Comparative Effectiveness and Safety of Osteoporosis Drug Therapies

骨质疏松症药物治疗的有效性和安全性比较

• 批准号: 10700169
• 负责人: Juan P Brito Campana
• 金额: $ 53.05万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10700169
• 关键词: Address; Adherence; Admission activity; Adult; Adverse effects; Advisory Committees; American; Anabolic Agents; Biometry; Black Populations; Bone necrosis; Caring; Cessation of life; Complement; Data; Data Set; Deductibles; Effectiveness; Electronic Health Record; Endocrinology; Ensure; Equity; Evaluation; Exclusion; Fee-for-Service Plans; Femoral Fractures; Fracture; Future; Gender; Geography; Glucocorticoids; Goals; Health; Health Services Research; Health system; Heterogeneity; Hip Fractures; Hispanic Populations; Holidays; Hospitalization; Human; Impairment; Interruption; Jaw; Knowledge; Link; Medical; Medical Care Costs; Medicare; Methods; Minerals; Modality; Nursing Homes; Observational Study; Office Visits; Osteoporosis; Outcome; Pain; Patient Care; Patient-Centered Care; Patients; Persons; Pharmaceutical Preparations; Pharmacotherapy; Population; Prevention; Privatization; Quality of life; Randomized, Controlled Trials; Recommendation; Recording of previous events; Regimen; Research; Risk; Risk Reduction; Safety; Sampling; Series; Societies; Spinal Fractures; Steroids; Subgroup; Time; Translating; Translational Research; Translations; Underrepresented Populations; Update; Woman; Work; aging population; beneficiary; bisphosphonate; bone; comparative effectiveness; comparative safety; compare effectiveness; cost; data warehouse; disability; economic impact; evidence base; experience; field study; fracture risk; fragility fracture; health plan; high risk; high risk population; improved; insurance plan; men; mortality; multidisciplinary; osteoporosis with pathological fracture; patient oriented; premature; prevent; primary care practice; primary outcome; randomized trial; secondary outcome; shared decision making; side effect; stem; therapy duration; tool; treatment effect; treatment strategy; trial comparing; uptake; wrist fracture

PROJECT SUMMARY Osteoporotic fractures threaten the health, independence, and survival of millions of people nationwide. An estimated 40% of women and 30% of men will suffer a hip, spine, or wrist fracture in their lifetime. Two million Americans experience a fracture annually, resulting in more than 430,000 hospital admissions, 2.5 million medical office visits, and 180,000 nursing home admissions. Due in part to an aging population, the cost of osteoporotic fracture-related care will exceed $25 billion by 2025. This suffering and cost is preventable. Large randomized controlled trials (RCT) have demonstrated the substantial benefit of osteoporosis drug therapies (ODT) in reducing the risk of osteoporotic fractures. Yet, fewer than 50-80% of patients at risk of fracture will receive ODT and half will discontinue them prematurely. Underuse of, and poor adherence to, ODTs stems in part from the lack of evidence about the effectiveness and safety long-term use of anti-resorptive ODT (i.e., bisphosphonates and denosumab), particularly with respect to rare side effects such as atypical femur fracture (AFF) and osteonecrosis of the jaw (ONJ). While interruption of long-term ODT (‘drug holiday’) and use of sequential therapies (i.e., anabolic ODT followed by anti-resorptive ODT) have been proposed as ways to limit risks of AFF and ONJ, it remains unknown whether these strategies actually reduce risk of harm without compromising ODT effectiveness with respect to fracture prevention. We will address these knowledge gaps by emulating a series of target RCTs examining the comparative effectiveness and safety of ODT regimens with respect to fragility fractures (primary outcome), AFF, ONJ, and other safety endpoints. We will use claims and electronic health record data from OptumLabs Data Warehouse, a dataset of privately-insured and Medicare Advantage beneficiaries, linked to a 100% sample of Medicare fee-for-service claims, to allow for an unprecedented evaluation of ODT over time and across populations, geographies, health systems, and health plans. We will emulate the following target RCTs (eRCTs): Aim 1) eRCT 1 comparing ≤3 years vs. >3 years non- interrupted anti-resorptive therapy. Aim 2) eRCT 2 comparing non-interrupted long-term biphosphonate ODT (>3 years) vs. short-term (≤3 years) ODT followed by either brief (≤3 years) or prolonged (>3 years) drug holiday. Aim 3) eRCT 3 comparing sequential therapy with anabolic ODT followed by >3 years bisphosphonate vs. denosumab treatment. Within each eRCT, we will assess for heterogeneity of treatment effects as a function of gender and risk profile (e.g. steroid use, etc). Finally, to address the gaps in translation of evidence to patient care decisions, Aim 4 will update and field test an effective but outdated shared decision-making tool (Osteoporosis Choice) with data produced by Aims 1-3. At the conclusion of this work, we will generate both the evidence to inform high quality osteoporosis care and a ready-to-use shared decision-making tool to support the implementation of this evidence into practice to improve the health of patients with osteoporosis.

