This document discusses stepped wedge cluster randomized trial designs and recent related research. It provides background on cluster studies over time and describes traditional parallel and crossover cluster designs. It then explains classic and modified stepped wedge designs, issues in methodology, and recent related papers addressing topics like sample size calculations and extending CONSORT guidelines. Finally, it proposes future projects on developing CONSORT standards for stepped wedge trials and exploring designs beyond the standard stepped wedge like "dog leg" and ladder designs to improve efficiency.

1. CLAHRC West Midlands
Beyond Stepped-Wedge
Dog-legs, Ladders and a
CONSORT statement
Alan Girling, Karla Hemming
University of Birmingham
06/07/2016 CLAHRC West Midlands

2. CLAHRC West Midlands
Stepped Wedge Designs
The State of the Art

3. CLAHRC West Midlands
Background: Cluster Studies over Time
• In contrast to an RCT, the intervention is delivered to a
Cluster, or to all members of a Cluster
• Measurements taken over time
– On new individuals (Cross-sectional designs)
– Repeatedly, on the same individuals (‘Cohort’ design)
– Repeatedly, on a shifting sample of individuals (Open
Cohort)
• At any one time, all members of a cluster experience the
same experimental condition

4. CLAHRC West Midlands
‘Traditional’ Cluster Designs
Parallel Study
Clusters
Time 
Treated
Controls

5. CLAHRC West Midlands
‘Traditional’ Cluster Designs
Parallel Study Cross-Over Before & After
Clusters
Time 
Before & After with
Control Clusters

6. CLAHRC West Midlands
Stepped Designs
Classic (‘Complete’)
Stepped Wedge
SW with Transition
Periods (‘Incomplete’)
‘Extended’ SW
Clusters
Time 
‘Hybrid’
An Essential
Feature here is that
Reverse Cross-
Over is not allowed

7. CLAHRC West Midlands
Stepped Designs in Practice
• Why Stepped-Wedge?
– Service-Delivery Interventions
– Logistical constraints
– Opportunistic evaluations
• Stepped-Wedge designs in Healthcare
– Prevalence is Low but Increasing
– Systematic Reviews (Brown 2006, Mdege 2011, Beard 2015,
Martin 2016, Barker 6th June 2016)
– Landmark studies (EPOCH,…)
• SW designs have been widely criticised in some quarters
– Implementation Issues
– Limitations of the experimental setting (not specific to SW)
– Sometimes SW is the only feasible possibility for an evaluation

8. CLAHRC West Midlands
(Statistical) Methodology for SW
• In a stepped-design the proportion of measurements under the treated
condition increases with time.
(Time is a potential ‘Confounder’)
• ‘Standard’ Statistical Model (Hussey & Hughes, 2007)
– Additive treatment and time effects
– Observations not independent - Correlation structure reflects variation
between and within clusters through the ICC
(exactly as in standard model for parallel cluster studies)
– Model used for analysis and (especially) for sample size calculations
– Straightforward extensions available to some other correlation
structures, encompassing cross-sectional & cohort studies, time-varying
cluster effects, nested clusters…
• ‘Vertical Analysis’ has been proposed as an alternative
– Loss of information (but efficiency has not been studied??)

9. CLAHRC West Midlands
Issues for SW Methodology
• Many issues for SW are mirrored in other designs (hitherto ignored or
glossed over) and are related to the setting rather than the design per se.
• “Inclusion of time-effects is opaque, and unnecessary in ‘traditional’ designs”
– Omission of time-effects in a Parallel or Cross-Over design can inflate
standard errors and lead to loss of power
• “Additivity of time & treatment effects is unwarranted”.
– Additivity (on some scale) implicitly assumed whenever measurements
are taken at different times (including in Parallel Studies)
• “The methodology for SW designs is sensitive to mis-specification of the
correlation structure”
– This applies also to ALL traditional designs.
(the community is only beginning to come to terms with this.)
• SW suffers from natural “aversion to complexity”
– “Everything should be made as simple as possible, but not simpler”

