Abstract

A whitepaper developed by the American Pharmacists Association. Summary: In 2006, HHS initiated the Personalized Health Care Initiative with the goal of building the foundation for the delivery of gene-based care, which may prove to be more effective for large patient subpopulations. In the years since the initiative was launched, drug manufacturers and FDA have begun to incorporate pharmacogenomic data and applications of this information into the drug development, labeling, and approval processes. New applications and processes for using this emerging pharmacogenomics data are needed to effectively integrate this information into clinical practice. Building from the findings of a stakeholder workshop convened by APhA and the advancement of the pharmacist's collaborative role in patient care through MTM, emerging roles for pharmacists using pharmacogenomic information to improve patient care are taking hold. Realizing the potential role of the pharmacist in pharmacogenomics through MTM will require connectivity of pharmacists into the electronic health record infrastructure to permit the exchange of pertinent health information among all members of a patient's health care team. Addressing current barriers, concerns, and system limitations and developing an effective infrastructure will be necessary for pharmacogenomics to achieve its true potential. J o u r n a l o f t h e A m e r i c a n P h a r m a c i s t s Conclusion: To achieve integration of pharmacogenomics into clinical practice via MTM, the pharmacy profession must define a process for the application of pharmacogenomic data into pharmacy clinical practice that is aligned with MTM service delivery, develop a viable business model for these practices, and encourage and direct the development of HIT solutions that support the pharmacist's role in this emerging field. Keywords: Pharmacogenomics, pharmacy practice, medication therapy management, health information technology, personalized health care. This systems approach to health care delivery is in the process of creating tools for electronic transmission of health records and information; conducting innovative research to delve more deeply into the effect of genes on disease progression; establishing a regulatory environment that supports effective development of drugs, diagnostics, and other means to reach specific patient subpopulations; and translating genetic information to clinical practice. One of the first priorities of the PHC Initiative was establishing a network of electronic health records (EHRs) to ensure the availability of complete patient health information. Individual EHRs give health care providers Health Insurance Portability and Accountability Act-compliant access to genetic testing data when applicable and family health histories to enable health care providers to make more effective treatment and medication decisions. Because EHRs include diagnosis, treatment decisions, and outcomes data for large populations, the information contained in these EHR networks could be potentially used to extend our understanding of best clinical practices, treatment effectiveness, variations in patient response to therapy, and safety issues and potentially through the FDA's evolving Sentinel Initiative, a national electronic system designed to improve FDA's ability to track the safety of drugs. 2 Other health information technology (HIT) efforts include creating secure EHRs that protect patient privacy and standards for metabolic data used in drug research and clinical decision making. A number of efforts focus on integrating genetic data into clinical practice. This requires developing new software packages that incorporate genetic data to help with clinical decisions. As the tests evolve and the results become less variable, decision support tools also should evolve to reflect added consistency. Another priority area for the PHC Initiative was to improve scientific understanding of the interplay between genetics, disease, lifestyle, and environment. Understanding the genetic and molecular disposition of diseases and chronic conditions also gives health care providers and patients tools to predict which patients may manifest a particular disease or condition. This information will allow patients and health care providers to take steps to prevent the onset of disease. If tests reveal certain disease biomarkers (i.e., chemical or molecular activity correspond- PhARMACOgENOMiCS iN PhARMACy PRACTiCE SPECIAL FEATURE ing to a disease), then treatments can be started before the disease becomes entrenched. Finally, an individual's genetic and personal health history provide a starting point for treatment decisions involving drug therapy. A patient's genetic blueprint can provide a roadmap to determining the drugs that will offer the most effective response. This has the potential to improve patient safety and outcomes. As PHC evolves and is integrated into practice, patients are benefiting from the application of genetic information. One of the earliest diagnostic tests developed gauges a patient's drug metabolism. The results of a simple assay can show if a patient has a specific combination of genetic variations in two liver enzymes that alone metabolize nearly 45% of all drugs. Depending on the outcome, physicians can tailor dosages based on molecular metabolism rather than weight. In cancer treatment, genetic testing can pinpoint patients who will benefit from certain drug therapies. For a woman with breast cancer, a diagnostic test can determine her tumor's genetic signature. If the patient tests positive for human epidermal growth factor receptor 2 (HER-2), she can be given trastuzumab, which suppresses excess HER-2 and cuts the risk of disease recurrence by 50%. The regulatory component of the PHC Initiative supports development of drugs, diagnostic tests, and medical products focused on specific patient subpopulations. Keeping pace with the rapid rate of scientific and medical advances is challenging to agencies charged with oversight. FDA's Critical Path Initiative-a national strategy for transforming the way FDA-regulated medical products are developed, evaluated, and manufacturedfor example, has identified 76 scientific and regulatory areas in which progress is needed to improve and expand the science base for medical product development. FDA also is working to evaluate in vitro diagnostic tests that will reveal predisposition to diseases. Bioinformatics is another important field in realizing