, there is a growing interest in real-world evidence to complement evidence from trials. However, RW-CEA is complicated by incomparability issues. Failure to account for these issues may lead to biased results and incorrect conclusions. This workshop focuses on three methods: PSM, DES, and data synthesis. The potentials and pitfalls of each method will be discussed by sharing theoretical and empirical insights based on our experiences in performing RW-CEA. First, the potential of PSM will be illustrated by matching real-world patients to create comparable groups for a RW-CEA in non-Hodgkin lymphoma. Second, the DES method will be explained using examples from two disease models spanning multiple lines of treatment (two and three treatment lines in renal-cell carcinoma and multiple myeloma, respectively). Third, data synthesis will be clarified using a RW-CEA for chronic lymphocytic leukemia in which trial data was used to determine progression-free survival and registry data was used to determine post-progression survival. The workshop will focus on the extent to which the three methods provide useful, valid and reliable information to healthcare decision makers, facilitate evidence-based decision-making, and ultimately improve health outcomes. An interactive discussion will encourage audience participation to contribute to further understanding whether it is feasible to calculate real-world cost-effectiveness.

Patient-Reported Outcomes & Patient Preference Research

16:30 - 17:30
Room: Brown 1-2 (L2)

W18: UTILITIES IN HTA: CHALLENGES FOR THEORY AND PRACTICE NOW AND IN THE FUTURE

Discussion Leaders:

Jenny Berg, PhD, Senior Scientist, Mapi, Stockholm, Sweden

Nancy Devlin, PhD, Director of Research, Office of Health Economics, London, UK

Michael Drummond, MCom, DPhil, Professor of Health Economics, Centre for Health Economics, University of York, Heslington, York, UK bio

PURPOSE:

This workshop will discuss methodological and practical challenges regarding generation and use of utility data in HTA. We will compare different sources for such information, using examples from the literature and recent analyses of real-world data. The objective is to provide guidance to manufacturers on how to generate data on utilities for HTA submissions to authorities with differing requirements and to discuss how these requirements might change in the future.

DESCRIPTION:

Utility weights are an integral part of economic evaluations in many jurisdictions, requiring an understanding of alternative sources and methods and the need to tailor these to the decision context. We will begin by outlining current HTA requirements for utility data. We then discuss the theoretical foundations of utilities, including newer methods such as discrete choice experiments, highlighting normative questions arising from these – such as the choice between experience-based utilities as an alternative to community-based utilities. Practical considerations around the use of available methods (including generic measures, direct elicitation, 'bolt-ons', and mapping from descriptive health-related quality of life measures) will be outlined and illustrated through examples. The impact of different elicitation and modelling techniques, as well as sources of utility data will be demonstrated based on a review of published data on health states in chronic heart failure, an area with promising clinical developments. This will be complemented by recent analyses based on a clinical quality registry from Sweden, where analyses for different value sets have been performed (experience-based value set from Sweden, community-based value sets from the UK and the US). The implications for cost-effectiveness results will be explored. Finally, we will provide a future outlook on potential methodological developments. We ensure audience participation by discussing the implications for manufacturers in terms of planning for different sources for utility data and suitable methods for obtaining these.

Wednesday, 11 November 2015
8:45 - 9:45
WORKSHOPS - SESSION IV
Use of Real World Data

8:45 - 9:45
Room: Brown 1 (L2)

W19: ESTIMATION AND PREDICTION OF RELATIVE EFFECTIVENESS USING REAL-WORLD EVIDENCE: CASE STUDIES

Discussion Leaders:

Keith R Abrams, PhD, Professor of Medical Statistics, Department of Health Sciences, University of Leicester, Leicester, UK

Reynaldo Martina, PhD, Research Associate, Department of Health Sciences, University of Leicester, Leicester, UK

Eva-Maria Didden, PhD, Researcher, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland

Sandro Gsteiger, PhD, HTA Statistician, MORSE - Health Technology Assessment Group, F. Hoffmann-La Roche Ltd, Basel, Switzerland

PURPOSE:

This workshop, organized by members of the IMI GetReal project, will demonstrate several statistical and mathematical approaches that incorporate real-world evidence (RWE) into the estimation and prediction of relative effectiveness pre-launch. It will provide a forum for workshop participants to both discuss the relative merits of the various approaches and their own experiences of using RWE in HTA. The methods will be illustrated with applications from various indications, with a special focus on rheumatoid arthritis (RA).

