![Page 1: Perspectives on Clinical Outcomes of Studies of Products for Use in Cartilage Repair Marc C. Hochberg, MD, MPH Professor of Medicine Head, Division of](https://reader035.vdocuments.us/reader035/viewer/2022072010/56649dc85503460f94abd4b1/html5/thumbnails/1.jpg)
Perspectives on Clinical Outcomes of Studies of Products
for Use in Cartilage Repair
Marc C. Hochberg, MD, MPHProfessor of Medicine
Head, Division of Rheumatology
University of Maryland School of Medicine
Baltimore, MD, USA
![Page 2: Perspectives on Clinical Outcomes of Studies of Products for Use in Cartilage Repair Marc C. Hochberg, MD, MPH Professor of Medicine Head, Division of](https://reader035.vdocuments.us/reader035/viewer/2022072010/56649dc85503460f94abd4b1/html5/thumbnails/2.jpg)
Outline
FDA Guidance for Development of Products for the Treatment of OA
Newer methods for measuring symptomatic outcomes– State measures– KOOS
Newer methods for measuring structural outcomes
![Page 3: Perspectives on Clinical Outcomes of Studies of Products for Use in Cartilage Repair Marc C. Hochberg, MD, MPH Professor of Medicine Head, Division of](https://reader035.vdocuments.us/reader035/viewer/2022072010/56649dc85503460f94abd4b1/html5/thumbnails/3.jpg)
Guidance for Industry:Clinical Development Programs for Products Intended for the Treatment
of Osteoarthritis
Food and Drug Administration
July 1999
![Page 4: Perspectives on Clinical Outcomes of Studies of Products for Use in Cartilage Repair Marc C. Hochberg, MD, MPH Professor of Medicine Head, Division of](https://reader035.vdocuments.us/reader035/viewer/2022072010/56649dc85503460f94abd4b1/html5/thumbnails/4.jpg)
Potential Claims for OA
Symptomatic treatment of pain and function
Delay in structural progression Prevention of the occurrence of OA
![Page 5: Perspectives on Clinical Outcomes of Studies of Products for Use in Cartilage Repair Marc C. Hochberg, MD, MPH Professor of Medicine Head, Division of](https://reader035.vdocuments.us/reader035/viewer/2022072010/56649dc85503460f94abd4b1/html5/thumbnails/5.jpg)
Symptomatic Treatment of Pain and Function Efficacy endpoints as specified in OARSI
Recommendations and at OMERACT 3– Pain and function should be disaggregated– Patient global assessment– Measurement of structure (x-ray) if trial lasts a
year or more for risk-benefit assessment Effects on non-signal joints and effects of
potential confounders should be standardized in protocol and analysis
![Page 6: Perspectives on Clinical Outcomes of Studies of Products for Use in Cartilage Repair Marc C. Hochberg, MD, MPH Professor of Medicine Head, Division of](https://reader035.vdocuments.us/reader035/viewer/2022072010/56649dc85503460f94abd4b1/html5/thumbnails/6.jpg)
Prevention of Occurrence of OA
Defined as incident symptomatic OA using clinical and radiographic criteria– Additional joints in patients with prevalent
OA– New joints in persons at risk for OA
![Page 7: Perspectives on Clinical Outcomes of Studies of Products for Use in Cartilage Repair Marc C. Hochberg, MD, MPH Professor of Medicine Head, Division of](https://reader035.vdocuments.us/reader035/viewer/2022072010/56649dc85503460f94abd4b1/html5/thumbnails/7.jpg)
Measurement of clinical outcomes WOMAC Osteoarthritis Index Lequesne Algofunctional Index
– GREES: Ann Rheum Dis 1996;55:552-7.
– Altman et al: OA Cart 1996;4:217-26.
– Bellamy et al: J Rheumatol 1997;24:799-802.
