Review

. 2015 May;23(5):686-97.

doi: 10.1016/j.joca.2015.03.002.

OARSI Clinical Trials Recommendations: Soluble biomarker assessments in clinical trials in osteoarthritis

V B Kraus¹, F J Blanco², M Englund³, Y Henrotin⁴, L S Lohmander⁵, E Losina⁶, P Önnerfjord⁷, S Persiani⁸

Affiliations

¹ Duke Molecular Physiology Institute and Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA. Electronic address: vbk@duke.edu.
² Grupo de Proteomica, ProteoRed/ISCIII, Servicio de Reumatologia, Instituto de Investigación Biomedica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas, Universidade da Coruña (UDC), As Xubias, 15006 A Coruña, Spain.
³ Orthopedics, Clinical Sciences Lund, Lund University, Lund, Sweden; Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston University, MA, USA.
⁴ Bone and Cartilage Research Unit, Arthropôle Liège, University of Liège, CHU Sart-Tilman, 4000 Liège, Belgium; Department of Physical Therapy and Rehabilitation, Princess Paola Hospital, Marche-en-Famenne, Belgium.
⁵ Department of Orthopedics, Clinical Sciences Lund, Lund University, Lund, Sweden; Research Unit for Musculoskeletal Function and Physiotherapy, and Department of Orthopedics and Traumatology, University of Southern Denmark, Odense, Denmark.
⁶ Orthopedic and Arthritis Center for Outcomes Research, Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
⁷ Molecular Skeletal Biology, Department of Clinical Sciences Lund, Lund University, Sweden.
⁸ Department of Translational Sciences and Pharmacokinetics, Rottapharm Biotech, Monza, Italy.

PMID: 25952342
PMCID: PMC4430113
DOI: 10.1016/j.joca.2015.03.002

Review

OARSI Clinical Trials Recommendations: Soluble biomarker assessments in clinical trials in osteoarthritis

V B Kraus et al. Osteoarthritis Cartilage. 2015 May.

. 2015 May;23(5):686-97.

doi: 10.1016/j.joca.2015.03.002.

Authors

V B Kraus¹, F J Blanco², M Englund³, Y Henrotin⁴, L S Lohmander⁵, E Losina⁶, P Önnerfjord⁷, S Persiani⁸

Affiliations

¹ Duke Molecular Physiology Institute and Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA. Electronic address: vbk@duke.edu.
² Grupo de Proteomica, ProteoRed/ISCIII, Servicio de Reumatologia, Instituto de Investigación Biomedica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas, Universidade da Coruña (UDC), As Xubias, 15006 A Coruña, Spain.
³ Orthopedics, Clinical Sciences Lund, Lund University, Lund, Sweden; Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston University, MA, USA.
⁴ Bone and Cartilage Research Unit, Arthropôle Liège, University of Liège, CHU Sart-Tilman, 4000 Liège, Belgium; Department of Physical Therapy and Rehabilitation, Princess Paola Hospital, Marche-en-Famenne, Belgium.
⁵ Department of Orthopedics, Clinical Sciences Lund, Lund University, Lund, Sweden; Research Unit for Musculoskeletal Function and Physiotherapy, and Department of Orthopedics and Traumatology, University of Southern Denmark, Odense, Denmark.
⁶ Orthopedic and Arthritis Center for Outcomes Research, Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
⁷ Molecular Skeletal Biology, Department of Clinical Sciences Lund, Lund University, Sweden.
⁸ Department of Translational Sciences and Pharmacokinetics, Rottapharm Biotech, Monza, Italy.

PMID: 25952342
PMCID: PMC4430113
DOI: 10.1016/j.joca.2015.03.002

Abstract

The objective of this work was to describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from both academia and industry, convened to discuss issues related to soluble biomarkers and to make recommendations for their use in OA clinical trials based on current knowledge and anticipated benefits. This document summarizes current guidance on use of biomarkers in OA clinical trials and their utility at five stages, including preclinical development and phase I to phase IV trials. As demonstrated by this summary, biomarkers can provide value at all stages of therapeutics development. When resources permit, we recommend collection of biospecimens in all OA clinical trials for a wide variety of reasons but in particular, to determine whether biomarkers are useful in identifying those individuals most likely to receive clinically important benefits from an intervention; and to determine whether biomarkers are useful for identifying individuals at earlier stages of OA in order to institute treatment at a time more amenable to disease modification.

Keywords: Biomarkers; Clinical trials; Guidelines; Osteoarthritis.

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Figures

**Figure 1. The qualification process for Drug Development Tools (DDTs)**
This schematic is based on a 2014 FDA guidance document related to the biomarker qualification process[7]. Since 2008, 4 submitters have been granted qualified biomarker status from the FDA for biomarkers related to nephrotoxicity, cardiotoxicity and lung infection with aspergillosis. Draft guidance and supporting information on these qualified biomarkers can be found listed at the FDA website on the Biomarker Qualification Program (http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugDevelopmentToolsQualificationProgram/ucm284076.htm). CDER=the Center for Drug Evaluation and Research; DDT=Drug Development Tool; QRT=Qualification Review Team; FDA=United States Food and Drug Administration

See this image and copyright information in PMC

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References

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OARSI Clinical Trials Recommendations: Soluble biomarker assessments in clinical trials in osteoarthritis

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