DESCRIPTION:

 Incorporating RWE into the drug development process pre-launch is receiving growing interest from pharmaceutical companies, regulators, and payers alike. Health technology assessment and reimbursement decisions could benefit from methods which are able to estimate and predict relative effectiveness of treatments at the time of launch. This workshop presents statistical and mathematical approaches that combine randomized controlled trials (RCT) data and RWE to inform HTA. In the first session, Dr. Martina will discuss how data from registries and RCTs can be used to estimate relative effects of second-line use of treatments in a network meta-analysis context. In the second session, Dr. Didden will present a predictive model that incorporates data from both RCTs and registries to bridge the efficacy-effectiveness gap, i.e. to generalize results observed in RCTs to a real-world setting. In the third session, Dr. Gsteiger will discuss potential applications and initiatives within pharmaceutical companies that aim at a more efficient use of RWE pre-launch. Prof. Abrams will moderate the workshop and facilitate participant discussion of both the three topics presented, and their own experiences of using RWE in a HTA context.

Health Policy Development Using Outcomes Research

8:45 - 9:45
Room: Brown 3 (L2)

W20: HOW TO BRING PRO DATA INTO PAYER DECISION MAKING: PRO STRATEGIES IN PHARMACEUTICAL DEVELOPMENT

Discussion Leaders:

Ari Gnanasakthy, PhD, Head, Patient-Reported Outcomes, RTI Health Solutions, Research Triangle Park, NC, USA

Lynda Doward, MRes, European Head, Patient Reported Outcomes, RTI Health Solutions, Manchester, UK

Vasudha Bal, MSc, MBA, Director, Patient Reported Outcomes, Worldwide Health Outcomes, Value & Access, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

Frank-Ulrich Fricke, PhD, Professor of Health Economics, Georg-Simon-Ohm University of Applied Science, Nurnberg, Neumarkt, Germany

PURPOSE:

Patient-reported outcomes (PROs) are an accepted and often actively solicited source of evidence in the evaluation and approval of pharmaceutical interventions based on their clinical efficacy.

The evaluation of new pharmaceuticals for reimbursement and/or health technology assessment (HTA) involves developing recommendations, typically of greatest interest to payers, that incorporate both clinical information about a treatment’s effectiveness and economic information about a treatment’s value (e.g., National Institute for Health and Care Excellence [NICE]). There is growing recognition that the patient perspective is also an important component in HTA. Thus, it is to be expected that PROs will be increasingly included in HTAs and will influence market access and pricing. A multitude of endpoints and variation in how payers in different countries assess evidence makes it difficult to understand the value of PRO data in reimbursement decisions. Understanding how decision makers utilize these data is critical in the increasingly constrained global health economic climate. This workshop aims to discuss the challenges, current research, and potential solutions associated with bringing patient perspectives into the reimbursement and market access decision-making process.

DESCRIPTION:

The workshop will begin by summarizing payer requirements for PRO data in different countries. Examples of reimbursement decisions that included PRO data will be presented. The discussion leaders in turn will introduce the challenges and opportunities currently faced within drug development in bringing the patient perspective into payer decision-making forums. Participants will be encouraged to share their experience on how they overcame the challenges when including PROs in clinical trials to satisfy the needs of the regulators as well as the payers.

Clinical Outcomes Research

8:45 - 9:45
Room: Space 1 (L0)

W21: OPTIMISING THE CONSTRUCTION OF INDIRECT TREATMENT COMPARISONS TO REFLECT COUNTRY-SPECIFIC HTA REQUIREMENTS

Discussion Leaders:

Christine G. Kohn, PharmD, Assistant Professor, School of Pharmacy, University of Saint Joseph/Hartford Hospital Evidence-Based Practice Center, Hartford, CT, USA

Rachel Beckerman, PhD, Principal, Maple Health Group, New York, NY, USA

Marc Bardou, MD, PhD, Gastroenterologist, Centre Hospitalier Universitaire Le Bocage, Dijon, France

Mathias Flume, PhD, Head of Department, Medical Association of Westphalia-Lippe (KVWL), Dortmund, Germany

PURPOSE:

The purpose of this workshop is to understand the rationale behind why manufacturers construct indirect treatment comparisons (ITCs) and mixed treatment comparisons (MTCs) for HTA submissions; to give an overview of the pros and cons of commonly employed ITC methodologies; and to survey payer ITC requirements to understand common barriers and best practices in designing these analyses.  

