Stepped-wedge trial

A stepped-wedge trial (or SWT) is a type of randomised controlled trial (or RCT), a scientific experiment which is structured to reduce bias when testing new medical treatments, social interventions, or other testable hypotheses. In a traditional RCT, half of the participants in the experiment are simultaneously and randomly assigned to a group that receives the treatment (the "treatment group") and half to a group that does not (the "control group"). In an SWT, typically a logistical constraint prevents the simultaneous treatment of half of the participants, and instead, participants receive the treatment in "waves" or "clusters."

For instance, suppose a researcher wanted to measure whether teaching college students how to make several meals increased their propensity to cook at home instead of eating out. In a traditional RCT, a sample of students would be selected and half would be trained on how to cook these meals, whereas the other half would not. Both groups would be monitored to see how frequently they ate out. In the end, the number of times the treatment group ate out would be compared to the number of times the control group ate out, most likely with a t-test or some variant. If, however, the researcher could only train a limited number of students each week, then the researcher could employ an SWT, randomly assigning students to which week they would be trained. In an SWT, a classic t-test is inappropriate, and different statistical methods must be used.

The term "stepped wedge" was coined by the Gambia Hepatitis Intervention Study due to the stepped-wedge shape that is apparent from a schematic illustration of the design.[1] The crossover is in one direction, typically from control to intervention, with the intervention not removed once implemented. The stepped-wedge design can be used for individually randomised trials,[2][3] i.e., trials where each individual is treated sequentially, but is more commonly used as a cluster randomised trial (CRT),[4] as in our example of groups of students being assigned to different weeks to be trained.

Experiment Design and Data Collection

In the context of a cluster randomised trial, the stepped-wedge design involves the collection of observations during a baseline period in which no clusters are exposed to the intervention. Following this, at regular intervals, or steps, a cluster (or group of clusters) is randomised to receive the intervention[4][5] and all participants are once again measured.[6] This process continues until all clusters have received the intervention. Finally, one more measurement is made after all clusters have received the intervention.

Model

While there are several other potential methods for modeling outcomes in an SWT,[7] the work of Hussey and Hughes[6] "first described methods to determine statistical power available when using a stepped wedge design."[7] What follows is their design.

Suppose there are samples divided into clusters. At each time point , preferably equally spaced in actual time, some number of clusters are treated. Let be if cluster has been treated at time and otherwise. In particular, note that if then .

For each participant in cluster , measure the outcome to be studied at time . We model these outcomes as

where

  • is a grand mean,
  • is a random, cluster-level effect on the outcome,
  • is a time point-specific fixed effect,
  • is the measured effect of the treatment, and
  • is the residual noise.

This model can be viewed as a Hierarchical linear model where at the lowest level where is the mean of a given cluster at a given time, and at the cluster level, each cluster mean .

Advantages

The primary advantage of the SWT is that it "can reconcile the need for robust evaluations with political or logistical constraints."[7] Specifically, when resources for performing an intervention are scarce, it can be used to measure the effects of treatment even when a treatment and control group cannot be compared simultaneously.

Disadvantages

In an SWT, more clusters are exposed to the intervention at later than earlier time periods. As such, it is possible that an underlying temporal trend may confound the intervention effect, and so the confounding effect of time must be accounted for in both pre-trial power calculations and post-trial analysis. [4][8][7]

The design and analysis of stepped-wedge trials is therefore more complex than for other types of randomised trials. Previous systematic reviews highlighted the poor reporting of sample size calculations and a lack of consistency in the analysis of such trials.[4][5] Hussey and Hughes were the first authors to suggest a structure and formula for estimating power in stepped-wedge studies in which data was collected at each and every step.[6] This has now been expanded for designs in which observations are not made at each step as well as multiple layers of clustering.[9] Additionally, a design effect (used to inflate the sample size of an individually randomised trial to that required in a cluster trial) has been established,[10] which has shown that the stepped wedge CRT could reduce the number of patients required in the trial compared to other designs.[10][11][12]

Ongoing Work

The number of studies using the design have been on the increase. In 2015, a thematic series was published in the journal Trials.[13] In 2016, the first international conference dedicated to the topic was held at the University of York.[14][15]

References

  1. ↑ The Gambia Hepatitis Study Group, The Gambia Hepatitis Intervention Study, Cancer Research, 1987;47(21):5782–87.
  2. ↑ Ratanawongsa N, Handley MA, Quan J, Sarkar U, Pfeifer K, Soria C, et al, Quasi-experimental trial of diabetes Self-Management Automated and Real-Time Telephonic Support (SMARTSteps) in a Medicaid managed care plan: study protocol., BMC health services research, 2012;12:22.
  3. ↑ Lohaugen GCC, Beneventi H, Andersen GL, Sundberg C, Ostgard HF, Bakkan E, et al., Do children with cerebral palsy benefit from computerized working memory training? Study protocol for a randomized controlled trial., Trials, 2014;15(1).
  4. 1 2 3 4 Brown CA, Lilford RJ. The stepped wedge trial design: a systematic review. BMC medical research methodology. 2006;6:54.
  5. 1 2 Mdege ND, Man MS, Taylor Nee Brown CA, Torgerson DJ. Systematic review of stepped wedge cluster randomized trials shows that design is particularly used to evaluate interventions during routine implementation. Journal of clinical epidemiology. 2011;64(9):936–48.
  6. 1 2 3 Hussey MA, Hughes JP. Design and analysis of stepped wedge cluster randomized trials. Contemp Clin Trials. 2007;28(2):182–91
  7. 1 2 3 4 Hemming, K.; Haines, T. P.; Chilton, P. J.; Girling, A. J.; Lilford, R. J. (2015-02-06). "The stepped wedge cluster randomised trial: rationale, design, analysis, and reporting". BMJ. 350: h391. doi:10.1136/bmj.h391. ISSN 1756-1833. PMID 25662947.
  8. ↑ Van den Heuvel ER, Zwanenburg RJ, Van Ravenswaaij-Arts CM. A stepped wedge design for testing an effect of intranasal insulin on cognitive development of children with Phelan-McDermid syndrome: A comparison of different designs. Statistical methods in medical research. 2014.
  9. ↑ Hemming K, Lilford R, Girling AJ. Stepped-wedge cluster randomised controlled trials: a generic framework including parallel and multiple-level designs. Statistics in medicine. 2015;34(2):181–96.
  10. 1 2 Woertman W, de Hoop E, Moerbeek M, Zuidema SU, Gerritsen DL, Teerenstra S. Stepped wedge designs could reduce the required sample size in cluster randomized trials. Journal of clinical epidemiology. 2013;66(7):752–58.
  11. ↑ de Hoop E, Woertman W, Teerenstra S. The stepped-wedge cluster randomized trial always requires fewer clusters but not always fewer measurements (participants) than a parallel cluster randomized trial in a cross-sectional design. In reply. Journal of clinical epidemiology. 2013;66(12):1428.
  12. ↑ Keriel-Gascou M, Buchet-Poyau K, Rabilloud M, Duclos A, Colin C. A stepped wedge cluster randomized trial is preferable for assessing complex health interventions. Journal of clinical epidemiology. 2014;67(7):831–33.
  13. ↑ Torgerson, David (2015). "Stepped Wedge Randomized Controlled Trials". Trials. 16: 350. Retrieved 17 February 2017.
  14. ↑ "University of York".
  15. ↑ Kanaan, Mona; Keding, Ada; Mdege, Noreen; Torgerson, David (2016). "Proceedings of the First International Conference on Stepped Wedge Trial Design". Trials. 17(Suppl 1): 311. Retrieved 17 February 2017.
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