Kathryn Teng

Implementation of Clinical Pharmacogenomics within a Large Health System: From Electronic Health Record Decision Support to Consultation Services

The number of clinically relevant gene‐based guidelines and recommendations pertaining to drug prescribing continues to grow. Incorporating gene–drug interaction information into the drug‐prescribing process can help optimize pharmacotherapy outcomes and improve patient safety. However, pharmacogenomic implementation barriers exist such as integration of pharmacogenomic results into electronic health records (EHRs), development and deployment of pharmacogenomic decision support tools to EHRs, and feasible models for establishing ambulatory pharmacogenomic clinics. We describe the development of pharmacist‐managed pharmacogenomic services within a large health system. The Clinical Pharmacogenetics Implementation Consortium guidelines for HLA‐B*57:01‐abacavir, HLA‐B*15:02‐carbamazepine, and TPMT‐thiopurines (i.e., azathioprine, mercaptopurine, and thioguanine) were systematically integrated into patient care. Sixty‐three custom rules and alerts (20 for TPMT‐thiopurines, 8 for HLA‐B*57:01‐abacavir, and 35 for HLA‐B*15:02‐anticonvulsants) were developed and deployed to the EHR for the purpose of providing point‐of‐care pharmacogenomic decision support. In addition, a pharmacist and physician‐geneticist collaboration established a pharmacogenomics ambulatory clinic. This clinic provides genetic testing when warranted, result interpretation along with pharmacotherapy recommendations, and patient education. Our processes for developing these pharmacogenomic services and solutions for addressing implementation barriers are presented.

Family history: still relevant in the genomics era.

Even at the dawn of the genomics era, the family history is still very relevant, being a proxy for genetic, environmental, and behavioral risks to health. The family history can be used to inform risk stratification, allowing for judicious use of screening and opening the door to early and even prophylactic treatment. This review aims to re-energize our use of the family history in primary care practice. Family history is still relevant, being a proxy for genetic, environmental, and behavioral risks to health.

Formative Evaluation of Clinician Experience with Integrating Family History-Based Clinical Decision Support into Clinical Practice

Family health history is a leading predictor of disease risk. Nonetheless, it is underutilized to guide care and, therefore, is ripe for health information technology intervention. To fill the family health history practice gap, Cleveland Clinic has developed a family health history collection and clinical decision support tool, MyFamily. This report describes the impact and process of implementing MyFamily into primary care, cancer survivorship and cancer genetics clinics. Ten providers participated in semi-structured interviews that were analyzed to identify opportunities for process improvement. Participants universally noted positive effects on patient care, including increases in quality, personalization of care and patient engagement. The impact on clinical workflow varied by practice setting, with differences observed in the ease of integration and the use of specific report elements. Tension between the length of the report and desired detail was appreciated. Barriers and facilitators to the process of implementation were noted, dominated by the theme of increased integration with the electronic medical record. These results fed real-time improvement cycles to reinforce clinician use. This model will be applied in future institutional efforts to integrate clinical genomic applications into practice and may be useful for other institutions considering the implementation of tools for personalizing medical management.

Premenopausal osteoporosis, an overlooked consequence of anorexia nervosa.

Many young women with anorexia nervosa develop premenopausal osteoporosis. In particular, female athletes have a much higher incidence of disordered eating than their peers and therefore are at a much higher risk of stress fractures and other traumatic bone pathology. This review summarizes factors affecting the development of premenopausal osteoporosis in these patients and identifies potential targets for intervention. Particularly at risk are female athletes. The etiology is complex; the key treatment is to restore body weight.

Building an innovative model for personalized healthcare

Personalized healthcare is the tailoring of medical management and patient care to the individual characteristics of each patient. This is achieved by incorporating the genetic and genomic makeup of an individual and his or her family medical history, environment, health-related behaviors, culture, and values into a complete health picture that can be used to customize care. Another level of personalization, often called personalized medicine, involves the selection of drug therapy through the use of tests to determine the genes and gene interactions that can reliably predict an individual’s response to a given therapy. This white paper focuses largely on the use of personalized healthcare as a risk prediction tool. 

