Abstract��OBJECTIVE To study and collate the literature on rare diseases in domestic and abroad, and comparative analysis, provide a scientific basis for the domestic rare diseases research. METHODS Retrieved the Web of Science, China National Knowledge Infrastructure from January 2011 to June 2016 published literature about rare diseases. RESULTS Through the screening of literature, finally determine the 200 articles for analysis. It is divided into seven research directions:rare diseases policy research, rare diseases legal and regulatory research, rare diseases medical social security study, orphan drugs availability research, orphan drugs economic evaluation study, orphan drug development research, rare diseases defined standard research. CONCLUSION Rare diseases policy research is the focus of research both domestic and abroad. Compared with foreign countries, the domestic research on the availability and economic evaluation of orphan drug is less, especially the economic evaluation research is almost blank. It is suggested that the researchers study the multiple aspects of rare diseases and drugs, and to provide the basis and reference for build rare disease policy in China.In addition to the field of rare diseases research, rare diseases drugs face many difficulties in pharmaceutical research, production and supply.The precondition to solve these problems is the nation formulate specific policies and regulations for rare diseases,and then clear the official definition standards of rare diseases,establish relevant policies to encourage pharmaceutical companies to develop rare diseases drugs.
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LI Tong-tong, DAI Gang, ZHANG Fang. Comparative Analysis on the Research Progress of Rare Diseases in Domestic and Abroad. Chinese Pharmaceutical Journal, 2017, 52(6): 506-512.
World Health Organization. These lection and use of essential medicines:report of The WHO Export Committee (including the 14th model list of essential medicines) [R]. Geneva:World Health Organization, 2006.
[2]
WANG C L. Please focus on rare disease research[J]. J Rare Uncommon Diseases(���ټ�����־), 2009, 16(2):9-10.
[3]
CHEN Y F, CHEN L. Enlightenment of the orphan drug policy and its effect in america[J]. Chin Pharm J(�й�ҩѧ��־), 2014, 49(22):2043-2046.
[4]
ZHANG Q L,SONG X L. Incentive mechanism and implications of orphan drug market in the United States[J]. Chin J Health Policy(�й����������о�), 2016, 9(2):36-44.
[5]
ZHAO Y,LIU A L,D G H. Comparative analysis of rare disease pharmaceuticalpolicies of China and America[J]. Chin J New Drugs(�й���ҩ��־), 2016, 25(1):31-35.
[6]
WANG Q,CHEN Y F. Orphan drug policy in european union and its implications for China[J]. Chin Hosp Manage(�й�ҽԺ����), 2015, 35(4):78-80.
[7]
LIN Y H,WU X M. Achievements and experience of EU orphan drug administration and its implications for China[J]. Chin J Mod Appl Pharm(�й��ִ�Ӧ��ҩѧ), 2012, 29(12):1154-1158.
[8]
WANG H,WU Z A. Incentives for orphan drugs R&D in Europe and am ericaand the enlightenment for China[J]. Chin J New Drugs(�й���ҩ��־), 2015, 24(15):1681-1685.
[9]
DING J X,MENG L L,LUO X W. Research on incentive policies of innovative drugs in Japan and itsenlightenment to China-an empirical study on research and development of edaravone[J]. Chin J New Drugs Clin Rem(�й���ҩ���ٴ���־), 2011, 30(11):839-847.
[10]
DING Z C, WEI G, DING J X. Orphan drug regime in Japan and enlightenment on China�Kbased on evaluation of orphan drug access in Japan[J]. Chin Pharm Univ J (�й�ҩ�ƴ�ѧѧ��), 2014, 45(1):118-124.
[11]
WANG P, ZHANG Y F. On the coping strategies of rare diseases in britain and its enlightenment to China[J]. Med Jurisprudence(ҽѧ�뷨ѧ), 2016, 8(2):62-67.
[12]
XIN X X, GUAN X D, SHI L W. International comparison of incentive policies for orphan drugand its enlightenment to China[J]. Chin J New Drugs(�й���ҩ��־), 2015, 24(6):605-609.
[13]
YANG P,GU D L. Development status of abroad orphan drug management systemsand suggestions on the relative policy in China[J]. Shanghai Med Pharm J (�Ϻ�ҽҩ), 2015, 36(9):64-67.
[14]
WANG Y W, MAO N Y, CHU S Z. The inspiration of the foreign innovation incentivesystem for orphan drug and its implication for China[J]. Shanghai Med Pharm J (�Ϻ�ҽҩ), 2014, 35(7):54-57.
