Background to the project
Stepped wedge trials are an increasingly popular way to evaluate the effects of health service and public health interventions (Hooper, J Clin Epi 2021;137:159-162). Since the onset of the COVID-19 pandemic, for example, they have been suggested as a potential way to evaluate vaccination and school re-opening programmes.
In a stepped wedge trial, a number of “clusters” (for example, sites delivering local health services) are followed over a number of “periods”. Different clusters cross over in different periods from delivering the current standard of care to delivering the intervention. In terms of trial design, there is now quite a good understanding of when (that is, in which periods) it is optimal to cross different clusters over in order to gain the most information on the effect of the intervention (Girling & Hemming, Stat Med 2016;35:2149-2166).
In more complex designs, we may want to stagger the implementation of more than one active intervention. Chinbuah et al did a cluster randomised trial of an antimalarial drug on its own, and an antimalarial plus an antibiotic, for home management of fever in Ghanaian children (Am J Trop Med Hyg 2012;87:11-20). Here we may be as keen to compare antimalarial+antibiotic with antimalarial alone, or antimalarial+antibiotic with routine care, as to compare antimalarial alone with routine care. How do we optimally schedule the successive implementations of antimalarial and antibiotic in a trial? This kind of design problem is more complicated than a conventional stepped wedge trial, but opens up their field of application considerably. There is surprisingly little work in this area to date (Lyons et al, J Clin Epi 2017;86:160-167; Grayling, Mander & Wason, Stat Med 2019;38:1103-1119; Zhang et al, Stat Med 2020;39:4147-4168).
One approach for solving complex design problem like this one is to generate stochastically a large number of alternative designs (hopefully giving good coverage of the whole “space” of possible designs), calculate how well each of these designs performs, and pick the best. This approach is simple and flexible, but has been little used (Grayling, Mander & Wason, Stat Med 2019;38:1103-1119). More guided, but still non-exhaustive search strategies have also received some attention (Hooper, Kasza & Forbes, BMC Med Res Methodol 2020;20:279).
An alternative is to search the design space exhaustively, perhaps using optimisation software, to arrive at a design that is demonstrably best. In unpublished work, Hooper and Grayling have explored this approach for stepped wedge design problems with just one active intervention.
This project will review the existing literature on stepped wedge designs with more than one active intervention, develop a framework for describing these problems, and investigate stochastic, exhaustive, or theoretical approaches to their optimal solution in particular cases, to arrive at a better understanding of how to approach the design of this kind of trial in general.
The two QMUL co-supervisors will be available on a weekly basis to discuss the project, and will schedule monthly supervision meetings. External advisors will join on a roughly quarterly basis.
The studentship will be embedded within the Pragmatic Clinical Trials Unit, a UKCRC-registered CTU working at the forefront of the science and execution of pragmatic clinical trials, with an international reputation for its research on stepped wedge trial design.
Candidates should have a good grounding in medical statistics (for example a Masters) and an interest in clinical trial design in particular. Some experience of coding could be beneficial, depending on the direction the project takes.
HOW TO APPLY
You are applying for a PhD studentship from the MRC TMRP DTP. A list of potential projects and the application form is available online at:
Please complete the form fully. Incomplete forms will not be considered. CVs will not be accepted for this scheme.
Please apply giving details for your first choice project. You can provide details of up to two other TMRP DTP projects you may be interested in at section B of the application form.
Before making an application, applicants should contact the project primary supervisor to find out more about the project and to discuss their interests in the research.
The deadline for applications is 4pm (GMT) 18 February 2022. Late applications will not be considered.
Completed application forms must be returned to: [Email Address Removed]
Informal enquiries may be made to [Email Address Removed]