Dr. Francis Collins discusses All of Us on CBS This Morning

The National Institutes of Health (NIH) director Dr. Francis Collins appeared on CBS This Morning to promote the All of Us program, a part of the Precision Medicine Initiative, which launches this Sunday, May 6th. 

When asked about what it hopes to accomplish, he explained:

“Do you ever feel when somebody is making recommendations to you about how to stay healthy or when you need a prescription and you’re wondering 'is this the right drug for me at the right dose?' A lot of what we do in medicine is one-size-fits-all. Precision medicine is this opportunity to make things much more individualized and more precise and more likely to result in a good outcome, but to get to that point we need to collect a lot of data on a lot of people…”

All of Us hopes to recruit 1 million Americans, and is particularly interested in recruiting subjects from communities that are typically underrepresented in biomedical research. Dr. Collins addressed questions about privacy concerns by explaining that all data will be de-identified, researchers pledged to not re-identify subjects and that data will be protected from use by law enforcement as a result of new legislation. 

You can find more information about pharmacogenomics (PGx) such as PGx-guided dosing/prescribing guidelines at CPIC and PharmGKB where you can also find curated information about drugs and genes, from the literature as well as from drug labels and other sources.

Promote the study of Pharmacogenomics in the All of Us cohort

The NIH is collecting suggestions for what to study in a new large cohort of one million or more people living in the United States. The All of Us research program is part of the Precision Medicine Initiative and will recruit volunteers across the USA to share their data with researchers to look at big questions. NIH is seeking input from the public on what questions to address with the All of Us data and asks people to vote on the ideas they value the most.


PharmGKB has submitted some questions related to PGx that need your vote!

Idea # 363: Does collecting side-effect data directly from patients improve compliance, personalized drug choice and efficacy? After a drug has been approved, big ADRs are reported to MEDRA, but smaller side effects are not usually reported. While some may be known and in the drug label, novel side effects may occur in populations not included in the original trials. Small effects may lead to discontinuation or poor compliance. Collecting better data about side effects and combining with genomic data could give improved pharmacogenomic prediction of side effects and allow for better selection of drugs for a patient.

Idea #379: Do tailored educational materials for patient-participants undergoing pharmacogenetic testing promote patient engagement? We will assess and compare the level of understanding, engagement and satisfaction in patients who received pharmacogenetic results and are randomized to 1) a web-based portal with personalized educational content tailored to subject's results or 2)standard of care. Subjects will be surveyed to determine 1) understanding 2) engagement and 3) satisfaction. Educational content will be created by and housed at PharmGKB, in collaboration with genetic counselors and science education specialists.

There are also several more questions regarding PGx that are tagged and worth our comments and votes. Click on Pharmacogenomics in “What we are discussing” on the right hand panel.  

Early Registration for Precision Medicine Conference ends Sunday

Early registration for the University of Florida Precision Medicine Conference, held from March 8-10 in Orlando, Florida, ends this Sunday, January 22 at midnight. Earn continuing education credit and learn how to translate pharmacogenomics into practice. The program, which includes speakers, case studies, and participant genotyping, will provide practical information on how to individualize drug therapy, how to perform genetic testing, and how to navigate reimbursement, in addition to providing information about other emerging topics in precision medicine. The conference is open to practitioners, faculty, students, residents, and fellows.

