Improving understanding of methotrexate-associated adverse events in patients with rheumatoid arthritis

Methotrexate (MTX) is currently recommended as the drug of first choice for the treatment of patients with rheumatoid arthritis (RA) based on its effectiveness, relatively good tolerance and low costs compared to other drugs for RA. However, many patienst with RA starting MTX have concerns about adverse events (AEs). In a recent survey by the National Rheumatoid Arthritis Society (NRAS) amongst patients with RA using MTX, 50% of patients said that they would stop MTX due to its AEs and 15% fear it being a cytotoxic drug and risk of getting cancer. To improve the understanding about MTX associated AEs we need to gain a better understanding which factors (eg demographic, disease related, dose MTX) are associated with having AEs including increased liver enzymes and other AEs such as nausea, oral ulcers and hair loss which may severyl impact on quality of life.

To improve evidence-based information about AEs for patients and clinicians, more studies of the occurrence of AEs using real-world data based on current best practice are required. The aim of this PhD studentship is to further our understanding of the occurrence of MTX related AEs and its predictors in patients with RA participating in a large national study, the Rheumatoid Arthritis Medication Study (RAMS).

To answer the research questions the PhD student will need to apply different analysis techniques such as text mining to evaluate diary data, regression analysis to determine predictors of AEs and more complex multilevel regression analysis.

The student will benefit from placement in the Centre for Musculoskeletal Research, with training provided via the Musculoskeletal Doctoral Training College, with a record of internationally renowned research in musculoskeletal conditions. The centre has a Teaching & Learning group (Lead Dr Suzan Verstappen) to ensure that the early careers researchers within the centre acquire the necessary scientific and methodological skills to become independent researchers. In addition, the Centre offers a range of supportive activities including an internal course in epidemiology, internal peer review club and a statisticians group. The centre also has its own Research User Group including patients with rheumatic diseases who have been and will be involved in determining the relevant research questions for patients and in translating the research results into relevant output.

In addition specific training will be provided where applicable. Training in text mining will be provided in collaboration with researchers working in the School of Computer Science, The University of Manchester.

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject. Candidates with experience in biostatistics, epidemiology or bioinformatics are encouraged to apply.