Towards prevention of post-traumatic osteoarthritis: report from an international expert working group on considerations for the design and conduct of interventional studies following acute knee injury

F E Watt; N Corp; S R Kingsbury; R Frobell; M Englund; D T Felson; M Levesque; S Majumdar; C Wilson; D J Beard; L S Lohmander; V B Kraus; F Roemer; P G Conaghan; D J Mason; Arthritis Research UK Osteoarthritis and Crystal Disease Clinical Study Group Expert Working Group

doi:10.1016/j.joca.2018.08.001

Towards prevention of post-traumatic osteoarthritis: report from an international expert working group on considerations for the design and conduct of interventional studies following acute knee injury

Osteoarthritis Cartilage. 2019 Jan;27(1):23-33. doi: 10.1016/j.joca.2018.08.001. Epub 2018 Aug 18.

Authors

Collaborators

Arthritis Research UK Osteoarthritis and Crystal Disease Clinical Study Group Expert Working Group:
J Adams¹⁶, M Blank, M Batt¹⁷, P Biggs¹⁸, M Busse-Morris¹⁹, K Button²⁰, J Calder²¹, J Cook²², C Edwards²³, E Fisheleva²⁴, D F Hamilton²⁵, H Harrison, C Holt¹⁸, M Jones²¹, R Jones²⁶, S Kluzek²², T Knight, G Nuki²⁷, S Parekh²⁸, G Peat²⁹, C Pothet²⁴, T Rainer¹⁹, N Robinson³⁰, L Sawle¹⁸, T Vincent³¹, A Williams²¹, E Wise³², W Zhang¹⁷, S Bierma-Zeinstra³³

Affiliations

¹ Arthritis Research UK Centre for Osteoarthritis Pathogenesis, Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Roosevelt Drive, Oxford, OX3 7FY, United Kingdom. Electronic address: [email protected].
² Arthritis Research UK Primary Care Centre, Institute for Primary Care & Health Sciences, Keele University, Keele, UK. Electronic address: [email protected].
³ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds & NIHR Leeds Biomedical Research Centre, Leeds, UK. Electronic address: [email protected].
⁴ Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Lund, Sweden. Electronic address: [email protected].
⁵ Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Lund, Sweden. Electronic address: [email protected].
⁶ Clinical Epidemiology Research & Training Unit, Boston University School of Medicine, Boston, MA, USA; NIHR Biomedical Research Centre, University of Manchester, Manchester, UK. Electronic address: [email protected].
⁷ Immunology Development, Abbvie Bioresearch Center, Worcester, MA, USA. Electronic address: [email protected].
⁸ Musculoskeletal Quantitative Imaging Research Group, Department of Radiology & Biomedical Imaging, University of California San Francisco, San Francisco, USA. Electronic address: [email protected].
⁹ Dept of Trauma and Orthopaedics, University Health Board, Cardiff, UK. Electronic address: [email protected].
¹⁰ Surgical Intervention Trials Unit (SITU), Nuffield Department of Orthopaedics, Rheumatology and Musculokeletal Sciences, University of Oxford, Oxford, UK. Electronic address: [email protected].
¹¹ Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Lund, Sweden. Electronic address: [email protected].
¹² Duke Molecular Physiology Institute and Division of Rheumatology, Duke University School of Medicine, Durham, USA. Electronic address: [email protected].
¹³ Department of Radiology, University of Erlangen-Nuremberg, Erlangen, Germany; Department of Radiology, Boston University School of Medicine, Boston, MA, USA. Electronic address: [email protected].
¹⁴ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds & NIHR Leeds Biomedical Research Centre, Leeds, UK. Electronic address: [email protected].
¹⁵ Arthritis Research UK Biomechanics and Bioengineering Centre, School of Biosciences, Cardiff University, Cardiff, UK. Electronic address: [email protected].
¹⁶ Faculty of Health Sciences, University of Southampton, UK.
¹⁷ Nottingham University Hospitals and Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, University of Nottingham, UK.
¹⁸ School of Engineering, Cardiff University, UK.
¹⁹ School of Medicine, Cardiff University, UK.
²⁰ School of Healthcare Sciences, Cardiff University, UK.
²¹ Fortius Clinic, London, UK.
²² Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK.
²³ Faculty of Medicine, University of Southampton, UK.
²⁴ Medicines Research Centre, Glaxo-SmithKline, UK.
²⁵ School of Clinical Sciences, University of Edinburgh, UK.
²⁶ University of Salford, UK.
²⁷ School of Molecular, Genetic and Population Health Sciences, University of Edinburgh, UK.
²⁸ Great Ormond Street Institute of Child Health, University College London, UK.
²⁹ Arthritis Research UK Primary Care Centre, Research Institute for Primary Care & Health Sciences, Keele University, UK.
³⁰ Health and Social Care/Allied Health Services, London South Bank University, UK.
³¹ Arthritis Research UK Centre for Osteoarthritis Pathogenesis, Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK.
³² Encompass Healthcare, Washington, Tyne and Wear, UK.
³³ Department of General Practice, Department of Orthopedics, Erasmus MC - University Medical Centre, Rotterdam, The Netherlands.

Abstract

Objective: There are few guidelines for clinical trials of interventions for prevention of post-traumatic osteoarthritis (PTOA), reflecting challenges in this area. An international multi-disciplinary expert group including patients was convened to generate points to consider for the design and conduct of interventional studies following acute knee injury.

Design: An evidence review on acute knee injury interventional studies to prevent PTOA was presented to the group, alongside overviews of challenges in this area, including potential targets, biomarkers and imaging. Working groups considered pre-identified key areas: eligibility criteria and outcomes, biomarkers, injury definition and intervention timing including multi-modality interventions. Consensus agreement within the group on points to consider was generated and is reported here after iterative review by all contributors.

Results: The evidence review identified 37 studies. Study duration and outcomes varied widely and 70% examined surgical interventions. Considerations were grouped into three areas: justification of inclusion criteria including the classification of injury and participant age (as people over 35 may have pre-existing OA); careful consideration in the selection and timing of outcomes or biomarkers; definition of the intervention(s)/comparator(s) and the appropriate time-window for intervention (considerations may be particular to intervention type). Areas for further research included demonstrating the utility of patient-reported outcomes, biomarkers and imaging outcomes from ancillary/cohort studies in this area, and development of surrogate clinical trial endpoints that shorten the duration of clinical trials and are acceptable to regulatory agencies.

Conclusions: These considerations represent the first international consensus on the conduct of interventional studies following acute knee joint trauma.

Keywords: Clinical trial; Considerations; Injury; Knee; Osteoarthritis; Outcome.

Publication types

Consensus Development Conference
Research Support, Non-U.S. Gov't

MeSH terms

Acute Disease
Clinical Trials as Topic / methods
Evidence-Based Medicine / methods
Humans
Knee Injuries / complications*
Osteoarthritis, Knee / etiology*
Osteoarthritis, Knee / prevention & control*
Research Design
Treatment Outcome

Abstract

Publication types

MeSH terms

Grants and funding