Propensity Scores and Preventive Drug Use in the Elderly

说明(申请人提供)：使用处方药和非处方药预防慢性病是老年人护理的一个主要特点。评估老年人慢性病药物预防有效性的随机对照试验非常昂贵，需要很长时间来设计和实施，而且由于参与者的选择、治疗持续时间较短以及试验过程中发生的治疗方法的变化，推广可能有限。然而，关于药物的有益和有害影响的非实验研究，包括基于行政数据的研究，往往是唯一可用的数据，经常被批评为产生有偏见的结果。因此，在评估老年患者用药预防效果的观察性研究中，开发和应用适当的方法来减少偏差是至关重要的。倾向性评分(PSS)是一种在非实验研究中越来越多地用于解决混淆问题的技术。在评估药物和医疗程序的有效性的非实验研究中，PSS通常被认为优于传统分析。在RO1AG023178的资助下，我们评估了倾向性评分(PS)在真实数据集和广泛模拟中的局限性和优势，并自2005年以来开发了基于PS的新分析技术。我们通过口头陈述(28个)、海报(16个)和研讨会/研讨会(4个)在主要的国际流行病学、药物流行病学、生物统计学和统计学会议上以及在一系列27个出版物中传播我们的结果，其中9个发表在排名最高的流行病学杂志(《美国流行病学杂志》)上。我们的研究集中在药物治疗有益和有害的非实验研究的主要问题之一，即不可测量的混杂问题。我们之前开发了一种创新的方法，通过结合PS和回归校准(倾向性得分校准)的外部验证研究，包括在主要研究中没有测量到的混杂因素的额外信息。我们最近发布了另一种创新方法，以处理由未测量的混杂因素造成的混杂偏见。这种方法是基于这样的假设，即接受与预测相反的治疗的患者更有可能存在无法测量的混杂因素，如虚弱，导致医生推翻预测的治疗。这是第一篇显示PS方法相对于传统多变量结果模型在未测量混杂因素方面的明显优势的论文。第二个相互竞争的延续将建立在我们过去7年工作的基础上，并将其扩展到同一领域-PSS的局限性和价值，以评估使用略有变化的研究团队在老年患者中使用药物的预防效果，同时保持相同的核心研究人员。利用新的数据来源，包括2007年、20008和2009年各300万名医疗保险受益人的全国随机大样本，我们将重点讨论几个尚未解决的新的和不同的主题，这些主题涉及PSS的实施和预防性药物在老年人中的使用的影响。 与公共健康相关：药物是当今医疗保健的支柱。普遍获得负担得起的药物，并使特定个人的利益与伤害达到最佳平衡，是全球、国家和地方公共和个人的一个主要健康目标。尽管上市前在随机试验中证明了有效性，但在药物批准时对危害(例如万络)知之甚少，而且大多数最终将成为 治疗，例如，患有共病和联合用药的老年人。非实验性的批准后研究可以填补做出最佳治疗决定所需的药物益处和危害方面的知识空白，但需要仔细设计才能有效。在NIA的资助下，我们在过去7年中成功地开发和评估了先进和新颖的方法，以提高非实验性批准后研究的有效性，并建议继续这样做，主要基于2007至2009年间每年约300万医疗保险受益人的代表性样本中的处方药使用和诊断数据。

DESCRIPTION (provided by applicant): The use of prescription and non-prescription drugs for prevention of chronic diseases is a central feature of the care of older adults. Randomized controlled trials assessing the effectiveness of pharmacoprevention of chronic diseases in older adults are very costly, take a long time to design and implement, and may be of limited generalizability due to selection of participants, shorter duration of treatment, and changes in therapies that occur over the course of the trial. Nonexperimental studies on beneficial and harmful effects of drugs, including studies based on administrative data that often are the only available data, however, have frequently been criticized as producing biased results. It is therefore vital to develop and apply adequate methods to reduce bias in observational studies that assess the preventive effects of medication use in older patients. Propensity scores (PSs) are an increasingly used technique to address confounding in nonexperimental research. PSs are often perceived as superior to conventional analyses in nonexperimental studies assessing the effectiveness of drugs and medical procedures. Funded by RO1 AG023178, we have assessed limitations and advantages of propensity scores (PS) in real datasets and extensive simulations and have developed novel analytic techniques based on PS since 2005. We have disseminated our results by means of oral presentations (28), posters (16), and workshops/symposia (4) at major international epidemiologic, pharmacoepidemiologic, biostatistics, and statistics meetings and in a series of 27 publications, including 9 in the highet ranked epidemiologic journal (the American Journal of Epidemiology). We have focused our research on one of the major problems of nonexperimental research of beneficial and harmful effects of drug treatments, i.e., the problem of unmeasured confounding. We previously had developed an innovative method to include additional information on confounders not measured in the main study from an external validation study combining PS and regression calibration (Propensity Score Calibration). We recently published another innovative method to deal with confounding bias by unmeasured confounders. This method is based on the assumption that patients treated contrary to prediction are more likely to have unmeasured confounders, like frailty, leading the physician to override the predicted treatment. This is the first paper ever showing a clear advantage of PS methods over conventional multivariable outcome models with respect to unmeasured confounders. The second competing continuation will build on our work over the last 7 years and extend it in the same domain - limitations and value of PSs to assess the preventive effects of medication use in older patients with a slightly changed team of researchers while keeping the same core investigators. Using new data sources, including a large random national sample of 3 million Medicare beneficiaries each for the years 2007, 20008, and 2009, we will focus on several unresolved new and distinct topics regarding the implementation of PSs and the effects of preventive drug use in the elderly. PUBLIC HEALTH RELEVANCE: Drugs are a mainstay of today's healthcare. Universal access to affordable drugs with the optimal benefit to harm balance for a given individual is a major global, national, and local public and individual health goal. Despite pre-marketing proof of efficacy in randomized trials, there is little known about harms at the time of drug approval (e.g. Vioxx) and data on benefits are usually lacking for the majority of patients who will ultimately be treated, e.g., older adults with co-morbidities and co-medications. Nonexperimental post-approval studies can fill this knowledge gap on drug benefits and harms needed to make optimal treatment decisions but need to be designed carefully to be valid. Funded by NIA we have successfully developed and evaluated advanced and novel methods to increase the validity of nonexperimental post- approval studies over the last 7 years and propose to continue to do so mainly based on data on prescription drug use and diagnoses from a representative sample of approximately 3 million Medicare beneficiaries per year for the years 2007 to 2009.