Applied Health Economics and Health Policy

, Volume 17, Issue 2, pp 143–162 | Cite as

Effectiveness of National Pricing Policies for Patent-Protected Pharmaceuticals in the OECD: A Systematic Literature Review

  • Dominik J. WettsteinEmail author
  • Stefan Boes
Systematic Review



The aim of this review is to assess the current state of empirical research regarding the effectiveness of national pricing regulations of the patent-protected market for prescription pharmaceuticals. Effectiveness is understood to be the capacity of policies to have a desired impact on outcomes, such as health status, patient access, healthcare expenditure, and research investments, among others.


A systematic review of the published literature on pricing regulations in OECD countries was performed. The PubMed, MEDLINE, Scopus, Web of Science, Cochrane Library and the OECD iLibrary databases were searched in September 2016 and December 2017, with an update in August 2018. Interrupted time series studies and additional empirical studies were included, as well as systematic reviews if appropriate methods were applied. The risk of bias was assessed based on the recommendations of the BMJ guidelines, Cochrane EPOC criteria, QHES instrument, HTA good practice guidelines, CRD’s guidance and the CHEC criteria. The quality of evidence was evaluated using the suggestions from EPOC and GRADE.


Thirty-one publications met the inclusion criteria. Most of the assessed empirical research included therapeutic (TRP) and/or external reference pricing (ERP), with a clear majority focusing on TRP. The main outcomes that were analysed were drug prices, expenditures and drug use. For value-based pricing (VBP), only limited empirical data were found.


We found evidence that TRP may reduce pharmaceutical prices and expenditures in the short term. Furthermore, TRP may lead to substitution effects towards lower-priced pharmaceuticals. The effects of TRP on patient access, healthcare utilisation and R&D investments were found to be uncertain. No conclusions were drawn for ERP and VBP. No evidence was found for the effects on health outcomes for any of the analysed policies. There is a strong need for evidence generation regarding effective pricing policies, particularly for VBP, managed entry agreements and non-financial outcomes.


Author Contributions

All of the authors (DJW and SB) fulfilled the authorship criteria and contributed to the design of the study, review of the search protocol, analysis and interpretation of the results, and writing and review of the manuscript. DJW prepared the search protocol, performed the database searches, screenings, categorisations, and assessments and prepared the draft of the manuscript. All of the authors are aware of the submission and are in agreement with the manuscript.

Compliance with Ethical Standards


No funding was received for the research performed or the writing of the manuscript.

Conflict of interest

DJW is an external PhD student at the University of Lucerne and was employed at the pharmaceutical company Takeda Pharma while performing this research. Neither the former employer of the first author nor any other private or public entity supported or influenced this research in any relevant way. SB has no conflicts of interest to declare. All of the authors submitted a signed Conflict of Interest disclosure form.

Supplementary material

40258_2018_437_MOESM1_ESM.pdf (194 kb)
Supplementary material 1 (PDF 194 kb)
40258_2018_437_MOESM2_ESM.pdf (900 kb)
Supplementary material 2 (PDF 900 kb)