Wall Street Journal Discusses Predispositional Personal Genome Sequencing, PGx

A recent article by Laura Landro in the Wall Street Journal titled “Why Knowing Your Genetic Data Can Be a Tricky Proposition” discusses the benefits and complications of Predisposition Personal Genome Sequencing (PPGS) and the Personal Genome Sequencing Outcomes, or PeopleSeq consortium. PPGS is preemptive genome sequencing of apparently healthy patients, which contrasts with genome sequencing  for diagnosis of genetic disease. The article highlights the efforts of private companies, health care systems and academic research centers, some of which include members of the Clinical Pharmacogenetics Implementation Consortium (CPIC) that conduct PPGS in healthy patients. Although it emphasizes how PPGS may help patients discover genetic pre-disposition to disease, many institutions, including those that collaborated as part of the PeopleSeq consortium, returned pharmacogenomics results for health records or to patients if requested.  Of 258 adults surveyed from the three PeopleSeq sites (Harvard Personal Genome Project, Illumina Understand Your Genome program and Mount Sinai HealthSeq), 81% said it was “very” or “somewhat important” to learn about personal response to medications. In addition, 99 and 98% had a “personal interest in genetics in general” and “curiosity about my genetic make-up”, respectively, while “92% had a desire to participate in research to help others”. The favorable attitude of many participants towards genome sequencing and pharmacogenomics, demonstrates a growing understanding and awareness of genomics, which is an encouraging sign for genomics and pharmacogenomics research.

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. 

CPIC Informatics Working Group publishes article in JAMIA

An article from the Clinical Pharmacogenetics Implementation Consortium (CPIC) Informatics Working Group has now been published ahead-of-print on the Journal of the American Medical Informatics Association (JAMIA) website. Within the paper, the authors discuss principles that will support the implementation of precision medicine, particularly pharmacogenomics, into routine clinical care.                                                                                

Hoffman et al. write that successful adoption of pharmacogenomics in the clinic requires a database of knowledge that can be used in an electronic health record (EHR) with Clinical Decision Support (CDS). To this end, the CPIC Informatics Working group has been developing and incorporating EHR vendor-agnostic resources into CPIC guidelines. Based on this experience, the working group outlines five principles that can apply to future knowledge resources that implement precision medicine. Though the principles are mainly in reference to pharmacogenomics, they are applicable any type of precision medicine initiative. The five principles cover the limitations of current genetic testing methods, the importance of levels of evidence, integration of different types of medical knowledge and handling of new knowledge, and the use of standardized terminology. By laying out these principles, the CPIC Informatics Working Group provides a reference for the design and implementation of future, national-level precision medicine resources.

CPIC is a shared project between PharmGKB and the Pharmacogenomics Research Network. Read more about CPIC and the Informatics Working Group at cpicpgx.org.

Read the paper on JAMIA:

Developing knowledge resources to support precision medicine: principles from the Clinical Pharmacogenetics Implementation Consortium (CPIC). James M. Hoffman; Henry M Dunnenberger; J Kevin Hicks; Kelly E Caudle; Michelle Whirl Carrillo; Robert R Freimuth; Marc S Williams; Teri E Klein; Josh F Peterson. Journal of the American Medical Informatics Association 2016; doi: 10.1093/jamia/ocw027.

The Precision Medicine Initiative: Consultative PGx and Data Sharing at Stanford University

On February 25th, one year after the announcement of the Precision Medicine Initiative (PMI), the White House hosted the Precision Medicine Summit. A White House press release described how various public and private groups will be taking steps to advance the goals of the PMI. As part of the PMI Stanford will launch a consultative pharmacogenetics practice for physicians to refer patients with unusual drug responses. Dr. Russ Altman, Co-Principal Investigator (Co-PI) of PharmGKB will lead the pharmacogenetics consultative practice. The consultative practice will evaluate genetic variants in patients with unusual drug responses and will use Clinical Pharmacogenetics Implementation Consortium (CPIC) dosing guidelines to focus attention on gene-drug pairs with the best evidence for actionability. In addition, Stanford University will also make the genomic data of 77 individuals of Iranian descent publicly available. The genomes of those 77 individuals were sequenced as part of the Iranian Genome Project, for which Dr. Altman is also the PI. Dr. Roxana Daneshjou, a former student in Dr. Altman’s lab is the lead researcher for the project.  Although Dr. Daneshjou is leading the data analysis for the project, Dr. Altman explained “we wanted to get the data out into the public as soon as possible, so (we) have taken the slightly unusual measure of making the data available before we get our paper out… we want people to use it.” A major goal of the PMI is to “open up data and technology tools to invite citizen participation, unleash new discoveries, and bring together diverse collaborators to share their unique skills.”