10. CLAHRC West Midlands
Recent Papers
• Girling A.J. & Hemming K. (2016) Statistical efficiency and optimal design for stepped cluster
studies under linear mixed effects models. Statistics in Medicine DOI: 10.1002/sim.6850
• Hemming K & Taljaard M (2016) Sample size calculations for stepped wedge and cluster
randomised trials: a unified approach. J. Clin. Epidemiol. Jan;69:137-46. doi:
10.1016/j.jclinepi.2015.08.015. Epub 2015 Sep 5.
• James Martin, Monica Taljaard, Alan Girling, and Karla Hemming (2015) A systematic review
finds major deficiencies in sample size methodology and reporting for stepped wedge cluster
randomised trials. BMJ Open 2016;6:e010166 doi:10.1136/bmjopen-2015-010166
• Hemming K., Haines T.P., Chilton P.J , Girling A.J., Lilford R.J. (2015) The stepped wedge cluster
randomised trial: rationale, design, analysis and reporting. BMJ. BMJ 2015; 350 doi:
http://dx.doi.org/10.1136/bmj.h391
• Karla Hemming, Richard Lilford and Alan J. Girling (2015) Stepped-wedge cluster randomised
controlled trials: a generic framework including parallel and multiple-level designs. Statistics in
Medicine 34(2), 181-196. DOI: 10.1002/sim.6325
• K. Hemming and A.J. Girling (2014) A menu-driven facility for power and detectable-difference
calculations in stepped-wedge cluster-randomized trials The STATA Journal 14(2): 363-380
+ Conference/Workshop contributions
… SCT2015, Trials meeting, RSS, York, SCT2016, ISCB2016, …
SW & WM CLARHC
Karla Hemming, Richard Lilford, Alan Girling + Collaborators

11. CLAHRC West Midlands
Future Projects (1)
Extension of CONSORT statement to
SW cluster randomised controlled trials
Karla Hemming1
, Alan Girling1, Monica Taljaard2
, Andrew
Forbes3, Richard Lilford4 and Jeremy Grimshaw2
1 University of Birmingham, Birmingham, UK
2 Ottawa Hospital Research Institute, Ottawa, Canada
3 Monash University, Melbourne, Australia
4 University of Warwick, Coventry, UK

12. • The CONSORT (CONsolidated Standards of Reporting Trials)
guidelines are intended to improve the reporting of RCTs
• Consist of:
– Statement
– Checklist
– Explanation and Elaboration document
• Initially developed for the RCT, extensions exist for different trial
designs:
– Cluster trial etc. .
The CONSORT Statement
Schulz KF, Altman DG, Moher D, for the CONSORT Group. CONSORT 2010 Statement: updated
guidelines for reporting parallel group randomised trials. Ann Int Med 2010;152. Epub 24 March.

13.  Protocol registered with EQUATOR
 a searchable database of 317 reporting guidelines
 Includes existing CONSORT guidelines (also STROBE & PRISMA)
 Outline process:
 Systematic review of quality of reporting SW-CRTs published to date
(Martin et al, 2016)
WIP: Systematic review of
 Methodology
 current recommended reporting items for SW-CRTS
Progress to date

14.  Map reporting items identified from the review process to CONSORT
statement for cluster trials
 Identify advisory team – with expertise in cluster trials, reporting
statements, statistics, clinical trials, ethics, policy development …
 Consensus meeting Liverpool May 2017
– Produce
 Statement
 Checklist
 Explanation and Elaboration document
Next Steps

15.  Expert and skilled advisory team – who have ample experience in
developing reporting guidelines
 Following good practice guidelines for development
Following appropriate methodology

16. CLAHRC West Midlands
Future Projects (2)
Beyond Stepped Wedge
“Dog-Legs & Ladder-Designs”

17. CLAHRC West Midlands
Beyond Stepped-Wedge:
Staggered Implementation with incomplete observations
• Most (if not all?) methodological work has focussed on complete
rectangular designs
• Some studies have used incomplete designs – for logistical reasons,
e.g. to allow for transition between experimental conditions (non-
instantaneous implementation)
• What about (statistical) efficiency?
– Are complete designs better?

