The authors state that they have no conflicts of interest.
Article first published online: 3 MAR 2008
Copyright © 2008 ASBMR
Journal of Bone and Mineral Research
Volume 23, Issue 8, pages 1155–1167, August 2008
How to Cite
Bouxsein, M. L. and Delmas, P. D. (2008), Considerations for Development of Surrogate Endpoints for Antifracture Efficacy of New Treatments in Osteoporosis: A Perspective. J Bone Miner Res, 23: 1155–1167. doi: 10.1359/jbmr.080301
Published online on March 3, 2008;
- Issue published online: 4 DEC 2009
- Article first published online: 3 MAR 2008
- Manuscript Accepted: 26 FEB 2008
- Manuscript Revised: 18 FEB 2008
- Manuscript Received: 12 DEC 2007
- surrogate endpoint;
- clinical trial;
Because of the broad availability of efficacious osteoporosis therapies, conduct of placebo-controlled trials in subjects at high risk for fracture is becoming increasing difficult. Alternative trial designs include placebo-controlled trials in patients at low risk for fracture or active comparator studies, both of which would require enormous sample sizes and associated financial resources. Another more attractive alternative is to develop and validate surrogate endpoints for fracture. In this perspective, we review the concept of surrogate endpoints as it has been developed in other fields of medicine and discuss how it could be applied in clinical trials of osteoporosis. We outline a stepwise approach and possible study designs to qualify a biomarker as a surrogate endpoint in osteoporosis and review the existing data for several potential surrogate endpoints to assess their success in meeting the proposed criteria. Finally, we suggest a research agenda needed to advance the development of biomarkers as surrogate endpoints for fracture in osteoporosis trials. To ensure optimal development and best use of biomarkers to accelerate drug development, continuous dialog among the health professionals, industry, and regulators is of paramount importance.