Journal of Personalized Medicine

2014

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Open AccessCase Report

Next Generation Sequencing As an Aid to Diagnosis and Treatment of an Unusual Pediatric Brain Cancer

by John Glod, Mihae Song, Archana Sharma, Rachana Tyagi, Roy H. Rhodes, David J. Weissmann, Sudipta Roychowdhury, Atif Khan, Michael P. Kane, Kim Hirshfield, Shridar Ganesan, Robert S. DiPaola and Lorna Rodriguez-Rodriguez

J. Pers. Med. 2014, 4(3), 402-411; https://doi.org/10.3390/jpm4030402 - 15 Jul 2014

Cited by 1 | Viewed by 9205

Abstract

Classification of pediatric brain tumors with unusual histologic and clinical features may be a diagnostic challenge to the pathologist. We present a case of a 12-year-old girl with a primary intracranial tumor. The tumor classification was not certain initially, and the site of [...] Read more.

Classification of pediatric brain tumors with unusual histologic and clinical features may be a diagnostic challenge to the pathologist. We present a case of a 12-year-old girl with a primary intracranial tumor. The tumor classification was not certain initially, and the site of origin and clinical behavior were unusual. Genomic characterization of the tumor using a Clinical Laboratory Improvement Amendment (CLIA)-certified next-generation sequencing assay assisted in the diagnosis and translated into patient benefit, albeit transient. Our case argues that next generation sequencing may play a role in the pathological classification of pediatric brain cancers and guiding targeted therapy, supporting additional studies of genetically targeted therapeutics. Full article

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Open AccessArticle

Knowledge, Attitudes and Referral Patterns of Lynch Syndrome: A Survey of Clinicians in Australia

by Yen Y. Tan, Amanda B. Spurdle and Andreas Obermair

J. Pers. Med. 2014, 4(2), 218-244; https://doi.org/10.3390/jpm4020218 - 12 May 2014

Cited by 9 | Viewed by 11556

Abstract

This study assessed Australian clinicians’ knowledge, attitudes and referral patterns of patients with suspected Lynch syndrome for genetic services. A total of 144 oncologists, surgeons, gynaecologists, general practitioners and gastroenterologists from the Australian Medical Association and Clinical Oncology Society responded to a web-based [...] Read more.

This study assessed Australian clinicians’ knowledge, attitudes and referral patterns of patients with suspected Lynch syndrome for genetic services. A total of 144 oncologists, surgeons, gynaecologists, general practitioners and gastroenterologists from the Australian Medical Association and Clinical Oncology Society responded to a web-based survey. Most respondents demonstrated suboptimal knowledge of Lynch syndrome. Male general practitioners who have been practicing for ≥10 years were less likely to offer genetic referral than specialists, and many clinicians did not recognize that immunohistochemistry testing is not a germline test. Half of all general practitioners did not actually refer patients in the past 12 months, and 30% of them did not feel that their role is to identify patients for genetic referral. The majority of clinicians considered everyone to be responsible for making the initial referral to genetic services, but a small preference was given to oncologists (15%) and general practitioners (13%). Patient information brochures, continuing genetic education programs and referral guidelines were favoured as support for practice. Targeted education interventions should be considered to improve referral. An online family history assessment tool with built-in decision support would be helpful in triaging high-risk individuals for pathology analysis and/or genetic assessment in general practice. Full article

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Open AccessConcept Paper

A Proposed Clinical Decision Support Architecture Capable of Supporting Whole Genome Sequence Information

by Brandon M. Welch, Salvador Rodriguez Loya, Karen Eilbeck and Kensaku Kawamoto

J. Pers. Med. 2014, 4(2), 176-199; https://doi.org/10.3390/jpm4020176 - 4 Apr 2014

Cited by 11 | Viewed by 10420

Abstract

Whole genome sequence (WGS) information may soon be widely available to help clinicians personalize the care and treatment of patients. However, considerable barriers exist, which may hinder the effective utilization of WGS information in a routine clinical care setting. Clinical decision support (CDS) [...] Read more.

