Last year marked the 10th anniversary of the first draft of the human genome, which was officially completed in 2003 with the mapping of 3.1 billion base pairs. This project, conducted by the U.S. Department of Energy and the NIH, took 13 years and cost more than $3 billion to complete.
Since that time, DNA sequencing technology has improved dramatically in terms of both speed and cost. It is predicted that, by the year 2013, sequencing a human genome could cost as little as $100 and take a matter of days to complete.1 As the technology for genome sequencing becomes less cost-prohibitive, more research will be done and clinical utility is likely to grow exponentially. One growing area of application is pharmacogenomics, the study of how variations in the human genome affect response to medications.
Health care systems and clinicians need to prepare now for an explosion of information and gain the skills to interpret when and how these tests can be used to make therapeutic decisions. The JASON report (http://www.fas.org/irp/agency/dod/jason/), published in December 2010, made specific recommendations to the DoD and VA to begin establishing an infrastructure and policies to support the collection of genotype and phenotype data. The report also outlined the need to address ethical and social issues that arise from use of this sensitive data.
Information from pharmaco-genomic research could change the landscape of how health care is administered in the United States. Most prescribing today is “one size fits all.” For example, if 100 patients were given the standard dose of the most appropriate approved medication, on average, only 70 or 80 of them would benefit. The other 30% would not, and a few will suffer adverse reactions. A 1998 study in the Journal of the American Medical Association concluded that adverse drug reactions were the fourth to sixth leading cause of hospitalizations and death in the United States.2
As of May 2011, 65 FDA approved medications with 70 genomic biomarkers are part of the FDA mandated package insert.3 National organizations such as the National Comprehensive Cancer Network, American College of Gastroenterology and American College of Cardiology have already included pharmacogenomic testing recommendations in their guidelines. These guidelines will inevitably drive the ordering of these tests and the need for interpretation by clinicians.
In addition to clinicians ordering these tests, a number of commercial websites offer genetic testing directly to consumers. Companies such as 23andMe, which is funded by Google and Genentech, are currently offering saliva-sample testing to analyze consumers’ “genetic propensity to certain drugs, risk for certain diseases and uncovering your ancestry” for only $99. 23andme already houses the largest set of genomic data in the world.4
As consumers rush to order these tests, it is highly probable that patients will present their genetic report to a health care facility. The ability to help patients interpret this information will be important. Patients may want assistance in personalizing their health regimens based on these tests. The purpose of this column is to describe one approach being taken at the Veterans Affairs San Diego Healthcare System (VASDHS).
Implementing Practical Management
At the VASDHS, a Clinical Pharmacist Specialist (CPS) position was created to focus on biologic medications, pharmacogenomic testing and specialty medications such as those requiring Risk Evaluation and Mitigation Strategies (REMS) processes. One of its major job functions is to specifically address the clinical and administrative needs associated with pharmacogenomic testing, including a focus on creation of guidelines and processes. As the volume of pharmaco-genomics information expands, these guidelines could be disseminated for use and application by all pharmacists and the medical center at large.
The CPS first worked with leadership to create a Pharmacogenomic Testing and Evaluation Committee. As chartered, the committee’s main function is to ensure appropriate and judicious use of pharmacogenomic tests and determine how these tests will be linked to medication usage criteria. Membership in the committee includes the Chief of Laboratory and Pathology, Director of Chemistry, two pharmacists, a physician and nursing representative. Ad hoc members from specialty areas such as oncology, infectious disease, psychiatry, or gastroenterology are invited to come and discuss pharmacogenomic tests used in their practice, as they relate to drug selection and dosing.
The committee established a standardized formulary-like process to evaluate all pharmacogenomics tests that are available or will come to market. Previously, no standardized process was in place for the coordination or evaluation of tests to check for redundancy, for management of costs associated with testing and subsequent treatments or for drug-usage guidelines that might already exist. The Pharmacogenomic Testing Evaluation Committee uses CDC guidelines to evaluate the analytic validity, clinical validity, clinical utility and ethical, legal or social implications of pharmacogenomic tests (ACCE). These guidelines are useful for making decisions on how pharmacogenomic or genomic testing should be incorporated into clinical practice.
One of the first actions by the committee was to establish a CPS-based process to review individual requests for pharmacogenomics tests related to specific patients and their treatment. Pharmacists were selected to conduct these reviews because they are already familiar with adjudicating requests for restricted and non-formulary medications and employing evidence-based criteria for use (CFU). Pharmacogenomics testing information is being incorporated into all future CFU for medications that are affected by a patient’s genetic make-up. Thus, having pharmacists review and approve pharmacogenetic testing seemed most appropriate. The CPS system could assure that all criteria for prescribing medications were met and, in some cases, tests could be mandated before ordering a medication to assure safety or improve efficacy.
