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Considerations for Development of Surrogate Endpoints for Antifracture Efficacy of New Treatments in Osteoporosis: A Perspective
Author(s) -
Bouxsein Mary L,
Delmas Pierre D
Publication year - 2008
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.080301
Subject(s) - surrogate endpoint , clinical trial , medicine , osteoporosis , clinical endpoint , biomarker , drug development , clinical study design , intensive care medicine , placebo , physical therapy , risk analysis (engineering) , alternative medicine , pathology , drug , pharmacology , biochemistry , chemistry
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.