Designing a stepped wedge trial: three main designs, carry-over effects and randomisation approaches.
BACKGROUND
There is limited guidance on the design of stepped wedge cluster randomised trials. Current methodological literature focuses mainly on trials with cross-sectional data collection at discrete times, yet many recent stepped wedge trials do not follow this design. In this article, we present a typology to characterise the full range of stepped wedge designs, and offer guidance on several other design aspects.


METHODS
We developed a framework to define and report the key characteristics of a stepped wedge trial, including cluster allocation and individual participation. We also considered the relative strengths and weaknesses of trials according to this framework. We classified recently published stepped wedge trials using this framework and identified illustrative case studies. We identified key design choices and developed guidance for each.


RESULTS
We identified three main stepped wedge designs: those with a closed cohort, an open cohort, and a continuous recruitment short exposure design. In the first two designs, many individuals experience both control and intervention conditions. In the final design, individuals are recruited in continuous time as they become eligible and experience either the control or intervention condition, but not both, and then provide an outcome measurement at follow-up. While most stepped wedge trials use simple randomisation, stratification and restricted randomisation are often feasible and may be useful. Some recent studies collect outcome information from individuals exposed a long time before or after the rollout period, but this contributes little to the primary analysis. Incomplete designs should be considered when the intervention cannot be implemented quickly. Carry-over effects can arise in stepped wedge trials with closed and open cohorts.


CONCLUSIONS
Stepped wedge trial designs should be reported more clearly. Researchers should consider the use of stratified and/or restricted randomisation. Trials should generally not commit resources to collect outcome data from individuals exposed a long time before or after the rollout period. Though substantial carry-over effects are uncommon in stepped wedge trials, researchers should consider their possibility before conducting a trial with closed or open cohorts.
MRC London Hub for Trials Methodology Research, MRC Clinical Trials Unit at University College London, Aviation House, 125 Kingsway, London, WC2B 6NH, UK. a.copas@ucl.ac.uk.
Andrew J
AJ
Copas
MRC Tropical Epidemiology Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK. James.Lewis@lshtm.ac.uk.
James J
JJ
Lewis
MRC London Hub for Trials Methodology Research, MRC Clinical Trials Unit at University College London, Aviation House, 125 Kingsway, London, WC2B 6NH, UK. Jennifer.Thompson@lshtm.ac.uk.|Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK. Jennifer.Thompson@lshtm.ac.uk.
Jennifer A
JA
Thompson
Department of Social and Environmental Health Research, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK. Calum.Davey@lshtm.ac.uk.
Calum
C
Davey
Department of Statistical Science, University College London, Gower Street, London, WC1E 6BT, UK. g.baio@ucl.ac.uk.
Gianluca
G
Baio
Department of Social and Environmental Health Research, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK. James.Hargreaves@lshtm.ac.uk.
James R
JR
Hargreaves
D015982:Bias; D006801:Humans; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D018401:Sample Size; D013997:Time Factors