www.advance-vaccines.eu Accelerated Development of VAccine beNefit-risk Collaboration in Europe Grant Agreement nº115557 D4.3 Report on appraisal of vaccine benefit-risk methodology WP4 Methods for burden of disease, vaccination coverage, vaccine safety and effectiveness, impact and benefit-risk monitoring V2.0 [Final] Lead beneficiary: P95 Date: 04/11/2014 Nature: Report Dissemination level: CO © Copyright 2013 ADVANCE Consortium D4.3 Appraisal of vaccine benefit-risk methodology WP4. Methods Version: v2.0 – Final IMI - 115557 Author(s): Advance Benefit-Risk Working Group Security: CO 2/86 TABLE OF CONTENTS DOCUMENT INFORMATION .................................................................................... 4 DOCUMENT HISTORY ............................................................................................. 5 DEFINITIONS ......................................................................................................... 6 EXECUTIVE SUMMARY ............................................................................................ 9 1. INTRODUCTION ............................................................................................... 10 1.1 ADVANCE PROJECT ................................................................................................ 10 1.2 OBJECTIVES AND SCOPE OF THE REPORT ....................................................................... 11 1.3 STRUCTURE OF THE REPORT ...................................................................................... 11 2. SPECIFICITIES OF BENEFIT-RISK ASSESSMENTS OF VACCINES ..................... 12 3. BENEFIT-RISK METHODOLOGY ........................................................................ 17 3.1 DESCRIPTIVE OR SEMI-QUANTITATIVE FRAMEWORKS ........................................................ 17 3.1.1 Summary tools ............................................................................................. 18 3.1.2 BRAT framework ........................................................................................... 20 3.1.3 PrOACT-URL framework ................................................................................ 24 3.1.4 Other frameworks ......................................................................................... 27 3.1.5 Concluding remarks ...................................................................................... 28 3.2 BENEFIT-RISK MEASURES .......................................................................................... 29 3.2.1 Numbers needed to treat and variants thereof ................................................ 29 3.2.2 Differences in benefits and risks ..................................................................... 33 3.2.3 Ratios in benefits and risks ............................................................................ 34 3.2.4 Concluding remarks ...................................................................................... 36 3.3 COMPOSITE HEALTH MEASURES ................................................................................. 37 3.3.1 QALY ........................................................................................................... 37 3.3.2 DALY ........................................................................................................... 38 3.3.2 HALE ........................................................................................................... 38 3.3.4 Concluding remarks ...................................................................................... 39 3.4 QUANTITATIVE BENEFIT-RISK FRAMEWORKS .................................................................. 39 3.4.1 ‘Principles of Threes’, TURBO and Beckmann ................................................... 39 3.4.2 Benefit-less-risk analysis ................................................................................ 40 3.4.3 Multi-criteria decision analysis and extensions ................................................. 40 3.4.4 Data-driven benefit-risk assessment (Sarac et al.) ........................................... 44 3.4.5 Clinical utility index ....................................................................................... 44 3.4.6 Concluding remarks ...................................................................................... 45 3.5 MODELLING APPROACHES (HTA) ................................................................................ 45 3.5.1 Decision trees ............................................................................................... 46 3.5.2 State transition models .................................................................................. 47 3.5.3 Discrete event simulation .............................................................................. 