Identification of high-impact gene–drug pairs for pharmacogenetic testing in Alberta, Canada

Abstract

Objectives To facilitate decision-making and priority-setting related to Alberta’s Pharmacogenomics (PGx) testing implementation strategy by identifying gene–drug pairs with the highest potential impact on prescribing practices in Alberta. Patients and methods Annual drug dispensing data for Alberta from 2012 to 2016 for 57 medications with PGx-based prescribing guidelines were obtained, along with population estimates and demographics (age and ethnicity). Frequencies of actionable PGx genotypes by ethnicity were obtained from the Pharmacogenomics Knowledgebase (PharmGKB). Annual dispensing activity for each of the 57 medications was calculated for the full population (all ages) and children/youth (0–19 years). Alberta ethnicity data were cross-referenced with genetic frequency data for each of the main ethnic groups from PharmGKB to estimate the proportion of individuals with actionable genotypes. Actionable genotype proportions and drug dispensing frequencies were collectively used to identify high impact gene–drug pairs. Results We found (a) half of the drugs with PGx-based prescribing guidelines, namely, analgesics, proton pump inhibitors, psychotropics, and cardiovascular drugs, were dispensed at high frequencies (>1% of the entire population), (b) the dispensing rate for about one-third of these drugs increased over the 5-year study period, (c) between 1.1 and 45% of recipients of these drugs carried actionable genotypes, and (d) the gene–drug pairs with greatest impact in Alberta predominatly included CYP2C19 or CYP2D6. Conclusions We uncovered specific patterns in drug dispensing and identified important gene–drug pairs that will inform the planning and development of an evidenced-based PGx testing service in Alberta, Canada. Adaptation of our approach may facilitate the process of evidence-based PGx testing implementation in other jurisdictions.

Prevalence of exposure to pharmacogenetic drugs by the Saudis treated at the health care centers of the Ministry of National Guard

“…Thus, our data are considered useful support to change medication use policy among Saudi society but may not be generalized to different populations. Consistent with previous studies conducted on Dutch, Americans, and Canadians ( Alshabeeb et al, 2019 , Samwald et al, 2016 , Fan et al, 2021 ), analgesics, cardiovascular drugs, proton pump inhibitors, and psychotropics were among the most prescribed drug categories. The analgesic group became the top category in this study as more medications belonging to the group, such as ibuprofen, celecoxib, and fentanyl were added to the screened list, wheras the psychotropic group was found to be the fifth used category as multiple agents of the group were excluded, such as clozapine, olanzapine and pimozide as a result of failure to fit the selected evidence level criteria or due to non-availability in MNG-HA formulary e.g.…”

“…Association of CYP2C9 ( *2 and *3 ) with warfarin dose variability was also investigated among 112 Saudi patients which emphasized a need for lower doses in patients positive for the variants particularly *3 than those with wild type ( Al-Saikhan et al, 2018 ). The studies conducted on Western population have shown that CYP2D6 genotypes was linked to the majority (46.8–60.3%) of drug response prediction in patients on PGx drugs ( Alshabeeb et al, 2019 , Fan et al, 2021 ). In contrast, the gene in our study was found to feasibly affect 14.3% of treatment outcomes among Saudi patients on PGx drugs.…”

Prescribing Prevalence of Medications With Potential Genotype-Guided Dosing in Pediatric Patients

“…One single-center study 19 reported similar prevalences of prescribing, which differed from prevalences in adults. 20 A 5-year study across Alberta, Canada, 21 demonstrated that codeine-containing medications and ondansetron were the most commonly prescribed medications with pharmacogenetic-based prescribing guidelines in pediatric patients.…”

“…[42][43][44] These characteristics, combined with increased liability concerns and lack of pharmacogenetic testing, suggest a shift in analgesic utilization toward oxycodone as a preferable option in pediatric patients in the US but not in Canada. 21 Unlike with codeine, the CYP2D6 genotype is not strongly associated with observed oxycodone response, [45][46][47] but oxycodone and its active metabolite oxymorphone can lead to opioid dependence, 48,49 raising reasonable concerns.…”

Single molecule long-read real-time amplicon-based sequencing ofCYP2D6: a proof-of-concept with hybrid haplotypes

“…Although CYP2D6 plays a key role in the metabolism of ~20-25% of clinically used drugs (Ingelman-Sundberg, 2005;Zanger et al, 2013), and is included in drug labelling by regulatory bodies (the U.S. Food and Drug Administration, the European Medicines Agency, the Pharmaceuticals and Medical Devices Agency) and prescribing recommendations by consortia (Clinical Pharmacogenetics Implementation Consortium, the Dutch Pharmacogenetics Working Group), identification of CYP2D6 variants is not yet routine in clinical practice. This is despite the fact that dispensing data indicate that many patients are being prescribed medications for which the identification of CYP2D6 variants prior to these medications being dispensed could be helpful (Fan et al, 2021) One of the reasons for this is the complexity of the locus, and in particular the fact that the fusion genes are challenging to identify and accurately characterize. Another reason is that clinical implementation requires an efficient, high throughput method that requires relatively little personnel time.…”