Relative Effectiveness Assessment: wie hilfreich sind die EUnetHTA Konzepte

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1 Relative Effectiveness Assessment: wie hilfreich sind die EUnetHTA Konzepte Alric Rüther 1, Annette Zentner² 1 IQWiG: Ressort Versorgungsqualität Internationale Beziehungen ² FG Management im Gesundheitswesen, TU Berlin

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3 HTA Europa: Hintergrund Report der High Level Group on Health Services and Medical Care (HLG) der Europäischen Kommission (30. November 2004): HTA has become a political priority and there is an urgent need for establishing a sustainable European network for HTA. DG SANCO Public Health Work Plan 2005: HTA wird Prioritätsgebiet Kommissar Kyprianou : (HTA 1 der 7 Haupt-Gebiete):.the usefulness of establishing a sustainable European health technology assessment network has been recognised.. I hope to see this network being set up this year, with support from the public health programme.

4 European Network for HTA EUnetHTA Projekt der Europäischen Kommission Ziel: Aufbau eines effektiven und zukunftsfähigen Netzwerks für HTA in Europa Strategische Ziele Basis für politische Entscheidungen Verbindung öffentlicher HTA-Agenturen, Forschungseinrichtungen und Gesundheitsministerien Effektiver Informationsaustausch Unterstützung politischer Entscheidungen durch Mitgliedsstaaten

5 EUnetHTA Project Partners: 55 Partners from 29 countries (21 EU Member States) including 9 International Partner Organisations Final Report published by European Commission Fourteen scientific articles published in Int J Technol Assess Health Care, 2009: 25 (Suppl. 2) 5&issueId=S2 5

6 The time-line of reaching a sustainable and permanent HTA network in Europe Health Programme 2005 Call for project proposals 2009 Call for Joint Action 2011 Call for Joint Action EUnetHTA Project 2009 EUnetHTA Collaboration EUnetHTA JA Legislation DG R&I 6

7 H T A C o r e M o d e l HTA Core Model and its application Pool of Structured HTA Information CORE HTA INFO = Assessment element = Core element = Non-core element = Locally produced information that does not follow HTA Core model LOCAL REPORT Domain 1 INFO Domain 2 INFO INFO Domain 3 Rapid HTA Domain 4 REA Takes into account local epidemiology, resources, values, etc. Kristensen FB_2 Croatia

8 HTA Core Model : structure Domain Topics- Issue Clinical effectiveness Topic 1: Mortality Issue 1: What is the effect of the intervention on overall Topic mortality? 2: Morbidity Issue 2: What is the effect of the Topic intervention 3 etc on mortality caused by the target disease? Issue 3: etc Health problem and current use of technology Technical characteristics Safety Clinical effectiveness Costs and economic evaluation Ethical analysis Organisational aspects Social aspects Legal aspects 8

9 Core HTA Structure Kristensen FB_2 Croatia

10 European network for HTA Joint Action between European Commission and EU Member States A total of 34 government appointed organisations from 23 EU Member States, Norway and Croatia and a large number of relevant regional agencies and non-for-profit organisations that produce or contribute to HTA EUnetHTA Joint Action

11 EUnetHTA JA organisation WP1 Coordination (Lead Partner (LP) NBoH, Denmark) WP2 Dissemination (LP IPH-RS, Slovenia; Co-LP SBU, Sweden) WP3 Evaluation (LP NETSCC, United Kingdom) WP4 Core HTA (LP THL, Finland; Co-LP AGENAS, Italy) WP5 Relative Effectiveness Assessment (REA) of Pharmaceuticals (LP CVZ, Netherlands; Co-LP HAS, France) WP6 Information Managment System (LP KCE, Belgium, Co-LP DIMDI, Germany) WP7 New Technologies (LP HAS, France, Co-LP LBI-HTA, Austria) WP8 Strategy and Business Model Development (LP NBoH, Denmark) a) HTA training and capacity building (focus on EUnetHTA tools) and b) facilitation of national HTA strategies. Responsible organisation for a) ISCIII, Spain Responsible for b) AHTAPol, Poland

