Abstract
There are many rare diseases and biomedical research efforts for treatment of each disease have been ongoing. However, few reports are available to analyze overall trends for how research and development have been performed for rare diseases generally. In this research, the correlations between research and development indicators of rare diseases were examined with international comparisons among Japan, the US, and Europe. The correlation between the number of clinical studies and orphan drug designations was lower in Japan than that in the US and Europe, while the correlation between the number of orphan drug designations and orphan drug approvals was higher in Japan than in the US and Europe. This analysis clarified differences in the orphan drug designation system, operational characteristics, and beneficial points in the regions. Based on the findings of the analysis of the research/regulatory system, earlier time of orphan drug designation in Japan was proposed as a policy implication.
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Altshuler, D., Brooks, L. D., Chakravarti, A., Collins, F. S., Daly, M. J., Donnelly, P., et al. (2005). A haplotype map of the human genome. Nature, 437, 1299–1320.
Amat, C. B., & Perruchas, F. (2016). Evolving cohesion metrics of a research network on rare diseases: a longitudinal study over 14 years. Scientometrics, 108(1), 41–56.
Ayme, S., & Schmidtke, J. (2007). Networking for rare diseases: a necessity for Europe. Bundesgesundheitsblatt-Gesundheitsforschung-Gesundheitsschutz, 50(12), 1477-1483.
Bell, S.A., & Smith, C.T. (2014). A comparison of interventional clinical trials in rare versus non-rare diseases: an analysis of ClinicalTrials.gov. Orphanet Journal of Rare Diseases, 9, 170.
Benjamini, Y., & Hochberg, Y. (1995). Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society: Series B (Methodological), 57(1), 298–300.
Braun, M. M., Farag-El-Massah, S., Xu, K., & Cote, T. R. (2010). Emergence of orphan drugs in the United States: a quantitative assessment of the first 25 years. Nature Reviews Drug Discovery, 9(7), 519–522.
Chesbrough, H. (2003). Open innovation: The new imperative for creating and profiting from technology. Boston: Harvard Business School Press.
Desser, A. S. (2013). Prioritizing treatment of rare diseases: A survey of preferences of Norwegian doctors. Social Science and Medicine, 94, 56–62.
Falagas, M. E., Pitsouni, E. I., Malietzis, G. A., & Pappas, G. (2008). Comparison of PubMed, Scopus, Web of Science, and Google Scholar: Strengths and weaknesses. The FASEB Journal, 22(2), 338–342.
Farkas, A. M., Mariz, S., Stoyanova-Beninska, V., Celis, P., Vamvakas, S., Larsson, K., et al. (2017). Advanced therapy medicinal products for rare diseases: State of play of incentives supporting development in Europe. Frontiers in Medicine, 4, 53.
Field, M. J., & Boat, T. F. (Eds.). (2010). Rare diseases and orphan products: Accelerating research and development. Washington, D.C.: Institute of Medicine, The National Academies Press.
Franco, P. (2013). Orphan drugs: The regulatory environment. Drug Discovery Today, 18(3–4), 163–172.
Galati, F., & Bigliardi, B. (2016). The unintended effect of the Orphan Drug Act on the adoption of open innovation. Science and Public Policy, 43(6), 840–848.
Giannuzzi, V., Conte, R., Landi, A., Ottomano, S. A., Bonifazi, D., Baiardi, P., et al. (2017a). Orphan medicinal products in Europe and United States to cover needs of patients with rare diseases: An increased common effort is to be foreseen. Orphanet Journal of Rare Diseases, 12(1), 64.
Giannuzzi, V., Landi, A., Bosone, E., Giannuzzi, F., Nicotri, S., Torrent-Farnell, J., et al. (2017b). Failures to further developing orphan medicinal products after designation granted in Europe: An analysis of marketing authorisation failures and abandoned drugs. British Medical Journal Open, 7(9), e017358.
Glickman, M. E., Rao, S. R., & Schultz, M. R. (2014). False discovery rate control is a recommended alternative to Bonferroni-type adjustments in health studies. Journal of Clinical Epidemiology, 67(8), 850–857.
Heemstra, H. E., de Vrueh, R. L. A., van Weely, S., Buller, H. A., & Leufkens, H. G. M. (2008). Orphan drug development across Europe: Bottlenecks and opportunities. Drug Discovery Today, 13(15–16), 670–676.