  1. 1.
    Belloni A, Morgan D, Paris V. Pharmaceutical expenditure and policies: past trends and future challenges. OECD Health Working Papers. 2016;(87):0_1–4,8–73.Google Scholar
  2. 2.
    Garattini L, Curto A, Freemantle N. Pharmaceutical price schemes in Europe: time for a ‘continental’ one? PharmacoEconomics. 2016;34(5):423–6.PubMedCrossRefGoogle Scholar
  3. 3.
    Kheirandish M, Rashidian A, Kebriaeezade A, Cheraghali AM, Soleymani F. A review of pharmaceutical policies in response to economic crises and sanctions. J Res Pharm Pract. 2015;4(3):115–22.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Vogler S, Zimmermann N, Ferrario A, et al. Pharmaceutical policies in a crisis? Challenges and solutions identified at the PPRI conference. J Pharm Policy Pract. 2016;9:9.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Banzi R, Gerardi C, Bertele V, Garattini S. Approvals of drugs with uncertain benefit-risk profiles in Europe. Eur J Intern Med. 2015;26(8):572–84.PubMedCrossRefGoogle Scholar
  6. 6.
    Aitken M, Kleinrock M. Global oncology trend report: a review of 2015 and outlook to 2020. IMS Institute for Healthcare Informatics; 2016.Google Scholar
  7. 7.
    Aitken M, Kleinrock M, Simorellis A, Nass D. Global oncology trends 2018, innovation, expansion and disruption. IQVIA Institute for Human Data Science; 2018.
  8. 8.
    Grossmann N, Wild C. Between January 2009 and April 2016, 134 novel anticancer therapies were approved: what is the level of knowledge concerning the clinical benefit at the time of approval? ESMO Open. 2016;1(6):e000125.PubMedGoogle Scholar
  9. 9.
    Vernon JA. Examining the link between price regulation and pharmaceutical R&D investment. Health Econ. 2005;14(1):1–16.PubMedCrossRefGoogle Scholar
  10. 10.
    Golec J, Vernon JA. Financial effects of pharmaceutical price regulation on R&D spending by EU versus US firms. PharmacoEconomics. 2010;28(8):615–28.PubMedCrossRefGoogle Scholar
  11. 11.
    Pani L, Montilla S, Nemeth G, Russo P, Viceconte G, Vogler S. Balancing access to medicines and sustainability in Europe: an analysis from the network of competent authorities on pricing and reimbursement (CAPR). Pharmacol Res. 2016;111:247–50.PubMedCrossRefGoogle Scholar
  12. 12.
    Paris V, Belloni A. Value in pharmaceutical pricing. OECD Health Working Papers, No. 63. Paris: OECD Publishing; 2013.
  13. 13.
    OECD. New health technologies: managing access, value and sustainability. Paris: OECD Publishing; 2017.
  14. 14.
    Expert Panel on effective ways of investing in Health (EXPH). Innovative payment models for high-cost innovative medicines. European Commission; 2018.
  15. 15.
    Vogler S, Paris V, Ferrario A, et al. How can pricing and reimbursement policies improve affordable access to medicines? Lessons learned from European countries. Appl Health Econ Health Policy. 2017;15(3):307–21.PubMedCrossRefGoogle Scholar
  16. 16.
    Lorenzoni L, Murtin F, Springare L-S, Auraaen A, Daniel F. Which policies increase value for money in health care? OECD Health Working Papers, No. 104. Paris: OECD Publishing. 2018.
  17. 17.
    Cole A, Towse A, Lorgelly P, Sullivan R. Economics of innovative payment models compared with single pricing of pharmaceuticals. OHE Research Paper 18/04, London: Office of Health Economics; 2018.
  18. 18.
    Panteli D, Arickx F, Cleemput I, et al. Pharmaceutical regulation in 15 European countries review. Health Syst Transit. 2016;18(5):1–122.PubMedGoogle Scholar
  19. 19.
    Espin J, Rovera J, de Labry AO. Working paper 1: external price referencing—review series on pharmaceutical pricing policies and interventions. Geneva: World Health Organization and Health Action International; 2011.Google Scholar
  20. 20.
    Acosta A, Ciapponi A, Aaserud M, et al. Pharmaceutical policies: effects of reference pricing, other pricing, and purchasing policies. Cochrane Database Syst Rev. 2014(10):CD005979.Google Scholar
  21. 21.
    Green CJ, Maclure M, Fortin PM, Ramsay CR, Aaserud M, Bardal S. Pharmaceutical policies: effects of restrictions on reimbursement. Cochrane Database Syst Rev. 2010(8):CD008654.Google Scholar
  22. 22.
    Lee IH, Bloor K, Hewitt C, Maynard A. International experience in controlling pharmaceutical expenditure: influencing patients and providers and regulating industry—a systematic review. J Health Serv Res Policy. 2015;20(1):52–9.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Vogler S, Zimmermann N. Glossary of pharmaceutical terms. In: WHO Collaborating Centre for Pharmaceutical Pricing and Reimbursement Policies, ed. WHO Collaborating Centre for Pharmaceutical Pricing and Reimbursement Policies; 2016.