DESCRIPTION:

In any given therapeutic area, the standard of care may be evolving and complex, and is likely to differ market to market. As a result, the standard of care at the time an asset’s actively-controlled registrational trial is designed may no longer be relevant once the product actually launches. Further, there are situations where an actively-controlled trial may not be run at all - due to ethical reasons, for example. Despite these realities, payers are increasingly requiring not just actively-controlled data for HTA submissions – but actively-controlled data versus their very specific ‘appropriate’ choice of comparator(s), which can vary by country. In order to meet these requirements, then, manufacturers are therefore encouraged to construct ITCs and MTCs, which can potentially introduce bias and uncertainty into the interpretation of their clinical data. In this workshop, an overview of the different types of methodologies used to construct ITCs and MTCs and their typical applications will first be given. Specific perspectives of payers’ ITC and MTC requirements across two different markets (Germany, France) will be discussed.  Then, case-based examples of how ITCs and MTCs have been considered by payers across markets will be critically appraised. Participants will come away with an understanding of market-specific requirements for ITCs, common pitfalls encountered when constructing these analyses, and best practice to employ in order to overcome them.

Economic Outcomes Research

8:45 - 9:45
Room: Space 2 (L0)

W22: HARNESSING “BIG DATA” AND TAMING HIGH DIMENSIONAL DECISION PROBLEMS FOR ECONOMIC EVALUATION

Discussion Leaders:

William H. Crown, PhD, Chief Scientific Officer, Optum Labs, Cambridge, MA, USA

Sarah Davis, MPhys, Senior Lecturer in Health Economics, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK

Bethan Woods, MSc, Research Fellow, Centre for Health Economics, University of York, Heslington, York, UK

Miqdad Asaria, MSc, Research Fellow, Centre for Health Economics, University of York, Heslington, York, UK

PURPOSE:

Recent discussions around “Big Data” have focused on the analysis of large data sets and the use of real world data for health care decision making broadly. In this workshop we focus this discussion on (i) how big data can be used to inform decision models for economic evaluation; and (ii) how decision models increasingly generate large data sets that need to be analysed in a way that is informative for decision makers. 

DESCRIPTION:

We will use a series of international examples to show how decision models can use and generate large data sets. We will present a case study in which four linked administrative data sets were used to inform a decision model of stable coronary artery disease (the CALIBER project). This work illustrates the potential value of large linked administrative datasets to develop an underlying disease and cost model. We will discuss methods for extracting information relevant to decision models from this type of data and alternative methods for analysing and presenting information relating to large numbers of subgroups. A second case study in diabetes will discuss the challenges of estimating treatment effects for economic evaluation from large observational data sets, and how this may be made more robust by using linked data. A third case study in osteoporosis will illustrate how meta-modeling can be used to analyse large probabilistic sensitivity analysis datasets that are generated by patient–level simulation decision models. Meta-modeling was used to estimate incremental net monetary benefit for alternative treatment strategies as a function of patient-level fracture risk, based on two million simulations whilst averaging over both patient-level heterogeneity and parameter uncertainty. We will conclude the workshop with an open discussion of the relative merits of the techniques proposed and the potential for these techniques to influence decision modeling practice and health care decisions.

Patient-Reported Outcomes & Patient Preference Research

8:45 - 9:45
Room: Brown 2 (L2)

W23: ADDING VALUE TO EQ-5D-3L VALUATION STUDIES: TAKING STOCK / REVIEWING OPTIONS

Discussion Leaders:

Paul Kind, Professor, Centre for Health Economics, Management and Policy, HSE University, St Petersburg, Russia

Roisin Adams, PhD, Deputy Head, National Centre for Pharmacoeconomics, Dublin, Ireland

Ling-Hsiang Chuang, PhD, Research Consultant, Pharmerit Europe, Rotterdam, The Netherlands

Luciana Scalone, PharmD, PhD, Head of Outcomes Research Unit, Research Centre on Public Health (CESP), University of Milan Bicocca, Monza, Italy

PURPOSE:

To explore the extent of support for creative innovation in developing the methods used to value EQ-5D-3L health states. To provide access to 

DESCRIPTION:

