Carolyn R. Rohrer Vitek

Preemptive genotyping for personalized medicine: design of the right drug, right dose, right time-using genomic data to individualize treatment protocol.

OBJECTIVE To report the design and implementation of the Right Drug, Right Dose, Right Time-Using Genomic Data to Individualize Treatment protocol that was developed to test the concept that prescribers can deliver genome-guided therapy at the point of care by using preemptive pharmacogenomics (PGx) data and clinical decision support (CDS) integrated into the electronic medical record (EMR). PATIENTS AND METHODS We used a multivariate prediction model to identify patients with a high risk of initiating statin therapy within 3 years. The model was used to target a study cohort most likely to benefit from preemptive PGx testing among the Mayo Clinic Biobank participants, with a recruitment goal of 1000 patients. We used a Cox proportional hazards model with variables selected through the Lasso shrinkage method. An operational CDS model was adapted to implement PGx rules within the EMR. RESULTS The prediction model included age, sex, race, and 6 chronic diseases categorized by the Clinical Classifications Software for International Classification of Diseases, Ninth Revision codes (dyslipidemia, diabetes, peripheral atherosclerosis, disease of the blood-forming organs, coronary atherosclerosis and other heart diseases, and hypertension). Of the 2000 Biobank participants invited, 1013 (51%) provided blood samples, 256 (13%) declined participation, 555 (28%) did not respond, and 176 (9%) consented but did not provide a blood sample within the recruitment window (October 4, 2012, through March 20, 2013). Preemptive PGx testing included CYP2D6 genotyping and targeted sequencing of 84 PGx genes. Synchronous real-time CDS was integrated into the EMR and flagged potential patient-specific drug-gene interactions and provided therapeutic guidance. CONCLUSION This translational project provides an opportunity to begin to evaluate the impact of preemptive sequencing and EMR-driven genome-guided therapy. These interventions will improve understanding and implementation of genomic data in clinical practice.

Implementing individualized medicine into the medical practice

There is increasing recognition that genomic medicine as part of individualized medicine has a defined role in patient care. Rapid advances in technology and decreasing cost combine to bring genomic medicine closer to the clinical practice. There is also growing evidence that genomic‐based medicine can advance patient outcomes, tailor therapy and decrease side effects. However the challenges to integrate genomics into the workflow involved in patient care remain vast, stalling assimilation of genomic medicine into mainstream medical practice. In this review we describe the approach taken by one institution to further individualize medicine by offering, executing and interpreting whole exome sequencing on a clinical basis through an enterprise‐wide, standalone individualized medicine clinic. We present our experience designing and executing such an individualized medicine clinic, sharing lessons learned and describing early implementation outcomes.

Pharmacokinetic Pharmacogenetic Prescribing Guidelines for Antidepressants: A Template for Psychiatric Precision Medicine

Antidepressants are commonly prescribed medications in the United States, and there is increasing interest in individualizing treatment selection for more than 20 US Food and Drug Administration-approved treatments for major depressive disorder. Providing greater precision to pharmacotherapeutic recommendations for individual patients beyond the large-scale clinical trials evidence base can potentially reduce adverse effect toxicity profiles and increase response rates and overall effectiveness. It is increasingly recognized that genetic variation may contribute to this differential risk to benefit ratio and thus provides a unique opportunity to develop pharmacogenetic guidelines for psychiatry. Key studies and concepts that review the rationale for cytochrome P450 2D6 (CYP2D6) and cytochrome P450 2C19 (CYP2C19) genetic testing can be delineated by serum levels, adverse events, and clinical outcome measures (eg, antidepressant response). In this article, we report the evidence that contributed to the implementation of pharmacokinetic pharmacogenetic guidelines for antidepressants primarily metabolized by CYP2D6 and CYP2C19.

Participant-perceived understanding and perspectives on pharmacogenomics: the Mayo Clinic RIGHT protocol (Right Drug, Right Dose, Right Time)

Purpose:To examine predictors of understanding preemptive CYP2D6 pharmacogenomics test results and to identify key features required to improve future educational efforts of preemptive pharmacogenomics testing.Methods:One thousand ten participants were surveyed after receiving preemptive CYP2D6 pharmacogenomics test results.Results:Eighty-six percent (n = 869) of patients responded. Of the responders, 98% were white and 55% were female; 57% had 4 years or more of post-secondary education and an average age of 58.9 ± 5.5 years. Twenty-six percent said that they only somewhat understood their results and 7% reported they did not understand them at all. Only education predicted understanding. The most common suggestion for improvement was the use of layperson’s terms when reporting results. In addition, responders suggested that results should be personalized by referring to medications that they were currently using. Of those reporting imperfect drug adherence, most (91%) reported they would be more likely to use medication as prescribed if pharmacogenomic information was used to help select the drug or dose.Conclusion:Despite great efforts to simplify pharmacogenomic results (or because of them), approximately one-third of responders did not understand their results. Future efforts need to provide more examples and tailor results to the individual. Incorporation of pharmacogenomics is likely to improve medication adherence.Genet Med advance online publication 05 January 2017

