CPIC launches second Term Standardization project – seeking PGx experts

CPIC leadership has put out a call for gene experts to participate in the second CPIC Term Standardization project, which will begin in early 2020.

This project continues the work of the first term standardization effort in 2016, where standardized terms for pharmacogenetic (PGx) allele function and associated phenotypes were developed and agreed upon by a Delphi process (see Caudle et al. 2017 for further details). The work of the previous project was adopted by many external groups and has helped build consensus between different PGx testing platforms, PGx implementation processes and scientific publications.

The second Term Standardization project will use the same Delphi process to find drug-agnostic allele function and phenotype terms that can be used by pharmacogenes not included in the 2016 work, including VKORC1, RYR1, mt-RNR1 and others. As with the first term standardization project, iterative surveys will be used to find consensus among the group. It is expected that 2-4 rounds of surveys will be needed to achieve consensus. As with the 2016 project, the resulting standardized terms will be published in a peer-reviewed journal and used in future CPIC guidelines.

If you meet the criteria below and would like to join this expert panel, please take this survey (5-10 minutes) to be included in the project. Further information can also be found at the CPIC website.

• Clinician with a working knowledge of pharmacogenetics (pharmacists, physicians, nurses, genetic counselors, etc).

• Researcher with at least 2 years of PGx research experience

• Clinical laboratory scientist or staff with at least 2 years of PGx experience

• EHR standards expert/medical informatic (PGx experience not required but involvement in HL7 or similar experience preferred)

• Gene specific experts and/or CPIC or DPWG guideline author for the following genes to be included in this project: RYR1, CACNA1S, CFTR, G6PD, IFNL3, mt-RNR1, GBA, NAGS, HPRT1, POLG, COMT, OPRM1, SCN1A, SLC6A4, F5, ABL2, ASL, ASS1, CPS1, and OTC

Call for clarification on antidepressant pharmacogenomics

A new Perspective in Clinical Pharmacology and Therapeutics outlines the need for improved communication from pharmacogenomic testing companies and regulators on the role of pharmacogenomics in antidepressant therapy.

Beginning antidepressant treatment can be an arduous experience for patients. Some patients fail to respond to first-line antidepressants, leading to an iterative process of trying different medications until depressive symptoms improve, while others experience antidepressant-induced adverse effects. This current situation highlights the need to make evidence-based improvements to the drug selection and dosing process.

Some pharmacogenomic information is included on the US Food and Drug Administration (FDA)-approved labels of a number of antidepressants. However, the actionability of this information can vary widely between labels and there is no guidance to clinicians on when to seek pharmacogenomic testing for a patient. PharmGKB assigns a PGx Level and tags to our drug label annotations to help users easily recognize labels containing actionable pharmacogenomic information such as recommendations for dose or altered drugs.

The publication’s authors, including Dr. Teri Klein and Dr. Katrin Sangkuhl (PharmGKB and CPIC), Dr. Andrea Gaedigk (PharmVar), as well as Dr. Kelly Caudle and Dr. Roseann Gammal (CPIC), argue that the inconsistencies in drug labels combined with the FDA’s recent communications on the safety and validity of pharmacogenomic testing has created confusion among clinicians and patients about pharmacogenomics in antidepressant prescribing. They also highlight the work of CPIC in producing evidence-based clinical guidelines that can be used to guide drug selection and dosing. In particular, the CPIC guidelines for selective serotonin reuptake inhibitors and tricyclic antidepressants are based on the critical review of decades of scientific evidence.

The article ends with a call for clarity on the level of evidence required to implement pharmacogenomic-guided prescribing in the clinic, particularly with reference to sertraline and escitalopram.

CYP2D6 Genotype to Phenotype Standardization Project results published

The consensus of the CYP2D6 Genotype to Phenotype Standardization Project is just published in Clinical and Translational Science. 

To address inconsistencies in the translation of CYP2D6 genotype to phenotype across guidelines (i.e. Clinical Pharmacogenetics Implementation Consortium (CPIC) and Dutch Pharmacogenetics Working Group (DPWG)) and between clinical genetic testing laboratories, CPIC recently conducted a modified-Delphi project to obtain consensus among a panel of international CYP2D6 experts for a uniform system for translating CYP2D6 genotype to phenotype (more information).

Modifications to CPIC’s prior system include downgrading the value assigned to the CYP2D6*10 allele for activity score calculation from 0.5 to 0.25 and changing the phenotype assignment for an activity score of 1 from normal metabolizer to intermediate metabolizer (see table of all previous and new phenotype groupings).

As a result changes have been made in the CYP2D6 allele functionality table and the CYP2D6 genotype to phenotype table and the impact on the CYP2D6-relevant guidelines is described on the individual guideline pages for atomoxetine, codeine,  ondansetron and tropisetron, SSRIs, tamoxifen, and tricyclic antidepressants on the CPIC website.

Characterization of CYP2D6 reference materials by GeT-RM

The CDC-based Genetic Testing Reference Material Coordination Program (GeT-RM) has published an extended panel of Coriell samples with CYP2D6 genotype information.

Not only have the existing 137 samples been extensively re-tested on different platforms, selected samples have also been sequenced to determine the haplotype of novel or rare allelic variants which have not been characterized in the past. Furthermore, an additional 42 samples with rare, unusual or complex diplotypes were extensively interrogated. All new information was submitted to PharmVar to facilitate dissemination to PharmGKB and CPIC.

These publicly available samples will support academic research as well as the quality-assurance and quality-control programs of clinical laboratories performing CYP2D6 testing. 

Dr. Lisa Kalman of the CDC will present the project at the Annual Meeting & Expo of the Association for Molecular Pathology on Nov 7-9 in Baltimore.

Annotated Swissmedic Drug labels now available on PharmGKB

PharmGKB now has annotated drug labels available from the Swiss Agency of Therapeutic Products (Swissmedic), a regulatory authority responsible for the authorization and supervision of therapeutic products in Switzerland.

The Swissmedic drug label annotations are sourced through a collaboration with the Pharmaceutical Care Research Group (PCRG), Department of Pharmaceutical Sciences, University of Basel. The PCRG group screened and translated pharmacogenomic (PGx) relevant information in the Summaries of Product Characteristics (SmPCs) of all Swissmedic labels through natural language processing (NLP). Using these translations and analysis, PharmGKB annotated Swissmedic drug labels based on our criteria for PGx information.

Like our FDA drug label information, we provide a summary and excerpt of PGx information from the Swissmedic SmPC. Each Swissmedic drug label annotation is also given a PGx level of evidence, and a link to the original full text label on the AmiKo Web (https://amiko.oddb.org/). If the label provides dosing adjustments based on genetic information or metabolizer phenotypes, or states that a drug is either indicated or contraindicated for a particular set of patients, the label annotation will be tagged with "dosing info" or "alternative drug" tag.

It is likely that there are other Swissmedic drug labels that contain PGx information, and PharmGKB welcomes any feedback regarding PGx information within the labels from Swissmedic or other medicine agencies around the world.

View our complete list of drug labels with PGx information.