Abstract
Background and Aims
There are fewer trials conducted in nephrology than any other speciality. Many trials fail to recruit to target and are therefore underpowered, resulting in unclear evidence and unlikely to be implemented into clinical practice. Carefully designed trials could improve the treatment options for haemodialysis patients. These could include designs other than individually randomised parallel group designs. We have reviewed cluster, stepped wedge and crossover randomised trials carried out in prevalent haemodialysis patients.
Method
A search for randomised controlled trials (RCTs) in haemodialysis patients was conducted across five databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) in October 2019. The first publication of a stepped wedge trial in haemodialysis was in 2013, so we searched from 2013-2019. Inclusion criteria were RCTs including adults receiving at least 3 months of haemodialysis. Once eligible studies were identified, we compared the sample size sections to the CONSORT requirements and extracted data on these parameters and assessed recruitment targets, attrition rates and primary outcome result.
Results
We identified 911 RCTs of which 13 (1.4%) cluster randomised trials, including one stepped wedge, and 145 (15.9%) crossover trials were identified. Data were extracted for 10 randomly selected crossover trials.
The total sample size required was not reported in 46% (n=6) cluster trials and 60% (n=6) crossover trials, with only 37.5% (n=3) of cluster trials and 50% (n=4) of crossover trials providing a justification for their sample size. In cluster trials, 13% (n=1) stated number of clusters required and 25% (n=2) gave the average cluster size, none of these stated the anticipated variance in cluster size and only 12.5% (n=1) stated the intracluster correlation (ICC) used to calculate the sample size, with none taking into account uncertainty in ICC. In 31% (n=4) of the cluster trials, the dialysis centre was the cluster and in the other 69% (n=9), the dialysis shift was the cluster. For crossover trials, within participant variability was only accounted for in 12.5% (n=1) of trials.
A CONSORT flow diagram was reported in 70% of the trials assessed, with 39% recruiting to target. There were also some differences seen between crossover and cluster designs. The average number of participants at the start of a cluster trial was 470, compared to 26 in crossover trials. Where able to assess, cluster trials had an average attrition rate of 25% this was lower in crossover trials, where the average attrition rate was 14%. Eighty five percent (n=11) of cluster trials had a primary outcome reaching statistical significance, however only 20% (n=2) of crossover trials reached statistical significance.
Conclusion
Cluster and crossover randomised trials are poorly reported. There was insufficient information provided for sample size calculations to be replicated in majority of trials. The average attrition rate was low in crossover trials, however a large proportion of these trials did not have a primary outcome reaching statistical significance, suggesting these trials could have been underpowered. Improvements in the design, conduct and reporting of cluster and crossover trials in the haemodialysis population is urgently required.
Power and sample size requirements for GEE analyses of cluster randomized crossover trials
