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Indeed, because the design and implementation of one-stage and two-stage random-effects models may substantially differ, it is important to ascertain whether the choice of method can influence the final conclusions about whether a factor has a (statistically) significant association with the outcome. It is important to consider if this recommendation is valid in other empirical examples, and if it translates to epidemiological studies.

This situation may also arise in clinical trials when interactions occur between treatment effects and covariates, or when adjustment is needed for prognostic factors that are unbalanced between groups.