Adherence to International Pharmacogenomic Recommendations in Paediatric Cancer Care: A Cohort Analysis Embedded Within the MARVEL-PIC Randomised Trial

BackgroundPharmacogenomic testing (PGx) can optimise drug efficacy and minimise toxicity, but the extent of prescriber adherence to PGx recommendations remains unclear. We aimed to quantify clinician adherence to international genotype-guided prescribing recommendations in a cohort of paediatric oncology patients. MethodsWe reviewed files of children enrolled in the MARVEL-PIC (NCT05667766) randomised control trial, who had PGx recommendations available. Patients were included if 12 weeks had passed since their PGx report was released to clinicians. Prescribing events were identified for actionable PGx recommendations, and classified as "explicitly followed", "inadvertently followed", or "not followed". Adherence was assessed by patient, drug, and recommendation. Results2,063 PGx recommendations were available for 216 patients. 64 (3.1%) recommendations were actionable for 44 patients and 10 drugs within the 12-week study period. Recommendations were explicitly followed in 57/288 (19.8%) of prescribing events, inadvertently followed in 145 (50.3%), and not followed in 86 (29.9%). Mercaptopurine demonstrated the highest rate of explicit adherence (87.5%). No significant associations were observed between adherence and age group, cancer type, drug type, or strength of recommendation. ConclusionAdherence to pharmacogenomic recommendations was very low, highlighting the need to understand barriers to PGx implementation, and consideration of clinical decision supports to facilitate adherence. Plain Language SummaryPharmacogenomic medicine (PGx) looks at how our genes affect our response to drugs, including their effectiveness and toxicity. Through genetic analysis we can create recommendations for drug dosing, avoidance, and monitoring. The MARVEL-PIC study aims to understand if having PGx recommendations decreases the rate of adverse events in children with cancer. We aimed to understand how often prescribers follow PGx recommendations after they are made available, in the MARVEL-PIC trial. To do this, we reviewed medical records and identified relevant prescribing events. We marked these as "recommendation explicitly followed", "recommendation not followed", or "recommendation inadvertently followed" (where the recommendation was followed, but it wasnt clear if this due to PGx). We found that when recommendations were available, they were only explicitly followed in around 20% of cases. In 50% of cases, they were followed but it was unclear whether this was due to PGx. In the remaining 30%, they were not followed. We also found that alerts on our electronic system were fired in about 80% of events where the recommendation was not followed, but did not change the outcome. These findings show that prescriber adherence to PGx recommendations is low. We need to better understand why this is the case and implement more specific tools to assist prescribers in following recommendations. Article HighlightsO_LIPharmacogenomic (PGx) testing can reduce adverse drug reactions by guiding drug choice, dosing, and monitoring. C_LIO_LI!Prescriber to PGx recommendation adherence has not been widely investigated. C_LIO_LIRetrospective analysis showed that explicit adherence to recommendations occurred in only 19.8% of relevant prescribing events. C_LIO_LIIn 50.1% of prescribing events, recommendations were followed, but there was no clear reference to PGx. C_LIO_LIMercaptopurine had the highest explicit adherence (87.5%) from the drugs analysed. C_LIO_LIThere were no statistically significant associations between adherence and age group, cancer type, drug type, or recommendation strength. C_LIO_LIRecommendations were explicitly followed in 29% of events where an interruptive alert was fired, and inadvertently followed in 8%. C_LIO_LITailored interruptive alerts have been shown to increase adherence in other studies, suggesting that the specific design of interruptive alerts may influence adherence. C_LIO_LIWe concluded that explicit prescriber adherence to PGx recommendations is very low (19.8%), and further research needs to be done to understand barriers to implementation. C_LI