Pharmacists can play an integral part in the coordination of pharmaco-genomics, and its impact on patient health and safety. The knowledge of adverse drug reactions associated with medications, drug interactions, drug-test interactions and dosing is the mainstay of pharmacy practice. Pharmacists also understand formulary processes and cost-effectiveness issues with medications and testing. As medication experts, it only seems natural for pharmacists to take the lead in the education and coordination of care in this burgeoning and exciting field.
Most computerized prescription ordering systems include drug-drug interaction and allergy checks. Computerized patient records also include laboratory values that are easily retrievable but often do not provide for automatic order checks. Unfortunately, no information-technology infrastructure is available to alert providers or pharmacists if a patient is prescribed a medication which may be inappropriate based on the patient’s own genetic profile. The ability to automate these processes is necessary in implementing pharmacogenomic medicine into clinical practice. In the interim, it is critical to use highly-trained professionals who understand these tests and have the working knowledge to take responsibility for the creation of this type of system.
Scope of practice for a Pharmacogenomics Pharmacist includes reviewing and completing pharmacogenomic consults that have been forwarded by the laboratory service. The pharmacist enters a progress note into the patient’s computerized medical record explaining the reason for approval or denial along with recommendations on medication use. The pharmacist may order a pharmacogenomic test if it is deemed appropriate. The pharmacy service at VASDHS also created a specific, virtual, pharmacogenomics clinic to document encounters and capture workload.
In addition to the scope of practice, VASDHS has also developed the first post-graduate, year two Biologics and Pharmacogenomics Pharmacy Residency Program to begin training pharmacists in these areas. The residency program focuses on the formulary and clinical management of biologic agents, REMS medications and pharmacogenomics. Standards for this program are being created through the American Society of Health Systems Pharmacists, and accreditation is pending.
Training and education for health care providers is lacking. The University of California at San Diego (UCSD) received a grant from CDC to help fill this gap. The program is called PharmGenEd, and education modules on pharmacogenomics may be viewed at http://www.pharmacogenomics.ucsd.edu/ for continuing education credit. The CPS at the VASDHS helped in editing the curriculum and has become a trainer, presenting these modules to health care professionals and students interested in pharmacogenomics.
Guidelines for pharmacogenomic tests are also lacking. A component of the Biologic and Pharmacogenomics residency project will be to develop national guidelines for one type of genetic test, which will be published later this year. The resident has also published two Google knolls, which are brief summaries of the current literature on the topic of Interleukin 28b and Thiopurine Methyltransferase, available on PubMed. Recently, at the National Pharmacy Conference in Denver, the CPS presented the topic “Applied Pharmacogenomics: Roles for Clinical Pharmacists.” The presentation was well-received and opened up needed dialogue on the topic of what the national VA Pharmacy’s role will be in implementing systems in pharmacogenomics.
A National Pharmacogenomics SharePoint site to showcase best practices throughout the VA as well as a repository for pharmacogenomic information that all VA Pharmacists can access have been created. It is being populated and will also include a communication list serve. Forums for pharmacists from all different practices need to be coordinated in order to facilitate idea-sharing and bring pharmaco-genomics to the forefront. The CPS is currently working with other health care systems to create a semi-annual meeting in California for the discussion of pharmacogenomics, to begin in the fall of 2011.
In the next 10 years, health care delivery is likely to shift because of the advances in genomic sequencing. There is an urgency to begin preparing for this transformation by educating health care professionals on interpretation of genomic data, including reports that patients may provide from direct-to-consumer services. Clinicians and administrators must be able to determine clinical utility and validity of these tests as well as understand economic impact from testing and how it will relate to the overall treatment of the patient. It also is time to begin discussions with all services within the health care system that will be affected by these changes, including information technology services, ethics committees and legal counsel. Finding practical ways to begin managing pharmacogenomic tests and developing the infrastructure for implementation of genomic medicine is something that all health care systems should be looking into for the future. As demonstrated with the VASDHS program, pharmacists can play a valuable role in understanding the implications that tests have on the usefulness or safety of specific medications and should be incorporated early into the process.
1. The $100 Genome: Implications for the DoD. Available at: http://www.fas.org/irp/agency/dod/jason/ Accessed 4/15/11.
2. Lazarou J. et al. Incidence of Adverse Drug Reactions in Hospitalized Patients: a meta-analysis of prospective studies. JAMA 1998;279(15):1200-5.
3. Table of Pharmacogenomic Biomarkers in Drug Labels. Available at: http://www.fda.gov.
4. Genetic Testing for Health, Disease, and Ancestry; DNA Test – 23andMe. Available at: https://www.23andme.com/. Accessed 4/29/11.