Enhancing the Utility of the Trend-in-Trend Research Design

增强趋势研究设计的实用性

• 批准号: 10162467
• 负责人: Sean Hennessy
• 金额: $ 56.18万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10162467
• 关键词: Acute myocardial infarction; Address; Adoption; Area; Calendar; Cardiovascular system; Characteristics; Clinical; Data; Deep Vein Thrombosis; Development; Dose; Drug Prescriptions; Effectiveness; Elderly; Enrollment; Environmental Exposure; Epidemiologic Research Design; Epidemiology; Evaluation; Healthcare; Heart Arrest; Heterogeneity; Hybrids; Hypoglycemia; Knowledge; Machine Learning; Marketing; Medical; Methodology; Methods; Modeling; Non-Steroidal Anti-Inflammatory Agents; Observational Study; Odds Ratio; Outcome; Paper; Patients; Performance; Pharmaceutical Preparations; Population; Prevalence; Probability; Procedures; Property; Public Health; Pulmonary Embolism; Research Design; Rofecoxib; Safety; Sampling; Speed; Stroke; Testing; Testosterone; Time; Time trend; To specify; Ventricular Arrhythmia; base; cardiovascular effects; cerebrovascular; cohort; cyclooxygenase 2; design; improved; lifestyle factors; male; men; method development; non-drug; novel; population health; prospective; randomized trial; rapid growth; response; safety outcomes; simulation; time use; treatment effect; trend; trend analysis; venous thromboembolism

Patients, clinicians, and policymakers often need valid information about the real-world effects of drugs and other exposures for which there have been pronounced time-trends in use. For example, the rapid growth in the use of rofecoxib in the early 2000s and of exogenous testosterone from 2000–2013 was accompanied by an urgent need for knowledge about the cardiovascular effects of those drugs. Randomized trials seldom enroll a sufficient number of subjects, or follow them long enough, to examine associations with rare outcomes. Therefore, non-randomized studies are needed, even though they are susceptible to unmeasured confounding and other forms of bias. To address these limitations of available epidemiologic designs, we recently introduced the trend-in-trend design: a novel, hybrid epidemiologic-ecologic research design that is applicable when there is a prominent trend in the use of the study exposure. Substantial additional development is needed to realize the full public health impact of the trend-in-trend research design. Areas in most need of development include: evaluation of a sequential analysis extension for real-time post-marketing safety surveillance; evaluation of machine learning to specify the trend-in-trend design’s underlying cumulative probability of exposure model; evaluation of dose-response relationships; and evaluation of treatment effect heterogeneity based on baseline patient characteristics. For each of these methodologic needs, we propose an approach for which we will: 1) assess its statistical properties, in particular large-sample validity through asymptotics and finite sample statistical power; 2) evaluate its performance in thorough simulation studies; and 3) proof-test the approach using the known association between rofecoxib-acute myocardial infarction in healthcare data. Finally, we will apply these developments to the unresolved and highly important question of the cardiovascular, cerebrovascular, and thromboembolic effects of exogenous testosterone in men. This study will have broad scientific, clinical, and public health impact by greatly extending the utility of a novel epidemiologic research design with demonstrated validity and is applicable to a broad range of exposures with a prominent trend in use. It will also evaluate the safety of exogenous testosterone, a question of tremendous clinical and public health importance. Examining the safety of prescription drugs is one enormously important application of this design that has the potential to benefit many millions of people. As the trend-in-trend design is also applicable to non-drug exposures that have a pronounced time-trend (e.g., medical procedures, lifestyle factors, environmental exposures, etc.), its potential impact on the population is even broader.

患者、人群和政策制定者通常需要有关药物和其他药物对现实世界影响的有效信息。 使用中存在明显时间趋势的暴露，例如罗非昔布的使用迅速增长。 2000年代初期和2000年至2013年外源性睾酮的出现伴随着对知识的迫切需求 关于这些药物对心血管的影响的随机试验很少招募足够数量的受试者，也很少进行跟踪。 因此，即使是非随机研究也是必要的。 尽管它们很容易受到无法测量的混杂因素和其他形式的偏见的影响，但要解决可用的这些限制。 流行病学设计，我们最近引入了趋势中的设计：一种新颖的、混合的流行病学-生态学研究 当研究暴露的使用存在显着趋势时适用的设计。 需要发展以实现最需要的趋势研究设计领域的全面公共卫生影响。 开发包括：评估用于实时上市后安全监测的序贯分析扩展； 评估机器学习以指定趋势设计的潜在累积暴露概率 模型；剂量反应关系的评估；以及基于基线的治疗效果异质性评估 对于每一种方法学需求，我们提出了一种方法，我们将：1）评估其方法。 统计特性，特别是通过渐进和有限样本统计功效实现的大样本有效性；2) 在彻底的模拟研究中评估其性能；3）使用已知的关联来验证测试该方法 最后，我们将把这些进展应用到医疗数据中。 尚未解决且非常重要的问题，即对心血管、脑血管和血栓栓塞的影响 男性外源性睾酮。 这项研究将极大地扩展一种新型药物的实用性，从而产生广泛的科学、临床和公共卫生影响。 流行病学研究设计已被证明有效，适用于广泛的暴露 它还将评估外源性睾酮的安全性，这是一个巨大的临床和研究问题。 检查处方药的安全性是其极其重要的应用之一。 设计有可能造福数百万人，因为流行设计也适用于非药物领域。 具有明显时间趋势的暴露（例如医疗程序、生活方式因素、环境暴露等）， 它对民众的潜在影响更为广泛。