[15]
CHEN M, ZHANG L L, LI Y P, et al. An evidence-based evaluation on orphan drug policies[J]. Chin J Evid-based Med(�й�ѭ֤ҽѧ��־), 2015, 15(7):802-809.
[16]
LI Y. Policy Recommendations regarding rare diseases in China��an analysis based on a survey of living conditions of the people with rare diseases[J]. China Soft Sci(�й����ѧ), 2014, 2:77-89.
[17]
LIU H M,MR. Accelerate the establishment of orphan drugs policy[J]. Chin J Drug Eval(�й�ҩ������), 2012, 29(2):176-179.
[18]
ZHANG N, SHEN A L. Current situation and development of orphan drug incentive policies and regulations in China[J]. Chin Hosp Pharm J(�й�ҽԺҩѧ��־), 2013, 33(1):63-65.
[19]
ELINE P, DAVID C, STEVEN S. Evaluating and improving orphan drug regulations in Europe:a delphi policy study[J]. Health Policy, 2012;108:1-9.
[20]
CHARLOTTE R, S�ZGOL�\NE A. Rare disease policies to improve care for patients in Europe[J]. Biochim Biophysica Acta (BBA) -Molecu Basis Dis, 2015, 1852(10):2329-2335.
[21]
GEORGI I, Tsonka Miteva-Katrandzhieva, Rumen Stefanov. Challenges to orphan drugs access in Eastern Europe:the case of bulgaria[J]. Health Policy, 2012, 108(1):10-18.
[22]
TAEHO G R. Policymaking for orphan drugs and Its challenges[J]. AMA J Ethics, 2015, 17(8):776-779.
[23]
HOLTZCLAW W P. Policy framework for rare disease health disparities[J]. Policy Politics Nursing Practice, 2011, 12(2):114-118.
[24]
ROBERTS, HERDER, HOLLIS. Fair pricing of ��old�� orphan drugs:considerations for Canada��s orphan drug policy[J]. Canadian Med Association J, 2015, 187(6):422-425.
[25]
HERDER M. When everyone is an orphan:against adopting a US-Styled Orphan Drug Policy in Canada[J]. Account Research-policies Quality Assurance, 2013, 20(20):227-269.
[26]
KOSZTOLANYI G. Hungarian national plan and strategy for rare diseases[J]. Orvosi Hetilap, 2014, 155(9):325-328.
[27]
TODD G, CHRISTINE Y L, ZAHEER U D B. Access to orphan drugs:a comprehensive review of legislations, regulations and policies in 35 countries[J]. PLoS One, 2015, 10(10):e0140002.
[28]
FORMAN J, Taruscio Domenica, Llera, VIRGINIA A, et al. The need for worldwide policy and action plans for rare diseases[J]. Acta Paediatr, 2012, 101(8):805-807.
[29]
DING. A review of the orphan drug act in the united states and its implications for China[J]. Chin J Health Policy(�й����������о�), 2014, 7(2):38-43.
[30]
YI B X,WANG G P,JI H H, et al. Improving Chinese innovation system of new drug accordingto 30-year history of US Orphan Drug Act[J]. Chin J New Drugs(�й���ҩ��־), 2014, 23(10):1107-1114.
[31]
LI C X,HU X. Study on enactment and adjustment of orphan drug act in america of health and its enlightenment to China [J]. J China Pharm(�й�ҩ��), 2013, 24(17):1550-1552.
[32]
LIN Y H, WU X M. The Enlightenment of the legal system of orphan drugs in Taiwan[J]. Res Rule Law(�����о�), 2012, 6:87-91.
[33]
GU J L, LU Y Q, XU L Z. Discussion on Chinese legislation progress practice of rare disease[J]. Soft Sci Health(�������ѧ), 2013, 27(3):129-131.
[34]
CHAI Y, WU Y, XIN X X, et al. On legislation of rare disease in China[J]. New West(������:���۰�), 2015, 15:75-76 .
[35]
LIN Y L, WU X M. Orphan drugs legal system to be established in China[J]. Science & Technology and Economy(�Ƽ��뾭��), 2012, 3:56-60.
[36]
GUO S X. A preliminary study on the legislative protection of patients with rare diseases[J]. Legality Vision(���Ʋ���:��Ѯ��), 2013, 4:67-68.