Whole genome sequence (WGS) information may soon be widely available to help clinicians personalize the care and treatment of patients. However, considerable barriers exist, which may hinder the effective utilization of WGS information in a routine clinical care setting. Clinical decision support (CDS) offers a potential solution to overcome such barriers and to facilitate the effective use of WGS information in the clinic. However, genomic information is complex and will require significant considerations when developing CDS capabilities. As such, this manuscript lays out a conceptual framework for a CDS architecture designed to deliver WGS-guided CDS within the clinical workflow. To handle the complexity and breadth of WGS information, the proposed CDS framework leverages service-oriented capabilities and orchestrates the interaction of several independently-managed components. These independently-managed components include the genome variant knowledge base, the genome database, the CDS knowledge base, a CDS controller and the electronic health record (EHR). A key design feature is that genome data can be stored separately from the EHR. This paper describes in detail: (1) each component of the architecture; (2) the interaction of the components; and (3) how the architecture attempts to overcome the challenges associated with WGS information. We believe that service-oriented CDS capabilities will be essential to using WGS information for personalized medicine. Full article

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Open AccessArticle

Personalized Medicine’s Bottleneck: Diagnostic Test Evidence and Reimbursement

by Joshua P. Cohen and Abigail E. Felix

J. Pers. Med. 2014, 4(2), 163-175; https://doi.org/10.3390/jpm4020163 - 4 Apr 2014

Cited by 27 | Viewed by 10426

Abstract

Background: Personalized medicine is gradually emerging as a transformative field. Thus far, seven co-developed drug-diagnostic combinations have been approved and several dozen post-hoc drug-diagnostic combinations (diagnostic approved after the drug). However, barriers remain, particularly with respect to reimbursement. Purpose, methods: This study analyzes [...] Read more.

Background: Personalized medicine is gradually emerging as a transformative field. Thus far, seven co-developed drug-diagnostic combinations have been approved and several dozen post-hoc drug-diagnostic combinations (diagnostic approved after the drug). However, barriers remain, particularly with respect to reimbursement. Purpose, methods: This study analyzes barriers facing uptake of drug-diagnostic combinations. We examine Medicare reimbursement in the U.S. of 10 drug-diagnostic combinations on the basis of a formulary review and a survey. Findings: We found that payers reimburse all 10 drugs, but with variable and relatively high patient co-insurance, as well as imposition of formulary restrictions. Payer reimbursement of companion diagnostics is limited and highly variable. In addition, we found that the body of evidence on the clinical- and cost-effectiveness of therapeutics is thin and even less robust for diagnostics. Conclusions, discussion: The high cost of personalized therapeutics and dearth of evidence concerning the comparative clinical effectiveness of drug-diagnostic combinations appear to contribute to high patient cost sharing, imposition of formulary restrictions, and limited and variable reimbursement of companion diagnostics. Our findings point to the need to increase the evidence base supportive of establishing linkage between diagnostic testing and positive health outcomes. Full article

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Open AccessArticle

Genetically Guided Statin Therapy on Statin Perceptions, Adherence, and Cholesterol Lowering: A Pilot Implementation Study in Primary Care Patients

by Josephine H. Li, Scott V. Joy, Susanne B. Haga, Lori A. Orlando, William E. Kraus, Geoffrey S. Ginsburg and Deepak Voora

J. Pers. Med. 2014, 4(2), 147-162; https://doi.org/10.3390/jpm4020147 - 27 Mar 2014

Cited by 31 | Viewed by 9962

Abstract

Statin adherence is often limited by side effects. The SLCO1B1*5 variant is a risk factor for statin side effects and exhibits statin-specific effects: highest with simvastatin/atorvastatin and lowest with pravastatin/rosuvastatin. The effects of SLCO1B1*5 genotype guided statin therapy (GGST) are unknown. Primary care [...] Read more.

Statin adherence is often limited by side effects. The SLCO1B1*5 variant is a risk factor for statin side effects and exhibits statin-specific effects: highest with simvastatin/atorvastatin and lowest with pravastatin/rosuvastatin. The effects of SLCO1B1*5 genotype guided statin therapy (GGST) are unknown. Primary care patients (n = 58) who were nonadherent to statins and their providers received SLCO1B1*5 genotyping and guided recommendations via the electronic medical record (EMR). The primary outcome was the change in Beliefs about Medications Questionnaire, which measured patients’ perceived needs for statins and concerns about adverse effects, measured before and after SLCO1B1*5 results. Concurrent controls (n = 59) were identified through the EMR to compare secondary outcomes: new statin prescriptions, statin utilization, and change in LDL-cholesterol (LDL-c). GGST patients had trends (p = 0.2) towards improved statin necessity and concerns. The largest changes were the “need for statin to prevent sickness” (p < 0.001) and “concern for statin to disrupt life” (p = 0.006). GGST patients had more statin prescriptions (p < 0.001), higher statin use (p < 0.001), and greater decrease in LDL-c (p = 0.059) during follow-up. EMR delivery of SLCO1B1*5 results and recommendations is feasible in the primary care setting. This novel intervention may improve patients’ perceptions of statins and physician behaviors that promote higher statin adherence and lower LDL-c. Full article

