Osteoarthritis Initiative

June 24, 1999 (historical)

OA Biochemical Biomarkers Subcommittee Discussions Summary

Attendees:

Thasia Woodworth, chair (Pfizer)
Bernadette Tyree (National Institute of Arthritis and Musculoskeletal and Skin Diseases)
David Eyre (University of Washington)
Kenneth Gruber (National Institute of Dental and Craniofacial Research)
Zeb Horowitz (Novartis)
Michael Lark (SmithKline Beecham)
Ruth Raiss (Hoechst AG (Germany))
Stephen Myers (Eli Lilly)
Yetunde Taiwo (Proctor & Gamble)
Robin Poole (McGill University)
Linda Sandell (Washington University)1
Jean-Claude Becker (Bristol-Myers Squibb)
_____________
1representing the Orthopaedic Research Society

Goals:

  • Long Term: To enhance the "clinical do-ability" of OA clinical trials, enabling expeditious identification of novel, disability-preventing treatments

  • Medium Term: To gain acceptance of identified markers as surrogate for OA status and improvement, or slowing of progression

  • Short Term: Establish a comprehensive understanding of available and candidate biochemical markers

    • Characterization of patients with measurably progressing OA, able to detect change < 1 year

    • Assays: validated methodology, reference standards

    • Facilitate recognition of validated clinical use (specimen archives with clinical data, comparisons among markers)

Actions for committee:

  • Submit* description of marker(s) which you believe may qualify to become surrogate"

    • Assay method, availability of reference standard, publications, list of needs for clinical validation

  • Suggest speakers for "Winter Meeting" - see list below *Submission: email: thasia_g_woodworth@groton.pfizer.com

Biochemical marker opportunities:

  • Characterize Patient Populations - "diagnostic" (med./Long term), monitoring need for therapy, effect of therapy, safety

  • Correlate with clinically relevant outcomes:

    • Pain

    • Disability - Health Economics

    • Function

    • Joint replacement

    • Maintenance of Structure (surrogate for function - how much better on treatment???)

Mechanisms for marker assessment:

  • Study design - specific patient subsets with CLINICAL DATABASE

    • Sample achives: Biofluids = serum/plasma

      • Urine

      • WBC/DNA

      • Synovial fluid

    • Associate with clinical data /outcomes, safety

    • Synchronize (collect archive samples anonymously) in clinical trials?

    • Relate to short, intermediate, and long-term outcomes, especially disability

Issues of concern:

  • Conditions of access

  • Confidentiality / Informed consent "Anonymous" databases

  • Proprietary concerns

  • Patents

  • Cost

  • Diagnosis, assessing progression

  • Which markers to assay?

  • Biochemical, genetic

  • Distinguish mechanism of agent from (measuring cartilage status)

  • Safety markers?

  • Patterns - bone, cartilage (degradation/synthesis)

  • Disease status

  • Pt. Management

Process:

Establish baseline: "OA Clinical Paradigms" - post-injury, genetic, degenerative, combinations

  • Define disease - where can we intervene with therapy?

  • Clinical end points to be measured

  • Critically evaluate current info.

  • Candidate markers - current available

  • Patient Populations

  • Current longitudinal studies

  • Guidance for future studies

  • Cross-sectional and longitudinal studies

  • Education - including the public

  • Hypotheses generated - priorities for current archives

Standards for collection, storage

  • Clinical data

  • Database acquisition

  • Structure for prospective

  • Methodology for samples - storage/cataloguing

  • Assay standards

  • Control population?

  • Recognize comorbidities