Reflection on modern methods: when is a stepped-wedge cluster randomized trial a good study design choice?

Karla Hemming, Monica Taljaard, Karla Hemming, Monica Taljaard

Abstract

The stepped-wedge cluster randomized trial (SW-CRT) involves the sequential transition of clusters (such as hospitals, public health units or communities) from control to intervention conditions in a randomized order. The use of the SW-CRT is growing rapidly. Yet the SW-CRT is at greater risks of bias compared with the conventional parallel cluster randomized trial (parallel-CRT). For this reason, the CONSORT extension for SW-CRTs requires that investigators provide a clear justification for the choice of study design. In this paper, we argue that all other things being equal, the SW-CRT is at greater risk of bias due to misspecification of the secular trends at the analysis stage. This is particularly problematic for studies randomizing a small number of heterogeneous clusters. We outline the potential conditions under which an SW-CRT might be an appropriate choice. Potentially appropriate and often overlapping justifications for conducting an SW-CRT include: (i) the SW-CRT provides a means to conduct a randomized evaluation which otherwise would not be possible; (ii) the SW-CRT facilitates cluster recruitment as it enhances the acceptability of a randomized evaluation either to cluster gatekeepers or other stakeholders; (iii) the SW-CRT is the only feasible design due to pragmatic and logistical constraints (for example the roll-out of a scare resource); and (iv) the SW-CRT has increased statistical power over other study designs (which will include situations with a limited number of clusters). As the number of arguments in favour of an SW-CRT increases, the likelihood that the benefits of using the SW-CRT, as opposed to a parallel-CRT, outweigh its risks also increases. We argue that the mere popularity and novelty of the SW-CRT should not be a factor in its adoption. In situations when a conventional parallel-CRT is feasible, it is likely to be the preferred design.

Keywords: Cluster randomized trial; design justification; stepped-wedge.

© The Author(s) 2020. Published by Oxford University Press on behalf of the International Epidemiological Association.

Figures

Figure 1
Figure 1
Schematic illustration of the parallel cluster randomized trial and the stepped-wedge cluster randomsed trial. (a) Parallel cluster randomized trial (parallel-CRT); (b) stepped-wedge cluster randomized trial (SW-CRT).

