S Kleijnen1, I Lipska2, T Leonardo Alves3, K Meijboom4, A Elsada5, V Vervölgyi6, A d'Andon7, A Timoney8, H G Leufkens3, A De Boer3, W G Goettsch9. 1. National Health Care Institute, Diemen, The Netherlands Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands skleijnen@zinl.nl. 2. Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands Center for Innovation in Regulatory Science, London, UK. 3. Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands. 4. VU University Amsterdam, Amsterdam, The Netherlands. 5. National Institute for Health and Care Excellence, Manchester, UK. 6. Department of Drug Assessment, Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, Cologne, Germany. 7. Medicines Evaluation Department, Haute Autorité de santé, Paris, France. 8. NHS Lothian and Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK. 9. National Health Care Institute, Diemen, The Netherlands Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.
Abstract
BACKGROUND: There is a debate on the added clinical value of new, expensive, anticancer treatments. Among European decision makers, the relevance of commonly used end points in trials, especially overall survival (OS), progression-free survival (PFS) and quality of life (QoL), varies, leading to the available evidence being valued differently. This research studies the extent to which the value of end points for cancer medicines differs among European decision makers. METHODS: We compared guidelines and relative effectiveness assessments (REAs) of medicines for pricing or reimbursement decisions in England, France, Germany, The Netherlands, Poland, and Scotland. Anticancer medicines that received marketing authorization in Europe between 2011 and 2013 with at least four available national REAs were evaluated. A total of 79 REAs were included. RESULTS: Health technology assessment (HTA) guidelines indicate a preference for clinically and patient relevant end points such as OS and QoL above surrogate end points. Most guidelines do not specify whether PFS is considered a surrogate or patient-relevant end point. The number of REAs included per jurisdiction varied between 7 (The Netherlands) and 18 (Germany). OS data were included in all REAs and were the preferred end point by HTA agencies, but these data were not always mature or robust. QoL data are included in only 54% of the REAs, with a limited impact on the recommendations. PFS data are included in 70% of the REAs, but the extent to which HTA agencies find PFS relevant varies. CONCLUSIONS: European decision-making on relative effectiveness of anticancer medicines is affected by a gap in requested versus available clinical evidence, mainly because the regulator is willing to accept some degree of clinical uncertainty. A multi-stakeholder debate would be essential to align concrete robust evidence requirements in oncology and a collectively shared definition for relevant clinical benefit, which will benefit patients and society in general.
BACKGROUND: There is a debate on the added clinical value of new, expensive, anticancer treatments. Among European decision makers, the relevance of commonly used end points in trials, especially overall survival (OS), progression-free survival (PFS) and quality of life (QoL), varies, leading to the available evidence being valued differently. This research studies the extent to which the value of end points for cancer medicines differs among European decision makers. METHODS: We compared guidelines and relative effectiveness assessments (REAs) of medicines for pricing or reimbursement decisions in England, France, Germany, The Netherlands, Poland, and Scotland. Anticancer medicines that received marketing authorization in Europe between 2011 and 2013 with at least four available national REAs were evaluated. A total of 79 REAs were included. RESULTS: Health technology assessment (HTA) guidelines indicate a preference for clinically and patient relevant end points such as OS and QoL above surrogate end points. Most guidelines do not specify whether PFS is considered a surrogate or patient-relevant end point. The number of REAs included per jurisdiction varied between 7 (The Netherlands) and 18 (Germany). OS data were included in all REAs and were the preferred end point by HTA agencies, but these data were not always mature or robust. QoL data are included in only 54% of the REAs, with a limited impact on the recommendations. PFS data are included in 70% of the REAs, but the extent to which HTA agencies find PFS relevant varies. CONCLUSIONS: European decision-making on relative effectiveness of anticancer medicines is affected by a gap in requested versus available clinical evidence, mainly because the regulator is willing to accept some degree of clinical uncertainty. A multi-stakeholder debate would be essential to align concrete robust evidence requirements in oncology and a collectively shared definition for relevant clinical benefit, which will benefit patients and society in general.
Authors: Oriana Ciani; Bogdan Grigore; Hedwig Blommestein; Saskia de Groot; Meilin Möllenkamp; Stefan Rabbe; Rita Daubner-Bendes; Rod S Taylor Journal: Med Decis Making Date: 2021-03-10 Impact factor: 2.583
Authors: Sarah Kleijnen; Teresa Leonardo Alves; Kim Meijboom; Iga Lipska; Anthonius De Boer; Hubertus G Leufkens; Wim G Goettsch Journal: Qual Life Res Date: 2017-04-11 Impact factor: 4.147
Authors: Amr Makady; Rachel R J Kalf; Bettina Ryll; Gilliosa Spurrier; Anthonius de Boer; Hans Hillege; Olaf H Klungel; Wim Goettsch Journal: Health Qual Life Outcomes Date: 2018-11-29 Impact factor: 3.186
Authors: Lourens T Bloem; Rick A Vreman; Niels W L Peeters; Jarno Hoekman; Menno E van der Elst; Hubert G M Leufkens; Olaf H Klungel; Wim G Goettsch; Aukje K Mantel-Teeuwisse Journal: Clin Transl Sci Date: 2021-05-01 Impact factor: 4.689
Authors: Amr Makady; Ard van Veelen; Páll Jonsson; Owen Moseley; Anne D'Andon; Anthonius de Boer; Hans Hillege; Olaf Klungel; Wim Goettsch Journal: Pharmacoeconomics Date: 2018-03 Impact factor: 4.981
Authors: Joost W Geenen; Svetlana V Belitser; Rick A Vreman; Martijn van Bloois; Olaf H Klungel; Cornelis Boersma; Anke M Hövels Journal: Eur J Health Econ Date: 2020-04-04
Authors: Rick A Vreman; Jacoline C Bouvy; Lourens T Bloem; Anke M Hövels; Aukje K Mantel-Teeuwisse; Hubert G M Leufkens; Wim G Goettsch Journal: Clin Pharmacol Ther Date: 2018-11-08 Impact factor: 6.875