![Page 8: Perspectives on Clinical Outcomes of Studies of Products for Use in Cartilage Repair Marc C. Hochberg, MD, MPH Professor of Medicine Head, Division of](https://reader035.vdocuments.us/reader035/viewer/2022072010/56649dc85503460f94abd4b1/html5/thumbnails/8.jpg)
State Measures - 1
OARSI Responder Criteria– Dougados et al: Osteoarthritis Cart
2000;8:395-403.
![Page 9: Perspectives on Clinical Outcomes of Studies of Products for Use in Cartilage Repair Marc C. Hochberg, MD, MPH Professor of Medicine Head, Division of](https://reader035.vdocuments.us/reader035/viewer/2022072010/56649dc85503460f94abd4b1/html5/thumbnails/9.jpg)
Dougados et al: Osteoarthritis Cart 2000;8:395-403.
OARSI Response Criteria
Derived from analysis of data from 14 clinical trials of 1886 patients with either hip or knee OA– Randomized, double-blind, placebo-
controlled parallel group trials– Variety of interventions
• Oral NSAIDs• Oral and IA OA specific drugs
![Page 10: Perspectives on Clinical Outcomes of Studies of Products for Use in Cartilage Repair Marc C. Hochberg, MD, MPH Professor of Medicine Head, Division of](https://reader035.vdocuments.us/reader035/viewer/2022072010/56649dc85503460f94abd4b1/html5/thumbnails/10.jpg)
OARSI Response Criteria
Two sets of criteria (Propositions A and B) Optimal cut-points differed by proposition, joint group,
type of intervention, and “high” or “moderate” improvement
Requirement for both absolute and percent change Limitations
– 62% of screened studies not included
– Lack of simplicity
– Increase in precision questionable
– Not validated in other datasets
![Page 11: Perspectives on Clinical Outcomes of Studies of Products for Use in Cartilage Repair Marc C. Hochberg, MD, MPH Professor of Medicine Head, Division of](https://reader035.vdocuments.us/reader035/viewer/2022072010/56649dc85503460f94abd4b1/html5/thumbnails/11.jpg)
State Measures - 1
OARSI Responder Criteria– Dougados et al: Osteoarthritis Cart
2000;8:395-403. OMERACT-OARSI Responder Index
– Pham T et al: J Rheumatol 2003;30:1648-54
![Page 12: Perspectives on Clinical Outcomes of Studies of Products for Use in Cartilage Repair Marc C. Hochberg, MD, MPH Professor of Medicine Head, Division of](https://reader035.vdocuments.us/reader035/viewer/2022072010/56649dc85503460f94abd4b1/html5/thumbnails/12.jpg)
OMERACT-OARSI Responder Index Objective: Development of a simplified set of
criteria Procedure: Compare performance of 6 different
scenarios using two databases– Original database (14 studies with 1886 patients)
– Revisit database (15 studies with 8164 patients) Expert opinion approach applied to results at
OMERACT 6 meeting
![Page 13: Perspectives on Clinical Outcomes of Studies of Products for Use in Cartilage Repair Marc C. Hochberg, MD, MPH Professor of Medicine Head, Division of](https://reader035.vdocuments.us/reader035/viewer/2022072010/56649dc85503460f94abd4b1/html5/thumbnails/13.jpg)
High improvement in pain or function > 50% and absolute change > 20
Responder
Yes No
Improvement in > 2 of the following 3
• Pain > 20% with absolute change > 10
• Function > 20% and absolute change > 10
• PGA > 20% and absolute change > 10
Responder Non-responder
Yes No
Pham T et al: J Rheumatol 2003;30:1648-54
OMERACT-OARSI Responder Index
![Page 14: Perspectives on Clinical Outcomes of Studies of Products for Use in Cartilage Repair Marc C. Hochberg, MD, MPH Professor of Medicine Head, Division of](https://reader035.vdocuments.us/reader035/viewer/2022072010/56649dc85503460f94abd4b1/html5/thumbnails/14.jpg)
Thank you for your time and attention.