Price and reimbursement of advanced therapeutic medicinal products in Europe: are assessment and appraisal diverging from expert recommendations?

References

• Official Journal of the European Union. Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004. https://ec.europa.eu/health//sites/health/files/files/eudralex/vol-1/reg_2007_1394/reg_2007_1394_en.pdf. Accessed Oct 2019.
   Google Scholar
• Jonsson B, et al. Advanced therapy medicinal products and health technology assessment principles and practices for value-based and sustainable healthcare. Eur J Health Econ. 2019;20(3):427–438.
   PubMed Web of Science ®Google Scholar
• Drummond MF, et al. Analytic considerations in applying a general economic evaluation reference case to gene therapy. Value Health. 2019;22(6):661–668.
   PubMed Web of Science ®Google Scholar
• Garrison LP, et al. Value-based pricing for emerging gene therapies: the economic case for a higher cost-effectiveness threshold. J Manag Care Spec Pharm. 2019;25(7):793–799.
   PubMed Web of Science ®Google Scholar
• Hettle R, et al. The assessment and appraisal of regenerative medicines and cell therapy products: an exploration of methods for review, economic evaluation and appraisal. Health Technol Assess. 2017;21(7):1–204.
   PubMed Web of Science ®Google Scholar
• Marsden G, Towse A, Pearson SD, et al. Gene therapy: understanding the science, assessing the evidence, and paying for value. Research Paper, OHE&ICER March 2017. https://www.ohe.org/publications/gene-therapy-understanding-science-assessing-evidence-and-paying-value. Accessed Oct 2019.
   Google Scholar
• Gemeinsamer Bundesausschuss. https://www.g-ba.de/. Accessed Dec 2019.
   Google Scholar
• National Institute for Health and Care Excellence – NICE. https://www.nice.org.uk//. Accessed Dec 2019.
   Google Scholar
• Haute Autorité de santé—HAS. https://www.has-sante.fr//. Accessed Dec 2019.
   Google Scholar
• Agence Nationale de Sécurité du Médicament et des Produits de Santé—ANSM. https://www.ansm.sante.fr/Recherche/. Accessed Dec 2019.
   Google Scholar
• Legifrance, le service public de la diffusion du droit par l’Internet. https://www.legifrance.gouv.fr/. Accessed Dec 2019.
   Google Scholar
• Agencia Española de Medicamentos y Productos Sanitarios - AEMPS. https://www.aemps.gob.es//. Accessed Dec 2019.
   Google Scholar
• Agenzia Italiana del Farmaco—AIFA. https://www.aifa.gov.it/archivio?strutture=96918/. Accessed Dec 2019.
   Google Scholar
• Gazzetta Ufficiale. https://www.gazzettaufficiale.it//. Accessed Dec 2019.
   Google Scholar
• Hanna E, et al. Advanced therapy medicinal products: current and future perspectives. J Mark Access Health Policy. 2016. https://doi.org/10.3402/jmahp.v4.31036
   Google Scholar
• Committee for Advanced Therapies (CAT)—Reflection paper on classification of advanced therapy medicinal products. 2015. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/06/WC500187744.pdf. Accessed Dec 2019.
   Google Scholar
• Orphanet. The portal for rare diseases and orphan drugs. https://www.orpha.net/consor/cgi-bin/index.php?lng=EN. Accessed Jul 2020.
   Google Scholar
• European Medicine Agency (EMA)—Development of medicines for rare diseases. https://www.ema.europa.eu/en/news/development-medicines-rare-diseases. Accessed Dec 2019.
   Google Scholar
• Holoclar (ex vivo expanded autologous human corneal epithelial cells containing stem cells). European public assessment report (EPAR). EMA https://www.ema.europa.eu/en/medicines/human/EPAR/holoclar. Accessed Jul 2020.
   Google Scholar
• Imlygic (talimogene laherparepvec). European public assessment report (EPAR). EMA. https://www.ema.europa.eu/en/medicines/human/EPAR/imlygic. Accessed Jul 2020.
   Google Scholar
• Strimvelis (autologous CD34+ enriched cell fraction that contains CD34+ cells transduced with retroviral vector that encodes for the human ADA cDNA sequence). European public assessment report (EPAR). EMA. https://www.ema.europa.eu/en/medicines/human/EPAR/strimvelis. Accessed Jul 2020.
   Google Scholar
• Spherox (spheroids of human autologous matrix-associated chondrocytes). European public assessment report (EPAR). EMA. https://www.ema.europa.eu/en/medicines/human/EPAR/spherox. Accessed Jul 2020.
