{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T03:25:12Z","timestamp":1769138712013,"version":"3.49.0"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dopaminergic therapies such as levodopa and dopamine receptor agonists (DRA) improve motor function in people with Parkinson's disease. These therapies are also linked to the advent of motor complications such as dyskinesias and wearing\u2010off episodes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We illustrate a method that creates a personalized treatment rule that takes patient\u2010specific information and provides a recommended first\u2010line therapy for Parkinson's disease that will provide the best mean improvement in motor function while constraining the probability of a motor complication within the first 2\u2009years of therapy below a level mutually deemed to be the maximum acceptable risk by the patient and clinician.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We apply a machine learning technique that simultaneously optimizes for benefit and risk outcomes to a harmonized clinical dataset based on the CALM\u2010PD and STEADY\u2010PD III randomized clinical trials. This generates a decision rule for allocating patients to levodopa or a DRA, based on a specified risk threshold. We evaluate the individualized decision rule by comparing the mean benefit and risk outcomes under the decision rule to the mean outcomes from policies that assign all patients to either levodopa or a DRA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The optimal decision rule improves the mean change from baseline in MDS\u2010UPDRS (Movement Disorder Society Unified Parkinson's Disease Rating Scale) motor (Part 3) score compared to assigning all patients to a DRA and provides a smaller mean probability of motor complications than assigning all patients to levodopa. More data are required to further develop and validate this decision rule.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>An optimal decision rule can provide improved data adaptive treatment decisions that balance benefit and risk outcomes given a maximum acceptable risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/phar.70069","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T11:36:08Z","timestamp":1764329768000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Constructing a Personalized Treatment Rule for Initial Therapy in Early Parkinson's Disease"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7351-3526","authenticated-orcid":false,"given":"Zachary P.","family":"Brehm","sequence":"first","affiliation":[{"name":"Department of Biostatistics and Computational Biology University of Rochester  Rochester New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8094-4041","authenticated-orcid":false,"given":"Ruth B.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Center for Health and Technology University of Rochester  Rochester New York USA"},{"name":"Department of Neurology University of Rochester  Rochester New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2394-9513","authenticated-orcid":false,"given":"Charles S.","family":"Venuto","sequence":"additional","affiliation":[{"name":"Center for Health and Technology University of Rochester  Rochester New York USA"},{"name":"Department of Neurology University of Rochester  Rochester New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0993-4136","authenticated-orcid":false,"given":"Greta","family":"Smith","sequence":"additional","affiliation":[{"name":"Center for Health and Technology University of Rochester  Rochester New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2781-5990","authenticated-orcid":false,"given":"Cuong Tuan","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Computational Biology University of Rochester  Rochester New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7443-9145","authenticated-orcid":false,"given":"Michael P.","family":"McDermott","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Computational Biology University of Rochester  Rochester New York USA"},{"name":"Center for Health and Technology University of Rochester  Rochester New York USA"},{"name":"Department of Neurology University of Rochester  Rochester New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2611-9512","authenticated-orcid":false,"given":"Ashkan","family":"Ertefaie","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Computational Biology University of Rochester  Rochester New York USA"},{"name":"Department of Neurology University of Rochester  Rochester New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012868"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002826-200001000-00007"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.284.15.1931"},{"issue":"7","key":"e_1_2_10_5_1","first-page":"1044","article-title":"Pramipexole vs Levodopa as Initial Treatment for Parkinson Disease: A 4\u2010Year Randomized Controlled Trial","volume":"61","author":"The Parkinson Study Group","year":"2004","journal-title":"Archives of 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