18. CLAHRC West Midlands
“Traditional” Cluster Designs:
Treatment effect computed by comparing unweighted “average”
treated outcome with unweighted “average” control.
So all experimental subjects have the same weighting,
irrespective of their position in the design.
0.125 0.125 0.125 0.125
0.125 0.125 0.125 0.125
-0.125 -0.125 -0.125 -0.125
-0.125 -0.125 -0.125 -0.125
0.125 0.125 -0.125 -0.125
0.125 0.125 -0.125 -0.125
-0.125 -0.125 0.125 0.125
-0.125 -0.125 0.125 0.125
-0.125 -0.125 0.125 0.125
-0.125 -0.125 0.125 0.125
-0.125 -0.125 0.125 0.125
-0.125 -0.125 0.125 0.125
Parallel Cross-Over Before & After

19. CLAHRC West Midlands
Stepped Wedge
-0.04 0.20 0.14 0.08 0.02 -0.04
-0.02 -0.08 0.16 0.10 0.04 -0.02
0.00 -0.06 -0.12 0.12 0.06 0.00
0.02 -0.04 -0.10 -0.16 0.08 0.02
0.04 -0.02 -0.08 -0.14 -0.20 0.04
0.00 0.24 0.13 0.09 0.06 0.00
0.00 -0.06 0.13 0.09 0.06 0.00
0.00 -0.06 -0.09 0.09 0.06 0.00
0.00 -0.06 -0.09 -0.13 0.06 0.00
0.00 -0.06 -0.09 -0.13 -0.24 0.00
Vertical Analysis Standard Model
(ICC =
0.025)
• Suggests the design could be improved(?) – by transferring some
observational effort from low-weight to high-weight cells
• If so (… it is!) the standard Stepped-Wedge is not an efficient design!
• Q: What do the efficient designs look like?
“The weighting varies with the position in the design”

20. CLAHRC West Midlands
RESEARCH QUESTIONS:
• To identify Efficient designs under different logistical
constraints.
• E.g. (for cross-sectional designs)
1. Fix total number of subjects over all clusters
2. Fix individual cluster sizes
3. As above, but with enforced empty cells (e.g.
transition periods)
• The solution to 1. is known
• There is an algorithm to solve 2. and 3. but its
consequences remain unexplored.

21. CLAHRC West Midlands
1. Fix Total number of observations.
The best design looks like:
OR
(Numbers of observations in each coloured cell are not equal in general.
In the first design these depend on the precise value of the ICC)
EITHER ICC ‘large’ ICC ‘small’

22. CLAHRC West Midlands
E.g. An optimal ‘Ladder’ Design
(with 6 groups of clusters) looks like:Clusters
Time 
(Uniform sampling rate over time – No. of observations  cell-width)
Treatment effect estimate is the difference between the (unweighted)
average treated outcome and the (unweighted) average control.

23. CLAHRC West Midlands
For 3 groups of clusters the ‘Best’ design is:
If the ICC is ‘small’, the first and last columns disappear,
and the best design is a “Dog-Leg” (cf. Hooper & Rourke 2014, 2015)

24. CLAHRC West Midlands
Prospects for optimal sampling
• When the total sample size is fixed, some of the optimal sampling
schemes offer realistic practical alternatives, especially if the number
of groups is small.
– Such designs may be more efficient than a complete SW with a
larger number of groups, or a simple parallel study.
– Details need further work.
• A similar approach can (probably) be applied where there are
enforced transition periods, or to handle more general cluster-level
constraints on the total sample size.
– WATCH THIS SPACE!

25. CLAHRC West Midlands
Further Information
Website: www.clahrc-wm.nihr.ac.uk
Twitter: @CLAHRC_WM
Sign up to our News Blog: http://eepurl.com/OMOEP
This work was funded by the National Institute of Health Research (NIHR)
Collaboration for Leadership in Applied Health Research and Care West
Midlands (CLAHRC WM). The views expressed are those of the author(s)
and not necessarily those of the NHS, NIHR, or Department of Health.