Advertisement

Involving Patients in Reducing Decision Uncertainties Around Orphan and Ultra-Orphan Drugs: A Rare Opportunity?

  • Devidas Menon
  • Tania Stafinski
  • Andrea Dunn
  • Hilary Short
Systematic Review

Abstract

Introduction

Uncertainty influences the amount of risk in decision making, and is typically related to clinical benefit, value for money, affordability, and/or adoption/diffusion of the technology (e.g., drug, device, procedure, etc.). Although evidence-based review processes within each stage of the technology lifecycle have been implemented to minimize uncertainty, high-quality information addressing that related to orphan and ultra-orphan drugs is often unavailable. The role that patients, as experts in their disease, may play in providing such information has yet to be fully explored.

Objective

The objective of this systematic review was to identify existing and proposed opportunities for patients with rare diseases and their families to provide input aimed at reducing decision uncertainties throughout the lifecycle of an orphan or ultra-orphan drug.

Methods

A comprehensive review of published and gray literature describing roles for patients and families in activities related to orphan and ultra-orphan drugs was conducted. In addition, the websites of regulatory and centralized reimbursement decision-making bodies in the top 22 OECD (Organisation for Economic Cooperation and Development) countries by gross domestic product (GDP) were scanned to identify current opportunities for patients with rare diseases in both stages. The websites of umbrella patient organizations for rare diseases in these countries were also scanned. These roles were then mapped onto a matrix to determine the stage in the technology lifecycle and types of uncertainties they directly or indirectly addressed.

Results

Across the 22 countries, nine roles for patients within regulatory related processes were identified, with at least one in each country. These roles were not specific to patients with rare diseases. Similarly, six different opportunities for patient input in centralized drug review processes were identified, all of which applied to patients, in general, rather than just those with rare diseases. ‘Real-world’ examples of patient involvement explicitly related to rare diseases centered around 11 different themes. Seven fell within the research and development or clinical trial stages of a drug’s lifecycle. Of the remaining four, three were associated with education and advocacy. All of the proposed roles identified focused on greater involvement in (1) the design and conduct of clinical trials, or (2) the ‘valuation’ of evidence during reimbursement decision making. When mapped onto the matrix of decision uncertainties, almost all of the existing and proposed roles addressed ‘clinical benefit’. Roles for patients in reducing ‘value for money’, affordability, or adoption/diffusion uncertainties were mainly indirect, and a result of patient involvement in activities aimed at generating information on clinical benefit, which is then used to inform discussions around these uncertainties.

Conclusions

While patient involvement in activities that directly address uncertainties in clinical benefit may not be ‘rare’, opportunities for reducing those related to ‘value for money’, affordability, and adoption/diffusion remain scarce.

Keywords

Rare Disease Orphan Drug Electronic Supplementary Material Table Patient Involvement Patient Organization 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The work reported in this paper was made possible by an Emerging Team Grant from the Canadian Institutes of Health Research on “Developing Effective Policies for Managing Technologies for Rare Diseases”.

Author contributions

D. Menon made a substantial contribution to the conception and planning of the work that led to this manuscript, to the interpretation of the data, to critical revision and final approval of the manuscript, and is the overall guarantor of the work.

T. Stafinski made a substantial contribution to the conception and planning of the work that led to this manuscript, to the analysis and interpretation of the data, to drafting, critical revision, and final approval of the manuscript.

A. Dunn made a substantial contribution to the analysis and interpretation of the data, to critical revision and final approval of the manuscript.

H. Short made a substantial contribution to the analysis and interpretation of the data, to critical revision, and final approval of the manuscript.

None of the authors has any financial or non-financial conflicts of interest to declare.

Supplementary material

40271_2014_106_MOESM1_ESM.docx (39 kb)
Supplementary material 1 (DOCX 38 kb)
40271_2014_106_MOESM2_ESM.docx (39 kb)
Supplementary material 2 (DOCX 39.1 kb)
40271_2014_106_MOESM3_ESM.docx (63 kb)
Supplementary material 3 (DOCX 62.6 kb)
40271_2014_106_MOESM4_ESM.docx (75 kb)
Supplementary material 4 (DOCX 75 kb)
40271_2014_106_MOESM5_ESM.docx (22 kb)
Supplementary material 5 (DOCX 22.1 kb)
40271_2014_106_MOESM6_ESM.docx (465 kb)
Supplementary material 6 (DOCX 465 kb)

