Designing clinical trials for amblyopia

•Randomized clinical trials are preferred in clinical amblyopia research.•Nevertheless, observational cohort studies have an important role.•Studies in amblyopia can be synthesized into an evidence-based treatment algorithm.•Future study design should consider issues that may affect study outcome.•Issues include regression to the mean, sample size, variability, and trial duration. Randomized clinical trial (RCT) study design leads to one of the highest levels of evidence, and is a preferred study design over cohort studies, because randomization reduces bias and maximizes the chance that even unknown confounding factors will be balanced between treatment groups. Recent randomized clinical trials and observational studies in amblyopia can be taken together to formulate an evidence-based approach to amblyopia treatment, which is presented in this review. When designing future clinical studies of amblyopia treatment, issues such as regression to the mean, sample size and trial duration must be considered, since each may impact study results and conclusions.