  24. 24.
    Verordnung über die Krankenversicherung (KVV). In: Bundesrat DS, ed. vol 832.102. Systematische Sammlung des Bundesrechts (SR). 1995.Google Scholar
  25. 25.
    Hughes DA. Value-based pricing: incentive for innovation or zero net benefit? PharmacoEconomics. 2011;29(9):731–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Ferrario A, Kanavos P. Managed entry agreements for pharmaceuticals: the European experience. 2013.
  27. 27.
    Klemp M, Fronsdal KB, Facey K, Forum HTP. What principles should govern the use of managed entry agreements? Int J Technol Assess Health Care. 2011;27(1):77–83.PubMedCrossRefGoogle Scholar
  28. 28.
    Garrison LP Jr, Towse A, Briggs A, et al. 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.PubMedCrossRefGoogle Scholar
  29. 29.
    Marshall AD, Cunningham EB, Nielsen S, et al. Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe. Lancet Gastroenterol Hepatol. 2018;3(2):125–33.PubMedCrossRefGoogle Scholar
  30. 30.
    Flume M, Bardou M, Capri S, et al. Feasibility and attractiveness of indication value-based pricing in key EU countries. J Mark Access Health Policy. 2016. Scholar
  31. 31.
    Spezialitätenliste: Avastin. BAG; 2018. Accessed 1 Aug 2018.
  32. 32.
    Persson U, Norlin JM. Multi-indication and combination pricing and reimbursement of pharmaceuticals: opportunities for improved health care through faster uptake of new innovations. Appl Health Econ Health Policy. 2018;16(2):157–65.PubMedCrossRefGoogle Scholar
  33. 33.
    PubMed. PubMed search. 2018; Accessed 31 Aug 2018.
  34. 34.
    Cochrane Effective Practice and Organisation of Care (EPOC). What study designs should be included in an EPOC review? EPOC Resources for review authors. Oslo: Norwegian Knowledge Centre for the Health Services; 2016.Google Scholar
  35. 35.
    Persson U, Jonsson B. The end of the international reference pricing system? Appl Health Econ Health Policy. 2016;14(1):1–8.PubMedCrossRefGoogle Scholar
  36. 36.
    World Bank Country and Lending Groups. 2016. Accessed 31 Dec 2016.
  37. 37.
    Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ (Clinical research ed.). 2009;339:b2535.Google Scholar
  38. 38.
    Drummond MF, Jefferson TO. Guidelines for authors and peer reviewers of economic submissions to the BMJ. The BMJ Economic Evaluation Working Party. BMJ (Clinical research ed.). 1996;313(7052):275–83.Google Scholar
  39. 39.
    Drummond M, Sculpher M, Torrance G, O’Brien BJ, Stoddart G, editors. Methods for the economic evaluation of health care programmes. 3rd ed. Oxford: Oxford University Press; 2005.Google Scholar
  40. 40.
    Cochrane Effective Practice and Organisation of Care (EPOC). Suggested risk of bias criteria for EPOC reviews. EPOC Resources for review authors. Oslo: Norwegian Knowledge Centre for the Health Services; 2015.Google Scholar
  41. 41.
    Ofman JJ, Sullivan SD, Neumann PJ, et al. Examining the value and quality of health economic analyses: implications of utilizing the QHES. JMCP. 2003;9(1):53–61.PubMedCrossRefGoogle Scholar
  42. 42.
    Philips Z, Bojke L, Sculpher M, Claxton K, Golder S. Good practice guidelines for decision-analytic modelling in health technology assessment: a review and consolidation of quality assessment. PharmacoEconomics. 2006;24(4):355–71.PubMedCrossRefGoogle Scholar
  43. 43.
    Tacconelli E. Systematic reviews: CRD’s guidance for undertaking reviews in health care. Heslington, York: University of York NHS Centre for Reviews & Dissemination; 2009. ISBN 978-1-900640-47-3.Google Scholar
  44. 44.
    Evers S, Goossens M, de Vet H, van Tulder M, Ament A. Criteria list for assessment of methodological quality of economic evaluations: Consensus on Health Economic Criteria. Int J Technol Assess Health Care. 2005;21(2):240–5.PubMedCrossRefGoogle Scholar
  45. 45.
    Balshem H, Helfand M, Schunemann HJ, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64(4):401–6.PubMedCrossRefGoogle Scholar
  46. 46.
    Cochrane Effective Practice and Organisation of Care (EPOC). Reporting the effects of an intervention in EPOC reviews. EPOC Resources for review authors. 2017:24.
  47. 47.
