title: Recommendations for an update of the 2010 European regulatory guideline on clinical investigation of medicinal products used in the treatment of osteoarthritis and reflections about related clinically relevant outcomes: expert consensus statement.
abstract: OBJECTIVE
  The European Society on Clinical and Economic aspects of Osteoporosis and Osteoarthritis (ESCEO) organised a working group to evaluate the need for updating the current European guideline on clinical investigation of drugs used in the treatment of osteoarthritis (OA).
  
  
  METHODS
  Areas of potential attention were identified and the need for modifications, update or clarification was examined. Proposals were then developed based on literature reviews and through a consensus process.
  
  
  RESULTS
  It was agreed that the current guideline overall still reflects the current knowledge in OA, although two possible modifications were identified. The first relates to the number and timing of measurements required as primary endpoints during clinical trials of symptom-relieving drugs, either drugs with rapid onset of action or slow acting drugs. The suggested modifications are intended to take into consideration the time related clinical need and expected time response to these drugs - i.e., a more early effect for the first category in addition to the maintenance of effect, a more continuous benefit over the long-term for the latter - in the timing of assessments. Secondly, values above which a benefit over placebo should be considered clinically relevant were considered. Based on literature reviews, the most consensual values were determined for primary endpoints of both symptom-relieving drugs (i.e., pain intensity on a visual analogue scale (VAS)) and disease-modifying drugs (i.e., radiographic joint-space narrowing).
  
  
  CONCLUSIONS
  This working document might be considered by the European regulatory authorities in a future update of the guideline for the registration of drugs in OA.
authors.affiliation: Department of Public Health Sciences, University of Liège and CHU Centre Ville, Liège, Belgium. Electronic address: jyreginster@ulg.ac.be.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Reginster
authors.affiliation: Federal Institute for Drugs and Medical Devices (BfArM), Bonn, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Reiter-Niesert
authors.affiliation: Department of Public Health Sciences, University of Liège and CHU Centre Ville, Liège, Belgium.
authors.forename: O
authors.initials: O
authors.lastname: Bruyère
authors.affiliation: Department of Rheumatology, University Pierre and Marie Curie AP-HP, Hôpital Saint-Antoine, Paris, France; University of Paris06, INSERM, UMR-S938, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Berenbaum
authors.affiliation: Department of Internal Medicine, University of Florence, Florence, Italy.
authors.forename: M-L
authors.initials: ML
authors.lastname: Brandi
authors.affiliation: CEDOC - Department of Rheumatology, Faculdade de Ciências Médicas, Universidade Novade Lisboa, Lisbon, Portugal; CHLO, EPE-Hospital Egas Moniz, Lisbon, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Branco
authors.affiliation: Department of Rheumatology, Saint-Luc University Hospital, Catholic University, Louvain, Belgium.
authors.forename: J-P
authors.initials: JP
authors.lastname: Devogelaer
authors.affiliation: Bone and Joint Research Unit, Fundación Jiménez Diaz, Madrid, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Herrero-Beaumont
authors.affiliation: Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK.
authors.forename: J
authors.initials: J
authors.lastname: Kanis
authors.affiliation: Aging Program, National Research Council, Padova, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Maggi
authors.affiliation: Rheumatology Department, AP-HP, St-Antoine Hospital, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Maheu
authors.affiliation: Paris Diderot University, UFR médicale, Paris, France; AP-HP, Hôpital Lariboisière, fédération de Rhumatologie, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Richette
authors.affiliation: Service of Bone Diseases, Department of Rehabilitation and Geriatrics, University Hospitals and Faculty of Medicine of Geneva, Geneva, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Rizzoli
authors.affiliation: NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK; MRC Epidemiology Resource Centre, University of Southampton, Southampton, UK.
authors.forename: C
authors.initials: C
authors.lastname: Cooper
mesh_terms: D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002809:Chondroitin Sulfates / Q000627:therapeutic use; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D005060:Europe; D005938:Glucocorticoids / Q000627:therapeutic use*; D005944:Glucosamine / Q000627:therapeutic use; D006801:Humans; D006820:Hyaluronic Acid / Q000627:therapeutic use; D007270:Injections, Intra-Articular; D010003:Osteoarthritis / Q000188:drug therapy*; D055675:Viscosupplements / Q000627:therapeutic use*
chemical_list: D000305:Adrenal Cortex Hormones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D005938:Glucocorticoids; D055675:Viscosupplements; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates; D005944:Glucosamine
keywords: Guideline; Osteoarthritis; Registration of drugs