Heemstra, H. E., van Weely, S., Buller, H. A., Leufkens, H. G. M., & de Vrueh, R. L. A. (2009). Translation of rare disease research into orphan drug development: Disease matters. Drug Discovery Today, 14(23–24), 1166–1173.
Hernberg-Ståhl, E., & Reljanović, M. (2013). Orphan drugs: Understanding the rare disease market and its dynamics. Sawston: Woodhead Publishing.
Igami, M., & Saka, A. (2016). Decreasing diversity in Japanese science, evidence from in-depth analyses of science maps. Scientometrics, 106(1), 383–403.
Japan Agency for Medical Research and Development. (2017). Support program for orphan drug prior to the designation. https://www.amed.go.jp/en/program/list/06/03/001_03-01.html. Accessed Apr 2018.
Joppi, R., Bertele, V., & Garattini, S. (2013). Orphan drugs, orphan diseases. The first decade of orphan drug legislation in the EU. European Journal of Clinical Pharmacology, 69(4), 1009–1024.
Julkowska, D., Austin, C. P., Cutillo, C. M., Gancberg, D., Hager, C., Halftermeyer, J., et al. (2017). The importance of international collaboration for rare diseases research: A European perspective. Gene Therapy, 24(9), 562–571.
Kaneko, K., Yamada, T., Kashitani, Y., Sato, Y., Arai, M., & Satou, H. (2014). Proposals from the pharmaceutical industry on the development and promotion of orphan drugs. Regulatory Science of Medical Products, 4(1), 41–48. (in Japanese).
Kneller, R. (2010). The importance of new companies for drug discovery: Origins of a decade of new drugs. Nature Reviews Drug Discovery, 9(11), 867–882.
Lander, B. (2013). Sectoral collaboration in biomedical research and development. Scientometrics, 94(1), 343–357.
Luzzatto, L., Hollak, C. E. M., Cox, T. M., Schieppati, A., Licht, C., Kaariainen, H., et al. (2015). Rare diseases and effective treatments: Are we delivering? The Lancet, 385(9970), 750–752.
McMillan, G. S., Narin, F., & Deeds, D. L. (2000). An analysis of the critical role of public science in innovation: The case of biotechnology. Research Policy, 29(1), 1–8.
Mizoguchi, H., Yamanaka, T., & Kano, S. (2016). Research and drug development activities in rare diseases: Differences between Japan and Europe regarding influence of prevalence. Drug Discovery Today, 21(10), 1681–1689.
Mizushima, H., Tanabe, M., & Kanatani, Y. (2014). Patient database and orphan drug development. Yakugaku Zasshi, 134(5), 599–605. (in Japanese).
Murakami, Y. (2016). Achievement of research on international research collaboration and suggestion to policy in Japan. The Journal of Science Policy and Research Management, 31, 130–144. (in Japanese).
Murakami, M., & Narukawa, M. (2016). Matched analysis on orphan drug designations and approvals: Cross regional analysis in the United States, the European Union, and Japan. Drug Discovery Today, 21(4), 544–549.
Pal, G., O’Keefe, J., Robertson-Dick, E., Bernard, B., Anderson, S., & Hall, D. (2016). Global cognitive function and processing speed are associated with gait and balance dysfunction in Parkinson’s disease. Journal of NeuroEngineering and Rehabilitation, 13, 94.
Patel, S., & Needleman, K. I. M. (2013). Funding grants for rare diseases at the food and drug administration. Expert Opinion on Orphan Drugs, 1(2), 99–102.
Phillips, M. I. (2013). Big Pharma’s new model in orphan drugs and rare diseases. Expert Opinion on Orphan Drugs, 1(1), 1–3.
Scannell, J. W., Blanckley, A., Boldon, H., & Warrington, B. (2012). Diagnosing the decline in pharmaceutical R&D efficiency. Nature Reviews Drug Discovery, 11(3), 191–200.
Tambuyzer, E. (2010). Rare diseases, orphan drugs and their regulation: Questions and misconceptions. Nature Reviews Drug Discovery, 9(12), 921–929.
Tatsumi, K. (2011). Development trends of orphan drugs in Japan, the US and the EU and issues for rare disease innovation in Japan. OPIR News, 32, 8–23. (in Japanese).
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Mizoguchi, H., Kano, S. Comparative analysis of correlations of research and development indicators for rare diseases among Japan, the US, and Europe. Scientometrics 120, 361–374 (2019). https://doi.org/10.1007/s11192-019-03129-5
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DOI: https://doi.org/10.1007/s11192-019-03129-5