The Osteoarthritis Initiative: Update on a NIH Public-Private Partnership

Updated April 5, 2016

Osteoarthritis (OA) affects more than 27 million individuals in the United States1. The NIH has long supported research to improve outcomes for patients with this debilitating disease. Knee OA is associated with significant pain and development of disability over time. People who are severely compromised have few effective treatment options other than joint replacement. There are differences in the prevalence, incidence and severity of OA between men and women and among races. Currently, there are no disease-modifying agents for the treatment of OA. The discovery of OA biomarkers—including structural characteristics that can be observed with MRI—could lead to identification of new treatment targets and mechanisms for shorter, more efficient trials of disease-modifying agents.

The Osteoarthritis Initiative (OAI) is a multicenter, longitudinal, prospective, observational study of knee OA that was launched by NIH in 2002. The overall aim of the OAI is to develop a public-domain research resource to facilitate the scientific evaluation of biomarkers for OA as potential surrogate endpoints for disease onset and progression. The goals of the OAI were to enroll approximately 5,000 volunteers with risk factors for early knee OA, and to collect clinical and imaging data and biological specimens from these participants for originally four, and now a total of eight years of follow up. Technical details on study start-up, protocol development, and recruitment and enrollment are available on the University of California, San Francisco, OAI website at External Web Site Policy.

Both NIH and private sector participants have contributed funding for the OAI. The private sector funding was initially provided by Pfizer, Merck, GlaxoSmithKline, and Novartis. The Foundation for the National Institutes of Health (FNIH) has coordinated private sector participation. Funding from the NIH institutes and centers initially included NIAMS, the National Institute on Aging (NIA), the National Center for Complementary and Integrative Health (NCCIH, formerly known as the National Center for Complementary and Alternative Medicine), the National Institute on Minority Health and Health Disparities (NIMHD), the National Institute of Dental and Craniofacial Research (NIDCR), the NIH Office of Research on Womens Health (ORWH), and the National Institute for Biomedical Imaging and Bioengineering (NIBIB). Financial support for the extension of follow up for the OAI cohort (additional four contacts, 2010-2014) has been provided by Pfizer and Novartis from the private sector and the NIAMS, NIA, NCCIH, NIMHD, ORWH, and NIBIB.

The OAI research team consists of the following centers and their principal investigators: University of Maryland School of Medicine, Baltimore: Marc Hochberg, M.D., M.P.H.; The Ohio State University, Columbus: Rebecca Jackson, M.D.; University of Pittsburgh: C. Kent Kwoh, M.D.; Memorial Hospital of Rhode Island, Pawtucket: Charles Eaton, M.D.; and University of California, San Francisco (data coordinating center): Michael Nevitt, Ph.D. A Steering Committee, comprised of representatives from these centers, the NIH, and the pharmaceutical partners, advises on the scientific aspects of the study. A representative from the U.S. Food and Drug Administration advises the Steering Committee.

The OAI cohort of 4,796 participants is 58% female and ranged in age from 45-79 at time of recruitment. Retention remained high throughout the study duration. Some participants (about 7%) from the original cohort did not continue for the additional four years of follow up. The rate of no-contact stabilized in the 15-18% range. The entire OAI cohort has completed baseline, 12-month, 24-month, 36-month, and 48-month visits in clinic with biospecimen collection and imaging. The 60-month and 84-month visits were conducted via mailed questionnaires and telephone interviews. The 72-month visit occurred in clinic with biospecimen collection and imaging. The 96-month visit occurred in clinic with imaging. All visits have been completed as of January 1, 2015. There are biological specimens available for baseline, 12-month, 24-month, 36-month, 48-month and the 72-month visits. A subset of participants in the progression cohort were also seen at 18 months (n=288) or 30 months (n=494) for knee MRI, blood collection, exam and questionnaire data to allow for analysis of change over shorter intervals.

Data and images have been publicly released by the University of California, San Francisco, through the OAI Online website. Data and images from all visits are currently available on the OAI website. Additional data from image and biospecimen analyses are being posted quarterly on the OAI website. As of March 23, 2016, there were 4,114 registered users of OAI Online from more than 90 countries, with over 30,260 datasets downloaded and 507 image sets distributed. To date, clinical data, images, and biospecimens (see above) are available for visits through 96 months. Over 300 manuscripts have been produced and published to date based on use of the OAI data and images (see External Web Site Policy).

In 2010, the NIAMS funded three contracts for analysis of OAI data to Dr. Charles Eaton at Memorial Hospital of Rhode Island, for "Osteoarthritis Patient-centered Outcomes and Complementary and Alternative Therapy (CAM)"; to Dr. C. Kent Kwoh at University of Pittsburgh, for "Pivotal Osteoarthritis Initiative Magnetic Resonance Imaging Analyses"; and to Dr. Michael Nevitt at University of California, San Francisco, for "Hip Morphology and Limb-specific Risk Factors for Radiographic Hip Osteoarthritis." All of these contracts have been completed. There are numerous publications from completed analyses, and more are being published yearly. New data generated from these studies are currently being posted on the OAI Online website.

This groundbreaking study is expected to advance our understanding of how modifiable and non-modifiable risk factors are linked to development and worsening of knee osteoarthritis. Such findings may, in turn, lead to improved strategies for prevention of disease and identification of novel treatment targets, which could result in prevention of later-life disability in individuals with knee osteoarthritis.

1 Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part II. Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG, Jordan JM, Katz JN, Kremers HM, Wolfe F; National Arthritis Data Workgroup. Arthritis Rheum. 2008, 58(1):26-35. doi: 10.1002/art.23176. PMID: 18163497