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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.

项目总结