Individual patient meta-analyses of randomized trials of aspirin for the primary prevention of cardiovascular disease (MRC PHRU)
This project is eligible to be funded by an MRC PHRU Studentship if there is a suitable candidate.
The Antithrombotic Treatment Trialists’ (ATT) Collaboration was established over 20 years ago to conduct worldwide meta-analyses of the effects of antithrombotic therapy on vascular events in particular types of patients, so as to provide reliable information about the benefits and hazards of such therapy. This work has resulted in major publications on the effects of antiplatelet regimens in various populations (BMJ 1994 and 2002, Lancet 2009) which have been highly cited and substantially influenced clinical guidelines.
The 2009 ATT paper included individual participant data (IPD) from six primary prevention trials that compared long-term aspirin versus control in 95,000 individuals at low average risk, (660,000 person-years, ~3500 serious vascular events). The resulting analyses showed that the expected excess absolute risks of bleeding are positively correlated with the absolute benefits of aspirin, indicating that aspirin is of uncertain net value in a primary prevention context. However, since 2009, several new trials in different populations (collectively including over 70,000 further participants) have been reported. Three of these trials (ASCEND, JPAD and POPADAD) specifically recruited a diabetic population. Several other trials have recruited diverse populations including other potentially prognostically important groups, such as the elderly (eg, the ASPREE trial).
In light of this additional significant new information, this DPhil project will involve updating previous IPD analyses of the effects of aspirin for the primary prevention of cardiovascular disease so as to further refine estimation of the benefits and risks of aspirin in specific patient types.
RESEARCH EXPERIENCE, RESEARCH METHODS AND TRAINING
The specific lines of investigation will include:
- Helping to establish an extended collaboration of trialists engaged in large-scale randomized controlled trials of aspirin in primary prevention
- Planning and drafting statistical analysis plans to examine the incremental effects of aspirin in different treatment comparisons for IPD.
Conducting and interpreting the findings of meta-analyses, and planning exploratory analyses based on preliminary findings.
FIELD WORK, SECONDMENTS, INDUSTRY PLACEMENTS AND TRAINING
Students will learn to develop collaboration with trialists, review and appraise clinical trials, develop statistical analysis plans, conduct and interpret meta-analytical analyses and draft manuscripts.
A clinically qualified doctor, or graduate in a related subject, with highly developed numeracy skills and an interest in the field of cardiovascular medicine.