 Valuation studies have been conducted in some 30 countries to establish social preferences for EQ-5D-3L health states. The overwhelming majority of these studies were based on the protocol design used in the original 1993 Measurement and Valuation of Health survey (MVH) which incorporated 3 preference elicitation methods (ranking, VAS rating and Time Trade-Off). Respondents valued a sample set of 13 health states selected from a pool of 43 drawn from across the severity range. The question at issue today is whether this study design continues to be fit for purpose and what scope there is for modifications that could enhance the robustness of EQ-5D value estimates that are increasingly required for economic evaluation of healthcare interventions. The workshop is specifically designed to be interactive and to provide the maximum possibility for attendee participation. Four key areas of methodological concern will be addressed – health state selection, preference elicitation methods, the valuation of dead and states worse than dead, constructing estimation models. Speakers from different countries with direct experience of MVH protocol modifications will review the issues and identify questions for discussion within each topic area. It is expected that workshop attendees without prior experience of valuation studies will acquire familiarity with the complexities of an often overlooked area of scientific enquiry. Attendees with relevant research experience will be actively encouraged to share their views and expertise. At key points in the workshop there will be the opportunity to test the collective views of attendees through ad hoc polling.

13:45 - 14:45
WORKSHOPS - SESSION V
Health Policy Development Using Outcomes Research

13:45 - 14:45
Room: Brown 3 (L2)

W24: ARE ANTIMICROBIALS PAVING THE WAY FOR ALL PHARMACEUTICALS? – A WORKSHOP ON THE COMMERCIAL SUSTAINABILITY OF R&D

Discussion Leaders:

Alistair Mcguire, PhD, Professor of Health Economics, LSE Health, London School of Economics, London, UK

Michael Drummond, MCom, DPhil, Professor of Health Economics, Centre for Health Economics, University of York, Heslington, York, UK bio

Monique Martin, PharmD, MSc, MBA, Vice President & General Manager HEOR Europe, MAPI, Uxbridge, UK

PURPOSE:

To discuss the sustainability of R&D in the pharmaceutical industry

DESCRIPTION:

The Review on Antimicrobial Resistance Report (May 2015), while recognizing that antibiotics are different in character from other pharmaceuticals, pursued an objective to make R&D in this area “commercially sustainable”. To do so they proposed establishing a global organization able to “commit lump-sum payments to successful drug developers”. This is an attempt to de-link the profitability of a pharmaceutical product from its volume of sales, eliminating the need for companies to enhance sales volumes to cover the fixed costs of R&D. This idea was supplemented by discussion of how to reduce drug development costs, improve the efficiency of research and reduce regulatory constraints. While recognizing the differential characteristics of antibiotics this workshop will take the Review on Antimicrobial Resistance as a staging point to consider whether there are general lessons to be applied to thinking about the funding of pharmaceutical R&D. The workshop will begin with an initial statement on the current levels of R&D expenditure, the returns to R&D in this sector and the problems associated with funding R&D in the pharmaceutical sector. The relationship between R&D funding and product price will then be considered. A review of alternative R&D and product pricing relationships will be outlined with a range of examples drawn from successful co-ordination activities across governments, companies and regulators will be discussed. Future potential developments will then be outlined as mechanisms for de-coupling R&D investment from sales volume targets and product price. Audience participation will be sought by means of a survey of likely developments (on entry to the room) and results will be discussed during the workshop.


13:45 - 14:45
Room: Space 1 (L0)

W25: INCORPORATING EQUITY INTO HEALTH TECHNOLOGY ASSESSMENT: AN ILLUSTRATION AND CRITICAL REVIEW OF GOOD PRACTICE

Discussion Leaders:

Kevin Marsh, PhD, Senior Research Scientist & EU Director of Modelling and Simulation, Evidera, London, UK

Vitaly V. Omelyanovskiy, MD, PhD, Director, Center of HTA, Moscow, Russia

Alec Morton, PhD, Professor, Management Science, University of Strathclyde, Glasgow, UK

Sumitra Sri Bhashyam, PhD, Research Associate III, Modelling and Simulation, Evidera, London, UK

PURPOSE:

Previous ISPOR workshops have identified that equity considerations, such as burden of illness, have an important role in health technology assessment (HTA), and that multi-criteria decision analysis (MCDA) can be used to incorporate equity into HTA. However, this faces a number of practical obstacles, including the violation of in the independence of criteria. Understanding these challenges and identifying potential solutions are not only the concern of health economics and outcomes research (HEOR), but have also had the attention of other areas of research, notably operational research. The objective of this workshop is to illustrate and critically review approaches available for incorporating equity into MCDA, and to provide recommendations on good practice.

