Propensity scores and preventive drug use in the elderly

摘要 医疗治疗，包括药物、手术干预和疫苗接种，在 预防和治疗老年人的慢性和传染性疾病。提供证据基础的研究 对于这些治疗的益处和危害，包括两个实验研究(随机对照试验， 随机对照试验)和非实验研究(观察性、流行病学，或最近的：真实世界证据)。 非实验研究为老年人提供了至关重要的证据，特别是那些患有多发性多发性硬化症的老年人 与多种药物有关的慢性疾病，因为这类成年人很少被纳入随机对照试验；这对 被种族边缘化的老年人，他们在试验中的代表性历来不足。这样的非实验研究 通常涉及混淆，而老年人的许多混淆因素--包括虚弱--可能很难捕捉到 真实世界的数据。如果不对这种令人困惑的情况进行调整，可能会扭曲研究结果，导致次优甚至是最优结果 有害的治疗决定(如果非实验研究是唯一可用的证据)或进行 治疗的随机对照试验费用高昂，但不能带来好处。及时评估老年人的治疗益处和危害 真实世界(与实验环境)的设置需要开发、改进和应用方法来 减少非实验研究中的混淆偏差。 自2005年以来，我们一直在R01/R56、AG023178和AG056479的资助下解决这个问题。这 努力在提高非实验研究应用的有效性的方法方面取得了实质性进展 倾向评分法。利用经验数据和广泛的模拟，我们开发出了新的 减少混淆的分析技术，包括倾向评分校准和排除患者 与预测相反的处理。我们已经通过口头演示、海报和 讲习班/专题讨论会和112份同行评议出版物，其中23份刊登在顶级流行病学期刊(AJE和 流行病学)，23篇发表在顶级药物流行病学杂志(PDS)上，10篇发表在医疗保健杂志上，几篇发表在顶级药物流行病学杂志上 医学期刊(JAMA、JNCI、糖尿病护理和JAGS)。 在过去15年工作的基础上，提高非实验方法评估的有效性 关于老年人治疗的预防效果，我们提出了重大和创新的目标，以改善 非实验研究的严谨性。我们将使用经验性的激励例子来解决这些目标 数据和广泛的模拟，以提高真实世界证据的有效性。我们将利用我们的 跨学科专业知识和访问与其他数据源链接的联邦医疗保险数据，以改善现实世界 使用倾向分数的研究。这一提议是及时的：关联数据正变得更加可用，其作用 在监管决策中使用真实世界的证据是一个中心讨论点。这项工作将直接告知 临床相关的治疗决策，提供随机对照试验无法获得的可靠证据，并改善个体 和老年人的人口健康。

ABSTRACT Medical treatments, including drugs, surgical interventions, and vaccinations, play a crucial role in the prevention and treatment of chronic and infectious disease in older adults. Studies providing the evidence base for the benefits and harms of these treatments include both experimental studies (randomized controlled trials, RCTs) and nonexperimental studies (observational, epidemiologic, or, more recently: real-world evidence). Nonexperimental studies provide critically important evidence for older adults, especially those with multiple chronic conditions with polypharmacy, as such adults are rarely included in RCTs; this is doubly important for racially marginalized older adults that are historically underrepresented in trials. Such nonexperimental studies often involve confounding, and many confounders in older adults-including frailty-can be difficult to capture in real-world data. Failure to adjust for this confounding can distort findings and lead to suboptimal or even harmful treatment decisions (if nonexperimental studies are the only evidence available) or the conduct of costly RCTs of treatments without benefits. Timely assessment of treatment benefit and harm in older adults in real-world (versus experimental) settings requires development, refinement, and application of methods to reduce confounding bias in nonexperimental studies. We have addressed this topic since 2005 with funding from R01/R56 AG023178 and AG056479. This effort has led to substantial advances in methods to improve the validity of nonexperimental research applying propensity score methods. Using both empirical data and extensive simulations, we have developed novel analytic techniques to reduce confounding, including propensity score calibration and the exclusion of patients treated contrary to prediction. We have disseminated our results in the form of oral presentations, posters, and workshops/symposia and 112 peer-reviewed publications, including 23 in top epidemiologic journals (AJE and Epidemiology), 23 in the top pharmacoepidemiologic journal (PDS), 10 in Medical Care, and several in top medical journals (JAMA, JNCI, Diabetes Care, and JAGS). Building on our work over the last 15 years to increase the validity of nonexperimental methods to assess the preventive effects of treatments in older adults, we propose significant and innovative aims that improve the rigor of nonexperimental research. We will address these aims using motivating examples from empirical data and extensive simulations to improve the validity of real-world evidence. We will take advantage of our interdisciplinary expertise and access to Medicare data linked with other data sources to improve real-world studies using propensity scores. This proposal is timely: linked data are becoming more available and the role of real-world evidence in regulatory decision making is a central discussion point. This work will directly inform clinically relevant treatment decisions, provide reliable evidence unavailable from RCTs, and improve individual and population health for older adults.