References

  1. 1.
    Canadian Drug Expert Committee final recommendation—plain language version: eltrombopag olamine (Revolade-GlaxoSmithKline Inc.). Indication: chronic immune (idiopathic) thrombocytopenic purpura. Common Drug Review (CDR). Ottawa: Canadian Agency for Drugs and Technologies in Health (CADTH); 2011.Google Scholar
  2. 2.
    CEDAC final recommendation: eculizumab (Soliris-Alexion Pharmaceuticals, Inc.). Indication: paroxysmal noctural hemoglobinuria. Common Drug Review (CDR). Ottawa: Canadian Agency for Drugs and Technologies in Health (CADTH); 2010.Google Scholar
  3. 3.
    CEDAC final recommendation on reconsideration and reasons for recommendation: pegvisomant (Somavert-Pfizer Canada Inc.). Common Drug Review (CDR). Ottawa: Canadian Agency for Drugs and Technologies in Health (CADTH); 2006.Google Scholar
  4. 4.
    CEDAC final recommendation: eltrombopag olamine (Revolade-GlaxoSmithKline Inc.). Indication: chronic immune (idiopathic) thrombocytopenic purpura. Common Drug Review (CDR). Ottawa: Canadian Agency for Drugs and Technologies in Health (CADTH); 2011.Google Scholar
  5. 5.
    CEDAC final recommendation: tocilizumab (Actemra-Hoffmann-La Roche). New indication: arthritis, systemic juvenile idiopathic. Common Drug Review (CDR). Ottawa: Canadian Agency for Drugs and Technologies in Health (CADTH); 2012.Google Scholar
  6. 6.
    About the Common Drug Review. Ottawa: Canadian Agency for Drugs and Technologies in Health (CADTH); 2014.Google Scholar
  7. 7.
    Elliott KC, Dickson M. Distinguishing risk and uncertainty in risk assessments of emerging technologies. In: Zülsdorf T, Coenen C, Ferrari A, Fiedeler U, Milburn C, Wienroth M, editors. Quantum engagements: social reflections of nanoscience and emerging technologies. Heidelberg: AKA; 2011, p. 165–76.Google Scholar
  8. 8.
    Riabacke A. Managerial decision making under risk and uncertainty. IAENG Int J Comput Sci. 2006;32(4), (IJCS_32_4_12). http://www.iaeng.org/IJCS/issues_v32/issue_4/IJCS_32_4_12.pdf. Accessed 4 Dec 2014.Google Scholar
  9. 9.
    Meekings KN, Williams CS, Arrowsmith JE. Orphan drug development: an economically viable strategy for biopharma R&D. Drug Discov Today. 2012;17(13–14):660–4.PubMedCrossRefGoogle Scholar
  10. 10.
    Garattini S. Time to revisit the orphan drug law. Eur J Clin Pharmacol. 2012;68(2):113.PubMedCrossRefGoogle Scholar
  11. 11.
    Kesselheim AS, Myers JA, Avorn J. Characteristics of clinical trials to support approval of orphan vs nonorphan drugs for cancer. JAMA. 2011;305(22):2320–6.PubMedCrossRefGoogle Scholar
  12. 12.
    RARE facts and statistics. Aliso Viejo: The Global Genes Project; 2012.Google Scholar
  13. 13.
    Cetel JS. Disease-branding and drug-mongering: could pharmaceutical industry promotional practices result in tort liability? Seton Hall Law Rev. 2012;42(2):643–702.PubMedGoogle Scholar
  14. 14.
    Clarke JT. 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. CMAJ. 2006;174(2):189–90.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Carmichael LE. Gene therapy. North Mankato: ABDO Publishing; 2014. p. 76.Google Scholar
  16. 16.
    Schey C, Milanova T, Hutchings A. Estimating the budget impact of orphan medicines in Europe: 2010–2020. Orphanet J Rare Dis. 2011;6:62.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Picavet E, Dooms M, Cassiman D, Simoens S. Drugs for rare diseases: influence of orphan designation status on price. Appl Health Econ Health Policy. 2011;9(4):275–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Orphanet website Canadian entry point. [Ottawa]: Orphanet; 2014. http://www.orpha.net/national/CA-EN/index/homepage/. Accessed 31 May 2014
  19. 19.
    Hughes DA, Tunnage B, Yeo ST. Drugs for exceptionally rare diseases: do they deserve special status for funding? QJM. 2005;98(11):829–36.PubMedCrossRefGoogle Scholar