    Armeni P, Jommi C, Otto M. The simultaneous effects of pharmaceutical policies from payers’ and patients’ perspectives: Italy as a case study. Eur J Health Econ. 2016;17(8):963–77.PubMedCrossRefGoogle Scholar
  48. 48.
    Augurzky B, Gohlmann S, Gress S, Wasem J. Effects of the German reference drug program on ex-factory prices of prescription drugs: a panel data approach. Health Econ. 2009;18(4):421–36.PubMedCrossRefGoogle Scholar
  49. 49.
    Barros PP, Nunes LC. The impact of pharmaceutical policy measures: an endogenous structural-break approach. Soc Sci Med. 2010;71(3):440–50.PubMedCrossRefGoogle Scholar
  50. 50.
    Grootendorst PV, Marshall JK, Holbrook AM, Dolovich LR, O’Brien BJ, Levy AR. The impact of reference pricing of nonsteroidal anti-inflammatory agents on the use and costs of analgesic drugs. Health Serv Res. 2005;40(5 Pt 1):1297–317.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Grootendorst P, Stewart D. A re-examination of the impact of reference pricing on anti-hypertensive drug plan expenditures in British Columbia. Health Econ. 2006;15(7):735–42.PubMedCrossRefGoogle Scholar
  52. 52.
    Morgan S, Cunningham C. The effect of evidence-based drug coverage policies on pharmaceutical r&d: a case study from british columbia. Healthc Policy. 2008;3(3):e128–53.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Stargardt T. The impact of reference pricing on switching behaviour and healthcare utilisation: the case of statins in Germany. Eur J Health Econ. 2010;11(3):267–77.PubMedCrossRefGoogle Scholar
  54. 54.
    Yfantopoulos J. Pharmaceutical pricing and reimbursement reforms in Greece. Eur J Health Econ. 2008;9(1):87–97.PubMedCrossRefGoogle Scholar
  55. 55.
    Kalo Z, Abonyi-Toth Z, Bartfai Z, Voko Z. Pitfalls associated with the therapeutic reference pricing practice of asthma medication. BMC Pulm Med. 2012;12:35.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Kanavos PG, Vandoros S. Determinants of branded prescription medicine prices in OECD countries. Health Econ Policy Law. 2011;6(3):337–67.PubMedCrossRefGoogle Scholar
  57. 57.
    Kyle MK. Pharmaceutical price controls and entry strategies. Rev Econ Stat. 2007;89(1):88–99.CrossRefGoogle Scholar
  58. 58.
    Leopold C, Mantel-Teeuwisse AK, Seyfang L, et al. Impact of external price referencing on medicine prices—a price comparison among 14 European countries. South Med Rev. 2012;5(2):34–41.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Stargardt T. Modelling pharmaceutical price changes in Germany: a function of competition and regulation. Appl Econ. 2011;43(29):4515–26.CrossRefGoogle Scholar
  60. 60.
    von der Schulenburg F, Vandoros S, Kanavos P. The effects of drug market regulation on pharmaceutical prices in Europe: overview and evidence from the market of ACE inhibitors. Health Econ Rev. 2011;1(1):18.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Atella V, Bhattacharya J, Carbonari L. Pharmaceutical price controls and minimum efficacy regulation: evidence from the United States and Italy. Health Serv Res. 2012;47(1 Pt 1):293–308.PubMedCrossRefGoogle Scholar
  62. 62.
    Kaiser U, Mendez SJ, Ronde T, Ullrich H. Regulation of pharmaceutical prices: evidence from a reference price reform in Denmark. J Health Econ. 2014;36:174–87.PubMedCrossRefGoogle Scholar
  63. 63.
    Koenig P, Macgarvie M. Regulatory policy and the location of bio-pharmaceutical foreign direct investment in Europe. J Health Econ. 2011;30(5):950–65.PubMedCrossRefGoogle Scholar
  64. 64.
    Comanor WS, Schweitzer SO, Riddle JM, Schoenberg F. Value based pricing of pharmaceuticals in the US and UK: does centralized cost effectiveness analysis matter? Rev Ind Organ. 2018;52(4):589–602.CrossRefGoogle Scholar
  65. 65.
    Galizzi MM, Ghislandi S, Miraldo M. Effects of reference pricing in pharmaceutical markets: a review. PharmacoEconomics. 2011;29(1):17–33.PubMedCrossRefGoogle Scholar
  66. 66.
    Lee JL, Fischer MA, Shrank WH, Polinski JM, Choudhry NK. A systematic review of reference pricing: implications for US prescription drug spending. Am J Manag Care. 2012;18(11):e429–37.PubMedGoogle Scholar
  67. 67.
    Morgan S, Hanley G, Greyson D. Comparison of tiered formularies and reference pricing policies: a systematic review. Open Med. 2009;3(3):e131–9.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Puig-Junoy J. What is required to evaluate the impact of pharmaceutical reference pricing? Appl Health Econ Health Policy. 2005;4(2):87–98.PubMedCrossRefGoogle Scholar
