Statistical methods for comparative treatment effectiveness using claims data

描述(申请人提供)：意义。在观察性研究中，采用二分法处理(暴露与未暴露)的倾向评分方法已被广泛评估，并被证明是减少偏倚和平衡对照组之间混杂因素分布的有效工具。已经开发了处理多级曝光、有顺序和无顺序以及连续曝光的倾向评分方法。然而，无论是在模拟研究还是实证研究中，这些方法的应用经验都非常有限。在确定药物的益处和风险方面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、持续效应和多重药物效应的估计。现实世界的药物使用涉及所有这三个问题，研究人员需要一种全面评估的分析方法才能应用于此类情况。在考虑以下三个重要问题时，我们将确定倾向性评分表现的概括性和实用洞察力：用药剂量、多药用药和持续治疗时间。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差距，并将加强和改进观察性比较有效性研究的质量。明确的目标。我们将(1)在考虑药物暴露的剂量-反应关系和多次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持续时间的影响时评估倾向评分的表现。研究设计。我们将进行模拟研究和对真实数据的分析，以回答两个具体目标的比较有效性研究问题。倾向得分被定义为患者在所有其他观察到的协变量的情况下接受特定治疗的条件概率。这种治疗可以根据治疗的类型、剂量和持续时间而有所不同。将根据受试者暴露的性质，使用适当的统计模型估计每个受试者的这一概率。剂量和持续时间的影响，以及不同药物之间的效果差异将进一步估计。将评估倾向分数的四个常见应用程序和经常应用倾向分数的四个场景的性能。结果将进一步与传统多变量回归模型的结果进行比较。冲击力。该项目将解决在观察性比较有效研究中遇到的极其重要的问题。它将通过为研究人员提供一种全面评估的分析方法来进行此类研究，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。。 公共卫生相关性：该项目将提供一种迫切需要的和彻底评估的统计技术，以利用观测数据进行比较有效性研究。我们将评估倾向评分方法在需要考虑药物剂量效应、持续时间效应和多次药物暴露的常见情况下的应用。该项目解决了当前药物比较有效性分析方法中的一个重要差距，并将加强和改进观察性比较有效性研究的质量，从而对公众健康产生广泛影响。

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.