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

基本信息

批准号：
10514723
负责人：
Juan P Brito Campana
金额：
$ 53.16万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
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/10514723
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 Evaluation 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 Lead Link Medical Medical Care Costs Medicare Methods Minerals Modality Nursing Homes Observational Study Office Visits Osteoporosis Osteoporosis prevention Outcome Pain Patient Care Patient-Centered Care Patients Persons Pharmaceutical Preparations Pharmacotherapy Population Prevention Primary Health Care Privatization Quality of life Randomized Controlled Trials Recommendation Recording of previous events Regimen Research Risk 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 outcome randomized trial secondary outcome shared decision making side effect stem therapy duration tool treatment effect treatment strategy trial comparing uptake wrist fracture

项目摘要

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.

项目摘要骨质疏松骨折威胁着全国数百万人的健康，独立性和生存。一个估计有40％的女性和30％的男性在其一生中会遭受臀部，脊柱或腕部骨折。两百万美国人每年经历骨折，导致430,000多个住院，250万医疗办公室访问和180,000名护士家庭入院。部分原因是人口老龄化的成本到2025年，与骨质疏松性骨折有关的护理将超过250亿美元。这是可预防的痛苦和成本。大的随机对照试验（RCT）证明了骨质疏松剂疗法的实质性好处（ODT）降低骨质疏松骨折的风险。然而，只有不到50-80％的骨折风险患者将接收ODT，一半将过早停止它们。 ODT踏入不足和依从性不足部分原因是缺乏有关反应性ODT的有效性和安全性长期使用的证据（即双膦酸盐和denosumab），特别是关于罕见的副作用，例如非典型股骨骨折（AFF）和颌骨（ONJ）。而长期ODT（“毒品假期”）中断并使用已经提出了顺序疗法（即合成代谢ODT，然后是反敏化ODT）作为限制的方法 AFF和ONJ的风险，这些策略是否真的降低了伤害的风险，没有损害预防断裂的ODT有效性。我们将通过模拟一系列目标RCT，以检查ODT方案的比较有效性和安全性尊重脆弱片段（主要结果），AFF，ONJ和其他安全终点。我们将使用索赔和来自optumlabs数据仓库的电子健康记录数据，这是一个私人保险和医疗保险的数据集优势受益人与100％的医疗保险费用索赔相关，以允许随着时间的推移以及人口，地理，卫生系统和卫生的空前评估ODT的空前评估计划。我们将模拟以下目标RCT（ERCT）：AIM 1）ERCT 1比较≤3年与> 3年非 - 中断的抗热疗法。 AIM 2）ERCT 2比较非中断的长期双磷酸ODT （> 3年）与短期（≤3年）ODT，然后是短暂（≤3岁）或延长（> 3年）药物假期。 AIM 3）ERCT 3将顺序治疗与合成代谢ODT进行比较，然后进行> 3年的双膦酸盐与。 Denosumab治疗。在每个ERCT中，我们将评估治疗效应的异质性性别和风险特征（例如类固醇使用等）。最后，解决将证据转换给患者的差距护理决策，AIM 4将更新和现场测试有效但过时的共享决策工具（骨质疏松症的选择），其数据由AIM 1-3产生。在这项工作结束时，我们将同时生成提供高质量骨质疏松症护理的证据，并提供了共同使用的共享决策工具，以支持实践将此证据实施，以改善骨质疏松症患者的健康状况。