{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:38:28Z","timestamp":1791322708870,"version":"4.3.1"},"reference-count":72,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,10,29]],"date-time":"2012-10-29T00:00:00Z","timestamp":1351468800000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Since the introduction of the Orphan Drug Act in 1983, designed to promote development of treatments for rare diseases, at least 378 orphan drugs have been approved. Incentives include financial support, tax credits, and perhaps most importantly, extended market exclusivity. These incentives have encouraged industry interest and accelerated research on rare diseases, allowing patients with orphan diseases access to treatments. However, extended market exclusivity has been associated with unacceptably high drug costs, both for newly developed drugs and for drugs that were previously widely available. We suggest that a paradoxical effect of orphan product exclusivity can be reduced patient access to existing drugs. In addition, the costs of each new drug are arguably unsustainable for patients and for the American health care system. Of all the specialties, neurology has the third highest number of orphan product designations, and neurological diseases account for at least one\u2010fifth of rare diseases. Citing the use of tetrabenazine for chorea in Huntington disease, adrenocorticotropic hormone for infantile spasms, and enzyme replacement therapy with alglucosidase alpha for Pompe disease, we highlight these paradoxical effects. ANN NEUROL 2012;72:481\u2013490<\/jats:p>","DOI":"10.1002\/ana.23672","type":"journal-article","created":{"date-parts":[[2012,10,29]],"date-time":"2012-10-29T21:43:00Z","timestamp":1351546980000},"page":"481-490","source":"Crossref","is-referenced-by-count":45,"title":["Unintended effects of orphan product designation for rare neurological diseases"],"prefix":"10.1002","volume":"72","author":[{"given":"Sin\u00e9ad M.","family":"Murphy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Araya","family":"Puwanant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Griggs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Consortium for Clinical Investigations of Neurological Channelopathies (CINCH) and Inherited Neuropathies Consortium (INC) Consortia of the Rare Disease Clinical Research Network","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,10,29]]},"reference":[{"key":"e_1_2_14_2_2","unstructured":"Department of Health and Human Services: Office of Inspector General. The Orphan Drug Act: implementation and impact. May 2001. Available at:http:\/\/oig.hhs.gov\/oei\/reports\/oei\u201009\u201000\u201000380.pdfAccessed February 14 2011."},{"key":"e_1_2_14_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2008.10.003"},{"key":"e_1_2_14_4_2","unstructured":"National Institutes of Health: Office of Rare Diseases. Available at:http:\/\/rarediseases.info.nih.gov\/Resources\/Rare_Diseases_Information.aspxAccessed February 4 2011."},{"key":"e_1_2_14_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2006.01666.x"},{"key":"e_1_2_14_6_2","doi-asserted-by":"publisher","DOI":"10.1177\/009127006600600202"},{"key":"e_1_2_14_7_2","volume-title":"Rare diseases and orphan product","author":"Field MJ","year":"2010"},{"key":"e_1_2_14_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-3-33"},{"key":"e_1_2_14_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3160"},{"key":"e_1_2_14_10_2","unstructured":"US Food and Drug Administration. Information on the Orphan Products Grants Program. May 2010. Available at:http:\/\/www.fda.gov\/ForIndustry\/DevelopingProductsforRareDiseasesConditions\/WhomtoContactaboutOrphanProductDevelopment\/ucm134580.htmAccessed February 14 2011."},{"key":"e_1_2_14_11_2","unstructured":"US Food and Drug Administration. Search orphan drug designations and approvals. Available at:http:\/\/www.accessdata.fda.gov\/scripts\/opdlisting\/oopd\/index.cfmAccessed February 12 2011."},{"key":"e_1_2_14_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd919"},{"key":"e_1_2_14_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMhle1002961"},{"key":"e_1_2_14_14_2","unstructured":"US Department of Health and Human Services: Office of Extramural Research. Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Programs. Available at:http:\/\/grants.nih.gov\/grants\/funding\/sbirsttr_programs.htmAccessed February 12 2011."},{"key":"e_1_2_14_15_2","unstructured":"Patient Protection and Affordable Care Act. Public Law 111\u2010148 111th Congress H.R. 3590 March 23 2010. Available at:http:\/\/www.gpo.gov\/fdsys\/pkg\/PLAW\u2010111publ148\/pdf\/PLAW\u2010111publ148.pdfAccessed October 12 2011."},{"key":"e_1_2_14_16_2","unstructured":"Preserving Access to Orphan Drugs Act of 2011. H.R. 2672 112th Congress. Available at:http:\/\/thomas.loc.gov\/Accessed October 12 2011."