The Evolution of AIFA Registries to Support Managed Entry Agreements for Orphan Medicinal Products in Italy

Overview

Journal Front Pharmacol

Date 2021 Aug 30

PMID 34456724

Citations 17

Authors

Entela Xoxi

Karen M Facey

Americo Cicchetti

Affiliations

Soon will be listed here.

Abstract

Italy has a well-established prominent system of national registries to support managed entry agreements (MEAs), monitoring innovative medicinal products (MPs) with clinical as well as economic uncertainties to ensure appropriate use and best value for money. The technological architecture of the registries is funded by pharmaceutical companies, but fully governed by the national medicines agency (AIFA). A desktop analysis was undertaken of data over a 15-year timeframe of all AIFA indication-based registries and associated EMA information. The characteristics of registries were evaluated, comparing orphan MPs vs. all MPs exploring cancer and non-cancer indications. OMP (orphan medicinal product) registries' type vs. AIFA innovation status and EMA approval was reviewed. Of the 283 registries, 182 are appropriateness registries (35.2% relate to OMPs, with an almost equal split of cancer vs. non-cancer for OMPs and MPs), 35 include financial-based agreements [20% OMPs (2 non-cancer, 5 cancer)], and 60 registries are payment by result agreements [23.3% OMPs (4 non-cancer, 10 cancer)]. Most OMPs (53/88) came through the normal regulatory route. With the strengthening of the system for evaluation of innovation, fewer outcomes-based registries have been instigated. AIFA has overcome many of the challenges experienced with MEA through developing an integrated national web-based data collection system: the challenge that remains for AIFA is to move from using the system for individual patient decisions about treatment to reviewing the wealth of data it now holds to optimize healthcare.

Citing Articles

Stakeholders' Perspectives Toward the Use of Patient Registry Data for Decision-Making on Medicines: A Cross-Sectional Survey.

Windfuhr F, de Vries S, Melinder M, Dahlqvist T, Almeida D, Sepodes B Drug Saf. 2025; .

PMID: 39987538 DOI: 10.1007/s40264-025-01528-7.

Analysis of drug pricing drivers under South Korea's pharmaco-economic evaluation exemption policy (2015-2022).

Yu S, Lee J Front Pharmacol. 2025; 15():1519491.

PMID: 39840116 PMC: 11746112. DOI: 10.3389/fphar.2024.1519491.

The value-for-money assessment and funding arrangements for high-priced drugs in an era of uncertainty: a comparative analysis of national health technology assessment agencies in South Korea, England, Australia, and Canada.

Hong J, Bae E, Cha S, Lee J BMC Health Serv Res. 2025; 25(1):74.

PMID: 39810177 PMC: 11731375. DOI: 10.1186/s12913-025-12207-9.

Advanced Therapy Medicinal Products: Availability, Access and Expenditure in Italy.

Rivetti di Val Cervo P, Alessi E, Lastella M, La Greca A, Trotta F BioDrugs. 2024; 38(6):831-844.

PMID: 39404995 PMC: 11530470. DOI: 10.1007/s40259-024-00683-0.

Can requests for real-world evidence by the French HTA body be planned? An exhaustive retrospective case-control study of medicinal products appraisals from 2016 to 2021.

Fernandez J, Babin C, Thomassin C, Pelon F, Kelley S, Cochat P Int J Technol Assess Health Care. 2024; 40(1):e33.

PMID: 38757153 PMC: 11569913. DOI: 10.1017/S0266462324000291.

References

Wonder M, Backhouse M, Sullivan S . Australian managed entry scheme: a new manageable process for the reimbursement of new medicines?. Value Health. 2012; 15(3):586-90. DOI: 10.1016/j.jval.2012.02.004. View

Berdud M, Drummond M, Towse A . Establishing a reasonable price for an orphan drug. Cost Eff Resour Alloc. 2020; 18:31. PMC: 7472708. DOI: 10.1186/s12962-020-00223-x. View

Garattini L, Curto A, van de Vooren K . Italian risk-sharing agreements on drugs: are they worthwhile?. Eur J Health Econ. 2014; 16(1):1-3. DOI: 10.1007/s10198-014-0585-5. View

Bouvy J, Blake K, Slattery J, De Bruin M, Arlett P, Kurz X . Registries in European post-marketing surveillance: a retrospective analysis of centrally approved products, 2005-2013. Pharmacoepidemiol Drug Saf. 2017; 26(12):1442-1450. DOI: 10.1002/pds.4196. View

Russo P, Mennini F, Siviero P, Rasi G . Time to market and patient access to new oncology products in Italy: a multistep pathway from European context to regional health care providers. Ann Oncol. 2010; 21(10):2081-2087. DOI: 10.1093/annonc/mdq097. View

