title: On the predictive utility of animal models of osteoarthritis.
abstract: Animal models of osteoarthritis are extensively used for investigating disease pathways and for preclinical testing of novel therapies. Their predictive utility, however, has often been questioned, mainly because preclinical efficacy of novel therapeutics is poorly translated in clinical trials. In the current narrative review, we consider the preclinical models that were used to support undertaking clinical trials for disease-modifying osteoarthritis drugs, and compare outcomes between clinical and preclinical studies. We discuss this in light of the 1999 Food and Drug Administration draft guidelines for industry for use in the development of drugs, devices, and biological products intended for the treatment of osteoarthritis, which raised five considerations on the usefulness of osteoarthritis models. We systematically discuss what has been learnt regarding these five points since 1999, with emphasis on replicating distinct risk factors and subtypes of human osteoarthritis, and on comprehensive evaluation of the disease in animals, including pathology of all joint tissues, biomarker analysis, and assessment of pain and joint function. Finally, we discuss lessons learnt and propose some recommendations for how the evidence from preclinical research might be strengthened with a view to improving success in clinical translation.
authors.affiliation: Department of Medicine, Division of Rheumatology, and Department of Biochemistry, Rush University Medical Center, Chicago, IL, 60612, USA. anne-marie_malfait@rush.edu.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Malfait
authors.affiliation: Raymond Purves Bone and Joint Research Laboratories, Kolling Institute of Medical Research, Institute of Bone and Joint Research, University of Sydney at Royal North Shore Hospital, St Leonards, NSW, 2065, Australia. christopher.little@sydney.edu.au.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Little
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D010003:Osteoarthritis / Q000188:drug therapy*; D015203:Reproducibility of Results; D057170:Translational Research, Biomedical / Q000379:methods
chemical_list: D018501:Antirheumatic Agents