},{"key":"e_1_2_14_17_2","unstructured":"Medical Innovation Prize Act. S. 1137 112th Congress. Available at:http:\/\/thomas.loc.gov\/cgi\u2010bin\/query\/z?c112:S.1137.ISAccessed October 12 2011."},{"key":"e_1_2_14_18_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.5654.422"},{"key":"e_1_2_14_19_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000198586.85250.13"},{"key":"e_1_2_14_20_2","doi-asserted-by":"crossref","unstructured":"PollockDL. Blame Canada (and the rest of the world): the twenty\u2010year war on imported prescription drugs. Bepress legal series 2005 paper 806. Available at:http:\/\/law.bepress.com\/cgi\/viewcontent.cgi?article=4130&context=expressoAccessed October 12 2011.","DOI":"10.1163\/221190011X00300"},{"key":"e_1_2_14_21_2","unstructured":"FDA Personal Use Import Policy. Available at:http:\/\/www.ceri.com\/import.htmAccessed October 12 2011."},{"key":"e_1_2_14_22_2","unstructured":"US Food and Drug Administration. Xenazine NDA approval. August 2008. Available at:http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/appletter\/2008\/021894s000ltr.pdfAccessed July 28 2011."},{"key":"e_1_2_14_23_2","unstructured":"Fallon Community Health Plan Department of Pharmacy Services. Prior authorization approval criteria: Xenazine (tetrabenazine). Available at:http:\/\/www.fchp.org\/\u223c\/media\/Files\/FCHP\/Imported\/Xenazine_tetrabenazine.pdf.ashx Accessed March 1 2011."},{"key":"e_1_2_14_24_2","volume-title":"British National Formulary","year":"2011"},{"key":"e_1_2_14_25_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.97.3.375"},{"key":"e_1_2_14_26_2","unstructured":"WatsanR. Drug price soars from $1 650 to $23 000 per vial to treat babies with infantile spasms: parents and physicians react. September 2007. Available at:http:\/\/professionals.epilepsy.com\/page\/ar_1189197304.htmlAccessed February 10 2011."},{"key":"e_1_2_14_27_2","unstructured":"Questcor Pharmaceuticals launches Acthar for the treatment of infantile spasms. November 2010. Available at:http:\/\/www.investorguide.com\/stock\u2010news\u2010show.php?story_id=35337060&topic=QCORAccessed February 6 2011."},{"key":"e_1_2_14_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healthpol.2009.12.001"},{"key":"e_1_2_14_29_2","unstructured":"Genzyme Corporation. Product lists. Available at:http:\/\/www.genzyme.com\/business\/biz_home.aspAccessed February 10 2011."},{"key":"e_1_2_14_30_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000253226.13795.40"},{"key":"e_1_2_14_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2008.11.007"},{"key":"e_1_2_14_32_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000251268.41188.04"},{"key":"e_1_2_14_33_2","unstructured":"US Food and Drug Administration. FDA news release. May 2010. Available at:http:\/\/www.fda.gov\/NewsEvents\/Newsroom\/PressAnnouncements\/ucm213212.htmAccessed February 4 2011."},{"key":"e_1_2_14_34_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0909859"},{"key":"e_1_2_14_35_2","unstructured":"ClarkT BerkrotB. Update 2: Genzyme wins FDA approval for Pompe drug. May 2010. Available at:http:\/\/www.reuters.com\/article\/2010\/05\/25\/genzyme\u2010idUSN2513053720100525?pageNumber=1Accessed February 8 2011."},{"key":"e_1_2_14_36_2","unstructured":"CVS Caremark. Specialty TrendsRx\u00ae Alert. Available at:https:\/\/www.caremark.com\/portal\/asset\/SpecialtyTrendsRxAlert_Lumizyme.pdfAccessed April 10 2011."},{"key":"e_1_2_14_37_2","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1017\/S0098858800009424","article-title":"Orphan drugs: the question of products liability","volume":"10","author":"Scharf SF","year":"1985","journal-title":"Am J Law Med"},{"key":"e_1_2_14_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2006.02579.x"},{"key":"e_1_2_14_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21676"},{"key":"e_1_2_14_40_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc0912463"},{"key":"e_1_2_14_41_2","unstructured":"US Food and Drug Administration. FDA approves colchicine for acute gout Mediterranean fever. July 2009. Available at:http:\/\/www.fda.gov\/NewsEvents\/Newsroom\/PressAnnouncements\/2009\/ucm174620.htmAccessed February 12 2011."},{"key":"e_1_2_14_42_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1003126"},{"key":"e_1_2_14_43_2","unstructured":"DerekLowe. Colchicine's price goes through the roof. Available at:http:\/\/pipeline.corante.com\/archives\/2010\/04\/14\/colchicines_price_goes_through_the_roof.phpAccessed October 12 2011."},{"key":"e_1_2_14_44_2","unstructured":"FDA approval of ancient remedy sends price soaring. Available at:http:\/\/www.cbsnews.com\/2100\u201018563_162\u201020118283.htmlAccessed March 1 2011."