Skip to main content

Advertisement

SpringerLink
Log in

The implementation of health technology assessment principles in public decisions concerning orphan drugs

  • Review
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Over the last few years, the share of public spending for orphan drugs (ODs) has increased in several western countries, raising concern on the exemptions granted to this sector with respect to the implementation of health technology assessment (HTA) principles. The aim of this paper is to shed light on both the HTA criteria adopted and the international agreements implemented in the OD regulation, given the new challenges imposed on western countries by a growing number of therapies for rare diseases.

Methods

We carried out a literature review to analyse the development of the international debate on the adaptability of HTA criteria for the OD assessment and regulation. The time span lies between January 1990 and May 2018, and the policies considered relate to both market authorization and reimbursement decisions within western countries. We focus specifically on HTA criteria in some of the dimensions included in the Core Model of the European net for HTA (EUnetHTA).

Results

OD high prices, the absence of clarity on the possible high revenues realized by the distribution of a new OD outside the national borders, the risk that – once marketed – a new OD can be used to treat common diseases, are all issues that raise concern on OD regulation and have to be carefully monitored by policymakers in the next future.

Conclusions

Across western countries, the preferential track granted to ODs in the implementation of HTA principles is not homogeneous, but fragmented and differentiated. The need for common rules at an international level is underlined, with a view to assessing the sustainability of a sector which, due to this regulatory void, can lend itself to producers’ strategic and opportunistic behaviours.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Notes

  1. Data on USA refer to 2015.

  2. In the USA, this guarantee is limited to 7 years.

References

  1. Richter T, Nestler-Parr S, Babela RM, Khan Z et al (2015) Rare Disease Terminology and Definitions—A Systematic Global Review: Report of the ISPOR Rare Disease Special Interest Group. Value Health 18:906–9 1 4

    Article  PubMed  Google Scholar 

  2. EMA, Annual report on the use of the special contribution for orphan medicinal products (2017)

  3. Schey C, Milanova T, Hutchings A (2011) Estimating the budget impact of orphan medicines in Europe: 2010-2020. Orphanet J Rare Dis 6:62

    Article  PubMed  PubMed Central  Google Scholar 

  4. Danzon PM (2018 Mar) Affordability challenges to value-based pricing: mass diseases, orphan diseases, and cures. Value Health 21(3):252–257

    Article  PubMed  Google Scholar 

  5. Paulden M, Stafinski T, Menon D, McCabe C (2015) Value-based reimbursement decisions for orphan drugs: a scoping review and decision framework. PharmacoEconomics 33:255–269

    Article  PubMed  Google Scholar 

  6. European Medicines Agency. European public assessment reports. Available from: http://www.ema.europa.eu/ema/index.jsp

  7. Drummond M, Towse A (2014) Orphan drugs policies: a suitable case for treatment. Eur J Health Econ 15:335–340

    Article  PubMed  Google Scholar 

  8. Iskrov G, Stefanov R (2014) Post-marketing access to orphan drugs: a critical analysis of health technology assessment and reimbursement decision-making considerations. Orphan Drugs: Res Rev 4:1–9

    Google Scholar 

  9. McCormick J, Berescu D, Tadros N (2018) Common drug review recommendations for orphan drugs in Canada: basis of recommendations and comparison with similar reviews in Quebec, Australia, Scotland and New Zealand. Orphanet Journal of Rare Diseases 13:27

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hughes-Wilson W, Palma A, Schuurman A, Simoens S (2012) Paying for the orphan drug system: break or bend? Is it time for a new evaluation system for payers in Europe to take account of new rare disease treatments? Orphanet J Rare Dis 7:74

    Article  PubMed  PubMed Central  Google Scholar 

  11. Michel M, Toumi M (2012) Access to orphan drugs in Europe: current and future issues. Expert Rev Pharmacoecon Outcomes Res 12:23–29

