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Statistics in Medicine
Article . 2020 . Peer-reviewed
License: Wiley Online Library User Agreement
Data sources: Crossref
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Analysis of counts for cluster randomized trials: Negative controls and test‐negative designs

Authors: Suzanne M. Dufault; Nicholas P. Jewell;

Analysis of counts for cluster randomized trials: Negative controls and test‐negative designs

Abstract

In cluster randomized trials (CRTs), the outcome of interest is often a count at the cluster level. This occurs, for example, in evaluating an intervention with the outcome being the number of infections of a disease such as HIV or dengue or the number of hospitalizations in the cluster. Standard practice analyzes these counts through cluster outcome rates using an appropriate denominator (eg, population size). However, such denominators are sometimes unknown, particularly when the counts depend on a passive community surveillance system. We consider direct comparison of the counts without knowledge of denominators, relying on randomization to balance denominators. We also focus on permutation tests to allow for small numbers of randomized clusters. However, such approaches are subject to bias when there is differential ascertainment of counts across arms, a situation that may occur in CRTs that cannot implement blinded interventions. We suggest the use of negative control counts as a method to remove, or reduce, this bias, discussing the key properties necessary for an effective negative control. A current example of such a design is the recent extension of test‐negative designs to CRTs testing community‐level interventions. Via simulation, we compare the performance of new and standard estimators based on CRTs with negative controls to approaches that only use the original counts. When there is no differential ascertainment by intervention arm, the count‐only approaches perform comparably to those using debiasing negative controls. However, under even modest differential ascertainment, the count‐only estimators are no longer reliable.

Keywords

Bias, Research Design, Cluster Analysis, Humans, Computer Simulation, Randomized Controlled Trials as Topic

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
5
Top 10%
Average
Top 10%
Green
bronze