Silverman Stuart L, Cummings Steven R, Watts Nelson B
Division of Rheumatology, Cedars-Sinai Medical Center and the David Geffen School of Medicine, University of California, Los Angeles, California, USA.
J Bone Miner Res. 2008 Jan;23(1):159-65. doi: 10.1359/jbmr.070905.
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.
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.
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.
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.
一个由美国骨与矿物质研究学会（ASBMR）、美国国家骨质疏松基金会（NOF）和国际临床骨密度测量学会（ISCD）的专家组成的小组审查了证据，并达成共识：骨质疏松症治疗方法的监管批准应基于以骨折为终点的试验，试验持续18 - 24个月，并将治疗延长至5年；其他适应症可根据骨密度和骨转换标志物批准。
应美国食品药品监督管理局（FDA）对骨质疏松症临床试验指南的要求，召集了一个专家小组，成员包括美国骨与矿物质研究学会、国际临床骨密度测量学会和美国国家骨质疏松基金会的代表。
该小组采用经过验证的基于证据的专家小组程序（兰德适宜性方法）来解决试验持续时间、试验设计、使用中间终点作为结果以及在高危患者中使用安慰剂对照试验等问题。
该小组得出结论，以骨折为终点的安慰剂对照试验是合适的，并且在获得知情同意的情况下，对于新化合物的注册是符合伦理的。为证明疗效，试验持续时间可为18 - 24个月，假设为证明安全性和持续降低骨折风险，持续时间延长至5年。一旦确定了某一特定药物的骨折疗效，除皮质类固醇诱导的骨质疏松症外，中间终点（如骨密度和骨转换标志物）可作为新适应症的结果。