References

    1. Murray DM. Design and Analysis of Group Randomized Trials. New York, NY: Oxford University Press, 1998.
    1. Donner A, Klar N.. Pitfalls of and controversies in cluster randomization trials. Am J Public Health 2004;94:416–22.
    1. Eldridge S, Kerry S.. A Practical Guide to Cluster Randomized Trials in Health Services Research. Chichester, UK: Wiley, 2012
    1. Ellenberg SS. The stepped-wedge clinical trial: evaluation by rolling deployment. JAMA 2018;319:607–08.
    1. Brown CA, Lilford RJ.. The stepped wedge trial design: a systematic review. BMC Med Res Methodol 2006;6:54..
    1. Grayling MJ, Wason JM, Mander AP.. Stepped wedge cluster randomized controlled trial designs: a review of reporting quality and design features. Trials 2017;18:33..
    1. Taljaard M, Hemming K, Shah L, Giraudeau B, Grimshaw JM, Weijer C.. Inadequacy of ethical conduct and reporting of stepped wedge cluster randomized trials: Results from a systematic review. Clin Trials 2017;14:333–41.
    1. Haines TP, Hemming K.. Stepped-wedge cluster-randomized trials: level of evidence, feasibility and reporting. J Physiother 2018;64:63–66.
    1. Hargreaves JR, Copas AJ, Beard E. et al. Five questions to consider before conducting a stepped wedge trial. Trials 2015;16:350..
    1. Doussau A, Grady C.. Deciphering assumptions about stepped wedge designs: the case of Ebola vaccine research. J Med Ethics 2016;42:797–804.
    1. Binik A. Delaying and withholding interventions: ethics and the stepped wedge trial. J Med Ethics 2019;45:662–67.
    1. Higgins JPT, Sterne JAC, Savović J. et al. A revised tool for assessing risk of bias in randomized trials. Cochrane Database Syst Rev 2016;10:1.
    1. Eldridge S, Campbell M, Campbell M, Dahota A, Giraudeau B, Higgins J. Barney Reeves and Nandi Siegfried Revised Cochrane risk of bias tool for randomized trials (RoB 2.0) Additional considerations for cluster randomized trials. 2016. Working Paper.
    1. Hemming K, Taljaard M, Forbes A.. Analysis of cluster randomized stepped wedge trials with repeated cross-sectional samples. Trials 2017;18:110..
    1. Hussey MA, Hughes JP.. Design and analysis of stepped wedge cluster randomized trials. Contemp Clin Trials 2007;28:182–91.
    1. Hooper R, Teerenstra S, de Hoop E, Eldridge S.. Sample size calculation for stepped wedge and other longitudinal cluster randomized trials. Stat Med 2016;35:4718–28.
    1. Kasza J, Hemming K, Hooper R, Matthews J, Forbes AB.. Impact of non-uniform correlation structure on sample size and power in multiple-period cluster randomized trials. Stat Methods Med Res 2019;28:703–16.
    1. Grantham KL, Kasza J, Heritier S, Hemming K, Forbes AB.. Accounting for a decaying correlation structure in cluster randomized trials with continuous recruitment. Stat Med 2019;38:1918–34.
    1. Thompson JA, Fielding KL, Davey C, Aiken AM, Hargreaves JR, Hayes RJ.. Bias and inference from misspecified mixed-effect models in stepped wedge trial analysis. Stat Med 2017;36:3670–82.
    1. Kasza J, Forbes AB.. Inference for the treatment effect in multiple-period cluster randomized trials when random effect correlation structure is misspecified. Stat Methods Med Res 2019;28:3112–22.
    1. Caille A, Kerry S, Tavernier E, Leyrat C, Eldridge S, Giraudeau B.. Timeline cluster: a graphical tool to identify risk of bias in cluster randomized trials. BMJ 2016;354:i4291.
    1. Puffer S, Torgerson D, Watson J.. Evidence for risk of bias in cluster randomized trials: review of recent trials published in three general medical journals. BMJ 2003;327:785–89.
    1. Bolzern J, Mnyama N, Bosanquet K, Torgerson DJ.. A review of cluster randomized trials found statistical evidence of selection bias. J Clin Epidemiol 2018;99:106–12.
    1. Eldridge S, Kerry S, Torgerson DJ.. Bias in identifying and recruiting participants in cluster randomized trials: what can be done? BMJ 2009;339:b4006.
    1. Giraudeau B, Ravaud P.. Preventing bias in cluster randomized trials. PLoS Med 2009;6:e1000065..
    1. Taljaard M, Weijer C, Grimshaw JM, Eccles MP.. The Ottawa Statement on the ethical design and conduct of cluster randomized trials: precis for researchers and research ethics committees. BMJ 2013;346:f2838.
    1. Copas AJ, Lewis JJ, Thompson JA, Davey C, Baio G, Hargreaves JR.. Designing a stepped wedge trial: three main designs, carry-over effects and randomization approaches. Trials 2015;16:352..
    1. Hemming K, Taljaard M, McKenzie JE. et al. Reporting of stepped wedge cluster randomized trials: extension of the CONSORT 2010 statement with explanation and elaboration. BMJ 2018;363:k1614.
    1. Ivers NM, Halperin IJ, Barnsley J. et al. Allocation techniques for balance at baseline in cluster randomized trials: a methodological review. Trials 2012;13:120..
    1. Li F, Turner EL, Heagerty PJ, Murray DM, Vollmer WM, DeLong ER.. An evaluation of constrained randomization for the design and analysis of group-randomized trials with binary outcomes. Stat Med 2017;36:3791–806.
    1. Moulton LH, Golub JE, Durovni B. et al. Statistical design of THRio: a phased implementation clinic-randomized study of a tuberculosis preventive therapy intervention. Clin Trials 2007;4:190–99.
    1. Ayorinde JO, Summers DM, Pankhurst L. et al. PreImplantation Trial of Histopathology In renal Allografts (PITHIA): a stepped-wedge cluster randomized controlled trial protocol. BMJ Open 2019;9:e026166.
    1. Edwards SJ, Braunholtz DA, Lilford RJ, Stevens AJ.. Ethical issues in the design and conduct of cluster randomized controlled trials. BMJ 1999;318:1407–09.
    1. Prost A, Binik A, Abubakar I. et al. Logistic, ethical, and political dimensions of stepped wedge trials: critical review and case studies. Trials 2015;16:351..
    1. Hemming K, Lilford R, Girling AJ.. Stepped-wedge cluster randomized controlled trials: a generic framework including parallel and multiple-level designs. Stat Med 2015;34:181–96.
    1. Heim N, van Stel HF, Ettema RG, van der Mast RC, Inouye SK, Schuurmans MJ.. HELP! Problems in executing a pragmatic, randomized, stepped wedge trial on the Hospital Elder Life Program to prevent delirium in older patients. Trials 2017;18:220..
    1. Girling AJ. Relative efficiency of unequal cluster sizes in stepped wedge and other trial designs under longitudinal or cross-sectional sampling. Stat Med 2018. doi: 10.1002/sim.7943.
    1. Hemming K, Eldridge S, Forbes G, Weijer C, Taljaard M.. How to design efficient cluster randomized trials. BMJ 2017;358:j3064.
    1. Campbell MK, Fayers PM, Grimshaw JM.. Determinants of the intracluster correlation coefficient in cluster randomized trials: the case of implementation research. Clin Trials 2005;2:99–107.
    1. Campbell MK, Grimshaw JM, Elbourne DR.. Intracluster correlation coefficients in cluster randomized trials: empirical insights into how should they be reported. BMC Med Res Methodol 2004;4:9..
    1. Cook JA, Bruckner T, MacLennan GS, Seiler CM.. Clustering in surgical trials - database of intracluster correlations. Trials 2012;13:2.
    1. Hemming K, Taljaard M.. Sample size calculations for stepped wedge and cluster randomized trials: a unified approach. J Clin Epidemiol 2016;69:137–46.
    1. Hemming K, Taljaard M, Forbes A.. Modeling clustering and treatment effect heterogeneity in parallel and stepped-wedge cluster randomized trials. Stat Med 2018;37:883–98.
    1. Hughes JP, Granston TS, Heagerty PJ.. Current issues in the design and analysis of stepped wedge trials. Contemp Clin Trials 2015. Nov;45:55–60.

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