Pharmacogenomics in Practice by Dr Hayley Wickens, Consultant Pharmacist Genomic Medicine, Central and South Genomic Medicine Service Alliance

1. Pharmacogenomics
in Practice
Dr Hayley Wickens
Consultant Pharmacist Genomic Medicine, Central and South GMSA
Alliance

2. • How pharmacogenomics can improve medicines optimisation and patient care
• Implementation of pharmacogenomics in the NHS
• PROGRESS pharmacogenomics study – delivering pharmacogenomics in primary
care
• Where to find out more
Overview

3. Why implement Pharmacogenomics?
• Common genetic variation is associated with
• Poor medicines effectiveness
• Adverse drug reactions
• Up to 99% of patients will have a pharmacogenetic
variant
• Estimated approx. 1 in 15 UK hospital admissions
related to ADRs at a cost >£2billion
• Approx. 20% of all new prescriptions in UK primary care
have an actionable drug-gene interaction#
• Prescribing = most common intervention in the NHS
# Youssef et al. 2021 https://doi.org/10.1111/bcp.14704
Drug A
Active
Metabolite
Enzyme B
Enzyme B
Active
Metabolite

4. 4 |
Genome UK; the future
of healthcare sets out a
10 year vision how we will
achieve progress in
genomic medicine across
Diagnosis & Personalised
medicine, Prevention and
Research
UK Life Sciences
Vision sets 10-year
strategy for sector to
solve some of the
biggest healthcare
problems of our
generation
Accelerating Genomic Medicine in the NHS
Key themes include:
1. Embedding genomics across the NHS, through a world leading innovative service model from
primary and community care through to specialist and tertiary care
2. Delivering equitable genomic testing for improved outcomes in cancer, rare, inherited and
common diseases and enabling precision medicine and reducing adverse drug reactions
3. Enabling genomics to be at the forefront of the data and digital revolution, ensuring genomic
data can be interpreted and informed by other diagnostic and clinical data;
4. Evolving the service driven by cutting-edge science, research and innovation to ensure that
patients can benefit from rapid implementation of advances
NHS Long Term Plan
genomics
commitments

5. National Genomic Test Directory
5
https://www.england.nhs.uk/publication/national-genomic-test-directories/
The National Genomic Test Directory is a published list of nationally commissioned genomic tests (and associated
eligibility criteria).​ There are three documents:
• National Genomic Test Directory for rare and inherited disease (Excel)
• Rare and inherited disease eligibility criteria (PDF)
• National Genomic Test Directory for cancer (Excel)
Pharmacogenomic testing is currently reflected on the Rare
Disease and Cancer Test Directories. In the future, this will move
towards one online directory that encompasses all three
specialities.
Aims
• To ensure the directory reflects latest technological
developments and scientific advances
• To support fair and equitable access to genomic testing
• To ensure best value is achieved for the NHS
• To improve our understanding of clinical utility of genomic
tests and the implications of testing on patients and the clinical
pathway.
Application process for new tests detailed in published policy
document alongside application forms and supplementary
guidance: https://www.england.nhs.uk/genomics/the-national-
genomic-test-directory/

6. Not all pharmacogenomic testing in the NHS is commissioned
by the Genomic Medicine Service
Slide credit SE GMSA

7. Despite Extensive Evidence for Multiple Gene-Drug Pairs,
There is a Translational Gap
4 Gene Drug
Pairs
26 Gene-Drug Pairs
with Explicit PGx
Guidelines
440 gene-drug pairs
with prescribing
evidence

8. MTRNR-1 Variants & Aminoglycoside Induced Hearing Loss
• CPIC guidelines for
Aminoglycosides and MT-RNR1
gene variants 2021
• 2021: UK MHRA issued a drug
safety update warning of this
risk
• Testing routinely available via
NHS GMS

9. PALOH (Pharmacogenetics to Avoid Loss Of Hearing) study
• Investigated point-of-care testing for m.1555A>G in
neonates
• Able to deliver test result in ~ 25 mins
• 3/751 babies variant identified and offered alternative
antibiotic
• NICE Early Value Assessment (EVA) March 2023
• Conditional recommendation with evidence
generation requirement – POCT not currently
centrally commissioned, so must be funded locally
McDermott et al. JAMA Pediatr. 2022;176(5):486-492

10. The Value of Panel Based PGx Testing
Swen JJ et al. Lancet 2023; 401: 347–56
The PREPARE Trial Demonstrated a 30% Reduction in ADRs

11. Health Economics
Implementation Science
Development and
Validation of a
Pharmacogenetic
Panel
Work Package 1 Work Package 2 Work Package 3
Development of an
Informatic Solution to
Support
Pharmacogenetic
Guided Prescribing
Implementation in
Practice
PPIE
The PROGRESS Programme: Implementing
Pharmacogenetics in the NHS

12. Genetic
Variation
c.636G>A p.(W212X)
c.1297C>T p.(R433W)
CYP2C19 Clopidogrel
Pharmacogenetic Data Must be Available in a Clinically Relevant
Format and a Clinically Relevant Timeframe
Genotype Haplotype Diplotype Phenotype Guidance
*3,*5 CYP2C19 (*3/*5) CYP2C19 PM Prescribe Alternative Antiplatelet
GPAS
CPIC API

13. Work-Package 2: Informatic Solution

14. Work-Package 2: Informatic Solution

15. Personalising Healthcare Through PGx
Prescription
Results Available Presentation
Prescription
Presentation
Prescription
Presentation
Pre-emptive
Panel Testing
Age 55
Requires
statin
PGx reduces
risk of
myopathy
Age 60
Back pain
PGx helps
selection of
analgesia
Age 68
ACS
Pgx avoids risk of
ineffective antiplatelet
and future cardiac events
Lifelong
Patient-held
data?

16. Implementing Pharmacogenomics in the NHS
1. The PROGRESS Study - Implementation of PGx in General Practice Across England (1500 Patients to
be Recruited)
2. ProgressRx – Facilitating an agnostic solution for embedding PGx data within EHRs across England
3. Empowering Patients – Providing a patient facing solution for accessing their pharmacogenomic
data
4. Health Economics – Modelling how clinical benefit can be best delivered whilst identifying required
resources
5. Population Datasets – Working across secure data environments to assess the “real world” value of
PGx testing in the population

17. Where to find out more
www.nw-gmsa.nhs.uk
https://www.genomicseducation.
hee.nhs.uk/education/
Pharmacogenomics — In the Clinic (hee.nhs.uk)
https://centralsouthgenomics.nhs.uk/

18. Any questions?
Email: Hayley.wickens@uhs.nhs.uk
Jessica.keen@mft.nhs.uk
@BugHayleyW
@JessicaKPharma1