  20. 20.
    Initial draft discussion document for a Canadian orphan drug regulatory framework. Ottawa: Health Canada, Office of Legislative and Regulatory Modernization; 2012.Google Scholar
  21. 21.
    The patient’s voice in the evaluation of medicines: how patients can contribute to assessment of benefit and risk. London: European Medicines Agency (EMA); 2013.Google Scholar
  22. 22.
    Patients and consumers. London: European Medicines Agency (EMA); 2014.Google Scholar
  23. 23.
    Pawson R. Evidence-based policy: in search of a method. Evaluation. 2002;8(2):157–81.CrossRefGoogle Scholar
  24. 24.
    Stafinski T, McCabe CJ, Menon D. Funding the unfundable: mechanisms for managing uncertainty in decisions on the introduction of new and innovative technologies into healthcare systems. Pharmacoeconomics. 2010;28(2):113–42.PubMedCrossRefGoogle Scholar
  25. 25.
    Consumer input to the Australian Drug Evaluation Committee (ADEC). Summary evaluation of 2002–04 pilot project. Manuka (ACT): Consumers’ Health Forum of Australia; 2006.Google Scholar
  26. 26.
    Towards a strategic science plan. Ottawa: Health Canada, Drugs and Health Products; 2009.Google Scholar
  27. 27.
    Spooner A. Implementing the new pharmacovigilance legislation. Dublin: Irish Medicines Board; 2011.Google Scholar
  28. 28.
    Intanza intradermal 9ug dose influenze vaccine for persons 18–59 years of age: data sheet. Wellington: New Zealand Medicines and Medical Devices Safety Authority (MEDSAFE); 2014.Google Scholar
  29. 29.
    The Patient Reported Outcomes (PRO) Consortium. Silver Spring: US Food and Drug Administration (FDA); 2010.Google Scholar
  30. 30.
    Framework on the interaction between the EMEA and patients’ and consumers’ organisations. London: European Medicines Agency (EMEA); 2006.Google Scholar
  31. 31.
    Consultation workshop report on patient involvement strategy. Ottawa: Health Canada. Office of Consumer and Public Involvement and Best Medicines Coalition (BMC); 2002.Google Scholar
  32. 32.
    Regulatory transparency and openness. Ottawa: Health Canada; 2009.Google Scholar
  33. 33.
    Report an adverse drug reaction. Reykjavik: Lyfjastofnun/Icelandic Medicines Agency (IMA); 2014.Google Scholar
  34. 34.
    The Pharmaceuticals and Medical Devices Agency: annual report fy 2008. Tokyo: Pharmaceuticals and Medical Devices Agency (PMDA); 2008.Google Scholar
  35. 35.
    Pharmacovigilance. Oslo: Statens Legemiddelverk/Norwegian Medicines Agency; 2012.Google Scholar
  36. 36.
    The voice of the patient: a series of reports from FDA’s Patient-Focused Drug Development Initiative. Silver Spring: US Food and Drug Administration (FDA); 2014.Google Scholar
  37. 37.
    Patient and consumer participation pool. Ottawa: Health Canada; 2011.Google Scholar
  38. 38.
    Public involvement framework. Ottawa: Health Canada. Health Products and Food Branch; 2005.Google Scholar
  39. 39.
    About the patient representative program. Silver Spring: US Food and Drug Administration (FDA); 2014.Google Scholar
  40. 40.
    FAQs: who can be a patient representative? Silver Spring: US Food and Drug Administration (FDA); 2014.Google Scholar
  41. 41.
    Korean pharmacopoeia. Chungcheongbuk-do (Korea): Korean Ministry of Food and Drug Safety; 2014.Google Scholar
  42. 42.
    Medicines Classification Committee. Public consultation on agenda items. Wellington: New Zealand Medicines and Medical Devices Safety Authority (MEDSAFE); 2014.Google Scholar
  43. 43.
    Bere N. Lifecycle of a new medicinal product—with emphasis on pharmacovigilance. London: European Medicines Agency (EMA); 2013.Google Scholar
  44. 44.
    FDA working with patients to explore benefit/risk: opportunities and challenges. Silver Spring (MD): US Food and Drug Administration (FDA); 2012.Google Scholar