Ferrario A, Kanavos P . Dealing with uncertainty and high prices of new medicines: a comparative analysis of the use of managed entry agreements in Belgium, England, the Netherlands and Sweden. Soc Sci Med. 2014; 124:39-47. DOI: 10.1016/j.socscimed.2014.11.003. View

Faulkner S, Lee M, Qin D, Morrell L, Xoxi E, Sammarco A . Pricing and reimbursement experiences and insights in the European Union and the United States: Lessons learned to approach adaptive payer pathways. Clin Pharmacol Ther. 2016; 100(6):730-742. DOI: 10.1002/cpt.508. View

Dias C, Godman B, Gargano L, Azevedo P, Garcia M, Souza Cazarim M . Integrative Review of Managed Entry Agreements: Chances and Limitations. Pharmacoeconomics. 2020; 38(11):1165-1185. DOI: 10.1007/s40273-020-00943-1. View

Villa F, Tutone M, Altamura G, Antignani S, Cangini A, Fortino I . Determinants of price negotiations for new drugs. The experience of the Italian Medicines Agency. Health Policy. 2019; 123(6):595-600. DOI: 10.1016/j.healthpol.2019.03.009. View

10.

Wakap S, Lambert D, Olry A, Rodwell C, Gueydan C, Lanneau V . Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. Eur J Hum Genet. 2019; 28(2):165-173. PMC: 6974615. DOI: 10.1038/s41431-019-0508-0. View

11.

Klemp M, Fronsdal K, Facey K . What principles should govern the use of managed entry agreements?. Int J Technol Assess Health Care. 2011; 27(1):77-83. DOI: 10.1017/S0266462310001297. View

12.

Breccia M, Olimpieri P, Olimpieri O, Pane F, Iurlo A, Foggi P . How many chronic myeloid leukemia patients who started a frontline second-generation tyrosine kinase inhibitor have to switch to a second-line treatment? A retrospective analysis from the monitoring registries of the italian medicines agency (AIFA). Cancer Med. 2020; 9(12):4160-4165. PMC: 7300412. DOI: 10.1002/cam4.3071. View

13.

McGettigan P, Olmo C, Plueschke K, Castillon M, Nogueras Zondag D, Bahri P . Patient Registries: An Underused Resource for Medicines Evaluation : Operational proposals for increasing the use of patient registries in regulatory assessments. Drug Saf. 2019; 42(11):1343-1351. PMC: 6834729. DOI: 10.1007/s40264-019-00848-9. View

14.

Facey K, Rannanheimo P, Batchelor L, Borchardt M, De Cock J . Real-world evidence to support Payer/HTA decisions about highly innovative technologies in the EU-actions for stakeholders. Int J Technol Assess Health Care. 2020; :1-10. DOI: 10.1017/S026646232000063X. View

15.

Morel T, Arickx F, Befrits G, Siviero P, van der Meijden C, Xoxi E . Reconciling uncertainty of costs and outcomes with the need for access to orphan medicinal products: a comparative study of managed entry agreements across seven European countries. Orphanet J Rare Dis. 2013; 8:198. PMC: 3882782. DOI: 10.1186/1750-1172-8-198. View

16.

Garrison Jr L, Towse A, Briggs A, de Pouvourville G, Grueger J, Mohr P . Performance-based risk-sharing arrangements-good practices for design, implementation, and evaluation: report of the ISPOR good practices for performance-based risk-sharing arrangements task force. Value Health. 2013; 16(5):703-19. DOI: 10.1016/j.jval.2013.04.011. View

17.

Atkins D, Best D, Briss P, Eccles M, Falck-Ytter Y, Flottorp S . Grading quality of evidence and strength of recommendations. BMJ. 2004; 328(7454):1490. PMC: 428525. DOI: 10.1136/bmj.328.7454.1490. View

18.

Fortinguerra F, Tafuri G, Trotta F, Addis A . Using GRADE methodology to assess innovation of new medicinal products in Italy. Br J Clin Pharmacol. 2019; 86(1):93-105. PMC: 6983505. DOI: 10.1111/bcp.14138. View

19.

Ferrario A, Araja D, Bochenek T, Catic T, Danko D, Dimitrova M . The Implementation of Managed Entry Agreements in Central and Eastern Europe: Findings and Implications. Pharmacoeconomics. 2017; 35(12):1271-1285. PMC: 5684278. DOI: 10.1007/s40273-017-0559-4. View

20.

Car J, Sheikh A, Wicks P, Williams M . Beyond the hype of big data and artificial intelligence: building foundations for knowledge and wisdom. BMC Med. 2019; 17(1):143. PMC: 6636050. DOI: 10.1186/s12916-019-1382-x. View