Screening for Abdominal Aortic Aneurysms in Outpatient Primary Care Clinics

BACKGROUND The US Preventive Services Task Force (USPSTF) guidelines recommend one-time abdominal aortic aneurysm ultrasound screening for men aged 65 to 75 years who ever smoked. Reported screening rates have been 13% to 26% but did not include computed tomography, magnetic resonance imaging, and nonaortic abdominal ultrasound, which provide adequate visualization of the aorta. The objective of this study was to evaluate rates of screening performed intentionally with ultrasound and incidentally with other abdominal imaging, determine rates of redundant screening, and evaluate patient and physician characteristics associated with screening. METHODS Cross-sectional study of patient encounters in 2007 and 2012 to determine abdominal aortic aneurysm screening trends in primary care practices. Participants included all patients who were seen in a primary care office and were eligible for screening by USPSTF guidelines. The primary outcome was percentage of eligible patients screened for abdominal aortic aneurysm by ultrasound or other abdominal imaging. RESULTS There were 15,120 patients eligible for screening in 2007, and 22,355 in 2012. Screening with ultrasounds increased from 3.6% in 2007 to 9.2% in 2012. Screening with any imaging that included the aorta increased from 31% in 2007 to 41% in 2012. Of 2595 screening ultrasounds performed in either cohort, 800 (31%) were performed on patients who had already undergone another imaging modality. Of 153 physicians who had >50 eligible patients, rates of abdominal aortic aneurysm screening ranged from 7.5% to 79% (median 39%, interquartile range 31%-47%), and rates of ultrasound screening ranged from 0% to 47% (median 6.3%, interquartile range 3.6%-11.4%). Physician characteristics positively associated with screened patients included female sex (odds ratio [OR] 1.32; 95% confidence interval [CI], 1.12-1.54), specialty (Internal Medicine vs Family Medicine: OR 1.32; 95% CI, 1.14-1.54), and location (academic medical center vs family health center: OR 1.30; 95% CI, 1.04-1.62). CONCLUSIONS Abdominal aortic aneurysm screening rates remain below 50%, but are improving over time. Screening by individual physicians varied widely, indicating substantial opportunity for educational interventions. Most abdominal aortic aneurysm screening is completed incidentally, and some patients later undergo unnecessary ultrasound screening. Before ordering screening, physicians and electronic health record-based reminder tools should ensure that the aorta has not been previously visualized.

Genomics in Primary Care Practice

This article discusses the clinical utility of genomic information for personalized preventive care of a healthy adult. Family health history is currently the most applicable genomic predictor for common, multifactorial diseases, and can also show patterns that suggest an inherited high susceptibility to a particular form of cancer or other disease. Both bloodline ancestry and shared environmental factors are important predictors for many disease states. DNA and family history analyses give information that is probabilistic, not deterministic. Therefore, family history can highlight behavioral, social, or cultural risk factors that can be modified to prevent diseases.

Institutional Profile: Cleveland Clinic’s Center for Personalized Healthcare: setting the stage for value-based care

Cleveland Clinic (OH, USA) launched the Center for Personalized Healthcare in 2011 to establish an evidence-based system for individualizing care by incorporating unique patient characteristics, including but not limited to genetic and family health history information, into the standard medical decision-making process. Using MyFamily, a web-based tool integrated into our electronic health record, a patients family health history is used as a surrogate for genetic, environmental and behavioral risks to identify those with an elevated probability of developing disease. Complementing MyFamily, the Personalized Medication Program was created for the purpose of identifying gene-drug pairs for integration into clinical practice and developing the implementation tools needed to incorporate pharmacogenomics into the clinical workflow. We have successfully implemented the gene-drug pairs HLA-B*57:01-abacavir and TPMT-thiopurines into patient care. Our efforts to establish personalized medical care at Cleveland Clinic may serve as a model for large-scale integration of personalized healthcare.

Pharmacogenomics for the primary care provider: why should we care?

Personalized medicine promises to improve the quality and lower the cost of care if physicians integrate into practice useful new findings, such as information gleaned from pharmacogenomic testing.

Medication adherence, medical record accuracy, and medication exposure in real-world patients using comprehensive medication monitoring

Background Poor adherence to medication regimens and medical record inconsistencies result in incomplete knowledge of medication therapy in polypharmacy patients. By quantitatively identifying medications in the blood of patients and reconciling detected medications with the medical record, we have defined the severity of this knowledge gap and created a path toward optimizing medication therapy. Methods and findings We validated a liquid chromatography-tandem mass spectrometry assay to detect and/or quantify 38 medications across a broad range of chronic diseases to obtain a comprehensive survey of patient adherence, medical record accuracy, and exposure variability in two patient populations. In a retrospectively tested 821-patient cohort representing U.S. adults, we found that 46% of medications assessed were detected in patients as prescribed in the medical record. Of the remaining medications, 23% were detected, but not listed in the medical record while 30% were prescribed to patients, but not detected in blood. To determine how often each detected medication fell within literature-derived reference ranges when taken as prescribed, we prospectively enrolled a cohort of 151 treatment-regimen adherent patients. In this cohort, we found that 53% of medications that were taken as prescribed, as determined using patient self-reporting, were not within the blood reference range. Of the medications not in range, 83% were below and 17% above the lower and upper range limits, respectively. Only 32% of out-of-range medications could be attributed to short oral half-lives, leaving extensive exposure variability to result from patient behavior, undefined drug interactions, genetics, and other characteristics that can affect medication exposure. Conclusions This is the first study to assess compliance, medical record accuracy, and exposure as determinants of real-world treatment and response. Variation in medication detection and exposure is greater than previously demonstrated, illustrating the scope of current therapy issues and opening avenues that warrant further investigation to optimize medication therapy.