  45. 45.
    Reporting problems. Canberra: Australian Government. Department of Health. Therapeutic Goods Administration; 2014.Google Scholar
  46. 46.
    Adverse reaction and medical device problem reporting. Ottawa: Health Canada; 2012.Google Scholar
  47. 47.
    Safety information: how to report a problem. Wellington: MEDSAFE: New Zealand Medicines and Medical Devices Safety Authority; 2013.Google Scholar
  48. 48.
    Pharmacovigilance. Bern: Swissmedic: Swiss Agency for Therapeutic Products; 2014.Google Scholar
  49. 49.
    Reporting serious problems to FDA. Silver Spring: US Food and Drug Administration (FDA); 2014.Google Scholar
  50. 50.
    Guidelines for preparing submissions to the Pharmaceutical Benefits Advisory Committee. Canberra: Australian Government, Department of Health, Pharmaceutical Benefits Advisory Committee (PBAC); 2014.Google Scholar
  51. 51.
    Obtaining consumer comments on submissions to the Pharmaceutical Benefits Advisory Committee meetings. Canberra: Australian Government. Department of Health. Pharmaceutical Benefits Advisory Committee (PBAC); 2014.Google Scholar
  52. 52.
    Guidelines for preparing submissions to the Pharmaceutical Benefits Advisory Committee (Version 4.3). Canberra: Australian Government. Department of Health, Pharmaceutical Benefits Advisory Committee (PBAC); 2008.Google Scholar
  53. 53.
    Germany—pharmaceutical. Lawrenceville: International Society for Pharmacoeconomics and Outcomes Research (ISPOR); 2009.Google Scholar
  54. 54.
    Fukuda T. Use of economic evaluation for policy making in Japan [conference presentation]. Pharmacoeconomics and Outcomes Research in Asia: what is next? ISPOR 16th European Congress in Dublin, Nov 5, 2013; 2013. http://www.ispor.org/congresses/Dublin1113/presentations/ISPOR20131105-fukuda.pdf. Accessed 8 Dec 2014.
  55. 55.
    Ngorsuraches S, Meng W, Kim BY, Kulsomboon V. Drug reimbursement decision-making in Thailand, China, and South Korea. Value Health. 2012;15(1 Suppl):S120–5.PubMedCrossRefGoogle Scholar
  56. 56.
    Liste des specialites (LS) [List of pharmaceutical specialties (LS)]. Berne: Swiss Federal Office of Public Health (FOPH); 2013.Google Scholar
  57. 57.
    Interim process and methods of the Highly Specialised Technologies Programme. London: National Institute for Health and Care Excellence (NICE); 2013.Google Scholar
  58. 58.
    Innovation pass pilot: a consultation on proposals for an innovation pass pilot. London: Department of Health, Medicines Pharmacy and Industry Group; 2009.Google Scholar
  59. 59.
    Templates/guidance for submission. Glasgow: Scottish Medicines Consortium (SMC); 2014.Google Scholar
  60. 60.
    All Wales Medicines Strategy Group: about us. Vale of Glamorgan: All Wales Medicines Strategy Group (AWMSG); 2014.Google Scholar
  61. 61.
    Patient input. Ottawa: Canadian Agency for Drugs and Technologies in Health (CADTH); 2014.Google Scholar
  62. 62.
    GUIDE—patient group input to the Common Drug Review at CADTH. Ottawa: Canadian Agency for Drugs and Technologies in Health (CADTH); 2014.Google Scholar
  63. 63.
    Pharmaceuticals Pricing Board legislation. Helsinki: Finland Ministry of Social Affairs and Health; 2013.Google Scholar
  64. 64.
    Garau M, Mestre-Ferrandiz J. Access mechanisms for orphan drugs: a comparative study of selected European countries. London: Office of Health Economics; 2009.Google Scholar
  65. 65.
    Barham L. Orphan medicines: special treatment required? London: 2020health.org; 2012.Google Scholar
  66. 66.
    Franken M, le Polain M, Cleemput I, Koopmanschap M. Similarities and differences between five European drug reimbursement systems. Int J Technol Assess Health Care. 2012;28(4):349–57.PubMedCrossRefGoogle Scholar
