Effectiveness of DiscontinuinG bisphosphonatEs Study (EDGE)

描述(申请人提供)：来自双膦酸盐长期延长试验的数据表明，对于某些类型的骨折，较短期的双膦酸盐可能相当于较长期的治疗，而且这些药物的长期使用已经出现了安全问题，特别是颌骨的骨坏死和不典型的股骨骨折。过去的研究对骨折和安全结果的样本量不足，对社区复杂患者的推广能力非常有限。为了解决这些明显的骨质疏松症证据缺口，我们建议为一项名为停止双磷酸盐(EDGE)研究的有效性的务实临床试验(PCT)提供规划拨款。EDGE将是一项“现实世界”的有效性试验，最初估计有4100名患者被随机分为继续或停止先前的阿仑磷酸钠治疗。这笔计划拨款的具体目标是：1)与联邦医疗保险联合大型简单临床试验扩展网络(MASIC)项目下设立的全国骨质疏松症、临床试验和社区研究专家咨询小组合作，以：a)敲定关于研究人群、招募计划、主要和次要结果、数据收集/分析计划的EDGE研究方案，以及b)制定程序手册和其他研究文件；2)建立与联邦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，在登记时接受过3年阿伦磷酸钠治疗的绝经后妇女中，与随机接受阿伦磷酸钠治疗的妇女(对照组)相比，在随机停止治疗的妇女(干预组)中，在登记后的3年内非脊椎骨折风险的降低不是次要的。UAB及其合作者在利用联邦医疗保险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，我们将与初级保健和专业保健网络合作，包括国家研究网络(NRN)，该网络累计代表近10,000个提供者和1000多万患者。我们将利用一支预先组建的专家顾问团队，并扩展我们的开发系统，以便在PCTS中轻松招生和监督研究科目。有了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.