Point of Care Pharmacogenetics in Routine Clinical Practice

Introduction: Medicines are the most common therapeutic intervention in healthcare, yet their effectiveness and safety show considerable inter-personal variation. There are many reasons for this, but there is an increasing awareness that response to medicine is affected by an individual’s genetic variation, a concept known as pharmacogenetics. Access to pharmacogenetic data at the point of prescribing could lead to improved medicines selection, leading to improved outcomes and better use of scarce healthcare resources. This is particularly true in the acute setting, where results would be required in a rapid timeframe to inform management.

Over the next 3-5 years it is increasingly likely that novel genomic point of care tests (POCTs) will become part of routine practice in some healthcare settings. These technologies have the potential to test for genetic changes in a clinically relevant timeframe. Nursing and midwifery colleagues are the professionals best placed to operate these systems, as the ambition is that they will become analogous to venous blood gases (VBGs) or blood sugar readings. Although this may sound ambitious, this has already been trialled successfully by nurses in the Neonatal Intensive Care Unit (NICU).

Exemplar: Aminoglycosides are commonly prescribed antibiotics used for the treatment of neonatal sepsis. The MT-RNR1 m.1555A>G variant predisposes to profound aminoglycoside-induced ototoxicity (AIO), present in 1 in 500 babies. Current genotyping approaches take several days, which is unacceptable in acute settings. The Pharmacogenetics to Avoid the Loss of Hearing (PALOH) project set out to develop a rapid POCT for the m.1555A>G variant before implementation of this technology in the acute neonatal setting to guide antibiotic prescribing and avoid AIO. This pragmatic prospective implementation trial recruited neonates admitted to 2 large neonatal intensive care units between January 6, 2020, and November 30, 2020, in the UK. Neonates were tested for the m.1555A>G variant via the rapid POCT on admission to the neonatal intensive care unit. The babies were tested 24 hours a day, 7 days a week by neonatal intensive care nurses, all of whom had undergone a brief (20 minute) training session prior to the study.

A total of 751 neonates were recruited across the study The MT-RNR1 POCT was able to genotype the m.1555A>G variant in 26 minutes. Three participants with the m.1555A>G variant were identified, all of whom avoided aminoglycoside antibiotics. Overall, 424 infants (80.6%) receiving antibiotics were successfully tested for the variant, and the mean time to antibiotics was equivalent to previous practice. No babies were missed due to the unavailability of nursing staff or lack of training. This rapid genetic POCT was integrated without disrupting normal clinical practice, and genotype was used to guide antibiotic prescription and avoid AIO. This approach identified the m.1555A>G variant in a practice-changing time frame, and wide adoption could significantly reduce the burden of AIO.

Recommendation: This represents just one example of a genetic change which could be used to tailor management in the acute setting. Nursing colleagues were essential to the delivery of this project and they will play a key role if similar technologies are to be implemented in other practice settings. Tailored, practice specific, education is required for nurses and midwives so they are aware of how genetics (and specifically pharmacogenetics) can be used to guide management of their patients. Support should be provided around how to discuss these new types of tests with their patients, especially in the acute setting where traditional consenting models might not be appropriate.