Evaluation of the use of clinical decision support and online resources for pharmacogenomics education

AIM To assess impact and value of using clinical decision support (CDS) to drive providers toward online pharmacogenomics education. MATERIALS & METHODS CDS was used to target prescribers of codeine/tramadol, send an educational email, display alert/inbox and provide links to an online resource. Providers were surveyed to assess impact. RESULTS Of the methods used to target providers, educational email was more effective (7.2%). Survey response rate was 29.2% (n = 528/1817). Of respondents, 57.4% reported opening the email and 27.1% accessed the online resource. Of those accessing the resource, 89% found it useful and learned something new about pharmacogenomics. CONCLUSION The impact of using CDS to target pharmacogenomics education was limited. However, providers accessing the online resource found it useful and educational.

Healthcare provider education to support integration of pharmacogenomics in practice: the eMERGE Network experience

Ten organizations within the Electronic Medical Records and Genomics Network developed programs to implement pharmacogenomic sequencing and clinical decision support into clinical settings. Recognizing the importance of informed prescribers, a variety of strategies were used to incorporate provider education to support implementation. Education experiences with pharmacogenomics are described within the context of each organizations prior involvement, including the scope and scale of implementation specific to their Electronic Medical Records and Genomics projects. We describe common and distinct education strategies, provide exemplars and share challenges. Lessons learned inform future perspectives. Future pharmacogenomics clinical implementation initiatives need to include funding toward implementing provider education and evaluating outcomes.

An inter-professional approach to personalized medicine education: one institution's experience

Personalized medicine offers the promise of better diagnoses, targeted therapies and individualized treatment plans. Pharmacogenomics is an integral component of personalized medicine; it aids in the prediction of an individuals response to medications. Despite growing public acceptance and emerging clinical evidence, this rapidly expanding field of medicine is slow to be adopted and utilized by healthcare providers, although many believe that they should be knowledgeable and able to apply pharmacogenomics in clinical practice. Institutional infrastructure must be built to support pharmacogenomic implementation. Multidisciplinary education for healthcare providers is a critical component for pharmacogenomics to achieve its full potential to optimize patient care. We describe our recent experience at the Mayo Clinic implementing pharmacogenomics education in a large, academic healthcare system facilitated by the Mayo Clinic Center for Individualized Medicine.

Are patients willing to incur out-of-pocket costs for pharmacogenomic testing?

Suzette J. Bielinski, PhD, MEd1, Jennifer L. St. Sauver, PhD1,2, Janet E. Olson, PhD1, Mark L. Wieland, MD3, Carolyn R. Vitek, MS4, Elizabeth J. Bell, PhD1, Michaela E. McGree, BS2,5, Debra J. Jacobson, MS2,5, Jennifer B. McCormick, PhD6, Paul Y. Takahashi, MD3, John L. Black, MD7, Pedro J. Caraballo, MD8, Richard R. Sharp, PhD6,9, Timothy J. Beebe, PhD2,9, Richard M. Weinshilboum, MD10, Liewei Wang, MD, PhD10, and Véronique L. Roger, MD, MPH1,2,11 1Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

Education and Knowledge in Pharmacogenomics: Still a Challenge?

A number of barriers exist for adoption of pharmacogenomics into practice. Physicians, pharmacists, and nurses report limited knowledge about pharmacogenomics and its use in patient care. Lack of pharmacogenomics education curricula as part of professional schools or postgraduate training programs has been reported as a potential cause. Understanding pharmacogenomics is further complicated by a complex and nonstandard lexicon, limited medication guidelines, rapidly changing evidence, and insufficient awareness of test availability and utility.

Practical considerations for implementing genomic information resources. Experiences from eMERGE and CSER.

OBJECTIVES To understand opinions and perceptions on the state of information resources specifically targeted to genomics, and approaches to delivery in clinical practice. METHODS We conducted a survey of genomic content use and its clinical delivery from representatives across eight institutions in the electronic Medical Records and Genomics (eMERGE) network and two institutions in the Clinical Sequencing Exploratory Research (CSER) consortium in 2014. RESULTS Eleven responses representing distinct projects across ten sites showed heterogeneity in how content is being delivered, with provider-facing content primarily delivered via the electronic health record (EHR) (n=10), and paper/pamphlets as the leading mode for patient-facing content (n=9). There was general agreement (91%) that new content is needed for patients and providers specific to genomics, and that while aspects of this content could be shared across institutions there remain site-specific needs (73% in agreement). CONCLUSION This work identifies a need for the improved access to and expansion of information resources to support genomic medicine, and opportunities for content developers and EHR vendors to partner with institutions to develop needed resources, and streamline their use - such as a central content site in multiple modalities while implementing approaches to allow for site-specific customization.