12 EUnetHTA JA Strategic position All activities of the EUnetHTA Joint Action arise from the premise that its outputs will be used to inform but not mandate the content of national / regional / institutional HTA reports

13 Kriterien für Bewertung und Entscheidung Kriterium Patientenrelevanter (Zusatz)Nutzen A T A U C A C Z D K E S F I F R G R H U X X X X X X X X X X X X X X X X X X X X Kosten-Nutzen X X X X X X X X X X X X X X Auswirkung auf Budget X X X X X X X X X X X X X X X X X Preise in anderen Ländern X X X X X X X X X X X X Zu erwartender Umsatz X X X Behandlungsalternativen X X X X X X X X X Soziale, ethische Erwägungen X X X X X X X X Bedarf der Gesellschaft X X X Public Health Auswirkungen X X Pharmakologische Merkmale X X X X X X F&E-Kosten der Hersteller X X X X Prioritäten der Regierung Dr. med. Annette Zentner MPH I T I R N L N O N Z X P L P T S E S K U K Quelle: Zentner et al. 2005; Kanavos et al. 2009

14 Levels of European HTA collaboration Level of welfare effects Scenario 3: Joint Assessments Scenario 2: Guideline development Scenario 1: ICT platform Common European assessments Common European guidelines Sharing national assessment reports in Europe EUnetHTA European network for Health Technology Assessment Joint Action

15 EUnetHTA JA1 WP5 REA Pharmaceuticals EUnetHTA was asked to take this work forward by the Steering Committee of the HL PF in autumn of EUnetHTA WP on REA started in 2010 EUnetHTA decided to work with the definitions that had been agreed in PF2008 According to the Pharmaceutical Forum: Relative effectiveness can be defined as the extent to which an intervention does more good than harm compared to one or more intervention alternatives for achieving the desired results when provided under the usual circumstances of health care practice. EUnetHTA European network for Health Technology Assessment Joint Action

16 The WP5 Partners JA1 1 Lead 1 Co-lead 17 Associated Partners 13 Collaborative Partners EUnetHTA European network for Health Technology Assessment Joint Action

17 EUnetHTA WP5 REA Pharmaceuticals Objective: Development of HTA tools and methods for REA Background review on national REA (CVZ) Development of model for Rapid REA (CVZ) Methodology guidelines for REA (HAS) Pilot of Rapid REA (CVZ) Collaboration with EMA (HAS) EUnetHTA European network for Health Technology Assessment Joint Action

18 Background review on national REA # Objective: provides an overview of the processes and methodologies used in national practice 29 countries included* Data gathered: Health care system Process Methodology Australia Austria Belgium Canada Czech Republic Denmark England& Wales (UK) Estonia Finland France Germany Hungary Ireland Italy Latvia Luxembourg Malta Netherlands New Zealand Norway Poland Portugal Scotland (UK) Slovakia Slovenia Spain Sweden Switzerland Turkey United States of America *Separate data abstraction for England/Wales & Scotland #Kleijnen et al. EUnetHTA European network for Health Technology Assessment Joint Action

19 Background review on national REA Conclusions and challenges Most of countries carry out some form of REA to support national reimbursement decisions of pharmaceuticals The scope and the methodology used vary across countries to some extent >> however not that much (TERMINOLOGY!) Rapid assessments are most common and relevant for reimbursement Purposes The differences between counties, as well as the reasons behind them, need to be considered in the development of a common European methodology for REA EUnetHTA European network for Health Technology Assessment Joint Action

