A Simulation Tool to Evaluate Calcium-41 Experimental Study Designs

评估 Calcium-41 实验研究设计的模拟工具

• 批准号: 9332814
• 负责人: Courtney Henry
• 金额: $ 3.55万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9332814
• 关键词: Address; Administrative Supplement; Affect; Alternative Therapies; Animal Model; Animals; Applications Grants; Berry; Biological; Bone Density; Bone Diseases; Bone Resorption; Calcium; Communication; Complementary therapies; Crossover Design; Data Set; Dietary Intervention; Disease; Effectiveness; Environment; Estrogens; Experimental Designs; Fracture; Future; Goals; Grant; Growth; Health; Hormone replacement therapy; Human; Incidence; Integrative Medicine; Intervention; Isotopes; Lifestyle Therapy; Measures; Mentorship; Metabolic Bone Diseases; Methodology; Modeling; Monitor; Nutritional Support; Oral; Osteoporosis; Output; Postmenopause; Production; Property; Public Health; Rattus; Reporting; Research; Research Design; Research Personnel; Research Training; Risk; Sample Size; Sampling; Science; Scientist; Strategic Planning; Structure; Study models; Targeted Research; Techniques; Time; Tracer; Training; Translational Research; Treatment Efficacy; United States National Institutes of Health; Woman; Workload; Writing; accelerator mass spectrometry; base; bone; bone health; bone loss; bone strength; calcium metabolism; career; cost; cost effective; design; dietary supplements; experimental study; improved; lifestyle intervention; method development; next generation; novel; older women; prevent; programs; public health relevance; research study; response; screening; simulation; skeletal; skills; skills training; tool; treatment effect; urinary

Project Summary/Abstract Osteoporosis is a progressive bone disease that reduces bone mineral density (BMD) leading to an increased risk of bone fracture. It largely affects women post-menopause who incur a sharp decline in estrogen production, which has a key role in the proper growth and maturation of bone. Alternative and integrative health approaches for preventing disease occurrence, primarily through use of natural dietary supplements, are currently being sought due to the adverse health risks associated with conventional hormone replacement therapies. To assess the effectiveness of these disease interventions, a well-established novel and sensitive screening technique incorporating a biological tracer, calcium-41 (41Ca), is used to rapidly and sensitively monitor bone resorption. Measured is the urinary 41Ca:Ca isotope ratio, monitored by Accelerator Mass Spectrometry (AMS) to detect changes in bone calcium metabolism. This study proposes to develop a 41Ca simulation study to serve as a tool to investigate how inputs of sample size, number of control periods, and number of control samples per period will affect the output: (1) the accuracy (standard error) of reported mean estimates of treatment effect (2) the power of the study to detect given effect sizes and (3) the cost of the experimental study. Ultimately, this tool will determine “optimal” 41Ca experimental designs, which are uniquely defined as the most efficient study designs that preserve the accuracy and reliability of the original experimental estimates but require a reduced number of experimental samples, which notably provides a cost reduction. In parallel, this study proposes to develop a 45Ca simulation tool using the ovariectomized (OVX) rat model to determine the optimal experimental design for treatment efficacy on bone calcium retention. Ultimately, these new designs will be implemented to further increase the practicality and utility of 41Ca and 45Ca methodology in future translational research studies, targeted to reduce the risk of osteoporosis. This proposal specifically addresses the 2016 NCCIH strategic plan Objective 1: Advance Fundamental Science and Method Development, by creating a novel research study tool for strengthening (statistical power) the experimental design of human and animal trials of alternative and complementary health approaches. In addition, this proposal will provide the necessary research training skills and mentorship opportunities for effective scientific communication through grant and proposal writing, oral presentations, and participation in collaborative research environments and science diversity mentorship programs. I anticipate that by acquiring these skills and opportunities, I will be successful in a professional career as independent research scientist.

项目摘要/摘要 骨质疏松症是一种进行性骨骼疾病，可降低骨矿物质密度（BMD），导致增加 骨折的风险。这在很大程度上影响了雌激素急剧下降的妇女 生产，在骨骼的正常生长和成熟中具有关键作用。替代和综合 预防疾病发生的健康方法，主要是通过使用自然饮食补充剂， 由于与常规激素更换有关的不利健康风险，目前正在受到伤害 疗法。为了评估这些疾病干预措施的有效性，一种公认的新颖而敏感的 结合生物示踪剂钙-41（41CA）的筛选技术用于快速而敏感 监控骨骼分辨率。测量的是尿41CA：Ca同位素比，通过加速器质量监测 光谱法（AMS）检测骨钙代谢的变化。 这项研究提案要开发41CA模拟研究，以作为研究样品输入的工具 每个周期的大小，控制周期数和控制样本数将影响输出：（1） 报告的平均治疗效果估计值的准确性（标准误差）（2）研究的能力检测 给定效果大小和（3）实验研究的成本。最终，此工具将确定“最佳” 41CA 实验设计，被唯一地定义为保存最有效的研究设计 原始实验估计的准确性和可靠性，但需要减少实验数量 样本，特别是降低成本。同时，这项研究的提案要开发45CA模拟 使用卵巢切除（OVX）大鼠模型的工具来确定治疗的最佳实验设计 骨钙保留的功效。最终，将实施这些新设计，以进一步增加 41CA和45CA方法在未来的转化研究中的实用性和实用性，旨在减少 骨质疏松症的风险。 该建议专门针对2016年NCCIH战略计划目标1：提前基本 科学和方法开发，通过创建一种新颖的研究工具来加强（统计能力） 人类和动物试验的替代和完整健康方法的实验设计。在 此外，该建议将为必要 通过赠款和提案写作，口头演示和参与的有效科学沟通 协作研究环境和科学多样性心态计划。我期望通过 这些技能和机会，我将在职业生涯中作为独立研究科学家取得成功。