项目总结 骨质疏松性骨折威胁着全国数百万人的健康、独立和生存。一个 据估计，40%的女性和30%的男性在有生之年会遭受髋部、脊柱或手腕骨折的痛苦。两百万 美国人每年都会经历骨折，导致超过43万人入院，250万人 医务室就诊和18万次疗养院入院。部分由于人口老龄化， 到2025年，骨质疏松性骨折相关护理将超过250亿美元。这种痛苦和代价是可以预防的。大型 随机对照试验(RCT)已经证明了骨质疏松症药物治疗的实质性益处。 (ODT)在降低骨质疏松性骨折风险方面的作用。然而，只有不到50%-80%的有骨折风险的患者会 接受ODT的人中有一半会过早地停止使用。ODTS使用不足和依从性差的根源在于 部分原因是缺乏关于长期使用抗吸收ODT的有效性和安全性的证据(即， 双磷酸盐和迪诺单抗)，特别是对于罕见的副作用，如不典型的股骨骨折 (AFF)和颌骨骨坏死(ONJ)。同时中断长期服药时间(“药物假期”)和使用 序贯疗法(即，合成代谢ODT后抗吸收ODT)已被提出作为限制 关于AFF和ONJ的风险，目前尚不清楚这些策略是否真的在没有 在预防骨折方面影响ODT的有效性。我们将通过以下方式解决这些知识差距 模拟一系列靶向RCT检查ODT方案的有效性和安全性 关于脆性骨折(主要结果)、AFF、ONJ和其他安全终点。我们将使用声明和 来自OptomLabs Data Warehouse的电子健康记录数据，这是私人保险和联邦医疗保险的数据集 优势受益人，链接到100%的联邦医疗保险服务收费索赔样本，以允许 随着时间的推移，以及跨人群、地理位置、卫生系统和健康状况，对ODT进行了前所未有的评估 计划。我们将模拟以下目标RCT(ERCT)：目标1)eRCT 1将≤3年与非3年进行比较 中断的抗吸收治疗。目的2)eRCT 2比较无间断长期双膦酸盐ODT (&gt；3年)与短期(≤3年)服药，然后是短暂的(≤3年)或延长(&gt；3年)的药物假期。 目的3)ERCT 3比较合成代谢ODT后&gt序贯治疗3年双磷酸盐与。 地诺单抗治疗。在每个eRCT中，我们将评估作为以下函数的治疗效果的异质性 性别和风险概况(例如类固醇的使用等)。最后，解决证据向患者翻译方面的差距 护理决策，Aim 4将更新和现场测试一个有效但过时的共享决策工具 (骨质疏松症选择)与AIMS 1-3提供的数据。在这项工作结束时，我们将生成 为高质量的骨质疏松症护理提供信息的证据和现成的共享决策工具 将这一证据落实到实践中，改善骨质疏松症患者的健康。