title: Can we improve the performance and reporting of investigator-initiated clinical trials? Rheumatoid arthritis as an example.
abstract: Investigator-initiated trials, some of which have been referred to as comparative effectiveness trials, pragmatic trials, or strategy trials, are sometimes considered to be of greater clinical importance than industry-driven trials, because they address important but unresolved clinical questions that differ from the questions asked in industry-driven trials. Regulatory authorities have provided methodological guidance for industry-driven trials for the approval of new treatments, but such guidance is less clear for investigator-initiated trials. The European League Against Rheumatism (EULAR) task force for the update of the recommendations for the management of rheumatoid arthritis has critically looked at the methodological quality and conduct of many investigator-initiated trials, and has identified a number of concerns. In this Viewpoint paper, we highlight commonly encountered issues that are discussed using examples of well-known investigator-initiated trials. These issues cover three themes: (1) design choice (superiority vs non-inferiority designs); (2) statistical power and (3) convenience reporting. Since we acknowledge the importance of investigator-initiated research, we also propose a shortlist of points-to-consider when designing, performing and reporting investigator-initiated trials.
authors.affiliation: Amsterdam Rheumatology & immunology Center, Academic Medical Center/University of Amsterdam, The Netherlands Department of Rheumatology, Atrium Medical Center Heerlen, The Netherlands.
authors.forename: Robert B M
authors.initials: RB
authors.lastname: Landewé
authors.affiliation: Division of Rheumatology, Department of Medicine Three, Medical University Vienna & Second Department of Medicine, Hietzing Hospital, Vienna, Austria.
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital Harvard Medical School, Boston, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Weinblatt
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.affiliation: Rheumatology Department, Paris Descartes University, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, INSERM (U1153): Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris, Fance.
authors.forename: Maxime
authors.initials: M
authors.lastname: Dougados
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Fleischmann
authors.affiliation: Division of Rheumatology, Department of Medicine Three, Medical University Vienna, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Aletaha
authors.affiliation: Rheumatology, Allergy, Immunology Division, University of California, San Diego, USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Kavanaugh
authors.affiliation: Department of rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Désirée
authors.initials: D
authors.lastname: van der Heijde
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D057186:Comparative Effectiveness Research / Q000379:methods / Q000592:standards; D004345:Drug Industry; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000592:standards*; D012107:Research Design; D012108:Research Personnel
chemical_list: D018501:Antirheumatic Agents
keywords: Anti-TNF; Rheumatoid Arthritis; Treatment