scholarly journals Equity and evidence during vaccine rollout: stepped wedge cluster randomised trials could help

BMJ ◽  
2021 ◽  
pp. n435
Author(s):  
Katy J L Bell ◽  
Paul Glasziou ◽  
Fiona Stanaway ◽  
Patrick Bossuyt ◽  
Les Irwig
Keyword(s):  
Randomised Trials ◽  
Stepped Wedge ◽  
Cluster Randomised Trials ◽  
Cluster Randomised

scholarly journals Group sequential designs for stepped-wedge cluster randomised trials

2017 ◽  
Vol 14 (5) ◽  
pp. 507-517 ◽  
Author(s):  
Michael J Grayling ◽  
James MS Wason ◽  
Adrian P Mander
Keyword(s):  
Randomised Trial ◽  
Cluster Randomised Trial ◽  
Type I ◽  
Randomised Trials ◽  
Early Stopping ◽  
Stepped Wedge ◽  
Group Sequential ◽  
Interim Analyses ◽  
Cluster Randomised Trials ◽  
Cluster Randomised

Background/Aims: The stepped-wedge cluster randomised trial design has received substantial attention in recent years. Although various extensions to the original design have been proposed, no guidance is available on the design of stepped-wedge cluster randomised trials with interim analyses. In an individually randomised trial setting, group sequential methods can provide notable efficiency gains and ethical benefits. We address this by discussing how established group sequential methodology can be adapted for stepped-wedge designs. Methods: Utilising the error spending approach to group sequential trial design, we detail the assumptions required for the determination of stepped-wedge cluster randomised trials with interim analyses. We consider early stopping for efficacy, futility, or efficacy and futility. We describe first how this can be done for any specified linear mixed model for data analysis. We then focus on one particular commonly utilised model and, using a recently completed stepped-wedge cluster randomised trial, compare the performance of several designs with interim analyses to the classical stepped-wedge design. Finally, the performance of a quantile substitution procedure for dealing with the case of unknown variance is explored. Results: We demonstrate that the incorporation of early stopping in stepped-wedge cluster randomised trial designs could reduce the expected sample size under the null and alternative hypotheses by up to 31% and 22%, respectively, with no cost to the trial’s type-I and type-II error rates. The use of restricted error maximum likelihood estimation was found to be more important than quantile substitution for controlling the type-I error rate. Conclusion: The addition of interim analyses into stepped-wedge cluster randomised trials could help guard against time-consuming trials conducted on poor performing treatments and also help expedite the implementation of efficacious treatments. In future, trialists should consider incorporating early stopping of some kind into stepped-wedge cluster randomised trials according to the needs of the particular trial.

scholarly journals Stepped-wedge cluster randomised trials: where, when and why?

Trials ◽  
2015 ◽  
Vol 16 (S2) ◽  
Author(s):  
Michael Grayling ◽  
James Wason ◽  
Adrian Mander
Keyword(s):  
Randomised Trials ◽  
Stepped Wedge ◽  
Cluster Randomised Trials ◽  
Cluster Randomised

scholarly journals Prevalence and Methodological Characteristics of Subgroup Analyses in Stepped Wedge Cluster Randomised Trials: Protocol for a Systematic Review

2020 ◽  
Author(s):  
Évèhouénou Lionel Adisso ◽  
Monica Taljaard ◽  
Louis-Paul Rivest ◽  
Hervé Tchala Vignon Zomahoun ◽  
Pierre Jacob Durand ◽  
...  
Keyword(s):  
Systematic Review ◽  
Statistical Methods ◽  
Open Science ◽  
Cochrane Library ◽  
Randomised Trials ◽  
Stepped Wedge ◽  
Cluster Randomised Trials ◽  
Cluster Randomised ◽  
Subgroup Analyses ◽  
Science Framework

Abstract Background: The stepped wedge cluster randomised trial is an increasingly common trial design. The design can be useful for informing real-world clinical decision-making, including decisions about the effectiveness of interventions in particular subgroups. However, there is little existing guidance about how to perform subgroup analyses in the stepped wedge design. We aim to determine the prevalence of subgroup analyses and describe statistical methods used to perform them in stepped wedge cluster randomised trials.Methods: We will conduct a systematic review following the methodology recommended in the Cochrane Handbook for Systematic Reviews of Interventions. We report this protocol according to the PRISMA-P checklist. The protocol has been registered in the Open Science Framework. We will search for terms related to ‘stepped wedge’. Sources will be PubMed, Embase, PsycINFO, Web of Science, CINAHL, Cochrane Library, and Current Controlled Trials Register up to 16 October 2020. Studies will be eligible if they are written in English, involve human participants and are primary or secondary reports of planned or completed stepped wedge cluster randomised trials. Two reviewers will first screen the titles and abstracts, then full texts, to select studies that should be included in the review. Disagreements will be solved by consensus through discussion with a third reviewer. We will extract data related to study characteristics including presence or absence of subgroup analyses, characteristics of subgroup variables examined, statistical methods used to perform subgroup analyses, and adherence to the most consistently recommendations suggested for subgroup analyses in general including in clinical trials. We will perform a qualitative synthesis of the extracted data.Discussion: This protocol offers a reproducible and transparent procedure for a systematic review of the literature. It will provide a portrait of the frequency and types of subgroup analyses performed in stepped wedge cluster randomised trials. These results will inform the development of recommendations for subgroup analyses in such trials.Systematic review registration: This protocol has been registered on Open Science Framework, Registration ID: https://osf.io/2kwrz.

scholarly journals Reporting of stepped wedge cluster randomised trials: extension of the CONSORT 2010 statement with explanation and elaboration

BMJ ◽  
2018 ◽  
pp. k1614 ◽  
Author(s):  
Karla Hemming ◽  
Monica Taljaard ◽  
Joanne E McKenzie ◽  
Richard Hooper ◽  
Andrew Copas ◽  
...  
Keyword(s):  
Randomised Trials ◽  
Stepped Wedge ◽  
Cluster Randomised Trials ◽  
Cluster Randomised

Inference for the treatment effect in multiple-period cluster randomised trials when random effect correlation structure is misspecified

2018 ◽  
Vol 28 (10-11) ◽  
pp. 3112-3122 ◽  
Author(s):  
Jessica Kasza ◽  
Andrew B Forbes
Keyword(s):  
Treatment Effect ◽  
Random Effect ◽  
Correlation Structure ◽  
Randomised Trials ◽  
Stepped Wedge ◽  
Cluster Randomised Trials ◽  
Cluster Randomised ◽  
Complex Models ◽  
The Impact ◽  
Cluster Correlation

Multiple-period cluster randomised trials, such as stepped wedge or cluster cross-over trials, are being conducted with increasing frequency. In the design and analysis of these trials, it is necessary to specify the form of the within-cluster correlation structure, and a common assumption is that the correlation between the outcomes of any pair of subjects within a cluster is identical. More complex models that allow for correlations within a cluster to decay over time have recently been suggested. However, most software packages cannot fit these models. As a result, practitioners may choose a simpler model. We analytically examine the impact of incorrectly omitting a decay in correlation on the variance of the treatment effect estimator and show that misspecification of the within-cluster correlation structure can lead to incorrect conclusions regarding estimated treatment effects for stepped wedge and cluster crossover trials.

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