NIH Request for Information: Metrics to Assess Value of Biomedical Digital Repositories

NIH has issued a Request for Information to gather input about metrics to assess the impact and value of biomedical digital data repositories, including deposition repositories and knowledgebases.  NIH is interested in collecting information about the usage, quality of data, quality of service and other aspects of existing repositories.  Community use of repositories, in addition to individual use, is emphasized.  Responses should include information such as how specific resources are used, and how community use or importance of a resource can be measured.

A full description of the RFI is available at: https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-133.html

Responses are due by September 30, 2016.  

CPIC and PGx discussed in recent GEN article

A recent article in Genetic Engineering & Biotechnology News (GEN) discusses the future of pharmacogenetics in the context of clinical practice. The article notes that personalized medicine will likely be enacted through the work of intermediary groups, such as the Clinical Pharmacogenetics Implementation Consortium (CPIC), who can help clinicians keep up with the latest genetic information. The article interviews Dr. Kelly Caudle, CPIC coordinator, and Dr. Robert Freimuth, co-chair of the CPIC Informatics Working Group, on how the consortium is working to enable the translation of genetic information into actionable clinical results. Ongoing work of Dr. Stuart Scott at the Icahn School of Medicine at Mount Sinai and several European institutes is also discussed.

Nature Outlook: Precision Medicine on Pharmacogenetics highlights its status, promise, and burdens

An outlook on precision medicine in Nature discusses the status, promise, and burdens of the implementation of pharmacogenetic knowledge into clinical care. It highlights the PGEN4Kids program at St Jude, which is implementing CPIC recommendations in a preemptive genetic testing program for pediatric patients. As discussed in the article, CPIC has published recommendations for genotype-guided therapy of 33 drugs, with more guidelines being released each year. CPIC guidelines can be read and downloaded here: https://cpicpgx.org/guidelines/.

The article reports successful implementation of using TPMT genotypes to adjust thiopurine treatment and of screening for HLA-B genotype to avoid hypersensitivity reactions to abacavir in treatment for HIV. Moving the field forward, we agree with Drew’s emphasis on the increased value of preemptive genetic testing compared to reactionary testing, on the need for sustainable program funding, and on the importance of developing strong infrastructure to support clinical decision making in response to test results.

The article points out the struggles of the pharmacogenetics field, citing the failure of clinical trials to show improved warfarin dosing when using a genotype-guided dosing algorithm compared to a clinical algorithm. However, as Daneshjou, et al. pointed out in NEJM in their 2014 letter to the editor, the finding that the genotype-guided dosing algorithm is inferior to a clinical-dosing algorithm may be biased by different important variants and different frequencies of the variants included in the algorithm in different populations globally. For example, the apparent ineffectiveness of a genotype-guided dosing algorithm for warfarin for people of African descent may be affected by low population frequencies of the CYP2C9*2 and *3 variants that are included in this algorithm. As a result, “the authors’ ability to draw appropriate conclusions about the usefulness of genetics when determining dosages of warfarin for patients of African descent is thus very limited, and the benefits for this population have not been adequately tested.” Furthermore, if a minority of patients receive altered drug treatment as a result of genetic test results in a clinical trial, these benefits may not appear in overall summary statistics. However, the improved personalized treatment for this subset of patients should not be undervalued.

Integrating pharmacogenetics in a conservative medical system seems subject to a genetic exceptionalism resulting in a high burden of proof. Drugs thought to be affected by pharmacogenetic variability comprise 18% of the US drug market, suggesting far-reaching benefits of preemptive testing programs. We see great power in implementing the information we have now, and recognize the need for additional research to expand knowledge of variation globally and of the impacts of variants on drug response so that the benefits of pharmacogenetic testing can continue to grow.

Join the CPT Webinar on CPIC Guidelines: Thursday, September 22, 12-1pm EDT

Click here to register.

PharmCAT poster to be presented at ASHG

At the American Society of Human Genetics annual meeting in October, PharmGKB will be presenting the new Pharmacogenomics Clinical Annotation Tool (PharmCAT) with our colleague, Dr. Marylyn Ritchie, who is pictured on the home page of the meeting website (http://www.ashg.org/2016meeting/).  We look forward to seeing everyone there!

CPIC Meeting at ASCPT on March 15, 2017

The Clinical Pharmacogenetics Implementation Consortium(CPIC®)  Meeting will be held on March 15, 2017, in conjunction with the 2017 Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics (ASCPT) on March 15-18, 2017 (Washington, DC).

The one-day symposium is organized by the Clinical Pharmacogenetics Implementation Consortium (CPIC®) (cpicpgx.org) as part of the Pharmacogenomics Research Network (PGRN) (www.pgrn.org).   The CPIC-PGRN Meeting is open to all and features presentations from a world-class group of speakers who will describe current examples of implementation of pharmacogenomics in the clinic. There will also be panel discussions to summarize topics and encourage audience participation. Presentations will include “best cases” as well as challenging cases for implementation, and will include international perspectives on clinical use of pharmacogenomics.  More details can be found at https://cpicpgx.org/meetings/

CPIC® is one of the enabling resources funded by the National Institutes of Health as part of the PGRN, and is a shared project between PharmGKB (www.pharmgkb.org) and the PGRN.  The mission of the PGRN is to catalyze and lead research in precision medicine for the discovery and translation of genomic variation influencing therapeutic and adverse drug effects. CPIC’s goal is to facilitate translation by overcoming some of the barriers to implementation of pharmacogenetic tests into clinical practice. Over 150 CPIC members from 19 countries participate to developing tools to facilitate clinical implementation of pharmacogenetics, primarily by developing freely available, peer-reviewed, updatable, and detailed gene/drug clinical practice guidelines.

CPIC Seeks Feedback on Recommendation Strength and Gene/Drug Pair Level Definitions

CPIC is proposing changes to CPIC Guideline grades for strength of recommendation and for definitions of CPIC Levels of gene/drug pairs. 

Based on a review of other practices and challenges presented by some CPIC gene/drug pairs, it is recommended that the option "no recommendation" be added to the three current recommendation strengths for diplotype/drugs: strong, moderate, optional. To reflect this additional prescribing recommendation category, the definition of a CPIC level C has been revised to include cases where there are few published studies or mostly weak evidence and the clinical actions are unclear.

Additionally, CPIC would like to assign a level (A, B, C or D) to drugs that are listed in CPIC guidelines as “not good alternatives” but are not explicitly the subject of a CPIC guideline recommendation (e.g. the codeine guideline recommends not using tramadol as an alternative). Also, some guidelines include recommendations that may be reasonably applied to similar agents (e.g. imipramine treated like other TCAs). By slightly revising the definition of an “optional” recommendation to include cases where the “evidence is weak or based on extrapolations,” some of these alternative drugs can be assigned a CPIC level B or C, depending on levels of evidence.

The proposed changes are found at the CPIC website and are open for comment.  Please send comments to cpic@pharmgkb.org by September 12, 2016.