Pharmacogenetics Guidelines: Overview and Comparison of the DPWG, CPIC, CPNDS, and RNPGx Guidelines

Abstract

Many studies have shown that the efficacy and risk of side effects of drug treatment is influenced by genetic variants. Evidence based guidelines are essential for implementing pharmacogenetic knowledge in daily clinical practice to optimize pharmacotherapy of individual patients. A literature search was performed to select committees developing guidelines with recommendations being published in English. The Dutch Pharmacogenetics Working Group (DPWG), the Clinical Pharmacogenetics Implementation Consortium (CPIC), the Canadian Pharmacogenomics Network for Drug Safety (CPNDS), and the French National Network (Réseau) of Pharmacogenetics (RNPGx) were selected. Their guidelines were compared with regard to the methodology of development, translation of genotypes to predicted phenotypes, pharmacotherapeutic recommendations and recommendations on genotyping. A detailed overview of all recommendations for gene-drug combinations is given. The committees have similar methodologies of guideline development. However, the objectives differed at the start of their projects, which have led to unique profiles and strengths of their guidelines. DPWG and CPIC have a main focus on pharmacotherapeutic recommendations for a large number of drugs in combination with a patient’s genotype or predicted phenotype. DPWG, CPNDS and RNPGx also recommend on performing genetic testing in daily clinical practice, with RNPGx even describing specific clinical settings or medical conditions for which genotyping is recommended. Discordances exist, however committees also initiated harmonizing projects. The outcome of a consensus project was to rename “extensive metabolizer (EM)” to “normal metabolizer (NM)”. It was decided to translate a CYP2D6 genotype with one nonfunctional allele (activity score 1.0) into the predicted phenotype of intermediate metabolizer (IM). Differences in recommendations are the result of the methodologies used, such as assessment of dose adjustments of tricyclic antidepressants. In some cases, indication or dose specific recommendations are given for example for clopidogrel, codeine, irinotecan. The following drugs have recommendations on genetic testing with the highest level: abacavir (HLA), clopidogrel (CYP2C19), fluoropyrimidines (DPYD), thiopurines (TPMT), irinotecan (UGT1A1), codeine (CYP2D6), and cisplatin (TPMT). The guidelines cover many drugs and genes, genotypes, or predicted phenotypes. Because of this and their unique features, considering the totality of guidelines are of added value. In conclusion, many evidence based pharmacogenetics guidelines with clear recommendations are available for clinical decision making by healthcare professionals, patients and other stakeholders.

Perception of personalized medicine, pharmacogenomics, and genetic testing among undergraduates in Hong Kong

“…In 2019, the provision of PGx testing in Hong Kong public hospitals was only limited to three drugs; in contrast, current clinical application of PGx in other countries is much more extensive with wider gene-drug coverage [67]. For instance, in the Netherlands, up to July 2020, more than 100 gene-drug pairs were examined by the Dutch Pharmacogenetics Working Group (DPWG) including 60 actionable gene-drug pairs [68]. In Austria, the clinical application of the Medial Safety Code, which is a QR code encompassing personal PGx information on 54 drugs, has been explored since 2013 [69].…”

A Comprehensive Review of HLA and Severe Cutaneous Adverse Drug Reactions: Implication for Clinical Pharmacogenomics and Precision Medicine

“…International pharmacogenetic working group such as the CPIC, the Dutch Pharmacogenetics Working Group (DPWG) and the Canadian Pharmacogenomics Network for Drug Safety (CPNDS) are reviewing the evidence of drug-gene interactions and are developing PGx based dosing guidelines for more than a decade [148][149][150][151].…”

“…Each of these PGx working group has its own method of assessing drug-gene interactions (DGIs), e.g., some group consider one drug and one gene for developing guidelines whereas others include one or more drugs with two to three genes. In addition, strategy of grading scientific evidence and the strength of the recommendation differ among these PGx-based dosing guideline developers [148,[152][153][154][155]. Of note, only the DPWG and CP-NDS provide PGx testing recommendations regarding a specific DGI for implementation in daily clinical practice.…”

The Influence of Pharmacogenetics on the Clinical Relevance of Pharmacokinetic Drug–Drug Interactions: Drug–Gene, Drug–Gene–Gene and Drug–Drug–Gene Interactions

“…Currently, most guidelines on DDIs neither consider the potential effect of genetic polymorphisms in the strength of the interaction nor do they account for the complex interaction caused by the combination of DDI and DGI when there are multiple biotransfor-mation pathways, referred to as DGGI. Not surprisingly those guidelines often contradict each other [8]. Therefore, all the studies with only PGx results, as well as studies in which only DDIs were reported, are probably incorrect and will, thus, lead to false conlusions and potentially damaging clinical recommendations.…”