  67. 67.
    Sorenson C, Drummond M, Kanavos P. Ensuring value for money in health care: the role of health technology assessment in the European Union. Copenhagen: World Health Organization/European Observatory on Health Systems and Policies; 2008.Google Scholar
  68. 68.
    Guidelines for funding applications to PHARMAC. Wellington: New Zealand Government, Pharmaceutical Management Agency (PHARMAC); 2010.Google Scholar
  69. 69.
    Highly Specialised Technologies Evaluation Committee. London: National Institute for Health and Care Excellence (NICE); 2013.Google Scholar
  70. 70.
    Mavris M, Le CY. Involvement of patient organisations in research and development of orphan drugs for rare diseases in Europe. Mol Syndromol. 2012;3(5):237–43.PubMedCentralPubMedGoogle Scholar
  71. 71.
    Polich GR. Rare disease patient groups as clinical researchers. Drug Discov Today. 2012;17(3–4):167–72.PubMedCrossRefGoogle Scholar
  72. 72.
    Boon W, Broekgaarden R. The role of patient advocacy organisations in neuromuscular disease R&D—the case of the Dutch neuromuscular disease association VSN. Neuromuscul Disord. 2010;20(2):148–51.PubMedCrossRefGoogle Scholar
  73. 73.
    Wastfelt M, Fadeel B, Henter JI. A journey of hope: lessons learned from studies on rare diseases and orphan drugs. J Intern Med. 2006;260(1):1–10.PubMedCrossRefGoogle Scholar
  74. 74.
    Rabeharisoa V. The struggle against neuromuscular diseases in France and the emergence of the “partnership model” of patient organisation. Soc Sci Med. 2003;57(11):2127–36.PubMedCrossRefGoogle Scholar
  75. 75.
    Rabeharisoa V, Callon M. The involvement of patients’ associations in research. Int Soc Sci J. 2002;54(171):57–63.CrossRefGoogle Scholar
  76. 76.
    PRO RETINA Germany eV. Aachen (Germany): PRO RETINA Deutschland e.V. http://www.pro-retina.de/ (2014). Accessed 31 May 2014.
  77. 77.
    Nierse CJ, Abma TA, Horemans AM, van Engelen BG. Research priorities of patients with neuromuscular disease. Disabil Rehabil. 2013;35(5):405–12.PubMedCrossRefGoogle Scholar
  78. 78.
    Davila-Seijo P, Hernandez-Martin A, Morcillo-Makow E, de Lucas R, Dominguez E, Romero N, et al. Prioritization of therapy uncertainties in dystrophic Epidermolysis bullosa: where should research direct to? An example of priority setting partnership in very rare disorders. Orphanet J Rare Dis. 2013;8:61.PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    Linertova R, Serrano-Aguilar P, Posada-de-la-Paz M, Hens-Perez M, Kanavos P, Taruscio D, et al. Delphi approach to select rare diseases for a European representative survey. The BURQOL-RD study. Health Policy. 2012;108(1):19–26.PubMedCrossRefGoogle Scholar
  80. 80.
    Wood J, Sames L, Moore A, Ekins S. Multifaceted roles of ultra-rare and rare disease patients/parents in drug discovery. Drug Discov Today. 2013;18(21–22):1043–51.PubMedCrossRefGoogle Scholar
  81. 81.
    Parkinson K. The involvement of patients in developing clinical guidelines [abstract]. Orphanet J Rare Dis. 2012;7(Suppl 2):A13.PubMedCentralCrossRefGoogle Scholar
  82. 82.
    Bacon CJ, Hall CA, Shy ME. The rare diseases clinical research network contact registry for the inherited neuropathies consortium. J Peripher Nerv Syst. 2013;18:S9.Google Scholar
  83. 83.
    Pattacini C, Rivolta GF, Di PC, Riccardi F, Tagliaferri A, Haemophilia Centres Network of Emilia-Romagna Region. A web-based clinical record ‘xl’Emofilia’ for outpatients with haemophilia and allied disorders in the Region of Emilia-Romagna: features and pilot use. Haemophilia. 2009;15(1):150–8.PubMedCrossRefGoogle Scholar
  84. 84.
    Frost JH, Massagli MP, Wicks P, Heywood J. How the Social Web Supports patient experimentation with a new therapy: the demand for patient-controlled and patient-centered informatics. AMIA Annu Symp Proc. 2008;2008:217–21.Google Scholar
