Benefits and Harms of Long-term Osteoporosis Pharmacotherapy: Impact of Treatment Length, Type, Switching, and Holidays

长期骨质疏松症药物治疗的好处和坏处：治疗长度、类型、转换和假期的影响

基本信息

批准号：
10515946
负责人：
Suzanne Cadarette
金额：
$ 63.7万
依托单位：
BROWN UNIVERSITY
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 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10515946
关键词：
Address Adherence Adverse event Age Alendronate Algorithms Benefits and Risks Canada Cessation of life Characteristics Clinical Clinical Trials Clinical assessments Communities Data Data Set Data Sources Decision Making Drug usage Educational workshop Elderly Electronic Health Record Exposure to Femoral Fractures Forteo Fracture Future Geographic Locations Goals Guidelines Harm Reduction Health Healthcare Hip Fractures Holidays Individual International Joints Knowledge Length Life Expectancy Link Long-Term Effects Longitudinal Studies Medicare Medicare claim Methods Modeling National Institute on Aging Nursing Homes Ontario Oral Osteoporosis Outcome Pain Pathway interactions Patient risk Patient-Focused Outcomes Patients Pattern Persons Pharmaceutical Preparations Pharmacoepidemiology Pharmacotherapy Population Prevention Raloxifene Recommendation Recording of previous events Research Research Personnel Risk Subgroup System Time Woman Work Zoledronate adverse event risk aged bisphosphonate comparative data cleaning disability epidemiology study evidence base experience follow-up fracture risk frailty high risk human old age (65+)improved individualized medicine men novel osteoporosis with pathological fracture patient subsets personalized medicine prediction algorithm premature prevent randomized trial risk benefit ratio risk minimization risk prediction model secondary analysis sex side effect study population therapy duration treatment strategy

项目摘要

Project Summary Sixty percent of older adults who start osteoporosis drug therapy (ODT) with an oral bisphosphonate (BP) have long-term exposure (3 or more years with 80% or higher adherence). Although a minimum of 6 to 12 months of BP treatment is required to reduce fracture risk, BPs have extended half-lives and can provide benefits long after discontinuation. Clinical trials have identified little difference in fracture risk for women who stopped versus continued BP after 3 to 5 years. Further, prolonged BP use has been linked to adverse events like atypical femoral fracture (AFF). Thus, guidelines recommend a drug holiday (pause in therapy) for most patients after 3 to 5 years of BP use. Patients at high fracture risk are recommended to continue BP or switch to another ODT, like denosumab, teriparatide, abaloparatide, or raloxifene. Several critical gaps in knowledge exist about the risks and benefits of long-term BP use, drug holidays, ODT switching on clinical outcomes and adverse events, particularly in groups with limited representation in trials like men and nursing home (NH) residents. This proposal has three specific aims: (1) Among community-dwelling older adults with at least 3 years of BP use, examine the effects of BP drug holidays and ODT switching on fractures, fracture sequelae (e.g., death, entry into NH), and AFF. (2) Among NH residents with at least 3 years of ODT, compare the effects of discontinuing versus continuing ODT on fractures/sequelae and patient-centered outcomes (e.g., functioning, pain); and (3) Develop and validate clinical prediction algorithms for osteoporotic fracture and AFF to guide clinicians making decisions on whether to initiate a drug holiday. Our central hypothesis is that the effects of long-term ODT strategies will be dependent on treatment length, type, and patient characteristics. The rigorous studies we propose will use multinational linked administrative and clinical datasets. The study population will comprise older adults aged 66 years or older in the US and Ontario, Canada who have at least 3 years of long-term ODT. Data for this study will come from 1) Linked, universal healthcare and medication claims data for all people (community-dwelling and NH) aged ≥65 years in Ontario; 2) U.S. Medicare claims on community-dwelling older adults; and 3) Electronic health record (EHR) data for up to 10,000 NHs linked to Medicare claims. We will implement a validated data cleaning algorithm for osteoporosis medication claims and novel rolling window method to capture long-term ODT. Time-varying propensity score approaches and novel causal inference methods like target trial emulation will be employed. This project will generate critical, generalizable evidence to guide long-term ODT, prevent fractures, and minimize AFF among older adults. This research will directly address RFA-AG-22-018, the Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention Pathways to Prevention Workshop Panel Recommendations 1 and 4, and Strategic Goal C of the National Institute on Aging. Additionally, the project will create an international data partnership to leverage EHR and universal healthcare data to answer emerging research questions on ODT.

项目摘要 60％的老年人开始用口服双膦酸盐（BP）开始骨质疏松药物治疗（ODT）长期暴露（3岁或更高的依从性，有80％或更高）。虽然至少6到12个月 BP治疗需要降低骨折风险，BP具有延长的半衰期，可以提供长时间的福利停产后。临床试验发现停止的妇女骨折风险几乎没有差异在3至5年后与BP相比。此外，长期使用的BP使用已与广告活动相关联非典型股骨骨折（AFF）。这，指南建议大多数药物假期（治疗停顿） BP使用3至5年后的患者。建议使用高骨折风险的患者继续BP或开关知识的几个关键差距存在长期使用BP的风险和益处，药物假期，ODT开发临床结果和不良事件，特别是在男性和护士之家（NH）等试验中代表有限的团体中居民。该提议具有三个具体的目标：（1）在社区居住的老年人中至少有3个 BP使用多年，检查BP药物假期和ODT开关对断裂，骨折后遗症的影响（例如，死亡，进入NH）和AFF。（2）在至少3年ODT的NH居民中，比较中断与持续ODT对骨折/后遗症和以患者为中心的结果的影响（例如，功能，疼痛）；（3）开发和验证骨质疏松骨折和AFF的临床预测算法指导临床医生做出决定是否启动毒品假期的决定。我们的核心假设是长期ODT策略的影响将取决于治疗长度，类型和患者特征。我们提出的严格研究将使用跨国链接的行政和临床数据集。研究在美国和加拿大安大略省，人口将完成66岁以上的老年人长期ODT 3年。这项研究的数据将来自1）链接，通用医疗保健和药物为安大略省≥65岁的所有人（社区居民和NH）索赔数据； 2）美国医疗保险提出的要求居住在社区的老年人； 3）多达10,000 NHS的电子健康记录（EHR）数据 Medicare主张。我们将针对骨质疏松药物主张实施经过验证的数据清洁算法和新颖的滚动窗户方法以捕获长期ODT。随时间变化的改进得分方法和将聘请新的因果推理方法（例如目标试验仿真）。这个项目将产生关键，可概括的证据指导长期ODT，预防骨折并最大程度地减少老年人的影响。这研究将直接解决RFA-AG-22-018（适当使用药物疗法骨质疏松剂）预防研讨会小组建议1和4的裂缝预防途径和战略目标国家老化研究所的C。此外，该项目将建立国际数据合作伙伴关系利用EHR和通用医疗保健数据回答有关ODT的新兴研究问题。