[37]
YOTI T. Navigating through orphan medicinal product regulations in EU and US-Similarities and differences[J]. Regula Toxicol Pharma, 2015, 71(1):63-67.
[38]
Pedro Franco. Orphan drugs:the regulatory environment[J]. Drug Dis Today, 2013, 18(3-4):163-172.
[39]
SONG P P, GAO J J, INAGAKI Y, et al. Rare diseases, orphan drugs, and their regulation in Asia:current status and future perspectives[J]. Intractable & Rare Dis Res, 2012, 1(1):3-9.
[40]
NOVIKOV P V. The problem of rare (orphan) diseases in the Russian Federation:Medical and normative legal aspects of its solution[J]. Terapevticheskiiarkhiv, 2014, 86(12):3-12.
[41]
SONG P P, TANG W, KOKUDO N. Rare diseases and orphan drugs in Japan:developing multiple strategies of regulation and research[J]. Expert Opinion on Orphan Drugs, 2013, 1(9):681-683.
[42]
GAO J J, SONG P P, TANG W. Rare disease patients in China anticipate the sunlight of legislation[J]. Drug Discoveries & Therapeutics, 2013, 7(3):126-128.
[43]
HYRY H I, ROOS J C P, MANUEL J, et al. The legal imperative for treating rare disorders[J]. Orphanet J Rare Disease, 2013, 8:135-141.
[44]
NA S M, YANG Y. Study on medical security system for rare diseases in China[J]. China Licensed Pharmacist(�й�ִҵҩʦ), 2016, 13(4):33-37.
[45]
ZHANG. Discussion on establishment of rare disease medical security system in China [J]. Harbin Med J(������ҽҩ), 2014, 34(2):85-86.
[46]
LIANG T K,SHANG K. The practice of Qingdao model of medical aid system for rare disease[J]. Soc Sec Studies, 2014, 3:64-73.
[47]
LI Q. Analysis of the present situation of supply mechanism of orphan drugs in China[J]. Legal System and Society(���������), 2014, 33:259-261.
[48]
MO Y. Discussion on social security of rare diseases[J]. Market Manage Rev(�ִ�Ӫ��:ѧԷ��), 2011, 10:207.
[49]
WANG Z G, TIAN K. Reflections on security system for rare diseases in China after the receding of ��Ice Bucket Challenge��Boom[J]. Chin Pharm Aff(�й�ҩ��), 2015, 29(10):1013-1017.
[50]
XIN X X,GUAN X D,SHI L W. Research on rare disease security mechanism in China based on the affordability evaluation of 5 rare diseases[J]. J China Pharm(�й�ҩ��), 2014, 25(5):404-407.
[51]
DING J X, JI N, BAI G L. Study of Orphan Drug Market Protection Policy in China[J]. Chin J Pharm(�й�ҽҩ��ҵ��־), 2012, 43(11):959-965.
[52]
ZHONG J, GAO W, HUO J P, et al. International comparative study about rare diseases�� medicare[J]. Drug Eval(ҩƷ����), 2014, 11(6):8-11.
[53]
HE J J, ZHANG Y B, XIA S, et al. Social security system of rare diseases in European Union and its implications for China[J]. Chin J Health Policy (�й����������о�), 2012, 5(7):52-59.
[54]
NI H P. Several researches on rare diseases medical security system[J]. China Health Insurance(�й�ҽ�Ʊ���), 2015, 5:18-20.
[55]
HU J J, CHEN X, LUO A Q, et al. Analysis on reimbursement level of orphan drugs in the medicare part D prescription drug plans in the US[J]. Chin Health Econom(���������), 2015, 34(8):71-73.
[56]
KAMUSHEVA MARIA, STOIMENOVAASSENA, DONEVAMIGLENA, et al. A cross-country comparison of reimbursed orphan medicines in bulgaria, greece and romania[J]. Biotechnol & Biotechnol Equip, 2013, 27(5):4186-4192.
[57]
PAVLOVIC N, STANIMIROV B, STOJANEVIC M, et al. An insight on differences in availability and reimbursement of orphan medicines among Serbia, Bulgaria and Sweden[J]. Biotechnol Biotechnol Equip, 2012, 26 (5):3236-3241.
[58]
ISKROV G G, RAYCHEVARALITSA D, STEFANOV R M S. Insight into reimbursement decision-making criteria in Bulgaria:implications for orphan drugs[J]. Folia Medica, 2013, 50(3-4):80-86.