  85. 85.
    Mallbris L, Nordenfelt P, Bjorkander J, Lindfors A, Werner S, Wahlgren CF. The establishment and utility of Sweha-Reg: a Swedish population-based registry to understand hereditary angioedema. BMC Dermatol. 2007;7:6.PubMedCentralPubMedCrossRefGoogle Scholar
  86. 86.
    TREAT-NMD: serving the neuromuscular community. Newcastle upon Tyne: TREAT-NMD Neuromuscular Network; 2014.Google Scholar
  87. 87.
    Terry SF, Terry PF, Rauen KA, Uitto J, Bercovitch LG. Advocacy groups as research organizations: the PXE International example. Nat Rev Genet. 2007;8(2):157–64.PubMedCrossRefGoogle Scholar
  88. 88.
    de Blieck EA, Augustine EF, Marshall FJ, Adams H, Cialone J, Dure L, et al. Methodology of clinical research in rare diseases: development of a research program in juvenile neuronal ceroid lipofuscinosis (JNCL) via creation of a patient registry and collaboration with patient advocates. Contemp Clin Trials. 2013;35(2):48–54.PubMedCentralPubMedCrossRefGoogle Scholar
  89. 89.
    Pierri P. A route map for the patients journey [abstract]. Orphanet J Rare Dis. 2012;7(Suppl 2):A40.PubMedCentralCrossRefGoogle Scholar
  90. 90.
    Ayme S, Kole A, Groft S. Empowerment of patients: lessons from the rare diseases community. Lancet. 2008;371(9629):20080614–20.CrossRefGoogle Scholar
  91. 91.
    Keeling P. Role of the opportunity to test index in integrating diagnostics with therapeutics. Personal Med. 2006;3(4):399–407.Google Scholar
  92. 92.
    Pypops U. Patient perspective on CT Involvement: Are they listening to my needs? [abstract]. Orphanet J Rare Dis. 2012;7(Suppl 2):A39.PubMedCentralCrossRefGoogle Scholar
  93. 93.
    Gupta S, Bayoumi AM, Faughnan ME. Rare lung disease research: strategies for improving identification and recruitment of research participants. Chest. 2011;140(5):1123–9.Google Scholar
  94. 94.
    Carroll R, Antigua J, Taichman D, Palevsky H, Forfia P, Kawut S, et al. Motivations of patients with pulmonary arterial hypertension to participate in randomized clinical trials. Clin Trials. 2012;9(3):348–57.PubMedCentralPubMedCrossRefGoogle Scholar
  95. 95.
    Sussex J, Rollet P, Garau M, Schmitt C, Kent A, Hutchings A. A pilot study of multicriteria decision analysis for valuing orphan medicines. Value Health. 2013;16(8):1163–9.PubMedCrossRefGoogle Scholar
  96. 96.
    History of the Australian Drug Evaluation Committee 1963–2009. Canberra: Australian Government, Department of Health, Therapeutic Goods Administration; 2010.Google Scholar
  97. 97.
    Australian public assessment report for sunitinib. Proprietary product name: Sutent. Sponsor: Pfizer Australia Pty Ltd. Canberra: Australian Government, Department of Health and Ageing, Therapeutic Goods Administration; 2011.Google Scholar
  98. 98.
    Harvey K. Consumer input in Medicines Australia’s code of conduct review. Conversation. 2012 Apr 16. http://theconversation.com/consumer-input-in-medicines-australias-code-of-conduct-review-6370. Accessed 4 Dec 2014.
  99. 99.
    Scientific advice/protocol assistance: experience and impact of patient involvement. London: EURORDIS: Rare Diseases Europe/European Medicines Agency (EMA); 2013.Google Scholar
  100. 100.
    Benefit-risk evaluation. Ottawa: Health Canada, Drugs and Health Products; 2007.Google Scholar
  101. 101.
    Consultation: draft guidance for industry—submission of risk management plans and follow-up commitments. Ottawa: Health Canada, Drugs and Health Products; 2014.Google Scholar
  102. 102.
    General information: pharmacovigilance. Reykjavik: Lyfjastofnun/Icelandic Medicines Agency (IMA); 2014.Google Scholar
  103. 103.
    Laws and regulations. Reykjavik: Lyfjastofnun/Icelandic Medicines Agency (IMA); 2014.Google Scholar
  104. 104.
