Recommendations for the clinical evaluation of agents for treatment of osteoporosis: consensus of an expert panel representing the American Society for Bone and Mineral Research (ASBMR), the International Society for Clinical Densitometry (ISCD), and the National Osteoporosis Foundation (NOF).
A panel of experts representing ASBMR, NOF, and ISCD reviewed evidence and reached consensus that regulatory approval of treatments for osteoporosis should be based on trials with fracture endpoints, lasting 18-24 mo, and extending treatment to 5 yr; other indications could be approved based on BMD and turnover markers.


BACKGROUND
In response to an FDA request for clinical trial guidance in osteoporosis, an expert panel was convened with representatives from the American Society of Bone and Mineral Research, the International Society of Clinical Densitometry, and the National Osteoporosis Foundation.


METHODS
The panel used a validated evidence-based expert panel process (the Rand Appropriateness Method) to address issues of trial duration, trial design, use of intermediate endpoints as outcomes, and use of placebo-controlled trials in high-risk patients.


CONCLUSIONS
The panel concluded that placebo-controlled trials with fracture endpoints are appropriate and, with informed consent, are ethical for registration of new compounds. Trials may be 18-24 mo in duration for efficacy, assuming longer duration to 5 yr for safety and demonstration of sustained fracture reduction. Once fracture efficacy has been established for a particular agent, intermediate endpoints (e.g., BMD and bone turnover markers) may be used as outcomes for new indications other than corticosteroid-induced osteoporosis.
Silverman
Stuart L
SL
Division of Rheumatology, Cedars-Sinai Medical Center and the David Geffen School of Medicine, University of California, Los Angeles, California, USA. stuarts@omcresearch.org
Cummings
Steven R
SR
Watts
Nelson B
NB
D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods*; D004341:Drug Evaluation / Q000379:methods; D050723:Fractures, Bone / Q000209:etiology; D006801:Humans; D007258:Informed Consent; D010024:Osteoporosis / Q000188:drug therapy*; D010919:Placebos; D012306:Risk; D012955:Societies, Medical
D050071:Bone Density Conservation Agents; D010919:Placebos