title: Creative trial design in RA: optimizing patient outcomes.
abstract: The rheumatology community has witnessed remarkable advances in the management of rheumatoid arthritis (RA) made possible by the development of highly effective biologic DMARDs. Robust randomized controlled trials of clinical efficacy, equipped with validated outcome measures, ensured these therapies could enter the clinical arena and thus substantially improve patient outcomes. Current management principles, which follow a 'treat-to-target' paradigm, advocate tight control of disease activity with the aim of achieving clinical remission. However, efficacy trials are not yet aligned with this approach, hampering patient recruitment. This impediment and the usual approach of inclusion of previously failed treatment arms (to protect methodological concerns) is prompting reappraisal of RA trial design and the consideration of more pragmatic studies that reflect real-life practice. In addition, the aspirations of the rheumatology community to strive for personalized medicine means innovative approaches to trial design are needed to complement the efficacy trial. This Review appraises the current trial landscape and provides insights and key concepts from other fields such as oncology as to the potential utility (as well as the limitations) of pragmatic trial designs such as adaptive trials and biomarker-driven trials.
authors: NIHR Leeds Musculoskeletal Biomedical Research Unit, Division of Rheumatic & Musculoskeletal Disease, University of Leeds, Chapel Allerton Hospital, Chapeltown Road, Leeds LS7 4SA, UK. m.buch@leeds.ac.uk
authors: Maya H
authors: MH
authors: Buch
authors: Sue
authors: S
authors: Pavitt
authors: Mahesh
authors: M
authors: Parmar
authors: Paul
authors: P
authors: Emery
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use; D017063:Outcome Assessment, Health Care; D016032:Randomized Controlled Trials as Topic; D012107:Research Design
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate
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