    New Zealand regulatory guidelines for medicines. Part A: when is an application for approval of a new or changed medicine required? 6.15 ed. Wellington: New Zealand Medicines and Medical Devices Safety Authority (MEDSAFE); 2011.Google Scholar
  105. 105.
    PHIS pharma profile template: Norway, Version 1. [n.s.]: Vienna: Pharmaceutical Health Information System (PHIS). 2011. http://www.legemiddelverket.no/English/the-norwegian-health-care-system-and-pharmaceutical-system/Documents/NO%20PHIS%20Pharma%20Profile%202011_links%20updated%20March%202014.pdf. Accessed 8 Dec 2014.
  106. 106.
    Regulations: regulation (EU) no 1235/2010 of the European Parliament and of the Council of 15 December 2010. Off J Eur Union. 2010;L348:1–16.Google Scholar
  107. 107.
    Good pharmacovigilance practices. London: European Medicines Agency (EMA); 2014.Google Scholar
  108. 108.
    Austria—pharmaceutical. Lawrenceville: International Society for Pharmacoeconomics and Outcomes Research (ISPOR); 2009.Google Scholar
  109. 109.
    Leopold C, Habl C. Pharmaceutical pricing and reimbursement information: Austria. Vienna: Pharmaceutical Pricing and Reimbursement Information (PPRI); 2008.Google Scholar
  110. 110.
    Medicinal products and health care in Austria: facts and figures 2013. Vienna: Pharmig; 2013.Google Scholar
  111. 111.
    Erstattungskodex-EKO [Code of reimbursement-Austria]. Stand 1 ed. Wien: Haputverband der osterreichischen Sozialversicherungstrager; 2013.Google Scholar
  112. 112.
    Rules of procedure for publishing the code of reimbursement according to 351g ASVG. [n.s.]: Vienna: Austrian Federation of Social Insurance Institutions/Osterreichische Sozialverischerung; 2007.Google Scholar
  113. 113.
    Guillaume P, Moldenaers I, Bulte S, Debruyene H, Devriese S, Kohn L, Pierart J, Vinck I. Optimisation of the operational processes of the Special Solidarity Fund. Brussels: Belgian Health Care Knowledge Centre; 2010.Google Scholar
  114. 114.
    Reimbursement of medicines. Copenhagen: Sundhedsstyrelsen/Danish Health and Medicines Authority; 2012.Google Scholar
  115. 115.
    Application for basic reimbursement status and reasonable wholesale price for a medicinal product subject to special licence. For applications by a patient or a pharmacy on behalf of the patient. [n.s.]: Laakkeiden Hintalautakunta/Government of Finland. Helsinki: Pharmaceuticals Pricing Board; 2011.Google Scholar
  116. 116.
    Guidelines for preparing a health economic evaluation. [n.s.]: Ministry of Social Affairs and Health, Helsinki: Pharmaceuticals Pricing Board; 2011.Google Scholar
  117. 117.
    Temporary authorisations for use (ATU). [n.s.]: Paris: Agence Francaise de Securite Sanitaire des Produits de Sante; 2001.Google Scholar
  118. 118.
    Meyer F. Orphan drugs assessment and reimbursement: the situation in France. Toronto: Canadian Organization for Rare Disorders (CORD); 2009.Google Scholar
  119. 119.
    Denis A, Simoens S, Fostier C, Mergaert L, Cleemput I. Policies for orphan diseases and orphan drugs. Brussels: Belgian Health Care Knowledge Centre (KCE); 2009.Google Scholar
  120. 120.
    Creation of a process for the exchange of knowledge between member states and European authorities on the scientific assessment of the clinical added value for orphan medicines. Reference: EAHC/2010/Health/05 ed. Brussels: European Commission. Executive Agency for Health and Consumers (EAHC); 2011.Google Scholar
  121. 121.
    Pelen F. Reimbursement and pricing of drugs in France: an increasingly complex system. HEPAC Health Econ Prev Care. 2000;3:20–3.CrossRefGoogle Scholar
  122. 122.
    Remuzat C, Toumi M, Falissard B. New drug regulations in France: what are the impacts on market access? Part 1—overview of new drug regulations in France. J Market Access Health Policy. 2013;1:1–9.Google Scholar
