LAUSR

Background In randomised controlled trials, the assumption of independence of individual observations is fundamental to the design, analysis and interpretation of studies. However, in individually randomised trials in primary care, this assumption may be violated because patients are naturally clustered within primary care practices. Ignoring clustering may lead to a loss of power or, in some cases, type I error. Methods Clustering can be quantified by intra-cluster correlation (ICC), a measure of the similarity between individuals within a cluster with respect to a particular outcome. We reviewed 17 trials undertaken by the Department of Primary Care at the University of Southampton over the last ten years. We calculated the ICC for the primary and secondary outcomes in each trial at the practice level and determined whether ignoring practice-level clustering still gave valid inferences. Where multiple studies collected the same outcome measure, the median ICC was calculated for that outcome. Results The median intra-cluster correlation (ICC) for all outcomes was 0.016, with interquartile range 0.00–0.03. The median ICC for symptom severity was 0.02 (interquartile range (IQR) 0.01 to 0.07) and for reconsultation with new or worsening symptoms was 0.01 (IQR 0.00, 0.07). For HADS anxiety the ICC was 0.04 (IQR 0.02, 0.05) and for HADS depression was 0.02 (IQR 0.00, 0.05). The median ICC for EQ. 5D-3 L was 0.01 (IQR 0.01, 0.04). Conclusions There is evidence of clustering in individually randomised trials primary care. The non-zero ICC suggests that, depending on study design, clustering may not be ignorable. It is important that this is fully considered at the study design phase.