Critically ill patients have high mortality, morbidity, and healthcare resource use. Up to 70% of patients in critical care receive antibiotics. In this high antibiotic environment there is a significant risk for emergence of antimicrobial resistant pathogens and antibiotic-associated toxicity. In this setting, there is considerable risk of antibiotic over-treatment and interventions to improve antibiotic stewardship is an ongoing unmet clinical need. Conducting trials in critical care poses several methodological challenges including intercurrent events during the trial intervention; using estimand frameworks in non-inferiority designs; and co-enrolment of patients into multiple critical care trials.
The studentship will be conducted alongside the NIHR HTA funded SHORTER trial, a non-inferiority trial of short, fixed-course antibiotics in critically ill patients with sepsis. The student’s work will be comprised of three pieces of work:
1. Systematic review of intercurrent events in trials conducted in a critical care setting. The objectives of the systematic review will be 1) to identify and characterise commonly occurring intercurrent events and their frequencies; and 2) to report current methods used to handle intercurrent events in trials conducted in a critical care setting.
2. Use the outcomes of the review to work with the Trial Management Group to develop estimands (following the estimand framework) for the SHORTER trial. The student will propose suitable approaches to handling expected intercurrent events which are aligned with the research questions of interest and the non-inferiority design.
3. Investigate the methodological implications of co-enrolment in critical care trials. The student will use mixed qualitative and quantitative methods to determine the extent of co-enrolment and how co-enrolment is managed among concurrent trials in the UK critical care setting. Examination of site records to capture data regarding number of patients enrolling in multiple studies as well as carrying out interviews with stakeholders (e.g. NHS research staff and study teams) will determine impact on trial recruitment and patient selection. Documentary analysis will capture individual trial policies on co-enrolment through examination of study protocols. Potential impacts of different co-enrolment strategies on trial outcomes will be modelled and evaluated by simulation. Methods for accounting for co-enrolment in trial statistical analysis will be reviewed and adapted if necessary.
Dr Tom Hellyer is a senior clinical fellow and honorary consultant in critical care medicine. Tom is the chief investigator for the SHORTER trial with expertise in antibiotic stewardship and clinical trials in critical care. Prof Dawn Teare is a senior biostatistician and deputy director of Newcastle Clinical Trials Unit with extensive experience of trials methodology. Ms Helen Mossop is senior research associate in biostatistics with extensive experience of clinical trials. Helen is the trial statistician for the SHORTER trial. Dr Matthew Breckons is a Senior Research Associate with experience of conducting qualitative research as part of clinical trials.
The student will be able to access a well-established network of critical care researchers to access trials teams, site documentation and trial protocols for critical care trials. In addition, interviews will be carried out with NHS research staff.
The SHORTER trial has public and patient involvement (PPI) through two PPI co-applicants. The student will be able to access these PPI members during the studentship.
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 supervisor to find out more about the project and to discuss their interests in the research before 09 January 2023.
The deadline for applications is 4pm (GMT) 16 January 2023. Late applications will not be considered.
Completed application forms must be returned to: [Email Address Removed]
Informal enquiries may be made to Dr Tom Hellyer - [Email Address Removed]