Clinical Trials

❘❙❚■ Chapter 15 | Cluster Randomized TrialsConclusionIn clinical research, CRTs have already become an important tool for the effectiveevaluation of health care interventions, in particular at the level of primary andsecondary health care institutes across a certain geographical area. In this chapter,we have illustrated various aspects of design and analysis using appropriatestatistical methods particular to CRTs, and discussed the ethical implications ofthis experimental design.We have highlighted that a cluster effect can influence or bias trial outcomes,particularly when the intervention cannot be blinded (such as organizationalinterventions offering additional services), and can lead to an over-inflation ofa treatment effect if this bias is not accounted for. It is also important torecognize that publication of CRT results need to follow CONSORT guidelines,and include (in particular) power calculations and statistical methods dealing withthe cluster effect. Further advanced issues regarding CRTs can be found inreferences [12,21,22].References1. Campbell M, Grimshaw J, Steen N. Sample size calculations for cluster randomized trials.Changing Professional Practice in Europe Group (EU BIOMED II Concerted Action).J Health Serv Res Policy 2000;5:12–16.2. Donner A, Klar N. Methods for comparing event rates in intervention studies when the unitof allocation is a cluster. Am J Epidemiol 1994;140:279–89.3. Donner A, Birkett N, Buck C. Randomization by cluster: sample size requirements and analysis.Am J Epidemiol 1981;114:906–14.4. Campbell MK, Grimshaw JM. Cluster randomized trials: time for improvement. The implicationsof adopting a cluster design are still largely being ignored. BMJ 1998;317:1171–2.5. Fayers PM, Jordhoy MS, Kaasa S. Cluster-randomized trials. Palliat Med 2002;16:69–70.6. Chuang JH, Hripcsak G, Heitjan DF. Design and analysis of controlled trials in naturallyclustered environments: implications for medical informatics. J Am Inform Assoc 2002;9:230–8.7. Cornfield J. Randomization by group: a formal analysis. Am J Epidemiol 1978;108:100–2.8. Donner A. An empirical study of cluster randomization. Int J Epidemiol 1982;11:283–6.9. Kerry SM, Bland JM. The intra-cluster correlation coefficient in cluster randomization.BMJ 1998;316:1455.10. Clinical Trials and Evaluation Unit. Study Protocol: PROMIS-UK ‘Prospective Registry ofOutcomes and Management in acute Ischaemic Syndromes-in United Kingdom.’ An ongoing trial.Designed by: Clinical Trials and Evaluation Unit, Royal Brompton and Harefield NHS Trust,Sydney Street, London. Personal communication, May 5, 2005.11. Mollison JA, Simpson JA, Campbell MK, et al. Comparison of analytical methods for clusterrandomized trials: an example from a primary care setting. J Epidemiol Biostat 2000;5:339–48.12. Donner A, Klar N. Design and Analysis of Cluster Randomization Trials in Health Research.London: Arnold, 2000.150