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：
10704180
负责人：
Suzanne Cadarette
金额：
$ 63.53万
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/10704180
关键词：
Address Adherence Adverse event Age Alendronate Algorithms Benefits and Risks Canada Cessation of life Characteristics Clinical Clinical Data 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-Focused Outcomes Patients Persons Pharmaceutical Preparations Pharmacoepidemiology Pharmacotherapy Population Prediction of Response to Therapy Prevention Raloxifene Recommendation Recording of previous events Research Research Personnel Risk Subgroup System Time Woman Work Zoledronate adverse event risk aged bisphosphonate clinical predictors 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 minimization risk prediction model risk/benefit ratio secondary analysis sex side effect study population therapy duration treatment pattern 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.

项目概要开始服用口服双膦酸盐 (BP) 的骨质疏松症药物治疗 (ODT) 的老年人中有 60% 患有骨质疏松症长期暴露（3年或更长时间，80%或更高的依从性）。需要进行 BP 治疗以降低骨折风险，BP 的半衰期较长，可以提供长期益处临床试验发现，停药后的女性骨折风险几乎没有差异。此外，长期使用血压与不良事件有关，例如因此，指南建议大多数人休药（暂停治疗）。使用 BP 3 至 5 年后，建议骨折风险高的患者继续使用 BP 或更换。与另一种 ODT 相比，如狄诺塞麦、特立帕肽、阿巴洛帕肽或雷洛昔芬，存在几个关键的知识空白。存在长期使用血压、药物假期、ODT 转换对临床结果的风险和益处，以及不良事件，特别是在试验中代表性有限的群体，如男性和疗养院 (NH) 该提案有三个具体目标： (1) 居住在社区且至少有 3 人的老年人。使用 BP 年数，检查 BP 药物假期和 ODT 转换对骨折、骨折后遗症的影响（例如，死亡、进入 NH）和 AFF (2) 在接受至少 3 年 ODT 的 NH 居民中，比较停止与继续 ODT 对骨折/后遗症和以患者为中心的结果的影响（例如， (3) 开发并验证骨质疏松性骨折和AFF的临床预测算法指导人们决定是否开始戒毒假期。长期 ODT 策略的效果将取决于治疗长度、类型和患者特征。我们建议的严格研究将使用跨国链接的管理和临床数据集。人口将包括美国和加拿大安大略省 66 岁或以上的老年人，他们至少拥有本研究的 3 年长期 ODT 数据将来自 1) 关联的全民医疗保健和药物治疗。安大略省所有年龄 ≥ 65 岁的人（社区居民和非居民）的索赔数据；2) 美国医疗保险索赔社区居住的老年人；以及 3) 最多 10,000 名 NH 的电子健康记录 (EHR) 数据我们将为骨质疏松症药物索赔实施经过验证的数据清理算法。以及新颖的滚动窗口方法来捕获长期 ODT 倾向评分方法和该项目将采用诸如目标试验仿真之类的新颖因果推理方法。指导老年人长期 ODT、预防骨折和尽量减少 AFF 的普遍证据。研究将直接解决 RFA-AG-22-018，骨质疏松症药物治疗的适当使用预防骨折的途径研讨会小组建议 1 和 4 以及战略目标此外，该项目将建立一个国际数据合作伙伴关系，以促进国家老龄化问题。利用 EHR 和全民医疗保健数据来回答有关 ODT 的新兴研究问题。