    Article  PubMed  Google Scholar 

  12. EUnetHTA, JA2 WP8 Deliverable, HTA Core ModelVersion 3.0 https://www.eunethta.eu/wp-content/uploads/2018/03/HTACoreModel3.0-1.pdf

  13. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009) Preferred reporting items for systematic reviews and Meta analyses: the PRISMA statement. PLoS Med 6(6):e1000097. https://doi.org/10.1371/journal.pmed1000097

    Article  PubMed  PubMed Central  Google Scholar 

  14. Downing NS, Aminawung, Shah N, Harlan M, Krumholz MDSM, Ross JS (2014) Clinical Trial Evidence Supporting FDA Approval of Novel Therapeutic Agents, 2005–2012. JAMA 311(4):368–377. https://doi.org/10.1001/jama.2013.282034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kesselheim AS, Myers JA, Avorn J (2011) Characteristics of clinical trials to support approval of orphan vs nonorphan drugs for cancer. JAMA 305:2320–2326

    Article  CAS  PubMed  Google Scholar 

  16. Joppi R, Bertele’ V, Garattini S. orphan drugs, orphan diseases. The first decade of orphan drug legislation in the EU. Eur J Clin Pharmacol 2013;69:1009–1024

    Article  PubMed  Google Scholar 

  17. Dunoyer M (2011) Accelerating access to treatments for rare diseases. Nature 10:475–476

    CAS  Google Scholar 

  18. Maresova P, Klimova B, Kuca K (2018) Legislation, regulation and policies issues of orphan drugs in developed countries from 2010 to 2016. J Appl Biomed 16:175–179. https://doi.org/10.1016/j.jab.2018.04.002

    Article  Google Scholar 

  19. Regulation (EC) No. 141/2000 of the European parliament and of the council of 16 December 1999 on orphan medicinal products. Off J Eur Communities 2000;L18:1–5

  20. Clarke JT (2006) Is the current approach to reviewing new drugs condemning the victims of rare diseases to death? A call for a national orphan drug review policy. Can Med Assoc J 174:189–190

    Article  Google Scholar 

  21. Winquist E, Bell CM, Clarke JTR, Evans G, Martin J, Sabharwal M, Gadhok A, Stevenson H, Coyle D (2012) An evaluation framework for funding drugs for rare diseases. Value Health 15:982–986

    Article  PubMed  Google Scholar 

  22. Wild C, Hintringer K, Nachtnebel A (2011) Orphan drugs in oncology. Pharm Policy Law 13:223–232

    Google Scholar 

  23. Janoudi G, Amegatse W, McIntosh B, Sehgal C, Richter T (2016) Health technology assessment of drugs for rare diseases: insights, trends, and reasons for negative recommendations from the CADTH common drug review. Orphanet J Rare Dis 11:164. https://doi.org/10.1186/s13023-016-0539-3

    Article  PubMed  PubMed Central  Google Scholar 

  24. Owen A, Spinks J, Meehan A, Robb T, Hardy M, Kwasha D, Wlodarczyk J, Reid C (2008) A new model to evaluate the long-term cost effectiveness of orphan and highly specialised drugs following listing on the Australian pharmaceutical benefits scheme: the Bosentan patient registry. J Med Econ 11:235–243

    Article  PubMed  Google Scholar 

  25. Denis A, Mergaert L, Fostier C, Cleemput I, Simoens S (2010) Budget impact analysis of orphan drugs in Belgium: estimates from 2008 to 2013. J Med Econ 13:295–301

    Article  PubMed  Google Scholar 

  26. McCabe C, Claxton K, Tsuchiya A (2005) Orphan drugs and the NHS: should we value rarity? BMJ. 331:1016–1019

    Article  PubMed  PubMed Central  Google Scholar 

  27. Claxton K, Briggs A, Buxton MJ, Culyer AJ, McCabe C, Walker S, Sculpher MJ (2008) Value based pricing for NHS drugs: an opportunity not to be missed? BMJ 336:251–254