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Open AccessCommentary

Ethics, Evidence and Economics in the Pursuit of “Personalized Medicine”

by Jan Lewis, Wendy Lipworth and Ian Kerridge

J. Pers. Med. 2014, 4(2), 137-146; https://doi.org/10.3390/jpm4020137 - 27 Mar 2014

Cited by 19 | Viewed by 8297

Abstract

Despite enthusiastic advocacy for what personalized medicine might be able to deliver and major investments into the development of this, there remain disappointingly few examples of personalized medicine in routine clinical practice today, particularly in high areas of unmet need such as cancer. [...] Read more.

Despite enthusiastic advocacy for what personalized medicine might be able to deliver and major investments into the development of this, there remain disappointingly few examples of personalized medicine in routine clinical practice today, particularly in high areas of unmet need such as cancer. We believe that this is because personalized medicine challenges the moral, economic and epistemological foundations of medicine. In this article, we briefly describe the scientific premises underpinning personalized medicine, contrast these with traditional paradigms of drug development, and then consider the ethical, economic and epistemological implications of this approach to medicine. Full article

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Open AccessArticle

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

by Megan Doerr, Emily Edelman, Emily Gabitzsch, Charis Eng and Kathryn Teng

J. Pers. Med. 2014, 4(2), 115-136; https://doi.org/10.3390/jpm4020115 - 26 Mar 2014

Cited by 38 | Viewed by 8662

Abstract

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 [...] Read more.

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. Full article

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Open AccessCommentary

DTC-and-Me: Patient, Provider, Proteins and Regulators

by Fintan R. Steele and Larry Gold

J. Pers. Med. 2014, 4(1), 79-87; https://doi.org/10.3390/jpm4010079 - 18 Mar 2014

Cited by 4 | Viewed by 8425

Abstract

The yet-unrealized potential for more “personalized” Direct-to-Consumer (DTC) tests to fundamentally alter the practice and economics of healthcare is undeniable. However, there are also many challenges to be met, including the herculean task of ensuring that the information provided by such tests is [...] Read more.

The yet-unrealized potential for more “personalized” Direct-to-Consumer (DTC) tests to fundamentally alter the practice and economics of healthcare is undeniable. However, there are also many challenges to be met, including the herculean task of ensuring that the information provided by such tests is scientifically sound and, ideally, medically actionable. We consider recent events in DTC testing and suggest a “thought experiment” of an approach that could ultimately meet the needs of patients, providers and regulatory authorities. Full article

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Open AccessArticle

Physician Attitudes toward Adopting Genome-Guided Prescribing through Clinical Decision Support

by Casey Lynnette Overby, Angelika Ludtke Erwin, Noura S. Abul-Husn, Stephen B. Ellis, Stuart A. Scott, Aniwaa Owusu Obeng, Joseph L. Kannry, George Hripcsak, Erwin P. Bottinger and Omri Gottesman

J. Pers. Med. 2014, 4(1), 35-49; https://doi.org/10.3390/jpm4010035 - 27 Feb 2014

Cited by 40 | Viewed by 9826

Abstract

This study assessed physician attitudes toward adopting genome-guided prescribing through clinical decision support (CDS), prior to enlisting in the Clinical Implementation of Personalized Medicine through Electronic Health Records and Genomics pilot pharmacogenomics project (CLIPMERGE PGx). We developed a survey instrument that includes the [...] Read more.

This study assessed physician attitudes toward adopting genome-guided prescribing through clinical decision support (CDS), prior to enlisting in the Clinical Implementation of Personalized Medicine through Electronic Health Records and Genomics pilot pharmacogenomics project (CLIPMERGE PGx). We developed a survey instrument that includes the Evidence Based Practice Attitude Scale, adapted to measure attitudes toward adopting genome-informed interventions (EBPAS-GII). The survey also includes items to measure physicians’ characteristics (awareness, experience, and perceived usefulness), attitudes about personal genome testing (PGT) services, and comfort using technology. We surveyed 101 General Internal Medicine physicians from the Icahn School of Medicine at Mount Sinai (ISMMS). The majority were residency program trainees (~88%). Prior to enlisting into CLIPMERGE PGx, most physicians were aware of and had used decision support aids. Few physicians, however, were aware of and had used genome-guided prescribing. The majority of physicians viewed decision support aids and genotype data as being useful for making prescribing decisions. Most physicians had not heard of, but were willing to use, PGT services and felt comfortable interpreting PGT results. Most physicians were comfortable with technology. Physicians who perceived genotype data to be useful in making prescribing decisions, had more positive attitudes toward adopting genome-guided prescribing through CDS. Our findings suggest that internal medicine physicians have a deficit in their familiarity and comfort interpreting and using genomic information. This has reinforced the importance of gathering feedback and guidance from our enrolled physicians when designing genome-guided CDS and the importance of prioritizing genomic medicine education at our institutions. Full article

