Senior investigator Professor Rachel Conyers
Genotype-informed prescribing has the potential to reduce use of ineffective medications and avoid adverse drug reactions but international pharmacogenomic (PGx) recommendations are only explicitly followed in 20% of paediatric cancer patients, Australian research suggests.
A retrospective review of adherence to PGx recommendations, published in the journal Pharmacogenomics [link here], suggested that limited awareness of PGx and its proven benefits in precision medicine may be the problem.
“Implementing targeted education strategies for healthcare professionals, including chemotherapy prescribers such as oncologists, would be a key step toward increasing PGx uptake,” it said.
“This may include formal integration of PGx into undergraduate curricula, as well as continuing professional education for practising clinicians.”
The study reviewed data from 216 children 0–18 years with solid and haematological cancers who received PGx testing and had successfully generated PGx reports uploaded to their EMR as part of the MARVEL-PIC study at the Royal Children’s Hospital Melbourne.
Overall, a total of 2,063 individual PGx recommendations were made including 1,132 deemed actionable but not relevant, 357 deemed not actionable, and 510 duplicates.
The remaining 64 recommendations for 10 drugs were considered both actionable and relevant in 44 patients across 288 prescribing events.
The study found PGx recommendations were explicitly followed in 19.8% of identified prescribing events, inadvertently followed in 50.3%, and not followed in 29.9% of events.
Mercaptopurine was the only drug with a high rate (87.5%) of explicit PGx adherence, the study found. For example, patients deemed poor or intermediate metabolisers due to variations in the NUDT15 or TPMT genes were started on reduced doses.
“Recommendations for thioguanine were explicitly followed in one of two total (50%) prescribing events,” the study said.
“Voriconazole, ondansetron/tropisetron, and omeprazole/pantoprazole also demonstrated above-zero rates of explicit adherence (41.4%, 30.4%, and 21.4%, respectively), whereas recommendations for amitriptyline/nortriptyline, carbamazepine, codeine/tramadol, and sertraline were not adhered to in any prescribing event.”
Examples of recommendations that were inadvertently followed include those where avoidance of codeine/tramadol was recommended due to poor or intermediate metaboliser phenotypes associated with CYP2D6 and a non-codeine/tramadol opioid was prescribed, but without reference to PGx.
“This is likely a reflection of local prescribing patterns; at our centre, oxycodone is the first-line opioid of choice, and gabapentin is the first-line drug to treat neuropathic pain,” the investigators said.
“As such, these recommendations were likely to have been followed regardless of PGx advice and cannot be considered as true adherence to recommendations.”
The study said the only given reason for non-adherence to PGx recommendations was clinician confusion with no further elaboration.
“There may have been prescribing events where recommendations were considered but deemed clinically inappropriate, but this was not clinically documented,” they said.
The investigators, including Professor Rachel Conyers from the Murdoch Children’s Research Institute and Royal Children’s Hospital Melbourne, said their findings were broadly consistent with a recent German study with an adult cohort [link here].
Given the poor levels of explicit adherence to PGx recommendations, they concluded further qualitative investigations into clinician attitudes were required to identify barriers to implementation along with educational interventions to address those barriers.