DESCRIPTION:

The workshop will be organised into three presentations. First, Sumitra Sri Bhashyam will summarise the results of a recent review of the HEOR and operational research literature to identify techniques to incorporate equity into MCDA, their advantages and disadvantages. Alec Morton will provide a critical assessment of these techniques from the perspective of HTA, identifying which are relevant to HTA, whether they are technically robust and justifiable; their accessibility to stakeholders; and the resources required to implement them. Vitaly Omelyanovskiy will present some of the possible issues for MCDA usage within the Russian healthcare environment and illustrate the incorporation of equity into MCDA using the case study of the pilot of a MCDA to value orphan drugs in Russia. The objective of the MCDA was to rank orphan drugs for central government investment. The presentation will report the criteria list, and the results of an online interview with decision makers to elicit criteria weights using the swing weighting approach. The audience will be invited to participate and share their experiences of dealing with equity in MCDAs and their thoughts on the most appropriate ways to do so.

Use of Real World Data

13:45 - 14:45
Room: Space 2 (L0)

W26: MAXIMIZING VALUE: REALIZING THE POTENTIAL OF ROUTINELY COLLECTED DATA

Discussion Leaders:

Heiner C. Bucher, MD, MPH, Professor, Department of Clinical Research, Basel Institute for Clinical Epidemiology & Biostatistics, Basel, Switzerland

Ed Mills, PhD, MSc, Director, Redwood Outcomes, Vancouver, BC, Canada

Christopher O'Regan, MSc, Head of Health Technology Assessment & Outcomes, Merck Sharp & Dohme Limited, Hertfordshire, UK

PURPOSE:

To present and discuss innovative approaches for: 1) the use of routinely collected claim data for large scale health care interventions by pragmatic trial design and 2) for system wide resource studies by privacy preserving data mining using probability-based data linkage of claim data with clinical cohort studies. We will use examples from settings representing both the developed and developing world.

DESCRIPTION:

Routinely collected data are traditionally used in phase IV decision-making, mainly for comparative effectiveness and safety studies. Routinely collected drug use data of high quality and density, however, can be also used for intervention trials. We show examples of pragmatic intervention trials to optimize drug use in different indications. Interventions can be done at the health system level to monitor drug prescribing, to promote more appropriate drug use and to benchmark individual physicians against their peers. Resource use of data in health economic analyses for a given patient population and setting is often lacking and has to be derived from different types of information. Privacy preserving data mining using probability-based linkage of claim data with cohort study data can overcome these limitations. We show and discuss the challenge of our data linkage approach and illustrate its relevance for the generation of high quality evidence using examples from HIV infection and hepatitis C. Heiner C. Bucher and Ed Mills will share their experience in comparative effectiveness research using large cohort studies and pragmatic trials in national and international networks. Chris O’Regan will moderate the session and stimulate the discussion on innovative approaches to better use of routinely collected data.

Economic Outcomes Research

13:45 - 14:45
Room: Brown 2 (L2)

W27: ASSESSING THE SOCIETAL, HEALTH CARE, AND PATIENT IMPACT OF LARGE HEALTHCARE INNOVATION PARTNERSHIPS USING HEALTH ECONOMIC MODELING METHODS: LESSONS FROM THE EUROPEAN INNOVATION PARTNERSHIP ON ACTIVE AND HEALTHY AGEING (EIP ON AHA)

Discussion Leaders:

Christian Ernst Heinrich Boehler, PhD, MSc, Scientific Officer, Joint Research Centre (JRC), Institute for Prospective Technological Studies (IPTS), European Commission, Seville, Spain

Gimon de Graaf, MSc, Consultant, Panaxea BV, Enschede, The Netherlands

Leandro Pecchia, PhD, MSc, Assistant Professor, School of Engineering, University of Warwick, Coventry, UK

PURPOSE:

On European and national levels substantial efforts have gone into setting up partnerships that aim to stimulate the development and implementation of healthcare innovations. This workshop will identify challenges with and novel solutions for monitoring and assessing the societal, healthcare and patient impact of such partnerships based on the experiences from the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA).

