Skip to main content

Advertisement

Log in

The impact of new (orphan) drug approvals on premature mortality from rare diseases in the United States and France, 1999–2007

  • Original Paper
  • Published:
The European Journal of Health Economics Aims and scope Submit manuscript

Abstract

This paper investigates the impact of the introduction of new orphan drugs on premature mortality from rare diseases using longitudinal, disease-level data obtained from a number of major databases. The analysis is performed using data from two countries: the United States (during the period 1999–2006) and France (during the period 2000–2007). For both countries, we estimate models using two alternative definitions of premature mortality, several alternative criteria for inclusion in the set of rare diseases, and several values of the potential lag between new drug approvals and premature mortality reduction. Both the United States and French estimates indicate that, overall, premature mortality from rare diseases is unrelated to the cumulative number of drugs approved 0–2 years earlier but is significantly inversely related to the cumulative number of drugs approved 3–4 years earlier. This delay is not surprising, since most patients probably do not have access to a drug until several years after it has been launched. Although the estimates for the two countries are qualitatively similar, the estimated magnitudes of the US coefficients are about four times as large as the magnitudes of the French coefficients. This may be partly due to greater errors in measuring dates of drug introduction in France. Also, access to new drugs may be more restricted in France than it is in the United States. Our estimates indicate that, in the United States, potential years of life lost to rare diseases before age 65 (PYLL65) declined at an average annual rate of 3.3% and that, in the absence of lagged new drug approvals, PYLL65 would have increased at a rate of 0.9%. Since the US population aged 0–64 was increasing at the rate of 1.0% per year, this means that PYLL65 per person under 65 would have remained approximately constant. The reduction in the US growth rate of PYLL65 attributable to lagged new drug approvals was 4.2%. In France, PYLL65 declined at an average annual rate of 1.8%. The estimates imply that, in the absence of lagged new drug approvals, it would have declined at a rate of 0.6%. The reduction in the French growth rate of PYLL65 attributable to lagged new drug approvals was 1.1%. Earlier access to orphan drugs could result in earlier reductions in premature mortality from rare diseases.

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

Access this article

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. Some, but not all, drugs for rare diseases have small markets. Firstly, certain orphan medicines are effective against multiple rare diseases. Secondly, an orphan drug is sometimes used to treat a more common disease as well. And third, it is possible that a drug for a common disease is used for an orphan indication as well (e.g. sildenafil). In these situations, a larger number of patients are targeted. According to the FDA’s Rare Disease Repurposing Database (http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/HowtoapplyforOrphanProductDesignation/ucm216147.htm), 32% of orphan-designated products have at least one marketing approval for a rare disease indication, 46% have at least one marketing approval for a common disease indication, and 22% have at least one marketing approval for both common and rare disease indications.

  2. Market exclusivity does not completely obstruct competition. In the 1990s, there were three beta-interferon’s to treat MS available in the United States. All three were protected by their market exclusivity but they had to share the market.

  3. In one respect, the EU’s definition of an orphan condition is broader than that of the USA, in that it also covers some tropical diseases that are primarily found in developing nations. However, it is stricter in another respect, because it stipulates the condition to be life-threatening or chronically debilitating.

  4. Some of the drugs developed to treat these conditions are not on the market yet. For example, Oncophage (or Vitespen) for the treatment of glioma has not yet received market authorization either in the United States or in the EU.

  5. The US Orphan Drug Act was passed 16 years before the US sample period, while the EU legislation was implemented at the beginning of the French sample period. I see no reason why this should cause estimates from the two countries to differ.

  6. Under this methodology, if a new drug replaced a previous treatment, DRUG_STOCK would increase, unless the database we rely on “de-listed” the previous treatment, which seems unlikely. Moreover, even if the number of drugs used to treat a disease did not increase, replacement of an old drug by a new drug indicates that pharmaceutical treatment has been advanced, and the increase in DRUG_STOCK would reflect that.

  7. Prevalence of rare diseases: Bibliographic data [14].

  8. The NCI’s Cancer Prevalence Database (part of its Cancer Query System [13]) provides data on cancer prevalence, by cancer site, but only for a single year (2007). The NCI’s SEER × Stat statistical software provides longitudinal data on (limited-duration) prevalence, but not by ICD10 code.

  9. Other data sources, such as the FDA’s List of Orphan Designations and Approvals [6], do not code rare diseases using ICD9 or ICD10 codes.

  10. In some cases, a disease has low prevalence because people who have the disease are subject to a high mortality rate.