    Article  PubMed  PubMed Central  Google Scholar 

  28. Hutchings A, Ethgen O, Schmitt C, Rollet P (2012) Defining elements of value for rare disease treatments. Value Health 15(4):A31

    Article  Google Scholar 

  29. McCabe C, Stafinski T, Menon D (2010) Is it time to revisit orphan drug policies? BMJ. 341:c4777

    Article  PubMed  Google Scholar 

  30. Mentzakis E, Stefanowska P, Hurley J (2011) A discrete choice experiment investigating preferences for funding drugs used to treat orphan diseases: an exploratory study. Health Econ Policy Law 6:405–433

    Article  PubMed  Google Scholar 

  31. Moberly T (2005) Rationing and access to orphan drugs. Pharm J 275:569–570

    Google Scholar 

  32. Pinxten W, Denier Y, Dooms M, Cassiman J, Dierickx K (2012) A fair share for the orphans: ethical guidelines for a fair distribution of resources within the bounds of the 10-year-old European orphan drug regulation. J Med Ethics 38:148–153

    Article  PubMed  Google Scholar 

  33. Prevot J, Watters D (2011) HTA’s and access to rare diseases therapies: the view from the PID community. Pharm Policy Law 11:177–181

    Google Scholar 

  34. Siddiqui M, Rajkumar SV (2012) The high cost of cancer drugs and what we can do about it. Mayo Clin Proc 87:935–943

    Article  PubMed  PubMed Central  Google Scholar 

  35. Sullivan SD (2008) The promise of specialty pharmaceuticals: are they worth the price? J Manag Care Pharm 14:S3–S6

    PubMed  Google Scholar 

  36. Laupacis A (2009) Evidence and values: requirements for public reimbursement of drugs for rare diseases: a case study in oncology. Can J Clin Pharmacol 16:e282–e284

    Google Scholar 

  37. Mycka J., Dellamano R., Lobb W. et al., Orphan drugs assessment in germany: a comparison with other international HTA agencies, Volume 18, Issue 7, 2015: A550-A551

  38. Kawalec P, Sagan A, Pilc A (2016) The correlation between HTA recommendations and reimbursement status of orphan drugs in Europe. Orphanet Journal of Rare Diseases 11:122

    Article  PubMed  PubMed Central  Google Scholar 

  39. Desser AS, Gyrd-Hansen D, Olsen JA, Grepperud S, Kristiansen IS (2010) Societal views on orphan drugs: cross sectional survey of Norwegians aged 40 to 67. Br Med J 341:c4715

    Article  Google Scholar 

  40. Largent EA, Pearson SD (2012) Which orphans will find a home? The rule of rescue in resource allocation for rare diseases. Hast Cent Rep 42:27–34

    Article  Google Scholar 

  41. Barrett P, Alagely A, Topol E (2012) Cystic fibrosis in an era of genomically guided therapy. Hum Mol Genet 21:R66–R71

    Article  CAS  PubMed  Google Scholar 

  42. Garattini S (2012) Time to revisit the orphan drug law. Eur J Clin Pharmacol 68:113

    Article  PubMed  Google Scholar 

  43. Gupta S (2012) Rare diseases : Canada’s “research orphans”. Open Med 6:23–27

    Google Scholar 

  44. Kanavos P, Nicod E (2012) What is wrong with orphan drug policies? Suggestions for ways forward. Value Health 15:1182–1184

    Article  PubMed  Google Scholar 

  45. Owen A, Spinks J, Meehan A, Robb T, Hardy M, Kwasha D, Wlodarczyk J, Reid C (2008) A new model to evaluate the long-term cost effectiveness of orphan and highly specialised drugs following listing on the Australian pharmaceutical benefits scheme: the Bosentan patient registry. J Med Econ 11:235–243

