Introducing the stepped wedge cluster randomised trial (SW-CRT)

Defining features, some salient examples and implications of consent processes on bias

Karla Hemming

15/04/2023

Richard Lilford, Alan Girling, Monica Taljaard

Why do we need another method of evaluation?

Evaluation of policy and service delivery interventions

The Matching Michigan Study

“A conventional narrative might run thus… the intervention resulted in a reduction in..

outcomes.”

“The marked reduction in rates in English ICUs found in this study is likely part of a wider secular trend for a system-wide improvement in healthcare-associated infections.”

Bion J, Richardson A, Hibbert P, Beer J, Abrusci T, McCutcheon M, Cassidy J, Eddleston J, Gunning K, Bellingan G, Patten M, Harrison D; Matching Michigan Collaboration & Writing Committee. 'Matching Michigan': a 2-year stepped interventional programme to minimise central venous catheter-blood stream nfections in intensive care units in England. BMJ Qual Saf. 2013 Feb;22(2):110-23. doi: 10.1136/bmjqs-2012 001325. Epub 2012 Sep 20. PubMed PMID: 22996571; PubMed Central PMCID: PMC3585494.

Evidence based policy interventions

Working constraints• Stakeholder’s desires

• Pragmatic limitations

• A priori beliefs

How the SW-CRT can help• All clusters ultimately get

intervention

• Sequential roll out

• Robust evaluation

What is the SW-CRT?

The Stepped Wedge Cluster Randomised Trial

Example 1: The Devon Active Trial

Example 1: The Devon Active trial

• Population– 128 rural villages in Devon

• Intervention– Community level intervention

providing physical activity opportunities

• Outcome – Meeting physical activity

guidelines, assessed using postal surveys

• Cross-sectional design

Solomon E, Rees T, Ukoumunne OC, Metcalf B, Hillsdon M. The Devon Active Villages Evaluation (DAVE) trial of a community-level physical activityintervention in rural south-west England: a stepped wedge cluster randomised controlled trial. Int J Behav Nutr Phys Act. 2014 Jul 18;11:94. doi:10.1186/s12966-014-0094-z. PubMed PMID: 25198068; PubMed Central PMCID: PMC4105855.

Example 2: Depression management trial

Example 2: Depression management trial

Leontjevas R, Gerritsen DL, Smalbrugge M, Teerenstra S, Vernooij-Dassen MJ, Koopmans RT. A structural multidisciplinary approach to depression management in nursing-home residents: a multicentre, stepped-wedge cluster-randomised trial. Lancet. 2013 Jun 9;381(9885):2255-64. doi: 10.1016/S0140-6736(13)60590-5. Epub 2013 May 2. PubMed PMID: 23643110.

• Population– Nursing home residents

• Intervention– Structural approach to

depression management

• Outcome– Depression prevalence

• Cohort design

Does a randomised evaluation always mean a robust evaluation… ??

Importance of allocation concealment…

• Lack of concealment of allocation – Risk of selection bias

• In CRTs this means:– Avoid individual patient

recruitment– Routinely collected

outcome dataChalmers:

“Although one of the reasons that the streptomycin trial has become iconic is … random number tables …. it was because successful concealment of allocation”

Example of a CRT with lack of concealment of allocation

• Results in baseline imbalance

• Due to recruitment of individuals after allocation known

• Empirical evidence: occurs in about 40% of CRTs

Puffer S, Torgerson D, Watson J. Evidence for risk of bias in cluster randomised trials: review of recent trials published in three general medical journals. BMJ. 2003 Oct 4;327(7418):785-9. Review. PubMed PMID: 14525877; PubMed Central PMCID: PMC214092.

Implications for SW-CRTs

• Currently most SW-CRTs use individual patient recruitment – Risk of bias

• If we want to promote the SW-CRT – Need to minimise risk of

bias• Independent recruitment• Use routine outcome data

(no consent model)

The new EU clinical trials regulation (2014)

• New remit: cluster trials

• Standard care medicinal products

• Article 30: informed consent in cluster trials

• simplified consent

But – SW-CRTs rarely used to evaluate medicinal products.. Not important???

NHS Health Research Authority

• Scope– Medicinal products

and service delivery interventions

• Means of consent– Proportionate– Documented– Only exceptional

cases should waiver be used

Interpretation for medicinal products

• E.g. head to head trial of statins

– Explicit consent (short information leaflet)

– Deemed consent (posters in weighting room)

Implication for service delivery interventions

• E.g. pressure relieving mattress trial– Outcome routine data

• Recommendation – No consent sought for

intervention– Consent sought for

use of data

Implications for SW-CRTs

Medicinal products

• Simplified consent model

• Potential to improve generalisability

• Potential to lessen the risk of bias

Service delivery interventions

• Waiver of consent model less favoured

• Need for consent for outcome use

• Increase risk of bias

Summary

• SW-CRT a pragmatic study design which reconciles the need for robust evaluations with political or logistical constraints.

• Currently framework for the evaluation of SDIs:– No consent taken for intervention – Waiver of consent obtained for use of routine outcome data

• Implications for SDIs under new HRA guidance:– Need to obtain consent for use of routine outcome data? – (Simplified consent welcome for standard care medicinal

products)