{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T09:55:16Z","timestamp":1777888516415,"version":"3.51.4"},"reference-count":25,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Parkinson\u2019s Disease"],"published-print":{"date-parts":[[2021,4,13]]},"abstract":"<jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>A global overview of drug development programs in Parkinson\u2019s disease over the last few decades is lacking, while such programs are challenging given the multifaceted and heterogeneous nature of the disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To indirectly assess drug development programs in Parkinson\u2019s disease, exploring some factors associated with compound attrition at different trial phases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We assessed all Parkinson\u2019s disease trials in the WHO trials portal, from inception (1999) to September 2019. Independent authors selected trials and extracted data. The success rate was the number of compounds that progressed to the next drug development phase divided by the number of compounds in that phase.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Overall, 357 trials (studying 152 compounds) fulfilled our inclusion criteria, with 62 (17.3%) phase 1 trials, 135 (37.8%) phase 2 trials, 85 (23.8%) phase 3 trials, and 53 (14.8%) phase 4 trials. The success rate was 42.4% from phase 2 to 3. Original compounds received regulatory approval by the FDA in 21.4% of cases, compared with 6.7% of repurposed compounds, representing an overall success rate of 14.9%. We found 172 trials (48.2%) conducted for repurposing previously licensed compounds. These figures were approximately the same regarding approval by the EMA. Most compounds were approved to treat parkinsonism and motor fluctuations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>We found a moderate-to-high success rate in all phases of drug development. This was largely based on the success of original compounds, despite almost half of the identified trials attempting compound repurposing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jpd-202184","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T19:47:51Z","timestamp":1610480871000},"page":"421-429","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":15,"title":["Parkinson\u2019s Disease Drug Development Since 1999: A Story of Repurposing and Relative Success"],"prefix":"10.1177","volume":"11","author":[{"given":"Deirdre M.","family":"Boucherie","sequence":"first","affiliation":[{"name":"University of Amsterdam","place":["The Netherlands"]},{"name":"Laboratory of Clinical Pharmacology and Therapeutics","place":["Portugal"]}]},{"given":"Gon\u00e7alo S.","family":"Duarte","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Therapeutics","place":["Portugal"]},{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal"},{"name":"Centro de Estudos de Medicina Baseada na Evid\u00eancia, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal"}]},{"given":"Tiago","family":"Machado","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Therapeutics","place":["Portugal"]},{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal"}]},{"given":"Patr\u00edcia R.","family":"Faustino","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Therapeutics","place":["Portugal"]},{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal"}]},{"given":"Cristina","family":"Sampaio","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal"},{"name":"CHDI Management\/CHDI Foundation, Princeton, NJ, USA"}]},{"given":"Olivier","family":"Rascol","sequence":"additional","affiliation":[{"name":"University of Toulouse 3","place":["France"]}]},{"given":"Joaquim J.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Therapeutics","place":["Portugal"]},{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal"},{"name":"CNS \u2013 Campus Neurol\u00f3gico S\u00e9nior, Torres Vedras, Portugal"}]}],"member":"179","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000247740.47667.03"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26082"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27372"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/1745-6215-15-428"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsa1012065"},{"key":"e_1_3_2_7_2","unstructured":"U.S National Library of Medicine (2007) Food and Drug Administration Amendments Act of 2007 Public Law No. 110-85 \u00a7801. 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