Combining comparative effectiveness research (CER) and dissemination and implementation research is playing an increased role in public health and health care service by allowing practitioners to make informed decisions about treatments and improving adoption of evidence-based practices. In circumstances where CER questions do not lend themselves to direct experimentation or in implementation trials where incomplete adoption of in- tervention occurs, causal inference tools for ??eld data? are recommended for evaluating treatment effects. The increased complexities in large national electronic health databases pose challenges for statistical analyses and demand approaches beyond conventional causal inference techniques, which have traditionally focused on bi- nary treatment. Given the wealth of information captured in large-scale data, it is rare that treatment regimens are de?ned in terms of two treatments only. The data are typically pooled from treating facilities across the nation with considerable variability in the institutional effect. Although it has been established that popular tools for bi- nary treatment are inappropriate for the multiple treatment setting, and that ignoring the multilevel data structure can bias the estimate of the treatment effect, few alternative methods have been proposed to deal with both complications simultaneously. The ?rst aim of our proposed project is to develop a novel and ?exible Bayesian approach to estimating the causal effects of multiple treatments on survival with clustered data. We then fully investigate the operating characteristics of our proposed method in a variety of simulated scenarios and contrast it with approaches often used in practice. For causal estimates to be unbiased, researchers commonly make the assumption of no unmeasured confounding (UMC). Though highly recommended with binary treatment, there is no known implementation or framework for sensitivity analysis with multiple treatments and multilevel survival data.
The second aim of our project is to develop and apply a ?exible and interpretable Bayesian approach to assessing the sensitivity of causal estimates to possible departures from the assumption of no UMC, at both cluster- and individual-level. This approach is capable of gauging the amount of unobserved confounding needed to change the direction of the observed treatment effects Our project will apply the developed methods in the ?rst two aims to a large representative high-risk localized prostate cancer population, drawn from the National Cancer Data Base, to evaluate the average causal effects of three popular treatment options on survival and evaluate how unmeasured confounding might alter causal conclusions. We also will estimate treatment heterogeneity and identify distinct subgroups of patients for which a treatment is effective or harmful. Our methods will establish the effectiveness component and lay the groundwork for building the cost-effectiveness models, and provide evidence for further investigations of variations in intervention implementation and modi?cations in recommendations for treatments leading to different patient outcomes. To facilitate the dissemination of our work, we will share the underlying statistical code via an R package.
As public health comparisons often involve more than two treatments on patients from multiple care centers, comparative effectiveness research and implementation research call for advanced causal inference techniques allowing for the estimation of multiple treatment effects while respecting the multilevel data structure. We de- velop a new approach to simultaneously contrast the effectiveness of multiple treatments on clustered survival outcomes, propose and apply a new framework for testing the assumptions behind these estimates, and propose a strategy for estimating treatment effect heterogeneity and identifying distinct subgroups of patients for which a treatment is harmful or effective. Our work will provide practitioners clarity with respect to estimating causes and effects from complicated health care databases in which the comparative assessment of multiple treatment options from multilevel survival data is challenging but imperative.