48 3.5.4 Dynamic transmission models ........................................................................ 49 3.5.5 Meta-analytic approaches .............................................................................. 50 3.5.6 Concluding remarks ...................................................................................... 51 3.6 PARAMETER ESTIMATION AND UNCERTAINTY .................................................................. 52 3.7 PREFERENCE ELICITATION ......................................................................................... 56 © Copyright 2013 ADVANCE Consortium D4.3 Appraisal of vaccine benefit-risk methodology WP4. Methods Version: v2.0 – Final IMI - 115557 Author(s): Advance Benefit-Risk Working Group Security: CO 3/86 4.7.1 Focus groups ................................................................................................ 58 4.7.2 Conjoint analysis overview ............................................................................. 61 4.7.3 Choice Based Conjoint methods ..................................................................... 62 4. DISCUSSION AND RECOMMENDATIONS .......................................................... 74 REFERENCES ............................................................................................................... 78 © Copyright 2013 ADVANCE Consortium D4.3 Appraisal of vaccine benefit-risk methodology WP4. Methods Version: v2.0 – Final IMI - 115557 Author(s): Advance Benefit-Risk Working Group Security: CO 4/86 DOCUMENT INFORMATION Grant Agreement 115557 Acronym ADVANCE Number Full title Accelerated Development of VAccine beNefit-risk Collaboration in Europe Project URL http://www.advance-vaccines.eu IMI Project officer Angela Wittelsberger ([email protected]) Report on appraisal on the vaccine benefit-risk Deliverable Number 4.3 Title methods Methods for burden of disease, vaccination coverage, Work package Number 4 Title vaccine safety and effectiveness, impact and benefit- risk monitoring Delivery date Contractual Month 12 Actual Status Current version / v2.0 Draft Final x Nature Report x Prototype Other Dissemination Level Public Confidential x Vincent Bauchau (GSK), Eduoard Ledent (GSK), Bennett Levitan (J&J), Authors (Partner) Thomas Verstraeten (P95), Yuan Zhong (J&J) Kaatje Bollaerts (P95) Email [email protected] Responsible Author Partner P95 Phone +32 485 78 96 57 Description of the Report deliverable Key words Benefit-risk, Methodology, Vaccine © Copyright 2013 ADVANCE Consortium D4.3 Appraisal of vaccine benefit-risk methodology WP4. Methods Version: v2.0 – Final IMI - 115557 Author(s): Advance Benefit-Risk Working Group Security: CO 5/86 DOCUMENT HISTORY NAME DATE VERSION DESCRIPTION Kaat Bollaerts (P95), Bennett Levitan (J&J),Eduoard Ledent 20/07/2014 1.0 First draft (GSK), Zhong Yuan (J&J), Vincent Bauchau (GSK), Thomas Verstraeten (P95) Vincent Bauchau(GSK), 10/08/2014 1.0 Reviewed Thomas Verstraeten (P95) Kaat Bollaerts (P95) 25/08/2014 1.1 Second draft Shahrul Mt-Isa (ICL), Bennett Levitan (J&J), Zhong Yuan (J&J), 07/10/2014 1.1 Reviewed Marianne Van Der Sande (RIVM), Matti Lehtinen (UTA),Tyra Krause (SSI) Kaat Bollaerts (P95), Bennett Levitan 22/10/2014 1.2 Third draft (J&J),Eduoard Ledent (GSK) Zhong Yuan (J&J), 25/10/2014 1.2 Reviewed Thomas Verstraeten (P95) Kaat Bollaerts (P95) 3/11/2014 2.0 Final version © Copyright 2013 ADVANCE Consortium D4.3 Appraisal of vaccine benefit-risk methodology WP4. Methods Version: v2.0 – Final IMI - 115557 Author(s): Advance Benefit-Risk Working Group Security: CO 6/86 DEFINITIONS . Participants of the ADVANCE Consortium are referred to herein according to the following codes: - EMC. Erasmus Universitair Medisch Centrum Rotterdam (Netherlands) - Coordinator - UNIBAS. Universitaet Basel (Switzerland) - Managing entity of the IMI JU funding - AEMPS. Agencia Española de Medicamentos y Productos Sanitarios (Spain) - ASLCR. Azienda Sanitaria Locale della Provincia di Cremona (Italy) - AUH. Aarhus Universitetshospital (Denmark) - CRX. Crucell Holland BV (Netherlands) - ECDC. European Centre for Disease Prevention and Control (Sweden) - EMA. European Medicines Agency (United Kingdom) - GSK. GlaxoSmithKline Biologicals, S.A. (Belgium) – EFPIA Coordinator - KI. Karolinska Institutet (Sweden) - LSHTM. London School of Hygiene and Tropical Medicine (United Kingdom) - MHRA. Medicines and Healthcare products Regulatory Agency (United Kingdom) - NOVARTIS. Novartis Pharma AG (Switzerland) - OU. The Open University (United Kingdom) - P95. P95 (Belgium) - PEDIANET. Società Servizi Telematici SRL (Italy) - PFIZER. Pfizer Limited (United Kingdom) - RCGP. Royal College of General Practitioners (United Kingdom) - RIVM. Rijksinstituut voor Volksgezondheid