Stepped Wedge Designs for Investigating Therapeutics and Vaccines: Review of past and ongoing trials

Authors

• A Doussau de Bazignan
• C Grady

Abstract

Introduction Ethical concerns about randomizing persons to placebo in the context of Ebola epidemic led to consideration of alternative designs. The stepped wedge (SW) design, in which participants or clusters are randomized to receive the experimental intervention at different time points, gained popularity. An appealing argument is that all participants or clusters might receive the experimental intervention at some time point during the study. We sought to identify and describe current or past trials employing a SW design for testing drugs or vaccines. Methods Two published systematic reviews and three clinical trial registries were reviewed. We identified trials testing drugs and vaccines and distinguished cluster vs. individual randomization. Results A total of 103 SW studies where identified. Only seven involved drugs (n=6) or vaccine (n=1). All 7 were studying the implementation of interventions already shown to be efficacious for infectious disease (Hepatitis B, malaria, HIV, infectious complications of HIV, chlamydia and gonorrhea). Six of seven were cluster randomized trials, and repeated cross-sectional (intervention was ultimately implemented in all clusters). One of seven was a cohort design – the inclusion of individual participants was randomly staggered and all participants received the intervention. No double-blind placebo controlled trial was found. Conclusion SW designs have rarely been used to study drugs or vaccines, and such use has been limited to drugs already shown to be efficacious. Implementing this design to test an experimental drug or vaccine would be a very innovative approach, as no such experience was previously reported.

Scientific Focus Area: Epidemiology

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