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Open AccessArticle

Barriers and Motivators for Referral of Patients with Suspected Lynch Syndrome to Cancer Genetic Services: A Qualitative Study

by Yen Y. Tan and Lisa J. Fitzgerald

J. Pers. Med. 2014, 4(1), 20-34; https://doi.org/10.3390/jpm4010020 - 18 Feb 2014

Cited by 17 | Viewed by 6964

Abstract

This article explores the views of general practitioners and specialists on their referral of patients with suspected Lynch syndrome to cancer genetic services. Using a purposive maximum variation sampling strategy, we conducted semi-structured interviews face-to-face with 28 general practitioners and specialists in public [...] Read more.

This article explores the views of general practitioners and specialists on their referral of patients with suspected Lynch syndrome to cancer genetic services. Using a purposive maximum variation sampling strategy, we conducted semi-structured interviews face-to-face with 28 general practitioners and specialists in public or private hospitals and specialist clinics between March and August 2011. General practitioners and specialists were recruited in a major metropolitan area in Australia. Interview transcripts were reviewed by two independent researchers, and thematic analysis was performed using NVivo10 software. The main barriers and motivators identified were: (1) clinician-related (e.g., familiarity with Lynch syndrome and family history knowledge); (2) patient-related (e.g., patients’ interests and personal experience with cancer); and (3) organizational-related (e.g., access to services, guidelines and referral pathway). Referral of patients with suspected Lynch syndrome to cancer genetic services is motivated and hindered by a range of individual, interpersonal and organizational factors. In order to improve the care and quality of life of patients and family with suspected Lynch syndrome, further research is needed to develop supportive tools for clinicians. Full article

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Open AccessArticle

Design and Implementation of a Randomized Controlled Trial of Genomic Counseling for Patients with Chronic Disease

by Kevin Sweet, Erynn S. Gordon, Amy C. Sturm, Tara J. Schmidlen, Kandamurugu Manickam, Amanda Ewart Toland, Margaret A. Keller, Catharine B. Stack, J. Felipe García-España, Mark Bellafante, Neeraj Tayal, Peter Embi, Philip Binkley, Ray E. Hershberger, Wolfgang Sadee, Michael Christman and Clay Marsh

J. Pers. Med. 2014, 4(1), 1-19; https://doi.org/10.3390/jpm4010001 - 8 Jan 2014

Cited by 20 | Viewed by 9974

Abstract

We describe the development and implementation of a randomized controlled trial to investigate the impact of genomic counseling on a cohort of patients with heart failure (HF) or hypertension (HTN), managed at a large academic medical center, the Ohio State University Wexner Medical [...] Read more.

We describe the development and implementation of a randomized controlled trial to investigate the impact of genomic counseling on a cohort of patients with heart failure (HF) or hypertension (HTN), managed at a large academic medical center, the Ohio State University Wexner Medical Center (OSUWMC). Our study is built upon the existing Coriell Personalized Medicine Collaborative (CPMC^®). OSUWMC patient participants with chronic disease (CD) receive eight actionable complex disease and one pharmacogenomic test report through the CPMC^® web portal. Participants are randomized to either the in-person post-test genomic counseling—active arm, versus web-based only return of results—control arm. Study-specific surveys measure: (1) change in risk perception; (2) knowledge retention; (3) perceived personal control; (4) health behavior change; and, for the active arm (5), overall satisfaction with genomic counseling. This ongoing partnership has spurred creation of both infrastructure and procedures necessary for the implementation of genomics and genomic counseling in clinical care and clinical research. This included creation of a comprehensive informed consent document and processes for prospective return of actionable results for multiple complex diseases and pharmacogenomics (PGx) through a web portal, and integration of genomic data files and clinical decision support into an EPIC-based electronic medical record. We present this partnership, the infrastructure, genomic counseling approach, and the challenges that arose in the design and conduct of this ongoing trial to inform subsequent collaborative efforts and best genomic counseling practices. Full article

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