Design and Implementation of an Opt-Out, End-to-End, Preemptive DPYD Testing Program for Patients Planned for a...

Area of Science:

• Pharmacogenomics
• Clinical Chemistry
• Oncology

Background:

• DPYD gene variants impair metabolism of fluoropyrimidines like 5FU and capecitabine.
• This impairment increases the risk of severe toxicity, particularly after capecitabine exposure.
• A multidisciplinary panel was formed to address capecitabine toxicity and DPD deficiency.

Purpose of the Study:

• To develop and implement an institution-wide strategy for preemptive DPYD testing.
• To reduce the risk of severe fluoropyrimidine toxicity in patients undergoing chemotherapy.

Main Methods:

• An opt-out testing strategy was implemented with a focus on reliable result reporting and education.
• An electronic health record automated reminder system was developed for chemotherapy orders.
• DPYD testing was standardized, and a closed-loop reporting system for abnormal results was established.

Main Results:

• Preemptive DPYD testing rates increased from 26% to over 90% within 10 months.
• Testing rates across six network sites rose from 9% to 96%.
• DPYD variants were found in 4.1% of 1,043 tested patients, leading to dose adjustments in 96% of evaluable cases.

Conclusions:

• Preemptive DPYD testing is feasible and achievable with high rates using an opt-out, reminder-based approach.
• The implementation details are provided to encourage emulation by other institutions.
• This strategy enhances patient safety in fluoropyrimidine chemotherapy.