  123. 123.
    Rochaix L, Xerri B. National Authority for Health: France. Issue Brief (Commonw. Fund). 2009;58:1–9.Google Scholar
  124. 124.
    Stafinski T, Menon D, Philippon D, McCabe C. Health technology funding decision-making processes around the world: the same yet different. Pharmacoeconomics. 2011;29(6):475–95.PubMedCrossRefGoogle Scholar
  125. 125.
    Fulda CB. A revolution of reimbursement in Germany. Jones Day; 2011. http://www.jonesday.com/revolution_of_reimbursement/. Accessed 4 Dec 2014.
  126. 126.
    Ordinance on the placing on the market of unauthorised medicinal products for compassionate use (Ordinance on Medicinal Products for Compassionate Use—AMHV). [n.s.]: Berlin: Bundesministerium fur Gesundheit/German Federal Minister of Health; 2010.Google Scholar
  127. 127.
    Kavanagh C, Diamond D, O’Gorman M. Ireland. Dublin: Arthur Cox; 2014.Google Scholar
  128. 128.
    Bakowska M, Berekmeri-Varro R, Biro H, Brandt S, Bruyndonckx A, Casanueva AEA. Pricing and reimbursement handbook. 1st ed. Geneva, USA: Baker & McKenzie; 2011.Google Scholar
  129. 129.
    Taruscio D, Capozzoli F, Frank C. Rare diseases and orphan drugs. Ann Ist Super Sanita. 2011;47(1):83–93.PubMedGoogle Scholar
  130. 130.
    C. Hable and F. Bachner. Initial investigation to assess the feasibility of a coordinated system to access orphan medicines. Vienna: European Commission, Directorate-General for Enterprise and Industry; European Medicine Information Network (EMINet); Gesundheit Osterreich GmbH; 2011.Google Scholar
  131. 131.
    Access to treatments that aren’t on the lists (NPPA). Wellington: New Zealand Government, Pharmaceutical Management Agency (PHARMAC); 2014.Google Scholar
  132. 132.
    PHIS pharma profile: Norway, Version 1. [n.s.]: Vienna: Pharmaceutical Health Information System (PHIS); 2011.Google Scholar
  133. 133.
    Disposiciones generales: Ministerio de Sanidad y Politica Social. Boletin Oficial del Estado. 2009;174 (Sec. 1):60904–13.Google Scholar
  134. 134.
    Switzerland—pharmaceutical. Lawrenceville: International Society for Pharmacoeconomics and Outcomes Research (ISPOR); 2011.Google Scholar
  135. 135.
    Process for advising on the feasibility of implementing a patient access scheme. Interim. London: National Institute for Health and Care Excellence (NICE), Patient Access Schemes Liaison Unit; 2009.Google Scholar
  136. 136.
    Komlos D. Focusing on patients in drug development. Life Sci Connect. 2013 Dec 20. pp. 1–5. http://lsconnect.thomsonreuters.com/patient-focused-drug-development/. Accessed 8 Dec 2014.
  137. 137.
    Bignami F, Kent AJ, Lipucci di PM, Meade N. Participation of patients in the development of advanced therapy medicinal products. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2011;54(7):839–42.Google Scholar
  138. 138.
    Crompton H. Mode 2 knowledge production: evidence from orphan drug networks. Sci Public Policy. 2007;34(3):199–211.CrossRefGoogle Scholar
  139. 139.
    Smith WB, McCaslin IR, Gokce A, Mandava SH, Trost L, Hellstrom WJ. PDE5 inhibitors: considerations for preference and long-term adherence. Int J Clin Pract. 2013;67(8):768–80.PubMedCrossRefGoogle Scholar
  140. 140.
    Licht C, Ardissino G, Ariceta G, Beauchamp J, Cohen D, Greenbaum L, et al. An observational, non-interventional, multicenter, multinational registry of patients with atypical hemolytic uremic syndrome (AHUS): methodology [abstract]. Pediatr Nephrol. 2013;28(8):1571.Google Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Devidas Menon
    • 1
  • Tania Stafinski
    • 1
  • Andrea Dunn
    • 1
  • Hilary Short
    • 1
  1. 1.Health Technology and Policy Unit, School of Public HealthUniversity of Alberta, 3021 Research Transition FacilityEdmontonCanada

Personalised recommendations