PHC. Computer models can assist in predicting drug effectiveness and safety and arrive at those predictions using genetic factors. A number of challenges must be overcome to fully realize the promise of PHC. First, biomedical research and HIT research must continue to move forward. This requires continued funding of innovative ideas. Translating these ideas into practical activities must be a priority. Second, user-friendly clinical decision support and information management tools are needed to drive evidence-based care into clinical settings. In addition, the relations among government, industry, and academia will continue to evolve as these groups work together to expand discovery opportunities, improve safety, and lower financial risks when developing molecular therapies and diagnostics. Finally, PHC must be delivered in a sound financial way. Preventing or treating disease early provides an intrinsic cost savings. Molecular information allows for more effective, tailored treatments that could reduce costs substantially by eliminating expensive, ineffective individual therapies. Because PHC requires integration of many components, former HHS Secretary Leavitt anticipated the time to implement the PHC paradigm would likely take a generation. What began as a federal program will transform into a collaborative effort engaging both private industry and academia. Physicians, pharmacists, other health professionals, and patients will work together with the architects of the PHC framework to realize the full potential of PHC Pharmacogenomics and FDA Drug manufacturers and FDA have already started incorporating pharmacogenomics into the drug development, labeling, and approval processes. Effectively transmitting genomic information to and from health care providers is challenging because of lack of awareness, privacy concerns, and the lack of a robust, nationwide electronic health care infrastructure. As progress is made in each of these areas, the potential of pharmacogenomics will be incorporated into improved patient-centered care processes resulting from the development of proactive safety tools that will be integrated into the health care system. Recognizing the valuable role that genomics data can play in evaluating drug safety and effectiveness, FDA initiated the a voluntary data exchange program (i.e., "safe harbor" agreement) in 2003. This program asked companies to submit voluntarily genomic data along with their drug submission packages. More drug companies are now including genomic and other biomarker information in their new drug applications. 3 These more comprehensive drug applications offer the potential for more targeted patient therapies. However, FDA Commissioner Margaret Hamburg acknowledged in 2009 that "genomics represents a chal- SPECIAL FEATURE PhARMACOgENOMiCS iN PhARMACy PRACTiCE lenge as well as a unique opportunity" for the agency. 3 To take advantage of genomics data, FDA participates in the HHS PHC Initiative, which is aimed at creating a foundation to use pharmacogenomic data in drug development and clinical practice. Through a number of working groups, the program also establishes a framework for electronic transmission of pharmacogenomic data from current EHR databases. FDA also is reexamining how it shares information among divisions and with other federal agencies. In 2009, Hamburg noted that "incorporating genomics into medical product review requires an interagency, multi-disciplinary effort that transcends the boundaries of an existing center." 3 Intra-and interagency collaboration in the areas of research, oversight, and enforcement will be a key mode of operation to managing genomic data successfully. In addition, regulatory bodies must seek input from industry and other stakeholders to discover barriers that may stall innovation and forward progress. Because personalized medicine requires close alignment of diagnostics and drugs, FDA currently is evaluating how it reviews drugs and diagnostics. In 2004, the agency found itself scrambling when presented with a microarray device to identify variations in cytochrome P450 (CYP)2D6 and CYP2C19, which are enzymes that play a major role in drug metabolism. At the time, FDA had few scientists on staff with sufficient knowledge to fully evaluate the product. Getting up to speed on the product and its intended use took time. The agency is developing new guidance for industry in personalized medicine. One guidance document will describe the criteria FDA will use to evaluate disease biomarkers. The second guidance document will clarify the agency's expectations for the kinds of clinical trials and levels of confidence needed to demonstrate that a diagnostic test is accurate and can be used for clinical assessments. For instance, breakthroughs in understanding the relationship between genetics and drug metabolism have caused FDA to issue changes to drug labels, most recently in the case of a number of approved drugs. In the case of clopidogrel, new findings demonstrating that patients with genetic variants of CYP2C19 may not effectively convert the drug to its active form caused FDA to issue a new label warning in March 2010. 5 Similar actions based on new genetic findings have been taken for warfarin and morphine. Pharmacogenomics: Pharmacist's role in personalizing medication therapy As the 21st century moves into its second decade, pharmacogenomics (i.e., the use of genetic information to predict an individual's response to a drug) will play an increasing role in drug development and clinical treatment decisions. Using patients' genetic information to tailor drug therapy will reduce the risk of adverse events, potentially improve patient outcomes through targeted therapies and dosing, and create a more efficient, cost-effective drug development process. By transforming a one-size-fits-all approach to drug therapy into a patient subpopulation or patientspecific approach, the pharmaceutical and clinical communities are one step closer to achieving the new medical paradigm of personalized health care. Pharmacists can serve an integral role in applying pharmacogenomics into clinical practice to improve the quality and safety of health care. As pharmacogenomic applications continue to advance, the pharmacy profession has begun to define its role and address steps to effectively integrate this emerging field into clinical practice. One avenue to implementing the PHC Initiative is by integrating it into clinical pharmacy practice through medication therapy management (MTM). This service optimizes therapeutic outcomes for individual patients. 