Methods for dealing with unequal cluster sizes in cluster randomized trials: A scoping review

In a cluster-randomized trial (CRT), the number of participants enrolled often varies across clusters. This variation should be considered during both trial design and data analysis to ensure statistical performance goals are achieved. Most methodological literature on the CRT design has assumed equal cluster sizes. This scoping review focuses on methodology for unequal cluster size CRTs. EMBASE, Medline, Google Scholar, MathSciNet and Web of Science databases were searched to identify English-language articles reporting on methodology for unequal cluster size CRTs published until March 2021. We extracted data on the focus of the paper (power calculation, Type I error etc.), the type of CRT, the type and the range of parameter values investigated (number of clusters, mean cluster size, cluster size coefficient of variation, intra-cluster correlation coefficient, etc.), and the main conclusions. Seventy-nine of 5032 identified papers met the inclusion criteria. Papers primarily focused on the parallel-arm CRT (p-CRT, n = 60, 76%) and the stepped-wedge CRT (n = 14, 18%). Roughly 75% of the papers addressed trial design issues (sample size/power calculation) while 25% focused on analysis considerations (Type I error, bias, etc.). The ranges of parameter values explored varied substantially across different studies. Methods for accounting for unequal cluster sizes in the p-CRT have been investigated extensively for Gaussian and binary outcomes. Synthesizing the findings of these works is difficult as the magnitude of impact of the unequal cluster sizes varies substantially across the combinations and ranges of input parameters. Limited investigations have been done for other combinations of a CRT design by outcome type, particularly methodology involving binary outcomes—the most commonly used type of primary outcome in trials. The paucity of methodological papers outside of the p-CRT with Gaussian or binary outcomes highlights the need for further methodological development to fill the gaps.

Impact of unequal cluster sizes for GEE analyses of stepped wedge cluster randomized trials with binary outcomes

The stepped wedge design is a type of unidirectional crossover design where cluster units switch from control to intervention condition at different pre-specified time points. While a convention in study planning is to assume the cluster-period sizes are identical, stepped wedge cluster randomized trials (SW-CRTs) involving repeated cross-sectional designs frequently have unequal cluster-period sizes, which can impact the efficiency of the treatment effect estimator. In this article, we provide a comprehensive investigation of the efficiency impact of unequal cluster sizes for generalized estimating equation analyses of SW-CRTs, with a focus on binary outcomes as in the Washington State Expedited Partner Therapy trial. Several major distinctions between our work and existing work include: (i) we consider multilevel correlation structures in marginal models with binary outcomes; (ii) we study the implications of both the between-cluster and within-cluster imbalances in sizes; and (iii) we provide a comparison between the independence working correlation versus the true working correlation and detail the consequences of ignoring correlation estimation in SW-CRTs with unequal cluster sizes. We conclude that the working independence assumption can lead to substantial efficiency loss and a large sample size regardless of cluster-period size variability in SW-CRTs, and recommend accounting for correlations in the analysis. To improve study planning, we additionally provide a computationally efficient search algorithm to estimate the sample size in SW-CRTs accounting for unequal cluster-period sizes, and conclude by illustrating the proposed approach in the context of the Washington State study.

Noise robust hybrid algorithm for segmenting image with unequal cluster sizes based on chaotic crow search and improved fuzzy c-means

Adding spatial penalty to fuzzy C-means (FCM) model is an important way to reduce the influence of noise in image segmentation. However, these improved algorithms easily cause segmentation failures when the image has the characteristics of unequal cluster sizes. Besides, they often fall into local optimal solutions if the initial cluster centers are improper. This paper presents a noise robust hybrid algorithm for segmenting image with unequal cluster sizes based on chaotic crow search algorithm and improved fuzzy c-means to overcome the above defects. Firstly, each size of clusters is integrated into the objective function of noise detecting fuzzy c-means algorithm (NDFCM), which can reduces the contribution of larger clusters to objective function and then the new membership degree and cluster centers are deduced. Secondly, a new expression called compactness, representing the pixel distribution of each cluster, is introduced into the iteration process of clustering. Thirdly, we use two- paths to seek the optimal solutions in each step of iteration: one path is produced by the chaotic crow search algorithm and the other is originated by gradient method. Furthermore, the better solutions of the two-paths go to next generation until the end of the iteration. Finally, the experiments on the synthetic and non–destructive testing (NDT) images show that the proposed algorithm behaves well in noise robustness and segmentation performance.