Clustering in randomized controlled trials

Randomized clinical trials often involve some sort of clustering. The most obvious is in a cluster randomized trial, where clusters form the unit of randomization. It is well known that in this case the clustering must be allowed for in the analysis. But even in the common setting where individuals are randomized, clustering may be present. Perhaps the most common situation is where a trial involves a number of hospitals or centres, and individuals are recruited into the trial when they attend their local centre. Another example is where the intervention is administered to each individual by some professional (e.g. surgeon, therapist), such that outcomes from individuals treated by the same professional may be more similar to each other. In both of these situations, an obvious question is whether we need to allow for the clustering in the analysis?

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