  11. Many of the drugs included in the Orphanet database have not been approved in the United States (or other countries). Only about half of the drugs included in the Orphanet database that have been approved in the United States are classified as orphan drugs by the FDA.

  12. In this calculation, if the same drug is used for N diseases, it is counted N times.

  13. Estimates of β hardly change when we replace fixed year effects by a time trend.

  14. uncond − δcond) is equivalent to β times the average annual growth rate of DRUG_STOCK i,t−3. The average annual growth rate of DRUG_STOCK i,t−3 was 4.8% in the United States and 5.7% in France.

References

  1. Centre d’épidémiologie sur les causes médicales de décès, http://www.cepidc.vesinet.inserm.fr/

  2. Centers for Disease Control: Compressed Mortality Database (http://wonder.cdc.gov/controller/datarequest/D43)

  3. Centers for Disease Control: Multiple Cause-Of-Death Public-Use Data Files, http://www.cdc.gov/nchs/products/elec_prods/subject/mortmcd.htm

  4. Cranston, J.W., Williams, M.A., Nielsen, N.H., Bezman, R.J., For the American Medical Association Council on Scientific Affairs: Unlabeled indications of food and drug administration: approved drugs. Drug Inf. J. 32, 1049–1061 (1998)

    Google Scholar 

  5. Food and Drug Administration: Drugs@FDA Database, http://www.fda.gov/cder/drugsatfda/datafiles/default.htm

  6. Food and Drug Administration: List of Orphan Designations and Approvals, http://www.fda.gov/orphan/designat/list.htm

  7. Groupement pour l ‘Elaboration et la Réalisation de Statistiques, http://www.gie-gers.fr/index.php3

  8. Lichtenberg, F.R.: Pharmaceutical knowledge-capital accumulation and longevity. In: Carol, C., John, H., Dan, S. (eds.) Measuring Capital in the New Economy, pp. 237–269. University of Chicago Press, Chicago (2005)

    Google Scholar 

  9. Lichtenberg, F.R.: The effect of new cancer drug approvals on the life expectancy of American cancer patients, 1978–2004. Econ. Innov. New Technol. 18(5), 407–428 (2009)

    Article  Google Scholar 

  10. Lichtenberg, F.R.: Have newer cardiovascular drugs reduced hospitalization? Evidence from longitudinal country-level data on 20 OECD countries, 1995–2003. Health Econ. 18, 519–534 (2009)

    Article  PubMed  Google Scholar 

  11. Lichtenberg, F.R., Waldfogel, J.: Does misery love company? Evidence from pharmaceutical markets before and after the orphan drug act. Mich. Telecomm. Tech. L. Rev. 335 (2009), http://www.mttlr.org/volfifteen/lichtenberg&waldfogel.pdf

  12. Liu, M., Davis, K.: A Clinical Trials Manual from the Duke Clinical Research Institute: Lessons from a Horse Named Jim. Wiley, USA (2010)

    Book  Google Scholar 

  13. National Cancer Institute: Cancer Prevalence Database, http://srab.cancer.gov/prevalence/canques.html

  14. Orphanet: Prevalence of Rare Diseases: Bibliographic Data. Orphanet Report Series. Rare Diseases Collection, May 2010, Number 1: Listed in Alphabetical Order of Diseases, http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf

  15. Répertoire des Spécialités Pharmaceutiques of the Agence Francaise de Securite Sanitaire des Produits de Sante, http://www.afssaps.sante.fr/htm/1/amm/amm0.htm

  16. Romer, P.: Endogenous technical change. J. Polit. Econ. 98, S71–S102 (1990)

    Article  Google Scholar 

Download references

Acknowledgments

This research was supported by the American Enterprise Institute, Novartis, and Pfizer Inc. The sponsors placed no restrictions or limitations on data, methods, or conclusions and had no right of review or control over the outcome of the research. I am grateful to Segolene Ayme, Marie Georget, and Ana Rath of Orphanet for providing their data to me.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Frank R. Lichtenberg.

Appendix

Appendix

See Table 5.

Table 5 Drugs listed in the order of FDA approval year for diseases with fewer than 6,400 US deaths/year

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lichtenberg, F.R. The impact of new (orphan) drug approvals on premature mortality from rare diseases in the United States and France, 1999–2007. Eur J Health Econ 14, 41–56 (2013). https://doi.org/10.1007/s10198-011-0349-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10198-011-0349-4

Keywords

JEL classification

Navigation