In assessing the mechanism of treatment efficacy in randomized clinical trials, investigators often perform mediation analyses by analyzing if the significant intent-to-treat treatment effect on outcome occurs through or around a third intermediate or mediating variable: indirect and direct...

Abstract We address several questions relating to the use of standard regression and Structural Nested Mean Model (SNMM) approach (e. g., Ten Have et al. 2007) to analyze post-randomization effect modifiers of the intent-to-treat effect of a randomized intervention on a subsequent outcome,...

An instrument or instrumental variable is often used in an effort to avoid selection bias in inference about the effects of treatments when treatment choice is based on thoughtful deliberation. Instruments are increasingly used in health outcomes research. An instrument is a haphazard push to...

Efficient semiparametric estimation of longitudinal causal effects is often analytically or computationally intractable. We propose a novel restricted estimation approach for increasing efficiency, which can be used with other techniques, is straightforward to implement, and requires no...

Clustered treatment assignment occurs when individuals are grouped into clusters prior to treatment and whole clusters, not individuals, are assigned to treatment or control. In randomized trials, clustered assignments may be required because the treatment must be applied to all children in a...

In a case-referent study, cases of disease are compared to noncases with respect to their antecedent exposure to a treatment in an effort to determine whether exposure causes some cases of the disease. Because exposure is not randomly assigned in the population, as it would be if the population...

In an observational study of treatment effects, subjects are not randomly assigned to treatment or control, so differing outcomes in treated and control groups may reflect a bias from nonrandom assignment rather than a treatment effect. After adjusting for measured pretreatment covariates,...