Statistical methods for comparative treatment effectiveness using claims data

说明（由申请人提供）：意义。采用二分法（暴露与未暴露）的倾向评分方法已被广泛评估，并被证明是观察性研究中减少偏倚和平衡对照组间混杂因素分布的有效工具。倾向评分方法处理多水平暴露，有和没有排序，和连续暴露已经发展。然而，在模拟或实证研究中应用这些方法的经验非常有限。确定药物获益和风险的重要信息包括在比较有效性和安全性调查中对剂量效应、持续时间效应和多种药物效应的估计。现实世界的药物使用涉及所有这三个问题，研究人员需要一种彻底评估的分析方法来应用于这种情况。当考虑到这三个重要问题：药物剂量、多种药物治疗和持续治疗时间时，我们将确定倾向评分表现的普遍性和实用性。该项目解决了目前评估药物比较有效性的分析方法中的一个重要空白，并将加强和改善观察性比较有效性研究的质量。具体的目标。我们将(1)在考虑药物暴露的剂量-反应关系和多种药物暴露的影响时，评估倾向评分的表现；(2)在考虑持续变化的治疗时间的影响时，评估倾向得分的表现。研究设计。我们将进行模拟研究和真实数据分析，以回答两个特定目标的比较有效性研究问题。倾向评分被定义为给定患者所有其他观察到的协变量，患者接受特定治疗的条件概率。这种治疗可以根据治疗的类型、剂量和持续时间而变化。将使用适当的统计模型，根据每个受试者暴露的性质来估计这种可能性。剂量和持续时间的影响，以及药物之间的效果差异将进一步估计。将评估倾向分数的四种常见应用和倾向分数经常应用的四种场景的性能。结果将进一步与传统的多变量回归模型的结果进行比较。的影响。该项目将解决观察比较有效研究中遇到的关键问题。它将为研究人员提供进行这类研究的全面评估的分析方法，从而产生广泛的公共卫生影响，并将加强和改进观察性比较有效性研究的质量。

DESCRIPTION (provided by applicant): Significance. Propensity score methods with a dichotomous treatment (exposed v. unexposed) have been extensively evaluated and proven to be an effective tool for reducing bias and balancing the distribution of confounders between comparison groups in observational studies. Propensity score methods to handle multi- level exposure, with and without ordering, and continuous exposures have been developed. However, there is very limited experience in the application of these methods in either simulated or empirical studies. Important information in establishing both the benefits and risks of medications includes the estimation of a dose effect, duration effect, and multiple medication effect in comparative effectiveness and safety investigations. Real- world medication use involves all three of these issues, and researchers need a thoroughly evaluated analytical method to apply in such scenarios. We will determine the generalizability and practical insight of the performance of propensity scores when considering these three important issues: medication dose, multiple medications, and continuous duration of therapy. This project addresses an important gap in the current analytical approach to evaluating the comparative effectiveness of medications, and will enhance and improve the quality of observational comparative effectiveness research. Specific Aims. We will (1) Evaluate the performance of propensity scores when considering a dose-response relationship of medication exposure and the effects of multiple medication exposures; and (2) Evaluate the performance of propensity scores when considering the effects of continuously varying duration of therapy. Research Design. We will conduct both simulation studies and analyses of real data to answer comparative effectiveness research questions for both specific aims. A propensity score is defined as the conditional probability that a patient receives a particular treatment given all her/his other observed covariates. Such treatment can vary with respect to type, dose, and duration of therapy. Appropriate statistical models will be used to estimate this probability for each subject according to the nature of her/his exposure. Dose and duration effects, and difference in effect among medications will be further estimated. Performance of four common applications of propensity scores and four scenarios for which propensity scores are often applied will be evaluated. Results will be further compared with results from conventional multivariable regression models. Impact. The project will address critically important issues encountered in observational comparative effective research. It will have a wide public health impact by providing researchers with a thoroughly evaluated analytical approach to conduct such studies, and will enhance and improve the quality of observational comparative effectiveness research. . PUBLIC HEALTH RELEVANCE: This project will provide a critically needed and thoroughly evaluated statistical technique to conduct comparative effectiveness research studies using observational data. We will evaluate the application of propensity score methods to common situations when medication dose effect, duration effect, and multiple medication exposures need to be considered. This project addresses an important gap in the current analytical approach to medication comparative effectiveness, and will enhance and improve the quality of observational comparative effectiveness research, and thus have a wide public health impact.