title: Cartilage-Repair Innovation at a Standstill: Methodologic and Regulatory Pathways to Breaking Free.
abstract: Articular cartilage defects strongly predispose patients to developing early joint degeneration and osteoarthritis, but for more than 15 years, no new cartilage-repair technologies that we know of have been approved by the U.S. Food and Drug Administration. Many studies examining novel approaches to cartilage repair, including cell, tissue, or matrix-based techniques, have shown great promise, but completing randomized controlled trials (RCTs) to establish safety and efficacy has been challenging, providing a major barrier to bringing these innovations into clinical use. In this article, we review reasons that surgical innovations are not well-suited for testing through RCTs. We also discuss how analytical methods for reducing bias, such as propensity scoring, make prospective observational studies a potentially viable alternative for testing the safety and efficacy of cartilage-repair and other novel therapies, offering the real possibility of therapeutic innovation.
authors.affiliation: Hospital for Special Surgery Healthcare Research Institute, New York, NY lymans@hss.edu.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lyman
authors.affiliation: Department of Orthopedics, Osaka Health Science University, Osaka, Japan.
authors.forename: Norimasa
authors.initials: N
authors.lastname: Nakamura
authors.affiliation: Department of Orthopedics, Rush University Medical Center, Chicago, Illinois.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Cole
authors.affiliation: Center for Biologic Joint Surgery, Department of Orthopaedic Surgery and Traumatology, University of Freiburg Medical Center, Freiburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Erggelet
authors.affiliation: Department of Orthopaedic Surgery, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Gomoll
authors.affiliation: Indiana University School of Medicine and OrthoIndy Hospital, Indianapolis, Indiana.
authors.forename: Jack
authors.initials: J
authors.lastname: Farr
mesh_terms: D002358:Cartilage, Articular / Q000601:surgery*; D006801:Humans; D019637:Orthopedic Procedures / Q000379:methods*; D010003:Osteoarthritis / Q000601:surgery*; D016032:Randomized Controlled Trials as Topic