10 By gathering key pieces of information (e.g., all medications a patient is taking, including supplements), pharmacists can assess potential interactions, recommend alternative therapies to reduce medication-related adverse effects, and effectively collaborate with the individual patient's other health care providers to improve overall care and treatment outcomes. In diverse patient care settings, pharmacists currently are providing MTM services to help patients achieve improved treatment outcomes. Pharmacist-provided MTM provides unique new and emerging opportunities to integrate pharmacogenomics into clinical practice and actively engage in collecting, interpreting, and using pharmacogenomic data to improve patient care. As stated by former HHS Secretary Leavitt, "Pharmacists have always been on the front line in guiding consumers about the appropriate use of their medical products. With the advent of pharmacogenomics and increasingly individualized care, pharmacists will continue to have an important role in improving the quality and safety of patient care." 11 At the patient-physician level, a new model is needed to advise on pharmacogenomic results because most genetic counselors are not equipped to fully assess the genetic contributions to the overall pharmacological treatment of medical conditions. Incorporating pharmacogenomics into MTM service delivery allows pharmacists to lend their expertise to the treatment planning process to optimize treatment outcomes. Because of their in-depth training specific to medications, pharmacists, working collaboratively with the prescriber and the lab, could review all of the medications prescribed for a patient and the patient's genomic data and offer an assessment on whether a prospective drug would provide the best fit for the condition and patient. As part of a collaborative Pharmacists and HIT The pharmacy profession has been a leader in the health care industry in electronic connectivity, establishing standards for real-time claims adjudication and other processes dating back several decades. This history combined with its strong foundation in e-prescribing platforms and evolving EHR infrastructures has positioned pharmacy for establishing a model for incorporating pharmacogenomics into EHR. Although e-prescribing offers one option for storing, transmitting, and sharing pharmacogenomic data, considerable work remains in developing and harmonizing standards to integrate the information into clinical and pharmacy records, transmitting the data between users, and creating interoperability among organizational systems. In the long run, connecting EHR through emerging health information exchanges and among various health care providers, including pharmacists, may be a more efficient and effective method for the movement of pharmacogenomic data than using e-prescribing. In the 2006 report Preventing Medication Errors, the Institute of Medicine recommended that all prescriptions be written and received electronically by 2010. 12 Although this goal was challenging, the pharmacy community was well equipped to move toward it. The profession has taken the lead in developing electronic formats to transmit and receive prescriptions. In 2001, the National Association of Chain Drug Stores and the National Community Pharmacists Association founded Surescripts, an e-prescribing network. By the middle of the decade, more than 90% of U.S. community pharmacies were connected and could receive prescriptions electronically. 13 According to Surescripts, by the end of 2010, nearly 235,000 prescribers were using e-prescribing and the number of prescriptions routed electronically had grown from 191 million in 2009 to 326 million in 2010. 12 Federal EHR programs The federal government has a number of programs to spur the adoption of e-prescribing tools and electronic health records through the American Recovery and Reinvestment Act of 2009 (PL 111-5). 14 Additional federal money is available to prescribers adopting e-prescribing tools through the Medicare Improvements for Patients and Providers Act of 2008 (PL 110-275). Stakeholder efforts In fall 2010, the Pharmacy e-Health Information Technology Collaborative was formed by nine national nonprofit pharmacy organizations. Since that time, the Collaborative has increased in size by the addition of several key industry stakeholders as associate members. The Collaborative's goal is to ensure that the pharmacist's role of providing patient care services, including MTM, is integrated into the national HIT interoperable framework. The Collaborative is pursuing EHR standards for pharmacists and pharmacy providers that effectively support the delivery, documentation, and billing of pharmacist-provided patient care services across all patient care settings. Efforts are under way currently to promote the adoption of the recently balloted and approved functional profile for pharmacist/pharmacy provider EHR that will facilitate the movement of relevant patient-specific information, including pharmacogenomic data, to a patient's entire health care team, including pharmacists, through a practice site's information management system. 16 Connectivity for pharmacists to the EHR infrastructure will be critical as pharmacists continue to expand their role as patient care providers and increase their involvement in the application of pharmacogenomics to improve patient care and outcomes. Personalized health care delivery Pharmacists will play a leading role as the health care system moves toward the paradigm of personalized health care. Through MTM initiatives, pharmacists have already been repositioning themselves as integral players in a coordinated health care approach to patients-one that emphasizes collaboration among health care providers, patients, and insurers. MTM is a comprehensive patient care service that provides valuable treatment information to all of the patient's health care providers. MTM focuses on the entire spectrum of medication used by a single patient. This approach gives patients a coordinated approach to therapies that may not be achieved using more traditional methods. Developing standardized processes for incorporating pharmacogenomic drug data in the MTM care process will contribute to improved decision making on the proper selection and use of medications and contribute to the achievement of the best outcomes for individual patients. J o u r n a l o f t h e