  69. 69.
    Relakis J, Maniadakis N, Kourlaba G, Shen J, Holtorf AP. Systematic review on the impacts of strict pharmaceutical price controls. Value Health. 2013;16(7):A486.CrossRefGoogle Scholar
  70. 70.
    Remuzat C, Urbinati D, Mzoughi O, El Hammi E, Belgaied W, Toumi M. Overview of external reference pricing systems in Europe. J Mark Access Health Policy. 2015. Scholar
  71. 71.
    Zhou W, Cui X, Qian Y. Review of reference pricing effects on pharmaceuticals. Value Health. 2014;17(7):A787.PubMedCrossRefGoogle Scholar
  72. 72.
    Gronde TV, Uyl-de Groot CA, Pieters T. Addressing the challenge of high-priced prescription drugs in the era of precision medicine: a systematic review of drug life cycles, therapeutic drug markets and regulatory frameworks. PLoS One. 2017;12(8):e0182613.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Cochrane Effective Practice and Organisation of Care (EPOC). Interrupted time series (ITS) analyses. EPOC resources for review authors. 2013.
  74. 74.
    Ramsay CR, Matowe L, Grilli R, Grimshaw JM, Thomas RE. Interrupted time series designs in health technology assessment: lessons from two systematic reviews of behavior change strategies. Int J Technol Assess Health Care. 2003;19(4):613–23.PubMedCrossRefGoogle Scholar
  75. 75.
    Shojania KG, Grimshaw JM. Evidence-based quality improvement: the state of the science. Health affairs (Project Hope). 2005;24(1):138–50.CrossRefGoogle Scholar
  76. 76.
    Eccles M, Grimshaw J, Campbell M, Ramsay C. Research designs for studies evaluating the effectiveness of change and improvement strategies. Qual Saf Health Care. 2003;12(1):47–52.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Ferrario A, Araja D, Bochenek T, et al. the implementation of managed entry agreements in Central and Eastern Europe: findings and implications. PharmacoEconomics. 2017;35(12):1271–85.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Piatkiewicz TJ, Traulsen JM, Holm-Larsen T. Risk-sharing agreements in the EU: a systematic review of major trends. PharmacoEcon Open. 2018;2(2):109–23.PubMedCrossRefGoogle Scholar
  79. 79.
    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. 2015;124:39–47.PubMedCrossRefGoogle Scholar
  80. 80.
    Vogler S, Vitry A, Babar ZU. Cancer drugs in 16 European countries, Australia, and New Zealand: a cross-country price comparison study. Lancet Oncol. 2016;17(1):39–47.PubMedCrossRefGoogle Scholar
  81. 81.
    Leopold C, Vogler S, Mantel-Teeuwisse AK, de Joncheere K, Leufkens HG, Laing R. Differences in external price referencing in Europe: a descriptive overview. Health Policy. 2012;104(1):50–60.PubMedCrossRefGoogle Scholar
  82. 82.
    Banzi R, Moja L, Pistotti V, Facchini A, Liberati A. Conceptual frameworks and empirical approaches used to assess the impact of health research: an overview of reviews. Health Res Policy Syst. 2011;9:26.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Cohen G, Schroeder J, Newson R, et al. Does health intervention research have real world policy and practice impacts: testing a new impact assessment tool. Health Res Policy Syst. 2015;13:3.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    EFPIA. EFPIA response to draft opinion on innovative payment models for high-cost innovative medicines. 2017.
  85. 85.
    European Parliament. European Parliament resolution of 2 March 2017 on EU options for improving access to medicines (2016/2057(INI)). European Parliament; 2017.
  86. 86.
    Godman B, Malmstrom RE, Diogene E, et al. Are new models needed to optimize the utilization of new medicines to sustain healthcare systems? Expert Rev Clin Pharmacol. 2015;8(1):77–94.PubMedCrossRefGoogle Scholar
  87. 87.
    Adamski J, Godman B, Ofierska-Sujkowska G, et al. Risk sharing arrangements for pharmaceuticals: potential considerations and recommendations for European payers. BMC Health Serv Res. 2010;10:153.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    HABERMAS, Jürgen. Verwissenschaftlichte Politik und öffentliche Meinung. Rentsch, 1964. In: (PUBLISHER) Bretscher, Willy. (1964). Humanität und politische Verantwortung. Erlenbach-Zürich.Google Scholar
  89. 89.
    Jasanoff S. States of knowledge : the co-production of science and the social order. London: Routledge; 2005.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Health Sciences and Health PolicyUniversity of LucerneLucerneSwitzerland

Personalised recommendations