   Google Scholar
• Alofisel (darvadstrocel). European public assessment report (EPAR). EMA. https://www.ema.europa.eu/en/medicines/human/EPAR/alofisel. Accessed Jul 2020.
   Google Scholar
• Kymriah (tisagenlecleucel). European public assessment report (EPAR). EMA. https://www.ema.europa.eu/en/medicines/human/EPAR/kymriah. Accessed Jul 2020.
   Google Scholar
• Yescarta (axicabtagene ciloleucel). European public assessment report (EPAR). EMA. https://www.ema.europa.eu/en/medicines/human/EPAR/yescarta. Accessed Jul 2020.
   Google Scholar
• Luxturna (voretigene neparvovec). European public assessment report (EPAR). EMA. https://www.ema.europa.eu/en/medicines/human/EPAR/luxturna. Accessed Jul 2020.
   Google Scholar
• Zynteglo (betibeglogene autotemcel). European public assessment report (EPAR). EMA. https://www.ema.europa.eu/en/medicines/human/EPAR/zynteglo. Accessed Jul 2020.
   Google Scholar
• Zolgensma (onasemnogene abeparvovec). European public assessment report (EPAR). EMA. https://www.ema.europa.eu/en/medicines/human/EPAR/zolgensma. Accessed Jul 2020.
   Google Scholar
• ChondroCelect (characterised viable autologous cartilage cells expanded ex vivo expressing specific marker proteins). European public assessment report (EPAR). EMA. https://www.ema.europa.eu/en/medicines/human/EPAR/chondrocelect. Accessed Jul 2020.
   Google Scholar
• Glybera (alipogene tiparvovec). European public assessment report (EPAR). EMA. https://www.ema.europa.eu/en/medicines/human/EPAR/glybera. Accessed Jul 2020.
   Google Scholar
• Provenge (autologous peripheral-blood mononuclear cells activated with prostatic acid phosphatase granulocyte-macrophage colony-stimulating factor (sipuleucel-T)). European public assessment report (EPAR). EMA. https://www.ema.europa.eu/en/medicines/human/EPAR/provenge. Accessed Jul 2020.
   Google Scholar
• Maci (matrix-applied characterised autologous cultured chondrocytes). European public assessment report (EPAR). EMA. https://www.ema.europa.eu/en/medicines/human/EPAR/maci. Accessed Jul 2020.
   Google Scholar
• Zalmoxis (allogeneic T cells genetically modified with a retroviral vector encoding for a truncated form of the human low affinity nerve growth factor receptor (ΔLNGFR) and the herpes simplex I virus thymidine kinase (HSV-TK Mut2)). European public assessment report (EPAR). EMA. https://www.ema.europa.eu/en/medicines/human/EPAR/zalmoxis. Accessed Jul 2020.
   Google Scholar
• Hecken J. ATMP im G‐BA zwischen AMNOG und Methodenbewertung 2018. https://www.mdk-wl.de/fileadmin/MDK-Westfalen-Lippe/user_upload/Hecken_atmp_im_g-ba.pdf. Accessed Oct 2019.
   Google Scholar
• Cassel D, Ulrich V. AMNOG-Daten 2018 - Funktionsweise und Ergebnisse der Preisregulierung für neue Arzneimittel in Deutschland: Bundesverband der Pharmazeutischen Industrie e. V. (BPI); 2018. https://www.bpi.de/fileadmin/user_upload/Downloads/Publikationen/AMNOG-Daten/AMNOG-Daten-2018.pdf. Accessed Oct 2019.
   Google Scholar
• Theidel U, von der Schulenburg JM. Benefit assessment in Germany: implications for price discounts. Health Econ Rev. 2016;6(1):33.
   PubMed Web of Science ®Google Scholar
• GKV-Spitzenverband. Rahmenvereinbarung nach § 130b Abs. 9 SGB V 2016. [cited 2019 October]; Available from: https://www.gkv-spitzenverband.de/media/dokumente/krankenversicherung_1/arzneimittel/rahmenvertraege/pharmazeutische_unternehmer/Rahmenvereinbarung_130b_Abs9__SGB_V_2016.pdf. Accessed Oct 2019.
   Google Scholar
• Brockis E, Marsden G, Cole A, Devlin N. A review of NICE methods across health technology assessment programmes: differences, justifications and implications. Office of Health Economics. April 2016. https://www.ohe.org/system/files/private/publications/NICE%20HTA%20methods%20RP%20FINAL_0.pdf. Accessed Oct 2019.
   Google Scholar
• Remuzat C, et al. Market access pathways for cell therapies in France. J Mark Access Health Policy. 2015. https://doi.org/10.3402/jmahp.v3.29094.
