An introduction to the stepped wedge cluster randomised trial, by Dr Karla Hemming for the CLAHRC West Midlands Scientific Advisory Group meeting, 9th June 2015, Birmingham, UK

1. Introducing the stepped wedge cluster
randomised trial (SW-CRT)
Defining features, some salient examples and implications of
consent processes on bias
Karla Hemming
12/06/2015
Richard Lilford, Alan Girling, Monica Taljaard

2. Why do we need another method of
evaluation?

3. 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.

4. 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

5. What is the SW-CRT?

6. The Stepped Wedge Cluster Randomised Trial

7. Example 1: The Devon Active Trial

8. 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 activity
intervention 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.

9. Example 2: Depression management trial

10. 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

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

12. Importance of allocation concealment…
• Lack of concealment
of allocation
– Risk of selection bias
• In CRTs this means:
– Avoid individual patient
recruitment
– Routinely collected
outcome data
Chalmers:
“Although one of the reasons that the streptomycin trial has
become iconic is … random number tables …. it was
because successful concealment of allocation”

13. 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.

14. 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)

15. 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???

16. NHS Health Research Authority
• Scope
– Medicinal products
and service delivery
interventions
• Means of consent
– Proportionate
– Documented
– Only exceptional
cases should waiver
be used

17. Interpretation for medicinal products
• E.g. head to head trial
of statins
– Explicit consent (short
information leaflet)
– Deemed consent
(posters in weighting
room)

18. 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

19. 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

20. 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)