20 Development of REA model Should be based on HTA Core Model (HTA Core Model = A structured manner of creating and presenting HTA information) WP5 HTA Core Model Model for Full REA Model for Rapid REA Health problem and current use of technology Description and technical characteristics of the technology Safety Effectiveness Cost and economic considerations Ethical analysis Organisational analysis Social aspects Legal aspects Health problem and current use of technology Description and technical characteristics of the technology Safety Effectiveness Cost and economic considerations Ethical analysis Organisational analysis Social aspects Legal aspects Health problem and current use of technology Description and technical characteristics of the technology Safety Effectiveness Cost and economic considerations Ethical analysis Organisational analysis Social aspects Legal aspects Mutliple comparators Years after market authorisation Indication based Limited number of comparators Soon after market authorisation EUnetHTA European network for Health Technology Assessment Joint Action

21 WP5 pilot of a rapid assessment Objective: Test the usability of the draft model for rapid REA and the draft guidelines Topic selection: List was produced of all pharmaceuticals that received market authorization between June 2010 and February 2011 Selection made based on exclusion criteria Manufacturers approached for willingness to provide submission file (2 out of 4 were willing) Pazopanib for the first-line treatment of metastatic renal cell cancer. Basic documentation: Manufacturer submission file Rapid REA model Methodological guidelines developed in WP5 EUnetHTA European network for Health Technology Assessment Joint Action

22 WP5 pilot of a rapid assessment Experience Participation of 29 organisations requires intense coordination on several levels 3,5 months timelines for scope/assessment phase if possible but very intense Relevance of all research questions (assessment elements) for a rapid assessment?! Harm/benefit analysis is still in development (synthesis). This model of collaboration is not sustainable if rapid assessments needs to be done within three months 22 EUnetHTA European network for Health Technology Assessment Joint Action

23 Primary objective: help assessors to make rapid assessment of pharmaceuticals - e.g. give clear recommendations, useful for HTA assessors Scope EUnetHTA methodology Terminology guidelines Structure of documents Consistency between guidelines e.g. clinical endpoints: should be consistent with other «endpoints» guidelines Define the most important concepts - e.g. (relative) efficacy and effectiveness, types of endpoints, comparator, applicability, surrogate endpoints EUnetHTA European network for Health Technology Assessment Joint Action

24 EUnetHTA methodology 9 guidelines: guidelines Criteria for choice of most appropriate comparator(s) Methods of comparison: direct and indirect comparisons Endpoints used for REA of pharmaceuticals: Clinical endpoints Surrogate endpoints Composite endpoints Health-related quality of life Safety Levels of evidence: Internal validity External Validity (Applicability) EUnetHTA European network for Health Technology Assessment Joint Action

25 Elaboration and review process Draft by individuals in partner HTA organisations Review and comments by HAS and WP5 members Comments incorporated by original authors Workshops on specific topics Revisions by original authors and HAS Consultation with Stakeholders and Public 25 EUnetHTA European network for Health Technology Assessment Joint Action

26 EUnetHTA methodology guidelines Consultation process Guidelines Composite endpoints Surrogate endpoints Choice of comparator Applicability Internal consultation (EUnetHTA partners and stakeholders representatives) Public consultation (including EMA) March 7 April 13 June 29 Sept 10 HRQoL Safety Internal validity Direct and indirect comparisons Clinical endpoints April 16 May 25 Sept 3 Oct 31 EUnetHTA European network for Health Technology Assessment Joint Action

27 EUnetHTA methodology guidelines Clinical endpoints Well defined and justified, clinically relevant to the disease. Both statistical and clinical relevance Objective EP, subjective EP and Patient-relevant EP Long-term or final EP where possible (OS, all-cause mortality); short-term endpoints are acceptable for acute conditions with no long-term consequences Sensitive to changes due to treatment Free from measurement or assessment error, unbiased Relative and absolute measures to be presented Adjustment for multiple hypothesis testing EP data analysis to explicitly state the handling of missing data EUnetHTA European network for Health Technology Assessment Joint Action

28 HTA Methoden und Qualität? Methoden auf Basis internationaler Standards der evidenzbasierten Medizin ( 139a SGB-V) Kausalitätsprinzip Transparenz Reliabilität Surrogate Dramatischer Effekt Bias. Schwarzer R, et al. Health Policy 2013 [in preparation]

29 Europäische Union Artikel 15 Zusammenarbeit bei der Bewertung von Gesundheitstechnologien Die Union unterstützt und erleichtert die Zusammenarbeit und den Austausch wissenschaftlicher Informationen zwischen den Mitgliedstaaten im Rahmen eines freiwilligen Netzwerks, das die von den Mitgliedstaaten benannten [ ] nationalen Behörden [ ] verbindet.

