Design and analysis of clinical trials with clustering effects due to treatment
Design and analysis of clinical trials with clustering effects due to treatment
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DOI：
10.1191/1740774505cn076oa
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发表时间：
2005-01-01
期刊：
影响因子：
2.7
通讯作者：
Roberts, SA
中科院分区：
文献类型：
--
作者：
Roberts, C;Roberts, SA
当患者作为一组接受治疗时，有充分的理论理由相信，同一组中治疗的患者的结果差异将小于不同组中治疗的患者的结果差异。类似地，当不同的治疗师治疗不同的患者组时，由同一治疗师治疗的患者的结果可能比由不同治疗师治疗的患者的结果差异更小。评估此类疗法的临床试验需要考虑这种潜在的独立性缺乏。与整群随机试验一样，这对治疗效果估计的精确度和统计功效有影响。然而，由于治疗组织而导致的聚类与由于随机化而导致的聚类之间存在差异。在整群随机试验中，每个治疗组的整群大小分布应与随机化的结果相似，除非随访损失存在差异。由于治疗组或治疗师造成的聚类，由于治疗组的规模或不同的健康专业病例量，治疗组之间的聚类大小可能会系统性地不同。治疗组之间的簇内相关性也可能不同。不同簇大小和簇内相关性对设计和分析的影响将通过两项试验的数据来说明，第一项试验比较护士执业护理与全科医生护理，第二项比较团体治疗与通常的个体治疗。使用模拟研究详细检查团体治疗或治疗师与非集群治疗进行比较的特殊情况。解决了差异聚类效应对样本大小和功效的影响。有人认为，此类试验的设计和分析应考虑簇大小和簇内相关性方面可能存在的异质性。
Where patients receive therapy as a group, there are good theoretical reasons to believe that variation in the outcome will be smaller for patients treated in the same group than for patients treated in different groups. Similarly, where different therapists treat different groups of patients, outcome for patients treated by the same therapist may differ less than outcome for patients treated by different therapists. Clinical trials evaluating such therapies need to consider this potential lack of independence. As with cluster-randomized trials, this has implications for the precision of treatment effects estimates and statistical power. There are nevertheless differences between clustering due to the organization of treatment and that due to randomization. In cluster-randomized trials the distribution of cluster sizes in each treatment arm should be similar as a consequence of randomization unless there is differential loss to follow-up. With clustering due to therapy group or therapist, cluster size may differ systematically between treatment arms, due to size of therapy groups or differing health professional caseload. Intra-cluster correlation may also differ between treatment arms. The implications of differential cluster size and intracluster correlation for design and analysis will be illustrated by data from two trials, the first comparing nurse practitioner care with general practitioner care, and the second comparing a group therapy with individual treatment as usual. The special case where a group therapy or therapist is compared with an unclustered treatment is examined in detail using a simulation study. The implications of differential clustering effects for sample size and power are addressed. It is argued that the design and analysis of this type of trial should take account of possible heterogeneity in cluster size and intracluster correlation.