[59]
DENIS A, MERGAERT L, FOSTIER C, et al. Critical assessment of belgian reimbursement dossiers of orphan drugs[J]. Pharmacol Economics, 2011, 29(10):883-893.
[60]
DING J X, SUN X D, JI N, et al. Evaluation on accessibility of Chinese and american rare diseases and its legal guarantee system[J]. Chin Pharm J (�й�ҩѧ��־), 2011, 46(14):1129-1132.
[61]
SHI L. International comparison of orphan drug accessibility[J]. J China Pharm(�й�ҩ��), 2013, 24 (45):4237-4239.
[62]
DING J X, LIU W J, LI W, et al. Analysis of orphan drug accessibility and marketing authorization system in China[J]. Chin Pharm Univ J(�й�ҩ�ƴ�ѧѧ��), 2014, 45(1):111-117.
[63]
ZHAO X Y, LIU Y. Analysis on accessibility evaluation index of orphan drugs[J]. Mod Business Trade Industry(�ִ���óҵ), 2013, 9:90-91.
[64]
GU J L, LU Y Q, ZHANG R, et al. Research on rare disease drugs attainability strategy in China[J]. Soft Sci Health(�������ѧ), 2013, 27(6):325-327.
[65]
GON S W, WANG Y X, PAN X Y, et al. The availability and affordability of orphan drugs for rare diseases in China[J]. Orphanet J Rare Dis, 2016, 11:20-31.
[66]
XIN X X, GUAN X D, SHI L W. Catastrophic expenditure and impoverishment of patients affected by 7 rare diseases in China[J]. Orphanet J Rare Dis, 2016, 11:74-80.
[67]
KUZELOVA M, ONDRIASOVA E, FOLTANOVA T. Analysis of the real availability of the orphan drugs in the Slovak Republic[J]. Int J Clin Pharm, 2011, 33(2):406-407.
[68]
BLANKART C R, STARGARDT T, SCHREYOGG J. Availability of and access to orphan drugs an international comparison of pharmaceutical treatments for pulmonary arterial hypertension, fabry disease, hereditary angioedema and chronic myeloid leukaemia[J]. Pharmacol Economics, 2011, 29 (1):63-82.
[69]
ZHAI W. The economic value of orphan drugs[J]. J North Pharm(����ҩѧ), 2013, 10(11):89-90.
[70]
THOMSON R. The economic power of orphan drugs[J]. Sci Focus(��ѧ�۲�), 2013, 8(1):8-12.
[71]
CHANG F, SHANG X T. Discussion about the orphan drug pricing regulation systemfrom the perspective of pricing and reimbursement[J]. Chin J New Drugs(�й���ҩ��־), 2015, 24(7):741-744.
[72]
EVERTON N S, TANARA R V Sousa. Economic evaluation in the context of rare diseases:is it possible?[J]. Cadernos Saude Publica, 2015, 31(3):496-506.
[73]
PLAVINSKY S I. Economic assessment of drugs for rare diseases: must it be done, if yes, which are its features?[J]. Terapevticheskiiarkhiv, 2014, 86(12):13-18.
[74]
ANGELIS A, TORDRUP D, KANAVOS P . Socio-economic burden of rare diseases:a systematic review of cost of illness evidence[J]. Health Policy, 2014, 119(7):964-979.
[75]
COYLE D, CHEUNG M C, EVANS G A. Opportunity cost of funding drugs for rare diseases:the dost-effectiveness of eculizumab in paroxysmal nocturnal hemoglobinuria[J]. Med Dec Making, 2014, 34(8):1016-1029.
[76]
SCHULLER Y, HOLLAK C E M, BIEGSTRAATEN M. The quality of economic evaluations of ultra-orphan drugs in Europe -a systematic review[J]. Orphanet J Rare Diseases, 2015, 10:92-103.
[77]
PICAVET E. What is known about the cost-effectiveness of orphan drugs? Evidence from cost-utility analyses[J]. J Clin Pharm Therap, 2015, 40(3):304-307.
[78]
Simoens Steven, Picavet Eline, Dooms Marc. Cost-effectiveness assessment of orphan drugs:a scientific and political conundrum[J]. Appl Health Econom Health Policy, 2013, 11(1):1-3.
[79]
HYRY H I, STERN A D, COX T M. Limits on use of health economic assessments for rare diseases[J]. QJM-An Int J Med, 2014, 107(3):241-245.
[80]
HE Y L, TIAN K. Discussion on the reference experience of european and american experiences on orphan drug development to China[J]. China Pharm(�й�ҩҵ), 2014, 23(24):6-8.