    Article  PubMed  Google Scholar 

  46. Stafinski T, Menon D, McCabe C, Philippon DJ (2011) To fund or not to fund: development of a decision-making framework for the coverage of new health technologies. Pharmacoeconomics 29:771–780

    Article  PubMed  Google Scholar 

  47. De Varax A, Letellier M, Börtlein G; for Alcimed. Study on orphan drugs, 2004. Paris; Alcimed; 2004. Available from: http://ec.europa.eu/health/files/orphanmp/doc/pricestudy/final_final_report_part_1_web_en.pdf. Accessed November 2, 2013

  48. Hutchings A, Schey C, Dutton R, Achana F, Antonov K (2014) Estimating the budget impact of orphan drugs in Sweden and France 2013–2020. Orphanet J Rare Dis 9:22

    Article  PubMed  PubMed Central  Google Scholar 

  49. Torrent-Farnell J, Comellas M, Poveda JL, Abaitua I, Gutiérrez-Solana LG, Pérez-López J, Cruz J, Urcelay J, Lizán L (2018 Mar) The view of experts on initiatives to be undertaken to promote equity in the access to orphan drugs and specialised care for rare diseases in Spain: a Delphi consensus. Health Policy 15

  50. Menon D, Stafinski T, Dunn A, Short H (2015) Involving patients in reducing decision uncertainties around orphan and ultra-orphan drugs: a rare opportunity? Patient 8:29–39

    Article  PubMed  Google Scholar 

  51. Gliklich R, Leavy M (2011) Patients registries and rare disease. Appl Clin Trials 20(3)

  52. Douglas CMW, Wilcox E, Burgess M, Lynd LD (2015) Why orphan drug coverage reimbursement decision-making needs patient and public involvement. Health Policy 119(5):588–596

    Article  PubMed  Google Scholar 

  53. Young A, Menon D, Street J, Al-Hertani W, Stafinski T (2017) Exploring patient and family involvement in the lifecycle of an orphan drug: a scoping review. Orphanet J Rare Dis 12:188. https://doi.org/10.1186/s13023-017-0738-6

    Article  PubMed  PubMed Central  Google Scholar 

  54. Zelei T, Molnar MJ, Szegedi M, Kalo Z (2016) Systematic review on the evaluation criteria of orphan medicines in central and eastern European countries. Orphanet J Rare Dis 11:72. https://doi.org/10.1186/s13023-016-0455-6

    Article  PubMed  PubMed Central  Google Scholar 

  55. Logviss K, Krievins D, Purvina S (2016) Impact of orphan drugs on Latvian budget. Orphanet J Rare Dis 11:59. https://doi.org/10.1186/s13023-016-0434-y

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was funded by OSSFOR (Osservatorio Farmaci Orfani).

Author information

Authors and Affiliations

  1. Department of Economics and Management, Università degli Studi di Pavia, Via San Felice, 5, 27100, Pavia, Italy

    Elenka Brenna

  2. Department of Economics and Finance, University of Rome Tor Vergata and C.R.E.A Sanità, Rome, Italy

    Barbara Polistena & Federico Spandonaro

Authors
  1. Elenka Brenna
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Barbara Polistena
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Federico Spandonaro
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Elenka Brenna, Barbara Polistena and Federico Spandonaro. The first draft of the manuscript was written by Elenka Brenna, and all authors commented on the previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Elenka Brenna.

Ethics declarations

Ethics approval

No plagiarism and no conflict of interest can be addressed to this research. The paper is authored jointly by Elenka Brenna, Barbara Polistena and Federico Spandonaro.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Appendix

Appendix

Table 1 Main findings from literature review addressing each of the selected domains – exemplar studies
Full size table

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Brenna, E., Polistena, B. & Spandonaro, F. The implementation of health technology assessment principles in public decisions concerning orphan drugs. Eur J Clin Pharmacol 76, 755–764 (2020). https://doi.org/10.1007/s00228-020-02855-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-020-02855-7

Keywords

Search

Navigation