   Google Scholar
• Chevreul K, et al. France: health system review. Health Syst Transit. 2015;17(3):1–218, xvii.
   PubMedGoogle Scholar
• Cour des comptes -Sécurité sociale 2017 – Chapitre 3: La fixation du prix des médicaments des résultats significatifs, des enjeux toujours majeurs d’efficience et de soutenabilité, un cadre d’action à fortement rééquilibrer. https://www.ccomptes.fr/sites/default/files/2017-09/20170920-rapport-securite-sociale-2017-fixation-prix-medicaments.pdf. Accessed Oct 2019.
   Google Scholar
• AEMPS. Propuesta de colaboración para la elaboración de los informes de posicionamiento terapéutico de los medicamentos. https://www.aemps.gob.es/medicamentosUsoHumano/informesPublicos/docs/propuesta-colaboracion-informes-posicionamiento-terapeutico.pdf. Accessed Oct 2019.
   Google Scholar
• Miniserio de Sanidad C y BS. Comisión Interministerial de precios de medicamentos y productos sanitarios. https://www.mscbs.gob.es/profesionales/farmacia/CIPMyPS.htm. Accessed Oct 2019.
   Google Scholar
• Jommi C, Minghetti P. Pharmaceutical pricing policies in Italy. In: Babar ZUD, editor. Pharmaceutical prices in the 21st century. Cham: Adis; 2015.
   Google Scholar
• Scavone C, Capuano A, Rossi F. New criteria of Italian Medicine Agency for the attribution of therapeutic innovation: viewpoint of the pharmacologist. Giornale Italiano di Farmacoeconomia e Farmacoutilizzazione. 2017;9(3):5–12.
   Google Scholar
• TIF. Bluebird puts €1.58m price on gene therapy Zynteglo. https://thalassaemia.org.cy/it/news/bluebird-puts-e1-57m-price-on-gene-therapy-zynteglo/. Accessed Jul 2020.
   Google Scholar
• GKV-Spitzenverband. Neue Untersuchungs- und Behandlungsmethoden (NUB) 2019. https://www.gkv-spitzenverband.de/krankenversicherung/krankenhaeuser/drg_system/neue_untersuchungs_und_behandlungsmethoden_nub/neue_untersuchungs_und_behandlungsmethoden_nub.jsp. Accessed Oct 2019.
   Google Scholar
• Institut für das Entgeltsystem im Krankenhaus (InEK GmbH). Neue Untersuchungs- und Behandlungsmethoden (NUB) 2019. https://www.g-drg.de/G-DRG-System_2019/Neue_Untersuchungs-_und_Behandlungsmethoden_NUB. Accessed Oct 2019.
   Google Scholar
• legifrance.gouv.fr. JORF n°0085 du 10 avril 2019. texte n° 21.Arrêté du 28 mars 2019 limitant l’utilisation de médicament de thérapie innovante à base de lymphocytes T génétiquement modifiés dits CAR-T Cells autologues indiqués dans le traitement de la leucémie aiguë lymphoblastique à cellules B et/ou du lymphome à grande cellule B, à certains établissements de santé en application des dispositions de l’article L. 1151–1 du code de la santé publique. https://www.legifrance.gouv.fr/eli/arrete/2019/3/28/SSAH1909328A/jo/texte. Accessed Oct 2019.
   Google Scholar
• Ministerio de Sanidad C y BS. Criterios y estándares para la designación de centros para utilización de CAR-T en Linfoma Difuso de Células B grandes recidivante o refractario y en Leucemia linfoblástica aguda de células B refractaria en el sistema nacional de salud. https://www.mscbs.gob.es/profesionales/farmacia/pdf/20190304_Criterios_Estandares_Desig_Centros_CAR_T.pdf. Accessed Oct 2019.
   Google Scholar
• Osservatorio Terapie Avanzate. CAR-T: arrivano i nomi dei primi centri accreditati in Italia. 11 Ottobre 2019. https://www.osservatorioterapieavanzate.it/regolatorio/car-t-arrivano-i-nomi-dei-primi-centri-accreditati-in-italia. Accessed Oct 2019.
   Google Scholar
• DETERMINA 7 agosto 2019. Regime di rimborsabilita’ e prezzo del medicinale per uso umano «Kymriah». (Determina n. 1264/2019). (19A05147) (GU Serie Generale n.188 del 12–08–2019). https://www.gazzettaufficiale.it/eli/id/2019/08/12/19A05147/SG. Accessed Oct 2019.
   Google Scholar
• NHS—CAR-T Therapy. https://www.england.nhs.uk/cancer/cdf/car-t-therapy/. Accessed Nov 2019.
   Google Scholar