[81]
LI R S, LI H B. Policies on orphan drug development in USA and european union and their implications to China[J]. Chin Pharm Aff(�й�ҩ��), 2014, 28(10):1109-1113.
[82]
YUAN F, SHEN S Y. Development and clinical evaluation of orphan drugs[J]. World Clin Drugs(�����ٴ�ҩ��), 2011, 32(5):307-311.
[83]
DU T, GONG Z L, GAO Y. Policies, strategies and practices of orphan drug development in the united states[J]. Prog Pharm Sci(ҩѧ��չ), 2015, 39 (8):566-570.
[84]
CHU S Z, LI W X. Incentive measures for orphan drug R&D in several Asian countries and regions and the enlightenment to China[J]. Chin Pharm Univ J (�й�ҩ�ƴ�ѧѧ��), 2014, 45(1):125-128.
[85]
CHEN M, FENG W H. Current situation of international and national research of orphan drugs[J]. Chin J New Drugs(�й���ҩ��־), 2014, 23(7):764-768.
[86]
CHEN H, LIAN J F, WANG Z R. Status quo of research and development of orphan drugs in our country[J]. China Pharm(�й�ҩҵ), 2015, 24(10):1-3.
[87]
JIANG H Y, ZHANG F, MO H S. Who is responsible for the rare disease research? Alert posed by Ebola Viral Disease outbreak (in Chinese)[J]. Chin Sci Bull(��ѧͨ��), 2015, 60(21):1958-1962.
[88]
SONG P P, GAO J J, KOKUDO N. New opportunity for orphan drug development in Japan:early exploratory clinical trial bases promote drug translation from basic studies to clinical application[J]. Intrac Rare Dis Res, 2012, 1(2):95-97.
[89]
TANG Q, SONG P P, CHEN Y. Measures to combat rare diseases and promote orphan drug development in Japan:government-funded special biomedical research programs to enhance basic and applied research[J]. Expert Opinion on Orphan Drugs, 2016, 4(6):613-619.
[90]
KAKKAR A K, DAHIYA N. The evolving drug development landscape: from blockbusters to niche busters in the orphan drug space[J]. Drug Develop Res, 2014, 75 (4):231-234.
[91]
BRADFORD D, REILLY K M, WIDEMANN B C, et al. Developing therapies for rare tumors:opportunities, challenges and progress[J]. Expert Opinion Orphan Drugs, 2016, 4(1):93-103.
[92]
KESSELHEIM A S, MC G, SARAH, et al. Development and use of new therapeutics for rare diseases:views from patients, caregivers, and advocates[J]. Patient-Patient-Centered Outcomes Research, 2015, 8 (1):75-84.
[93]
MAVRIS M, LE CAM Y. Involvement of patient organisations in research and development of orphan drugs for rare diseases in europe[J]. Molecular Syndromology, 2012, 3 (5):237-243.
[94]
ZANG Y C, TIAN K, YU X Y. Enlightenment of world orphan drug definition policy to China[J]. Chin J New Drugs Clin Rem(�й���ҩ���ٴ���־), 2015, 34(1):20-22.
[95]
CHEN Y F, WU L. Preliminary study on Chinese standards for defining rare diseases [J]. Chin J Health Policy(�й����������о�), 2014, 7(10):16-20.
[96]
LI C X, XIE J, HU X. Analysis of definition of rare diseases and orphan drugs in developed countries[J]. China Licensed Pharmacist(�й�ִҵҩʦ), 2013, 10(3):51-56.
[97]
YI B X, WANG G P, HUO Y F, et al. Research on definition of rare diseases drug basing on affordability[J]. Chin J Pharm(�й�ҽҩ��ҵ��־), 2015, 46 (6):658-664.
[98]
RICHTER T, NESTLER-PARR S, BABELA R, et al. Rare disease terminology and definitions-a systematic global review:report of the ISPOR rare disease special interest group[J]. Value Health, 2015, 18(6):906-914.
[99]
CUI Y Z, HAN J X. A proposed definition of rare diseases for China:from the perspective of return on investment in new orphan drugs[J]. Orphanet J Rare Diseases, 2015, 10:28-30.
[100]
CLARKE J T R, COYLE D, EVANS G. Toward a functional definition of a "Rare Disease" for regulatory authorities and funding agencies[J]. Value in Health, 2014, 17(8):757-761.
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