Evaluating the extent and cost of suboptimal prescribing of common medications using pharmacogenomics

Pharmacogenomic (drug-gene) testing seeks to identify genetic variation in drug metabolising enzymes that will identify if someone is a poor, normal, or rapid metaboliser of a drug. Those who fall into the poor or rapid metaboliser groups are likely to experience drug failure and/or adverse reactions. This project will focus on the benefits of pharmacogenomic-informed prescribing of common medications including statins, pain medications and anti-depressants. Emerging pharmacogenomic data suggests that 25-40% of prescriptions for these drugs require dose amendments or an alternative drug.

The aims of this project are to

The project will draw on two existing and independent datasets. The UK Biobank holds data for 500,000 patients, but did not recruit from Northern Ireland. Therefore, we will also use data from a cohort of 4,500 local research participants.

We will identify copy number variation in drug metabolising enzymes (CYP2C19, CYP2C9, CYP2D6, CYP3A4, TPMT, VKORC1).  The suitability of 22 common medications for the treatment of cardiovascular disease, mental health conditions and pain will be assessed for those identified as poor or rapid metabolisers. Suboptimal prescribing will be quantified using pharmacogenomic guidelines from the Dutch Pharmacogenetics Working Group and the Clinical Pharmacogenetics Implementation Consortium. Health economic assessments will examine potential cost savings that may be achieved through correction of suboptimal prescriptions.

The successful candidate will be supervised by a multidisciplinary team from Ulster University and ATU (Sligo) and will gain expertise in genomics, bioinformatics and health economics. Project findings will help advance the evidence base for implementation of pharmacogenomic testing as part of routine care.

Important Information: Applications for more than one PhD studentship are welcome, however if you apply for more than one PhD project within Medicine, your first application on the system will be deemed your first-choice preference and further applications will be ordered based on the sequential time of submission. If you are successfully shortlisted, you will be interviewed only on your first-choice application and ranked accordingly. Those ranked highest will be offered a PhD studentship. In the situation where you are ranked highly and your first-choice project is already allocated to someone who was ranked higher than you, you may be offered your 2nd or 3rd choice project depending on the availability of this project.

Applicants should hold, or expect to obtain, a First or Upper Second Class Honours Degree in a subject relevant to the proposed area of study.

We may also consider applications from those who hold equivalent qualifications, for example, a Lower Second Class Honours Degree plus a Master’s Degree with Distinction.

In exceptional circumstances, the University may consider a portfolio of evidence from applicants who have appropriate professional experience which is equivalent to the learning outcomes of an Honours degree in lieu of academic qualifications.

• Experience using research methods or other approaches relevant to the subject domain
• Sound understanding of subject area as evidenced by a comprehensive research proposal
• A comprehensive and articulate personal statement
• Research proposal of 1500 words detailing aims, objectives, milestones and methodology of the project

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

• First Class Honours (1st) Degree
• Masters at 70%
• Research project completion within taught Masters degree or MRES
• Experience using research methods or other approaches relevant to the subject domain
• Publications record appropriate to career stage
• Experience of presentation of research findings

The University offers the following levels of support:

The following scholarship options are available to applicants worldwide:

• Full Award: (full-time tuition fees + £19,000 (tbc))
• Part Award: (full-time tuition fees + £9,500)
• Fees Only Award: (full-time tuition fees)

These scholarships will cover full-time PhD tuition fees for three years (subject to satisfactory academic performance) and will provide a £900 per annum research training support grant (RTSG) to help support the PhD researcher.

Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Please note: you will automatically be entered into the competition for the Full Award, unless you state otherwise in your application.

The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £19,000 (tbc) per annum for three years (subject to satisfactory academic performance).

This scholarship also comes with £900 per annum for three years as a research training support grant (RTSG) allocation to help support the PhD researcher.

• Candidates with pre-settled or settled status under the EU Settlement Scheme, who also satisfy a three year residency requirement in the UK prior to the start of the course for which a Studentship is held MAY receive a Studentship covering fees and maintenance.
• Republic of Ireland (ROI) nationals who satisfy three years’ residency in the UK prior to the start of the course MAY receive a Studentship covering fees and maintenance (ROI nationals don’t need to have pre-settled or settled status under the EU Settlement Scheme to qualify).
• Other non-ROI EU applicants are ‘International’ are not eligible for this source of funding.
• Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Due consideration should be given to financing your studies. Further information on cost of living

Montastruc et al. Fatal adverse drug reactions: A worldwide perspective in the World Health Organization pharmacovigilance database. Br J Clin Pharmacol. 2021 Nov;87(11):4334-4340. doi: 10.1111/bcp.14851.

Swen et al. Ubiquitous Pharmacogenomics Consortium. A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study. Lancet. 2023 Feb 4;401(10374):347-356. doi: 10.1016/S0140-6736(22)01841-4.

Pratt et al. CYP3A4 and CYP3A5 Genotyping Recommendations: A Joint Consensus Recommendation of the Association for Molecular Pathology, Clinical Pharmacogenetics Implementation Consortium, College of American Pathologists, Dutch Pharmacogenetics Working Group of the Royal Dutch Pharmacists Association, European Society for Pharmacogenomics and Personalized Therapy, and Pharmacogenomics Knowledgebase. J Mol Diagn. 2023 Sep;25(9):619-629. doi: 10.1016/j.jmoldx.2023.06.008.

https://www.pharmgkb.org/