DESCRIPTION:

Monitoring and assessing the societal, healthcare and patient impact of large innovation partnerships is challenging for many reasons, including 1) the wide range of interventions developed; 2) the variety in target populations; 3) the need for fast, iterative assessments of technologies from development to implementation stages; 4) the need for ready available repositories of (country-specific) epidemiology and cost data; and 5) the need to extrapolate results over time and across different settings. Dr. Boehler will introduce the topic and discuss the rationale for, and challenges associated with, assessing the health and economic outcomes of large innovation partnerships in the context of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA).  Gimon de Graaf will discuss the use of iterative health economic modelling and present an online tool based on a highly adaptable Markov model that allows stakeholders of the EIP on AHA to estimate the health economic impact of their interventions in real-time. Dr. Pecchia will present a case study on the cost-effectiveness of a planned device to predict falls in the elderly in order to illustrate this novel approach. Participants in the workshop will be invited to answer a survey asking for their views on methods to assess the impact of large-scale innovation partnerships and all will be encouraged to share their experience and views during the workshop.

Patient-Reported Outcomes & Patient Preference Research

13:45 - 14:45
Room: Brown 1 (L2)

W28: SECONDARY ANALYSIS OF QUALITATIVE DATA TO INFORM THE DEVELOPMENT OF PRO INSTRUMENTS

Discussion Leaders:

Monica Hadi, PhD, Research Manager, Patient-Centered Outcomes, Mapi Group, London, UK

Paul Swinburn, MRes, Research Director, Patient-Centered Outcomes, Mapi Group, London, UK

Elizabeth Gibbons, MSc, Senior Research Scientist, Health Services Research Unit, University of Oxford, Oxford, UK

PURPOSE:

This workshop will demonstrate the use of secondary analysis of qualitative data for the development of PRO instruments. The session will provide an overview of the technique and methodological underpinnings, its application to different types of data, and its use in the analysis of existing qualitative data for the development of new PRO instruments. 

DESCRIPTION:

The FDA recognises the use of qualitative interviews with patients as an important step in the development of a new PRO instrument. Secondary analysis of qualitative interviews allows for an independent investigation of a new research question, different from the intentions pursued in the primary study. This is a useful technique which allows for the use of existing data whilst preserving valuable patient input. This session will be presented in 3 steps. The first section will cover the underpinnings of secondary analysis and its application, particularly for the development of PROs. The second section will involve the demonstration of secondary analysis on existing patient and clinician interviews to derive themes for a new PRO. At this stage, the audience will be invited to think of a new research question and, with the use secondary analysis techniques on interview transcripts, generate codes and themes to be used in the development of a new PRO. The final section will discuss the challenges faced by this approach as well as the more general benefits for development of PRO instruments. Audience participation in discussions will be encouraged throughout the session. 

15:00 - 16:00
WORKSHOPS - SESSION VI
Health Policy Development Using Outcomes Research

15:00 - 16:00
Room: Brown 3 (L2)

W29: HOW SHOULD WE BE RESPONDING TO CONDITIONAL APPROVALS FROM HTA BODIES?

Discussion Leaders:

Mondher Toumi, MD, MSc, PhD, Professor of Public Health, Department of Public Health, Aix-Marseille University, Marseilles, France

Alan A Martin, MSc, Director, Value Evidence Analytics, Research and Development, GlaxoSmithKline, Uxbridge, UK

Yumi Asukai, MSc, Director Value Evidence Analytics, Research and Development, GlaxoSmithKline, Uxbridge, UK

PURPOSE:

This workshop will discuss different real-world evidence options available to respond to conditional reimbursement decisions that require further evidence generation. We will review the pros and cons associated with each option as well as explore how and whether economic models continue to have a role in the post-launch space in the face of empirical evidence

DESCRIPTION:

Economic models are often the cornerstone of value demonstration of a new product at time of launch. However, data on actual use in the real-world is necessarily limited for a new product and conditional reimbursement is becoming increasingly common. The debate on real-world data has dominated many discussion forums from a payer perspective. Here, we discuss the pros and cons of two main types of real-world research, specifically in the context of responding to payer queries. We will also explore how these types of data fit back into the original economic model; or, whether it is necessary to revert back to modelling at all when real-world evidence is available. Mondher Toumi will review prospective and retrospective observational studies in the context of responding to likely questions from reimbursement authorities; he will also highlight weaknesses of observational studies and suggest how these issues can be addressed. Alan Martin will discuss when pragmatic trials are the evidence of choice, and can overcome limitations of observational studies as seen by reimbursement bodies. Yumi Asukai will discuss which data type best fits into the modelling framework when refining the original economic model. Additionally, she will discuss whether the totality of the evidence collected could mean that modelling be abandoned in favour of ‘empirical evaluation’ when responding to HTA bodies’ request for further value demonstration. Comment  and discussion will be sought by all three discussion leaders, on the issues and suggested remedies

