Cluster randomised trials have diminishing returns in power and precision as cluster size increases. Making the cluster a lot larger while keeping the number of clusters fixed might yield only a very small increase in power and precision, owing to the intracluster correlation. Identifying the point at which observations start making a negligible contribution to the power or precision of the study—which we call the point of diminishing returns—is important for designing efficient trials. Current methods for identifying this point are potentially useful as rules of thumb but don’t generally work well. We introduce several practical aids to help researchers design cluster randomised trials in which all observations make a material contribution to the study. Power curves enable identification of the point at which observations begin to make a negligible contribution to a study for a given target difference. Under this paradigm, the number needed per arm under individual randomisation gives an upper bound on the cluster size, which should not be exceeded. Corresponding precision curves can be useful for accommodating flexibility in the choice of target difference and show the point at which confidence intervals around the estimated effect size no longer decrease. To design efficient trials, the number of clusters and cluster size should be determined concurrently, not independently. Funders and researchers should be aware of diminishing returns in cluster trials. Researchers should routinely plot power or precision curves when performing sample size calculations so that the implications of cluster sizes can be transparent. Even when data appear to be “free,” in the sense that few resources are needed to obtain the data, excessive cluster sizes can have important ramifications

This is a repository copy of Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH) : a stepped-wedge cluster-randomised trial. Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH) : a stepped-wedge cluster-randomised trial. The Lancet. ISSN 0140-6736 https://doi.org/10.1016/S0140-6736(18)32521-2 eprints@whiterose.ac.uk https://eprints.whiterose.ac.uk/ ReuseThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs (CC BY-NC-ND) licence. This licence only allows you to download this work and share it with others as long as you credit the authors, but you can't change the article in any way or use it commercially. More information and the full terms of the licence here: https://creativecommons.org/licenses/ Implications of all the available evidenceDespite the success of some smaller projects, there was no survival benefit from a national quality improvement programme to implement a care pathway for patients undergoing emergency abdominal surgery. To succeed, large national quality improvement programmes need to allow for differences between hospitals and ensure teams have both the time and resources needed to improve patient care.

BackgroundCluster randomised trials (CRTs) are commonly analysed using mixed-effects models or generalised estimating equations (GEEs). However, these analyses do not always perform well with the small number of clusters typical of most CRTs. They can lead to increased risk of a type I error (finding a statistically significant treatment effect when it does not exist) if appropriate corrections are not used.MethodsWe conducted a small simulation study to evaluate the impact of using small-sample corrections for mixed-effects models or GEEs in CRTs with a small number of clusters. We then reanalysed data from TRIGGER, a CRT with six clusters, to determine the effect of using an inappropriate analysis method in practice. Finally, we reviewed 100 CRTs previously identified by a search on PubMed in order to assess whether trials were using appropriate methods of analysis. Trials were classified as at risk of an increased type I error rate if they did not report using an analysis method which accounted for clustering, or if they had fewer than 40 clusters and performed an individual-level analysis without reporting the use of an appropriate small-sample correction.ResultsOur simulation study found that using mixed-effects models or GEEs without an appropriate correction led to inflated type I error rates, even for as many as 70 clusters. Conversely, using small-sample corrections provided correct type I error rates across all scenarios. Reanalysis of the TRIGGER trial found that inappropriate methods of analysis gave much smaller P values (P ≤ 0.01) than appropriate methods (P = 0.04–0.15). In our review, of the 99 trials that reported the number of clusters, 64 (65 %) were at risk of an increased type I error rate; 14 trials did not report using an analysis method which accounted for clustering, and 50 trials with fewer than 40 clusters performed an individual-level analysis without reporting the use of an appropriate correction.ConclusionsCRTs with a small or medium number of clusters are at risk of an inflated type I error rate unless appropriate analysis methods are used. Investigators should consider using small-sample corrections with mixed-effects models or GEEs to ensure valid results.

Summary Background Sperm selection strategies aimed at improving success rates of intracytoplasmic sperm injection (ICSI) include binding to hyaluronic acid (herein termed hyaluronan). Hyaluronan-selected sperm have reduced levels of DNA damage and aneuploidy. Use of hyaluronan-based sperm selection for ICSI (so-called physiological ICSI [PICSI]) is reported to reduce the proportion of pregnancies that end in miscarriage. However, the effect of PICSI on livebirth rates is uncertain. We aimed to investigate the efficacy of PICSI versus standard ICSI for improving livebirth rates among couples undergoing fertility treatment. Methods This parallel, two-group, randomised trial included couples undergoing an ICSI procedure with fresh embryo transfer at 16 assisted conception units in the UK. Eligible women (aged 18–43 years) had a body-mass index of 19–35 kg/m 2 and a follicle-stimulating hormone (FSH) concentration of 3·0–20·0 mIU/mL or, if no FSH measurement was available, an anti-müllerian hormone concentration of at least 1·5 pmol/L. Eligible men (aged 18–55 years) had not had a vasovasostomy or been treated for cancer in the 24 months before recruitment and were able, after at least 3 days of sexual abstinence, to produce freshly ejaculated sperm for the treatment cycle. Couples were randomly assigned (1:1) with an online system to receive either PICSI or a standard ICSI procedure. The primary outcome was full-term (≥37 weeks' gestational age) livebirth, which was assessed in all eligible couples who completed follow-up. This trial is registered, number ISRCTN99214271. Findings Between Feb 1, 2014, and Aug 31, 2016, 2772 couples were randomly assigned to receive PICSI (n=1387) or ICSI (n=1385), of whom 2752 (1381 in the PICSI group and 1371 in the ICSI group) were included in the primary analysis. The term livebirth rate did not differ significantly between PICSI (27·4% [379/1381]) and ICSI (25·2% [346/1371]) groups (odds ratio 1·12, 95% CI 0·95–1·34; p=0·18). There were 56 serious adverse events in total, including 31 in the PICSI group and 25 in the ICSI group; most were congenital abnormalities and none were attributed to treatment. Interpretation Compared with ICSI, PICSI does not significantly improve term livebirth rates. The wider use of PICSI, therefore, is not recommended at present. Funding National Institute for Health Research Efficacy and Mechanism Evaluation Programme.

Nurse residency programs are designed to support graduate nurses as they assume the professional role. Evaluation of these programs has been inconsistent. The purpose of this descriptive research study was to evaluate a year-long nurse residency program using a nonexperimental, repeated measures design with qualitative questions. Results showed statistically significant differences in new nurse confidence, skills, and abilities at 12 months. Nursing turnover was one third of the national average. The metatheme that emerged from the data was "I see that I am not the only one."