NHS East Genomics has 4 main partner NHS Trusts: Cambridge University Hospitals | Norfolk and Norwich University Hospitals Nottingham University Hospitals | University Hospitals of Leicester www.eastgenomics.nhs.uk Learning from the implementation of DPYD pharmacogenetic testing across 18 acute NHS Trusts Authors: Aris Saoulidis1, Paul Selby1, James Drummond1, Sarah Hunter1, Colin Spencer1, Sarah Pacey1, Richard Sandford1 1NHS East Genomic Medicine Service Alliance & Genomic Laboratory Hub (East Genomics). Correspondence: Aris.Saoulidis@nhs.net Informatics interoperability between genetic labs and prescribing software is key Clinical teams have no or limited functionality to seamlessly track the test progress, and test results are primarily transferred as PDF reports. Current manual methods of tracking and reporting test results to clinicians contribute to perceived longer test turnaround times by clinicians, despite timely lab reporting. Thus, automated reporting between NHS systems is needed. The current healthcare informatics exchange standards and channels (HL7 and FHIR) offer opportunities to support PGx interoperability.4 However, the community requires consensus on standardising the nomenclature of PGx reporting to clinicians agnostic to prescribing systems. Currently, Ontology and Medical terms (SNOMED CT) are not aligned with clinical PGx guidelines, introducing challenges of clinical PGx reporting, as for example, the UK Chemo Board guidance have six levels of DPD classification as opposed to three SNOMED CT codes. Figure 1: Number of medicines with pharmacogenomic potential prescribed by pharmaceutical class Patient outcomes and data collection Interoperability will support systematic data collection needed on treatment efficacy and toxicity for large scale adoption of PGx. Finally, we welcome the community’s approach to further identify how to increase and review systematic toxicity reporting, alongside re-assessment of expanded testing for other DPYD variants across different ethnicities. Background Fluoropyrimidines (capecitabine, 5-fluorouracil/5FU) are systemic anti-cancer therapy (SACT) in solid cancer. Fluoropyrimidines are metabolised by the enzyme dihydropyrimidine dehydrogenase, encoded by the DPYD gene. Pre-treatment genetic screening for DPYD pharmacogenetic (PGx) variants can predict and prevent fluoropyrimidine toxicity and was mandated prior to 5FU/capecitabine treatment by the MHRA in October 20201; a Clinical Commissioning Urgent Policy Statement was published by NHS England in November 20202. DPYD testing already takes place across 18 East of England and East Midlands NHS Trusts offering fluoropyrimidine systemic anti-cancer treatment, albeit with significant variation. Most Trusts are currently following the UK Chemotherapy Board’s 2020 Personalised Medicine Approach for fluoropyrimidine-based therapies3. Overall, DPYD testing is now established in the NHS, preventing toxicity and improving treatment for patients with clinically-significant DPYD variants. We share our key learnings from the East Genomics DPYD transformation project. 1. 5-fluorouracil (intravenous), capecitabine, tegafur: DPD testing recommended before initiation to identify patients at increased risk of severe and fatal toxicity. Medicines and Healthcare products Regulatory Agency. October 2020 accessible from https://www.gov.uk/drug-safety-update/5-fluorouracil-intravenous-capecitabine-tegafur-dpd-testing-recommended-before-initiation-to-identify- patients-at-increased-risk-of-severe-and-fatal-toxicity 2. Clinical Commissioning Urgent Policy Statement Pharmacogenomic testing for DPYD polymorphisms with fluoropyrimidine therapies– NHS England, November 2020 (URN 1869) accessible from: https://www.england.nhs.uk/publication/clinical-commissioning-urgent-policy-statement-pharmacogenomic-testing-for-dpyd-polymorphisms-with-fluoropyrimidine-therapies/ 3. Personalised Medicine Approach For Fluoropyrimidine-based Therapies. UK Chemother