{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:00:42Z","timestamp":1792458042668,"version":"4.5.0"},"reference-count":46,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,6,6]],"date-time":"2018-06-06T00:00:00Z","timestamp":1528243200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR\u201047785"],"award-info":[{"award-number":["AR\u201047785"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:p>At a time when advancing understanding of osteoarthritis (<jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content>) has created opportunities for new treatments, development of treatments has remained considerably behind advances in other rheumatic diseases. We describe elements of trial design and measurements that have inhibited success and offer suggestions that may help break the log jam. Among the problems with trials that include pain as an outcome measure are reliance on a single, non\u2010optimal pain outcome, overestimation of likely effects of treatments on pain, and failure to identify patient subgroups most likely to respond to specific treatments. With regard to the use of structure modification as an outcome measure, demonstrating structure modification is often highly challenging, even with the use of magnetic resonance imaging. Many <jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content> patients have advanced disease that is unlikely to respond to treatments that prevent cartilage loss. Further, prevention of cartilage loss and reduction of pain correlate weakly at best, and in at least some patients, reduction in pain may actually increase joint damage, making it impossible to demonstrate dual treatment effects on structure and pain in such scenarios. For structure outcomes, treatment effects on pain\u2010sensitive structures such as bone and synovium may be more achievable than preventing cartilage loss. We suggest that changes in trial design related to some of these issues may increase the chances that new exciting and effective <jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content> treatments will become available.<\/jats:p>","DOI":"10.1002\/art.40515","type":"journal-article","created":{"date-parts":[[2018,4,2]],"date-time":"2018-04-02T18:55:16Z","timestamp":1522695316000},"page":"1175-1181","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Emerging Treatment Models in Rheumatology: Challenges for Osteoarthritis Trials"],"prefix":"10.1002","volume":"70","author":[{"given":"David T.","family":"Felson","sequence":"first","affiliation":[{"name":"Boston University School of Medicine Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuhina","family":"Neogi","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31678-6"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-200704000-00012"},{"key":"e_1_2_7_4_1","first-page":"1833","article-title":"Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee","volume":"15","author":"Bellamy N","year":"1988","journal-title":"J Rheumatol"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.170928"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.22823"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39271"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(86)90120-X"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/03009742.2016.1203988"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2012.02.021"},{"issue":"10","key":"e_1_2_7_11_1","article-title":"Reducing heterogeneity in OA clinical trials: data from a phase 2 study of SM04690, a novel, intra\u2010articular, Wnt pathway inhibitor in knee osteoarthritis [abstract]","volume":"69","author":"Conaghan PG","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"e_1_2_7_12_1","first-page":"CD005328","article-title":"Intra\u2010articular corticosteroid for knee osteoarthritis","author":"Juni P","year":"2015","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_7_13_1","first-page":"CD000957","article-title":"Methotrexate for treating rheumatoid arthritis","author":"Lopez\u2010Olivo MA","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kel100"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199107113250203"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2011.04.013"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0901510"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2014.10.003"},{"key":"e_1_2_7_19_1","unstructured":"Osteoarthritis Research Society International.Osteoarthritis: a serious disease. 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