scholarly journals Estimation of treatment effects in matched-pair cluster randomized trials by calibrating covariate imbalance between clusters

Biometrics ◽  
2014 ◽  
Vol 70 (4) ◽  
pp. 1014-1022 ◽  
Author(s):  
Zhenke Wu ◽  
Constantine E. Frangakis ◽  
Thomas A. Louis ◽  
Daniel O. Scharfstein
2014 ◽  
Vol 26 (2) ◽  
pp. 583-597 ◽  
Author(s):  
JoAnna M Scott ◽  
Allan deCamp ◽  
Michal Juraska ◽  
Michael P Fay ◽  
Peter B Gilbert

Stepped wedge designs are increasingly commonplace and advantageous for cluster randomized trials when it is both unethical to assign placebo, and it is logistically difficult to allocate an intervention simultaneously to many clusters. We study marginal mean models fit with generalized estimating equations for assessing treatment effectiveness in stepped wedge cluster randomized trials. This approach has advantages over the more commonly used mixed models that (1) the population-average parameters have an important interpretation for public health applications and (2) they avoid untestable assumptions on latent variable distributions and avoid parametric assumptions about error distributions, therefore, providing more robust evidence on treatment effects. However, cluster randomized trials typically have a small number of clusters, rendering the standard generalized estimating equation sandwich variance estimator biased and highly variable and hence yielding incorrect inferences. We study the usual asymptotic generalized estimating equation inferences (i.e., using sandwich variance estimators and asymptotic normality) and four small-sample corrections to generalized estimating equation for stepped wedge cluster randomized trials and for parallel cluster randomized trials as a comparison. We show by simulation that the small-sample corrections provide improvement, with one correction appearing to provide at least nominal coverage even with only 10 clusters per group. These results demonstrate the viability of the marginal mean approach for both stepped wedge and parallel cluster randomized trials. We also study the comparative performance of the corrected methods for stepped wedge and parallel designs, and describe how the methods can accommodate interval censoring of individual failure times and incorporate semiparametric efficient estimators.


2021 ◽  
pp. 174077452110568
Author(s):  
Fan Li ◽  
Zizhong Tian ◽  
Jennifer Bobb ◽  
Georgia Papadogeorgou ◽  
Fan Li

Background In cluster randomized trials, patients are typically recruited after clusters are randomized, and the recruiters and patients may not be blinded to the assignment. This often leads to differential recruitment and consequently systematic differences in baseline characteristics of the recruited patients between intervention and control arms, inducing post-randomization selection bias. We aim to rigorously define causal estimands in the presence of selection bias. We elucidate the conditions under which standard covariate adjustment methods can validly estimate these estimands. We further discuss the additional data and assumptions necessary for estimating causal effects when such conditions are not met. Methods Adopting the principal stratification framework in causal inference, we clarify there are two average treatment effect (ATE) estimands in cluster randomized trials: one for the overall population and one for the recruited population. We derive analytical formula of the two estimands in terms of principal-stratum-specific causal effects. Furthermore, using simulation studies, we assess the empirical performance of the multivariable regression adjustment method under different data generating processes leading to selection bias. Results When treatment effects are heterogeneous across principal strata, the average treatment effect on the overall population generally differs from the average treatment effect on the recruited population. A naïve intention-to-treat analysis of the recruited sample leads to biased estimates of both average treatment effects. In the presence of post-randomization selection and without additional data on the non-recruited subjects, the average treatment effect on the recruited population is estimable only when the treatment effects are homogeneous between principal strata, and the average treatment effect on the overall population is generally not estimable. The extent to which covariate adjustment can remove selection bias depends on the degree of effect heterogeneity across principal strata. Conclusion There is a need and opportunity to improve the analysis of cluster randomized trials that are subject to post-randomization selection bias. For studies prone to selection bias, it is important to explicitly specify the target population that the causal estimands are defined on and adopt design and estimation strategies accordingly. To draw valid inferences about treatment effects, investigators should (1) assess the possibility of heterogeneous treatment effects, and (2) consider collecting data on covariates that are predictive of the recruitment process, and on the non-recruited population from external sources such as electronic health records.


Author(s):  
Eva Lorenz ◽  
Sabine Gabrysch

In cluster-randomized trials, groups or clusters of individuals, rather than individuals themselves, are randomly allocated to intervention or control. In this article, we describe a new command, ccrand, that implements a covariate-constrained randomization procedure for cluster-randomized trials. It can ensure balance of one or more baseline covariates between trial arms by restriction to allocations that meet specified balance criteria. We provide a brief overview of the theoretical background, describe ccrand and its options, and illustrate it using an example.


2010 ◽  
Vol 8 (1) ◽  
pp. 27-36 ◽  
Author(s):  
Zhiying You ◽  
O Dale Williams ◽  
Inmaculada Aban ◽  
Edmond Kato Kabagambe ◽  
Hemant K Tiwari ◽  
...  

2021 ◽  
Author(s):  
L Miriam Dickinson ◽  
Patrick Hosokawa ◽  
Jeanette A Waxmonsky ◽  
Bethany M Kwan

Author(s):  
John A. Gallis ◽  
Fan Li ◽  
Elizabeth L. Turner

Cluster randomized trials, where clusters (for example, schools or clinics) are randomized to comparison arms but measurements are taken on individuals, are commonly used to evaluate interventions in public health, education, and the social sciences. Analysis is often conducted on individual-level outcomes, and such analysis methods must consider that outcomes for members of the same cluster tend to be more similar than outcomes for members of other clusters. A popular individual-level analysis technique is generalized estimating equations (GEE). However, it is common to randomize a small number of clusters (for example, 30 or fewer), and in this case, the GEE standard errors obtained from the sandwich variance estimator will be biased, leading to inflated type I errors. Some bias-corrected standard errors have been proposed and studied to account for this finite-sample bias, but none has yet been implemented in Stata. In this article, we describe several popular bias corrections to the robust sandwich variance. We then introduce our newly created command, xtgeebcv, which will allow Stata users to easily apply finite-sample corrections to standard errors obtained from GEE models. We then provide examples to demonstrate the use of xtgeebcv. Finally, we discuss suggestions about which finite-sample corrections to use in which situations and consider areas of future research that may improve xtgeebcv.


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