},{"key":"e_1_2_14_45_2","unstructured":"The price of gout drug colchicine goes up. Available at:http:\/\/www.arthritistoday.org\/news\/colchicine\u2010gout\u2010drug\u2010price053.phpAccessed March 1 2011."},{"key":"e_1_2_14_46_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1009918"},{"key":"e_1_2_14_47_2","unstructured":"National Institutes of Health: Office of Rare Diseases Research. Rare diseases and related terms. Available at:http:\/\/rarediseases.info.nih.gov\/RareDiseaseList.aspx?PageID=1Accessed July 28 2011."},{"key":"e_1_2_14_48_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.298.1.61"},{"key":"e_1_2_14_49_2","unstructured":"US Food and Drug Administration: Drug Safety and Availability. Hawaii: Governor Linda Lingle. September 2009.http:\/\/www.fda.gov\/Drugs\/DrugSafety\/ucm179204.htmAccessed February 12 2011."},{"key":"e_1_2_14_50_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp0908496"},{"key":"e_1_2_14_51_2","doi-asserted-by":"publisher","DOI":"10.1136\/medethics-2011-100094"},{"key":"e_1_2_14_52_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp0804261"},{"key":"e_1_2_14_53_2","unstructured":"IMS Consulting. Orphan drugs: rarity no guarantee of access. Available at:http:\/\/www.onlymedics.com\/documents\/download\u2010medics\u2010KsCzr.pdfAccessed October 12 2011."},{"key":"e_1_2_14_54_2","doi-asserted-by":"publisher","DOI":"10.2165\/11531880-000000000-00000"},{"key":"e_1_2_14_55_2","unstructured":"BCC Research. Global market for orphan drugs. Available at:http:\/\/www.bccresearch.com\/report\/orphan\u2010drugs\u2010market\u2010phm038b.htmlAccessed March 30 2011."},{"key":"e_1_2_14_56_2","unstructured":"BCC Research. Global markets for orphan drugs. Available at:http:\/\/www.bccresearch.com\/report\/orphan\u2010drugs\u2010market\u2010phm038c.html?tab=scope&highlightKeyword=orphan+drugs+sales+2008Accessed March 31 2011."},{"key":"e_1_2_14_57_2","unstructured":"Orphan drugs. Nature.2010. Available at:http:\/\/www.nature.com\/news\/2010\/101201\/pdf\/468604a.pdfAccessed October 11 2011."},{"key":"e_1_2_14_58_2","doi-asserted-by":"publisher","DOI":"10.3111\/13696998.2010.491427"},{"key":"e_1_2_14_59_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.fpc.0000220571.20961.dd"},{"key":"e_1_2_14_60_2","unstructured":"Acorda's MS drug Ampyra looks good now but that probably won't last. Available at:http:\/\/www.cbsnews.com\/8301\u2010505123_162\u201043240646\/acordas\u2010ms\u2010drug\u2010ampyra\u2010looks\u2010good\u2010now\u2010but\u2010that\u2010probably\u2010wont\u2010last\/Accessed March 31 2011."},{"key":"e_1_2_14_61_2","unstructured":"Multiple sclerosis: 4\u2010aminopyridine. Available at:http:\/\/www.thecompounder.com\/alternative\u2010treatments\/multiple\u2010sclerosis\/4\u2010aminopyridineAccessed March 31 2011."},{"key":"e_1_2_14_62_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.331.7523.1016"},{"key":"e_1_2_14_63_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.331.7523.1019"},{"key":"e_1_2_14_64_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.a1225"},{"key":"e_1_2_14_65_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.c6471"},{"key":"e_1_2_14_66_2","first-page":"183","article-title":"Orphan drug policies: implications for the United States, Canada, and developing countries","volume":"12","author":"Cheung RY","year":"2004","journal-title":"Health Law J"},{"key":"e_1_2_14_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/449176a"},{"key":"e_1_2_14_68_2","doi-asserted-by":"publisher","DOI":"10.1377\/hlthaff.2010.0902"},{"key":"e_1_2_14_69_2","first-page":"7","article-title":"On rare and \u201csuper\u2010rare\u201d diseases: an insight from the Republic of Macedonia","volume":"32","author":"Gucev ZS","year":"2011","journal-title":"Prilozi"},{"key":"e_1_2_14_70_2","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8603-7-30"},{"key":"e_1_2_14_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healthpol.2010.05.017"},{"key":"e_1_2_14_72_2","unstructured":"National Institute for Health and Clinical Excellence. Appraising Orphan Drugs Proposal. Available at:http:\/\/www.nice.org.uk\/aboutnice\/whoweare\/seniormanagementteam\/meetings\/2005\/12july2005\/appraising_orphan_drugs.jspAccessed March 10 2012."},{"key":"e_1_2_14_73_2","doi-asserted-by":"publisher","DOI":"10.1136\/jme.2007.021683"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.23672","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.23672","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T21:34:36Z","timestamp":1714512876000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.23672"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,10]]},"references-count":72,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2012,10]]}},"alternative-id":["10.1002\/ana.23672"],"URL":"https:\/\/doi.org\/10.1002\/ana.23672","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,10]]}}}