{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T04:46:21Z","timestamp":1777869981874,"version":"3.51.4"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Disease\u2010modifying treatments are a critical unmet need in Parkinson's disease (PD). Phase 2 futility trials using the Simon two\u2010stage design offer an efficient strategy to evaluate candidate treatments in an early PD population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The aim was to assess the feasibility of Simon two\u2010stage futility trials in early, levodopa\u2010treated PD subjects using historical patient\u2010level clinical trial datasets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed patient\u2010level data from two completed trials, that is, STEADY\u2010PD 3 (n\u2009=\u2009336, untreated at baseline) and NET\u2010PD LS1 (n\u2009=\u20091741, treated at baseline). We defined disability progression as a\u2009\u22655\u2010point worsening on the motor (Part III) subscore of the Unified Parkinson's Disease Rating Scale at 12 and 24\u2009months. We tested multiple scenarios, including the reanalysis of STEADY\u2010PD 3 participant data after starting dopaminergic treatment. We assessed predictors of progression using logistic regression analysis and calculated sample size estimates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Both trials showed similar progression rates at 12\u2009months (~26%) and 24\u2009months (~35%). In NET\u2010PD LS1, older age and lower baseline motor scores were associated with worsening; no predictors were significant in STEADY\u2010PD 3. We estimate that in futility trials that use OFF\u2010state scores to assess motor performance, 39 early PD participants are required to detect significant disability worsening over an observation period of 12\u2009months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Phase 2 futility trials using the Simon two\u2010stage methodology are feasible in early PD, including in treated and untreated patients. OFF\u2010state scores are preferable to ON\u2010state scores as the primary outcome measure. Futility trials offer a smaller\u2010scale, faster, and cost\u2010effective approach to assessing new candidate treatments in PD. \u00a9 2025 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70090","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T04:16:09Z","timestamp":1761020169000},"page":"190-199","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Feasibility of Simon Two\u2010Stage Futility Trials in People with Early, Symptomatically Treated Parkinson's Disease"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9972-5092","authenticated-orcid":false,"given":"Marcus W.","family":"Koch","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9384-1305","authenticated-orcid":false,"given":"Lorraine V.","family":"Kalia","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine, Tanz Centre for Research in Neurodegenerative Diseases University of Toronto; Krembil Research Institute, Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University Health Network  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justyna","family":"Sarna","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila","family":"Aquino","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daryl","family":"Wile","sequence":"additional","affiliation":[{"name":"Centre for Chronic Disease Prevention and Management, University of British Columbia Southern Medical Program, Kelowna, Canada; Division of Neurology, Department of Medicine University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6973-7479","authenticated-orcid":false,"given":"Tiago A.","family":"Mestre","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine University of Ottawa, The Ottawa Hospital Ottawa; University of Ottawa Brain and Mind Research Institute  Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael G.","family":"Schlossmacher","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine University of Ottawa, The Ottawa Hospital Ottawa; University of Ottawa Brain and Mind Research Institute  Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"D'Haeseleer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Universitair Ziekenhuis Brussels; Neuroprotection and Neuromodulation (NEUR) Research Groups, Center for Neurosciences Vrije Universiteit Brussel; National Multiple Sclerosis Center  Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jop","family":"Mostert","sequence":"additional","affiliation":[{"name":"Department of Neurology Rijnstate Hospital  Arnhem The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva M.M.","family":"Strijbis","sequence":"additional","affiliation":[{"name":"Department of Neurology, MS Center Amsterdam Amsterdam University Medical Centers  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard","family":"Uitdehaag","sequence":"additional","affiliation":[{"name":"Department of Neurology, MS Center Amsterdam Amsterdam University Medical Centers  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tarrant","family":"McPherson","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics Emory University  Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Cutter","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61393-3"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-024-01023-0"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.34"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000201252.57661.e1"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000210079"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1989.00520460028009"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000277648.63931.c0"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe1814611"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.120"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.7326\/M19-2534"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(89)90015-9"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2007.00818.x"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22340"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25122"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.17.5.427"},{"key":"e_1_2_8_17_1","volume-title":"R: 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