title: Guidelines for the Design and Conduct of Clinical Studies in Knee Articular Cartilage Repair: International Cartilage Repair Society Recommendations Based on Current Scientific Evidence and Standards of Clinical Care.
abstract: OBJECTIVE
  To summarize current clinical research practice and develop methodological standards for objective scientific evaluation of knee cartilage repair procedures and products.
  
  
  METHODS
  A comprehensive literature review was performed of high-level original studies providing information relevant for the design of clinical studies on articular cartilage repair in the knee. Analysis of cartilage repair publications and synopses of ongoing trials were used to identify important criteria for the design, reporting, and interpretation of studies in this field.
  
  
  RESULTS
  Current literature reflects the methodological limitations of the scientific evidence available for articular cartilage repair. However, clinical trial databases of ongoing trials document a trend suggesting improved study designs and clinical evaluation methodology. Based on the current scientific information and standards of clinical care, detailed methodological recommendations were developed for the statistical study design, patient recruitment, control group considerations, study endpoint definition, documentation of results, use of validated patient-reported outcome instruments, and inclusion and exclusion criteria for the design and conduct of scientifically sound cartilage repair study protocols. A consensus statement among the International Cartilage Repair Society (ICRS) and contributing authors experienced in clinical trial design and implementation was achieved.
  
  
  CONCLUSIONS
  High-quality clinical research methodology is critical for the optimal evaluation of current and new cartilage repair technologies. In addition to generally applicable principles for orthopedic study design, specific criteria and considerations apply to cartilage repair studies. Systematic application of these criteria and considerations can facilitate study designs that are scientifically rigorous, ethical, practical, and appropriate for the question(s) being addressed in any given cartilage repair research project.
authors.affiliation: Harvard Vanguard Medical Associates, Harvard Medical School, Boston, MA, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Mithoefer
authors.affiliation: University Medical Centre, Utrecht, the Netherlands.
authors.forename: Daniel B F
authors.initials: DB
authors.lastname: Saris
authors.affiliation: OrthoIndy Knee Care Institute, Indianapolis, IN, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Farr
authors.affiliation: Rizzoli Orthopedic Institute, Bologna, Italy.
authors.forename: Elizaveta
authors.initials: E
authors.lastname: Kon
authors.affiliation: Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Zaslav
authors.affiliation: Rush University Medical Center, Chicago, IL, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Cole
authors.affiliation: Lund University Hospital, Lund, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Ranstam
authors.affiliation: Zimmer Orthobiologics, Austin, TX, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Yao
authors.affiliation: Biosyntech, Laval, QC, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Shive
authors.affiliation: Genzyme Biosurgery, Cambridge, MA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Levine
authors.affiliation: Tigenix, Leuven, Belgium.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Dalemans
authors.affiliation: University of Gothenburg, Kungsbacka, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Brittberg
keywords: cartilage repair repair; clinical trial general; general; knee joint involved; randomized controlled trials diagnostics; regulatory issues