Use of Real World Data

15:00 - 16:00
Room: Space 1 (L0)

W30: MANAGING THE EFFECTS OF CHANNELING IN RELATIVE EFFECTIVENESS STUDIES OF NEWLY LAUNCHED MEDICATIONS

Discussion Leaders:

Jessica Jalbert, PhD, Director of Pharmacoepidemiology, LASER Analytica, New York, NY, USA

Christiane Gasse, PhD, Senior Researcher, Aarhus Universitet, Aarhus, Denmark

Tjeerd Van Staa, MD, PhD, Professor of Health Research, Farr Institute of Health Informatics Research, University of Manchester, Manchester, UK

Billy Amzal, PhD, Global Scientific Vice President, LASER Analytica, London, UK

PURPOSE:

The goal of relative effectiveness (RE) is to inform decision-making by stakeholders in the healthcare system by comparing healthcare interventions in routine clinical practice. Secondary data sources such as administrative claims data are widely used for RE studies and while they can be a source of longitudinal, comprehensive information on drug dispensations and healthcare encounters, they often lack detailed clinical data. This may be particularly problematic in RE studies of newly launched medications, as newer medications may be selectively prescribed to patients for the same indication but with more severe disease, with expectations of increased effectiveness or better tolerability. As many post-marketing commitments are initiated shortly after launch, findings from RE studies may be biased against the newly launched medication if the potential for channeling is ignored. The purpose of this workshop is to explain how channeling may arise and to present ways of detecting, quantifying, and mitigating the effects of channeling, using recent or ongoing post-marking RE studies as case examples.

DESCRIPTION:

The workshop will consist of three 15-minute presentations. First, Dr. Gasse will demonstrate how and under what circumstances channeling may arise in the context of RE studies of newly launched medications. Dr. Jalbert will then discuss the types of RE studies that may be particularly prone to the effects of channeling and methods that can be used to detect channeling, including stratification and propensity score modelling. Dr. Amzal will then demonstrate statistical modelling options and discuss data requirements needed to quantify the effects of channeling. These presentations will be followed by an interactive panel discussion moderated by Dr. Van Staa during which the audience will be encouraged to ask questions and share their experiences as well as approaches to detecting, quantifying, and mitigating the effects of channeling in RE studies of newly launched medications.

Clinical Outcomes Research

15:00 - 16:00
Room: Brown 2 (L2)

W31: NETWORK META ANALYSIS MODELS FOR DOSE-RESPONSE AND CLASS EFFECTS IN DECISION MAKING

Discussion Leaders:

Rhiannon Kate Owen, MSc, Research Associate/NIHR Doctoral Research Fellow, Department of Health Sciences, University of Leicester, Leicester, UK

Kristian Thorlund, PhD, MSc, Vice President of Health Analytics, Precision Health Economics, Vancouver, BC, Canada

David Mawdsley, PhD, Research Associate, School of Social and Community Medicine, University of Bristol, Bristol, UK

Timothy Reason, MSc, Senior Consultant, Real-World Evidence Solutions, IMS Health, London, UK

PURPOSE:

This workshop presents recently proposed models to incorporate dose-response and class effects in network meta-analysis and to discuss the interpretation of the results and implications for decision making.

DESCRIPTION:

Network Meta-Analysis (NMA) allows the synthesis of relative treatment effects from randomised controlled trials that form a connected network of treatment comparisons. A common challenge in NMA is how to deal with multiple doses, treatments and classes that are available for a given indication. There is usually a choice between ’grouping’ vs ‘splitting’ treatments reflecting a trade-off between precision and generalisability. Recently, several statistical methods have been proposed to incorporate dose and class effects in NMA. In this workshop we describe these different approaches, and end with a discussion of how to interpret the results and the implications for decision making. Rhiannon Owen will show how to fit hierarchical models where treatment effects at the ‘dose’, ‘agent’ and ‘class’ level are modelled simultaneously within a multi-level structure, including models that incorporate dose-response constraints. Kristian Thorlund will show how to model dose-response explicitly as a covariate, including how to model dose-related effects as a fraction of the minimally therapeutic dose. David Mawdsley will show how to fit models where richer dose-response profiles such as those seen in Emax models can be parameterised. Finally Tim Reason will lead a discussion of the advantages and disadvantages of the different methods and their interpretation for decision making. We will end the session by asking the audience for questions and feedback to facilitate an open discussion of the methods presented in the workshop.