30 Ziele des EU-Netzwerks a) die Unterstützung der Zusammenarbeit zwischen nationalen Behörden beziehungsweise anderen Stellen; b) die Unterstützung der Mitgliedstaaten bei der Bereitstellung objektiver, zuverlässiger, rechtzeitiger, transparenter, vergleichbarer und übertragbarer Informationen über die relative Wirksamkeit sowie gegebenenfalls über die kurz- und langfristige Wirksamkeit von Gesundheitstechnologien und die Schaffung der Voraussetzungen für einen effizienten Austausch dieser Informationen zwischen den nationalen Behörden beziehungsweise anderen Stellen; c) Unterstützung der Analyse des Inhalts und der Art der Informationen, die ausgetauscht werden können; d) Vermeidung von Doppelarbeit bei den Bewertungen. Dr. med. Annette Zentner MPH

31 The time-line of reaching a sustainable and permanent HTA network in Europe Health Programme 2005 Call for project proposals 2009 Call for Joint Action 2011 Call for Joint Action European network for HTA Legislation EUnetHTA Project 2009 EUnetHTA Collaboration Draft Cross Border Healthcare Directive Article on HTA network EUnetHTA EUnetHTA JA JA CBHC Directive now decided CBHC Directive Expert Group for HTA network implementation Legal basis: Cross Border Healthcare Directive Financial support: 1) EU Budget 2) Member States DG R&I 2011 FP7-Health 2012-Innovation-1 New methodologies for HTA 31

32 WP5 Joint Action 2 ( ) Ten pilots on rapid REA of pharmaceuticals between Collaboration model: One organisation is author and one organisation is co-author A number of WP5 partners will be dedicated reviewers Other WP5 partners will be consulted after this dedicated review EUnetHTA European network for Health Technology Assessment Joint Action

33 WP5 Joint Action 2 ( ) Important issues: Input of submission files is central part of assessment Active involvement of industry is essential European submission file format needs to be developed (WP7) Close collaboration with EMA is needed Implementation of (parts of) rapid assessment in national assessments must be stimulated Analysis of implementation hurdles (started in JA1) Timing of assessment is crucial; ideally REA report should become available just after the publication EPAR Broad selection of pilot pharmaceuticals Inclusion of assessments of orphan drugs! EUnetHTA European network for Health Technology Assessment Joint Action

34 Ausblick Länderübergreifende Zusammenarbeit wird in der EU mit Priorität gefördert Die Bewertungsprozesse der einzelnen Länder unterscheiden sich im Detail Methodische Anforderungen sind oft unterschiedlich EUnetHTA versucht über das Core-Modell: Einfache Werkzeuge zur Zusammenarbeit zu etablieren und bereitzustellen Methodisch einen kleinsten gemeinsamen Nenner zu definieren Akzeptanz herzustellen Hilfreich für uns?

35 Dank an Wim Goettsch (CVZ) und Mira Pavlovic (HAS) für Unterstützung und Slides Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) Im Mediapark 8 D Köln Telefon / Telefax / Photo:

36 REA CER

37 REA versus CER REA CER europa.eu Arzneimittel Erstattung/Preis politische Steuerung Sekundäranalysen alle Verfahren Patientenversorgung/ Prävention Forschungsförderung Sekundäranalysen und Primärstudien Dr. med. Annette Zentner MPH

38 HTA