NIGMS Request for Information: Approaches for Supporting Team Science in the Biomedical Research Community

The National Institute of General Medical Sciences (NIGMS) has issued a request for information (RFI: Approaches for Supporting Team Science in the Biomedical Research Community) in order to seek input on how best to support team-based scientific research. The NIGMS defines team science as research that requires multiple investigators to answer research questions that cannot be answered by one investigator or a group supported by a multi-PI R01 grants (Notice number: NOT-GM-16-107).

A full description of the RFI is available at: 

http://grants.nih.gov/grants/guide/notice-files/NOT-GM-16-107.html

The responses to the RFI will be accepted through June 17, 2016. Responses may be submitted as text or an attachment in an e-mail to TeamScience@mail.nih.gov or may be submitted anonymously with a web form (https://www.research.net/r/Team_Science). 

We encourage our scientific community to communicate their thoughts to these important initiatives to NIH. 

Race and Pharmacogenetics discussed in the New England Journal of Medicine

The authors of a new Perspective in the New England Journal of Medicine (“Will precision medicine move us beyond race?”) focus on the potential pitfalls of using race based categories as proxies for pharmacogenetic variants. Self-identified race may not predict genotype or drug response in individual patients and the use of race as a proxy for ancestry and genetic variants is controversial and problematic. As an example of the power of precision medicine, and specifically pharmacogenetics, Bonham et al. discuss a 2014 lawsuit by the Hawaiian attorney general against the manufacturers of clopidogrel. The lawsuit claims that clopidogrel was marketed and sold to Hawaiians despite well-established studies showing that specific alleles in CYP2C19 (*2 and *3) compromise its efficacy and that those alleles are also known to be common in a significant proportion of Hawaii’s population (East Asian, Native Hawaiian and other Pacific Islanders). Bonham et al. believe that greater cohort diversity in prospective longitudinal drug studies will improve understanding of how genetic variability may affect drug response and safety between and within populations. In addition, they argue that sub-populations that respond best to targeted drug therapies would also benefit from these studies because the studies would provide the necessary evidence of therapeutic efficacy to justify the increased costs of treatment in those groups. Finally, evidence from such studies will be necessary to mobilize training resources for clinicians and health care systems so that they can incorporate pharmacogenetic information into routine dosing and prescribing decisions to ultimately improve treatment.   

More information about CYP2C19, and clopidogrel, including the FDA-approved drug label with annotated pharmacogenetic information can be found on PharmGKB. Dosing guidelines for CYP2C19 and clopidogrel are available on PharmGKB and CPIC. 

Pharmacogenetics in Scientific American

Dina Fine Maron discusses pharmacogenetics and pharmacogenomics (PGx) in a new video and article titled “A Very Personal Problem” in this week’s issue of Scientific American. In that article, Fine Maron describes the science of PGx and tells the personal stories of two pediatric patients who received care at St. Jude’s. She also includes discussions with Dr. Mary Relling, co-principal investigator of the Clinical Pharmacogenetics Implementation Consortium (CPIC) and Dr. Dan Roden, CPIC steering committee member. CPIC is a shared project with PharmGKB and the Pharmacogenetics Research Network (PGRN). In the article, Dr. Relling and Dr. Roden discuss the utility of and impediments to pre-emptive PGx testing and how their respective institutions have successfully implemented pre-emptive PGx testing as a routine part of care. The CPIC dosing guidelines for all gene-drug pair interactions that were discussed in the article (CYP2D6 and codeine, CYP2C19 and clopidogrel, SLCO1B1 and simvastatin and G6PD and rasburicase) and a list of institutions that are currently implementing PGx testing can be found on the CPIC and PharmGKB websites. 

European Union awards €15 million to U-PGx consortium

The European Union H2020 programme has awarded a €15 million grant to the Ubiquitous Pharmacogenomics (U-PGx) consortium for an international pharmacogenomics research and implementation project.

The aim of the U-PGx consortium is to make actionable pharmacogenomic data and effective treatment optimization accessible to every European citizen. The objective of the research and implementation project is to map genetic profiles of 8,000 patients, and then implement stratified prescribing of drugs in these patients based on the Dutch Pharmacogenetics Working Group guidelines. The cost-effectiveness and clinical-effectiveness of this approach will then be evaluated. Educational activities are also planned to assist in the training and education of health care professionals and patients regarding pharmacogenomics.

U-PGx will host its 1st annual consortium meeting in Athens, Greece in September 2016; Teri Klein, co-principal investigator of PharmGKB and the Clinical Pharmacogenetics Implementation Consortium (CPIC), will be in attendance. Dr. Russ Altman, co-principal investigator of PharmGKB, is on the advisory board for U-PGx.

Visit the U-PGx website

Evidence of pharmacogenetics in aiding polypharmacy outcomes

Many drugs interact with the same enzymes and transporters. As a result, variation in the genes encoding these proteins can affect risks of side effects and likelihood of treatment success for patients taking many medications. These interactions may be different and not necessarily predicted from trials of single drugs. Knowing a patient’s genotypes for pharmacogenes can help optimize these treatment regimes. PharmGKB provides resources for exploring these relationships between genetic variation and drug response.

The recent article, “Potential utility of precision medicine for older adults with polypharmacy: a case series study” illustrates increased risk of hospitalization in patients taking multiple medications who also have variants in cytochrome P450 genes. Finkelstein, et al. present the cases of 3 older adults with chronic heart and lung disease, who were taking between 17 and 26 medications each. One of these patients had genotypes predicting normal metabolizer status for CYP2C19, CYP2C9, CYP2D6, and CYP3A4/5. This patient had no hospitalizations in the previous 5 years. The other two patients, one who was a CYP2D6 rapid metabolizer and the other who was a CYP3A4/5 poor metabolizer, had 6 and 23 hospitalizations related to adverse cardiovascular events. While this is a small number of cases, it illustrates the power of pharmacogenomics in optimizing medication regimes in cases of polypharmacy.