Economic Outcomes Research

15:00 - 16:00
Room: Space 2 (L0)

W32: HOW TO COMBINE OPEN ACCESS ARTICLES AND OPEN ACCESS ECONOMIC EVALUATION MODELS IN HEALTH CARE PROGRAMMES: REAL TIME UPDATING AND LOCAL CUSTOMIZATION OF PUBLISHED ECONOMIC MODELS

Discussion Leaders:

Giorgio L. Colombo, MSc, Professor Department of Drug Sciences, School of Pharmacy, University of Pavia, Milan, Italy

Sandra Le, PhD, Editorial Development Manager, Dove Medical Press Limited, Macclesfield, UK

Stefano Govoni, Pharmacologist & Professor Department of Drug Sciences, School of Pharmacy, University of Pavia, Milan, Italy

Laura Caresia, Physician & Medical Director, McCann Complete Medical, Milan, Italy

PURPOSE:

Economic models need to be constantly updated. The aim of this workshop is to provide new tools  to combine the analysis of research articles with a web-based model through the Open Access System publication.

DESCRIPTION:

Models in economic evaluation of health care programmes extrapolate the comparative trial data and epidemiologic data to a patient lifetime horizon by using literature-derived estimates and different scenarios of treatment outcomes, to identify: the utility value of each health state, the probabilities of transition among health states, resource use and costs. Over time these economic models need to be constantly update on cost data to guarantee a valid comparison between the different countries in which the analysis has been conducted. The Open Acces System Publication’s principal aim is to disseminate the results of the project in its scholarly journals. In this workshop we will show a practical framework which combines the analysis, the publication and the update of the data through a web-based platform. Based on their experience, the contributors will involve short presentations about 1)     Introduction to dynamic economic model of simulation 2)     How an Open Access System works from publication to the customization of the models 3)     How data work in the model a) enter all the data across European countries b) customize and change the parameters on the base of the different countries c) compare data and create a benchmark database of the outcomes d) identify the best practices in the clinical practice of particular therapeutic area. 4)     How the different data can be modified and how the model can be adapted in real time Audience participants will be encouraged to try different simulations on models and their application. This workshop is suitable for health economic modelers, individuals responsible for health outcomes and health economic strategy, payers, and other decision makers.


15:00 - 16:00
Room: Brown 1 (L2)

W33: UNCERTAINTY OF UNCERTAINTY ESTIMATES IN ECONOMIC MODELLING OF ONCOLOGY

Discussion Leaders:

T Lanitis, MSc, Senior Research Associate, Evidera, London, UK

Zoltán Kaló, PhD, Professor of Health Economics, Department of Health Policy and Economics, Faculty of Social Sciences, Eötvös Loránd University, Budapest, Hungary

Noemi Muszbek, MSc, Senior Research Scientist, Evidera, London, UK

PURPOSE:

In oncology, the role of biomarkers and personalized medicine is rising, as are pressures for early access, resulting in adaptive pathways. Patient populations are therefore increasingly fragmented, whilst timelines for evidence generation are shortened. Consequently, uncertainty is becoming a key factor in reimbursement decisions. Assessment of uncertainty tends to focus on parameter uncertainty using probabilistic sensitivity analysis (PSA). However PSA can be based on conventions and convenience, with the results often representing assumptions of the underlying uncertainty, rather than uncertainty in the assumptions adopted in the model. The purpose of this workshop is to highlight, discuss the current approaches and underlying assumptions used in PSA and illustrate their effect on results contrasting them to current guidelines. How the uncertainty assessment should be used in decision making will be discussed with the audience. 

DESCRIPTION:

The discussion leaders will highlight the scope, methods, presentation of results used in current practice of PSA based on a recent review of NICE technology appraisals. These will be contrasted with guidelines, highlighting the underlying implicit assumptions. To demonstrate the impact of alternative methodological approaches and assumptions, a case-study using a 3-state cohort Markov model in advanced oncology will be presented. Implicit assumptions underpinning commonly used methods regarding distributions, correlations, variations and structural choices will be drawn out and examined in terms of their face validity and impact on results. The presentations will conclude with an illustration of how uncertainty is taken into account in decision making, the role parameter uncertainty plays and scenarios in which such results are of major significance. The changing role of uncertainty in the decision making and the limitations and interpretation of PSA will be discussed with the audience.

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