Clinical Trials

❘❙❚■ Chapter 15 | Cluster Randomized TrialsIntroductionIn conventional randomized trials, the unit of randomization is usually theindividual subject. In interventions that address organizational changes, however,it is not always feasible to randomize at the individual level. Trials that randomizegroups of subjects are called cluster randomized trials (CRTs). When individualrandomization proves inappropriate, CRTs can be used to reduce the potential forcontamination within treatment groups (see Table 1). Examples of clusters areshown in Table 2.In recent years, CRTs have become an important tool in clinical research,particularly since the interventions being evaluated tend to be relatively complexand diversified. CRTs are particularly used in the evaluation of health care,screening, and educational interventions, where patients are nested within largergroup settings such as practices, hospitals, or communities.Design of cluster randomized trialsThe methodological quality of these trials is diverse. Due to the dual nature ofCRTs – focusing on both the cluster and the individual – the design, size, andanalysis of these trials can be complex [1–3]. Therefore, there should be a clearjustification and rationale for using the CRT design.Cluster effectIndividuals randomized in a clinical trial are assumed to have an independentchance of being given a placebo or active treatment, and an independentprogression through the trial. However, if the intervention cannot be blinded(eg, a counseling service for a disease) then patients and clinicians are likely toinfluence the outcome of this intervention.For example, a physician might show frustration at having to give additionalreassurance to a patient who is not being counseled, or make earlier therapydecisions for patients who are being counseled. Patients being counseled mightreport fewer side-effects of other therapies or be more compliant, or be receivingsupport from other patients who are also in counseling. This exchange ofinformation will bias the effect of the intervention, and so it is easier to offer allof the patients of one hospital counseling, while those in a similar, nearby hospitalreceive no counseling. This enables us to see the impact of this interventionwithout the trial being contaminated by the cluster effect.142