Genomic medicine strategy 2024 to 2029

15. Pharmacogenomics

Pharmaco-genomics

We recognise the enormous potential of pharmacogenomics for the health and social care system in Scotland with genomic information used to tailor treatment and guide the choice and use of different medicines to ensure the best clinical outcome for patients and minimise side effects and adverse reactions. The infrastructure and expertise needed to support robust pharmacogenomics is considerable and we recognise the role that Scotland’s genomic medicine service will need to play as a key collaborator.

Background

The introduction of pharmacogenomics into routine clinical practice has the potential to transform the use of medicines.

• Pharmacogenomics: using an individual’s genetic information to maximise the safety and effectiveness of medicines

In 2022, a joint publication by the Royal College of Physicians and British Pharmacological Society called for pharmacogenomic testing, and pharmacogenomic-based prescribing, to be made available in the NHS to improve patient outcomes.^[37] There is also growing clinical evidence of the effectiveness of pharmacogenomics based on testing for a wide range of medicines, with incorporation of pharmacogenomic testing included within best practice clinical guidelines for a number of common conditions affecting patients in Scotland. Pharmacogenomics is required to support prescribing decisions, optimise existing medicines and contribute to the safer use of medicines in future, regardless of who the prescriber is and where they are based across the health service.^{37, 38}

Where we are now

Pharmacogenomic testing is already available in Scotland and Case Study 15.1. on DPYD testing for people with cancer prior to the use of medicines known as fluoropyrimidines, outlines one application. There is growing evidence to support testing for an increasing number of widely used medications but, to date, there are no nation-wide infrastructure or mechanisms to efficiently link individual pharmacogenetic (single gene tests for individual medicines) or pharmacogenomic information (genome-wide panels supporting the use of multiple medicines) with prescribing across health and social care systems.

Multi-disciplinary collaboration across Scotland is key to the successful implementation of both pharmacogenetic testing and the more comprehensive pharmacogenomic panels into clinical practice to improve patient care. Pharmacists have a pivotal role to play, working with other professions, in the delivery of many aspects of pharmacogenomics. They are well placed to contribute in a leadership capacity to the effective and equitable local implementation of pharmacogenomics into clinical practice to improve patient care.

Where we want to be

We will support the development of a scalable pharmacogenomics service with delivery models that are both person-centred and evidence-based, with consistent Scotland-wide information governance, consent models and agreed assessment criteria to use for additional targets.

Developing an evaluation framework for new targets

We recognise the need to ensure that any new pharmacogenomic targets are evidence-based as tests are commissioned, drawing on resources available through PharmGKB and the Clinical Pharmacogenetics Implementation Consortium (CPIC) and working in collaboration with partners across the UK and Europe. There is also a need for clear structures in place at implementation to assess patient outcomes and the health economic impact, and the SSNGM will support the development of a framework to support these assessments and integrate this into the existing SGTAG process.

Development of delivery models

The development and delivery of pharmacogenomics as an integral part of precision medicine on a national basis will require collaborative working and interaction across a range of different disciplines and organisations across Scotland. We will work closely with the Innovation Design Authority (IDA)’s Accelerated National Innovation Adoption (ANIA) pathway to support the development of a national pharmacogenetic panel (Case study 16.2). We will also continue to work with European partners to optimise the role of pharmacogenomics in routinely used medicines for non-communicable diseases (NCD), enabling a person-centred approach, so that outcomes are optimised and harm from medicines minimised.

15.1. Case study: Pharmacogenomics testing for DPYD for people with cancer who require fluoropyrimidine chemotherapy medicines

Fluoropyrimidines (including fluorouracil or 5FU, capecitabine and tegafur) are widely used chemotherapy medicines. We know that some people with cancer treated with these medicines (around 15-30%) may experience severe or life-threatening side effects because of a genetic variation in the dihydropyrimidine dehydrogenase (DPYD) gene. This gene provides the body with the instructions it needs to produce the dihydropyrimidine dehydrogenase enzyme that helps break down one of the compounds in the fluoropyrimidine class of medicines. If a person has low or no levels of this enzyme then these medicines build up in the body and can cause more side effects than normal, some of which can be life threatening. In Scotland a pilot programme for DPYD genetic testing was initiated for colorectal cancer patients in 2019 and was extended during the COVID-19 pandemic to cover all cancers eligible for treatment with fluoropyrimidines. In April 2020 the European Medicines Agency (EMA) recommended that all patients eligible for treatment with fluorouracil, capecitabine or tegafur should have DPYD genetic testing before starting treatment. Health Improvement Scotland and the Scottish Health Technologies Group have published their findings justifying the economic case for DPYD genetic testing before patients are prescribed fluoropyrimidine-based chemotherapy in October 2020. DPYD testing has been incorporated into the Scottish test directory and has been available to all eligible cancer patients^[39] since July 2020.

15.2. Case study: The Tayside P4Me Clopidogrel pharmacogenomics initiative

Patients prescribed a medicine called clopidogrel who are unable to metabolise or process it effectively have a significantly increased risk of stroke. An NHS Tayside pilot study, P4Me – Clopidogrel (from P4 Medicine: predictive, personalised, preventative and participatory), in the Acute Stroke Unit ran from April 2022 to March 2023, in which a genetic test specific for clopidogrel metabolism was developed to NHS laboratory standards. The test could be requested through routine hospital blood testing procedures and the ward pharmacist ensured it was carried out for all patients with an indication for antiplatelet therapy. Clinically interpretable results were returned through a service-specific email and directly integrated into electronic patient records. For people identified with impaired metabolisms, a standardised clinical decision support communication was sent to GPs with a clinically appropriate, regionally approved recommendation for alternative therapy, specified in the Local Area Formulary. The NHS Tayside Stroke Liaison Nurse team also helped ensure appropriate long term antiplatelet prescribing in the community. During the project 723 genetic tests were reported, 204 (28.2%) people with impaired metabolisms were identified and 168 (23.2%) prescribed an effective alternative. The project’s success led to long-term adoption by NHS Tayside, creating a necessary foundation of knowledge and experience for more general and wider implementation of pharmacogenomics in the NHS.

Gene testing for clopidogrel is now being considered for adoption by the IDA’s ANIA pathway as a potential pathfinder project for the development of a wider national pharmacogenomics panel.

What will this mean for people of Scotland?

Targeted treatment that suits the individual and their condition has the potential to be transformative for many people. Increasing the understanding of pharmacogenomics will allow more people to benefit from treatment that can improve their lives, and promote the safer and more effective use of medicines.