Effectiveness of DiscontinuinG bisphosphonatEs Study (EDGE)

描述（由申请人提供）：来自双膦酸盐长期扩展试验的数据表明，对于某些类型的骨折，短期双膦酸盐可能等同于长期治疗，并且已经出现了关于长期使用这些药物的安全性问题，特别是颌骨骨坏死和非典型股骨骨折。过去的研究对于骨折和安全性结局的样本量不足，并且对于社区中复杂患者的普遍性非常有限。为了解决这些相当大的骨质疏松症的证据差距，我们提出了一个实用的临床试验（PCT）的计划补助金名为中止G双磷酸盐（EDGE）研究的有效性。EDGE将是一项“真实的世界”有效性试验，最初估计有4100名患者随机接受继续或停止既往阿仑膦酸钠治疗。这项计划拨款的具体目的是：1）与国家骨质疏松症，临床试验和社区研究专家咨询小组合作，该小组是在医疗保险联合大型简单临床试验扩展网络（MUSCLE）项目下建立的：a）最终确定EDGE研究方案，包括研究人群、招募计划、主要和次要结局、数据收集/分析计划，和B）制定程序手册和其他研究文件; 2）建立医疗保险数据和国家死亡指数（NDI）的有效联系，以便对参与者进行长期监测。EDGE试验中要检验的主要假设是，在入组时已接受3年既往阿仑膦酸钠治疗的绝经后女性中，随机停止治疗的女性（干预组）在入组后3年内的非椎骨骨折风险降低与随机继续阿仑膦酸钠治疗的女性（对照组）相比无差异。UAB及其合作者在利用Medicare索赔和其他大型数据库进行多站点研究方面具有丰富的专业知识。在EDGE，我们将与包括国家研究网络（NRN）在内的初级保健和专业医疗保健网络合作，该网络累计代表近10，000家提供商和1000多万患者。我们将利用一个预先组建的专家顾问团队，并扩大我们的开发系统，以方便PCT研究受试者的招募和监测。通过关联的医疗保险索赔和药房数据，EDGE将以相当低的成本满足大型骨质疏松症有效性研究的主要需求。

DESCRIPTION (provided by applicant): Data from bisphosphonate long-term extension trials suggest that shorter term bisphosphonates may be equivalent to longer-term therapy for certain fractures types, and safety concerns have emerged about longer-term use of these agents, particularly osteonecrosis of the jaw and atypical femur fractures. Past studies had insufficient sample sizes for fracture and safety outcomes and very limited generalizability to complex patients in the community. To address these considerable osteoporosis evidence gaps, we propose a planning grant for a Pragmatic Clinical Trial (PCT) entitled the Effectiveness of DiscontinuinG bisphosphonatEs (EDGE) Study. EDGE will be a "real world" effectiveness trial of an initially estimated 4100 patients randomized to continuation or discontinuation of prior alendronate therapy. The specific aims of this planning grant are: 1) To collaborate with an advisory group of national osteoporosis, clinical trial, and community research experts established under the Medicare United with large Simple CLinical Trials Expanded network (MUSCLE) project to: a) finalize the EDGE study protocol with respect to the study population, recruitment plan, primary and secondary outcomes, data collection/analysis plan, and b) develop a manual of procedures and other study documents; 2) To develop effective linkages to Medicare data and the National Death Index (NDI) allowing for long-term surveillance of participants. The primary hypothesis to be tested in the EDGE trial is that among a postmenopausal women who have received 3 years of prior alendronate therapy at the time of enrollment non-vertebral fracture risk reduction in the 3 years following enrollment is non-inferio in women randomized to stop (intervention arm) compared to women randomized to continue alendronate therapy (comparator arm). UAB and its collaborators bring substantial expertise in conducting multi-site studies with Medicare claims and other large databases. In EDGE, we will partner with primary care and specialty health care networks, including the National Research Network (NRN), which cumulatively represent close to 10,000 providers and more than 10 million patients. We will draw on a preassembled team of expert advisors and expand our developing system for easy enrollment and surveillance of study subjects in PCTs. With linked Medicare claims and pharmacy data, EDGE will fill a major need for large osteoporosis effectiveness research at a considerably lower cost.