Deep analysis of large international clinical trials for bloodstream infections

There are 50 million cases of sepsis worldwide each year, leading to 11 million sepsis-related deaths.

Bloodstream infections are a key cause and manifestation of sepsis.

Associate Professor Daneman and Associate Professor Tong lead two large international clinical trials for bloodstream infections.

BALANCE, led by Associate Professor Daneman, investigates the optimal duration of antibiotics needed to treat bloodstream infections. SNAP, led by Associate Professor Tong, aims to determine the optimal antibiotic regimens for bloodstream infections caused by Staphylococcus aureus.

These are the two largest clinical trials for bloodstream infections to date and collectively will include more than 10,000 participants, providing an unprecedented opportunity to embed additional mechanistic and epidemiologic sub-studies.

The PhD project will involve multiple nested sub-studies within each of these two trials. These projects are best suited to a clinician aiming to develop expertise in infectious diseases clinical research.

Project goals

The two different clinical trials each have their distinct project goals. The BALANCE trial involves:

1. Evaluating the predictive utility of procalcitonin and other novel biomarkers to offer a precision-medicine approach to bloodstream treatment durations
2. Exploring the concordance of clinician and patient perceptions of the daily probability of cure during the treatment trajectory, and whether these perceptions are predictive of treatment success and survival
3. Examining patient, pathogen, and syndrome predictors of protocol non-adherence (and treatment prolongation) among patients randomized to shorter-duration treatment for bacteremia

The SNAP trial involves:

4. Determining predictors of outcomes within specific sub-groups of patients (e.g., those with methicillin-resistant S. aureus [MRSA] infection)
5. Improving and assessing consent processes, particularly for disadvantaged or marginalised patients
6. Microbiology focussed questions such as the impact of the cefazolin inoculum effect on patient outcomes
7. Pharmacokinetic / pharmacodynamics (PK/PD) questions such as the impact of β-lactam drug levels on outcomes
8. Comparison of outcomes for patients enrolled in the trial vs those not enrolled (but who are part of a broader registry of S. aureus bloodstream infections

Supervision team

• The University of Melbourne: Associate Professor Steven Tong and Professor Joshua Davis
• The University of Toronto: Associate Professor Nick Daneman and Doctor Rob Fowler

*Click on the researcher's name above to learn more about their publication and grant successes.

Who we are looking for

We are seeking a PhD candidate with the following skills:

• Demonstrated experience in the field of biomedical sciences
• Demonstrated ability to work independently and as part of a team
• Demonstrated time and project management skills
• Demonstrated ability to write research reports or other publications to a publishable standard (even if not published to date)
• Excellent written and oral communication skills.
• Demonstrated organisational skills, time management and ability to work to priorities.
• Demonstrated problem-solving abilities.
• The ability to work independently and as a member of a team.

Further details

The PhD candidate will benefit from the combined expertise of the project supervisors, and the embedding into two research environments.

Associate Professor Steven Tong and Professor Joshua Davis at the University of Melbourne will contribute their expertise in infectious diseases, the conduct of clinical trials, and translational science.  Associate Professor Nick Daneman and Dr Rob Fowler at the University of Toronto will contribute expertise in the conduct of clinical trials, critical care medicine, and data-driven implementation science.

This PhD project will be based at the University of Toronto with a minimum 12-month stay at the University of Melbourne.

The candidate will be enrolled in the PhD program at the Department of Institute of Health Policy, Management and Evaluation (IHPME) in the Dalla Lana School of Public Health (DLSPH)at the University of Toronto, and in the PhD program at the Department of Infectious Diseases, Melbourne Medical School at the University of Melbourne.

To apply for this joint PhD opportunity, and to view the entry requirements, visit How to apply.