MARVEL-PIC: minimising adverse drug reactions and verifying economic legitimacy: pharmacogenomic implementation in children

Background: Adverse drug reactions account for 30% of hospital admissions and cost the healthcare system 1.4 billion per annum.1 Concerningly, 60% of paediatric oncology patients experience adverse drug reactions during cancer treatment, of which 20% are severe or life threatening. Importantly, 75% of adverse drug reactions reported in paediatric patients are preventable through greater pharmacovigilance and pharmacogenetic testing. Objective: The objective of this research program (MARVEL-PIC) is to reduce preventable adverse drug reactions in paediatric oncology patients through an extensive pharmacogenetics program that integrates broad pharmacogenomic implementation and education and training frameworks. Method: This first of its kind in paediatric oncology randomised control trial (RCT) randomises patents to receive extended pharmacogenomic results (derived from all current actionable pharmacogenomics variants as per international guidelines (PGx) or standard of care (SoC) (control arm) for a period of 12 weeks. Symptom reporting will be performed via prospective surveys (NCI Ped-PRO-CTCAE) followed by formal CTCAE grading of symptoms by academic pharmacists. The Liverpool adverse drug reaction (ADR) causality assessment tool (CAT) will be used to ascribe causality. Health economics analysis will involve actual costs calculation collected via the Department of Health and the Centre for Victorian Data Linkage (CVDL) and Services Australia. Results: We have piloted a pipeline for using a whole genome sequencing approach to call and verify diplotypes (and subsequent metaboliser states) for a range of pharmacogenes. To date this approach is feasibly and 80% of paediatric patients have a high risk genotype identified. Conclusion: We have piloted a WGS bioinformatic approach to verifying pharmacogenes for the purposes MARVEL-PIC. This approach allows for rapid turnaround and repurposes WGS used for tumour biology for the purposes of precision medicine, in an effort to reduce AME. We look forward to reporting on the results of the MARVEL-PIC trial in due course.