The Joint NHLBI-PMC-ACC-AMA-GWU Conference, “New Frontiers in Personalized Medicine: Cardiovascular Research and Clinical Care”, Workshop

Executive Summary

Cardiovascular disease (CVD) remains the number one cause of death in the U.S. and will likely become the number one cause of death globally. New understanding of individual variations is increasingly reshaping our ability to treat various aspects of CVD. A special report in Nature noted that, after oncology, cardiology holds the most promise in personalizing, and therefore improving, therapies. Hence, the National Heart, Lung, and Blood Institute (NHLBI), the Personalized Medicine Coalition (PMC), the American College of Cardiology (ACC), the American Medical Association, and the Cheney Cardiovascular Research Institute at the George Washington University (GWU) jointly convened a national conference, “New Frontiers in Personalized Medicine: Cardiovascular Research & Clinical Care” on January 6, 2011, at the GWU campus in Washington, D.C. The conference brought together leaders from academia, industry, and government to 1) discuss personalized medicine's current and potential impact on cardiovascular patient outcomes; 2) review emerging technologies and applications that may shape the field in the future; 3) discuss the results of an ACC survey examining personalized medicine adoption rates among U.S. cardiologists; 4) identify the barriers to adoption of pharmacogenetics-based personalized medicine in cardiovascular practice; and 5) develop recommendations for next steps with an emphasis on actions and evidence generation that are needed for adoption and improved quality of cardiovascular patient care. The conference agenda external link

included three keynote addresses and four panel discussions, each with a specific task.

Discussion

From Science to Practice. Delivered by Victor Dzau, MD, of Duke University, this opening keynote address focused on how to integrate emerging biological science with medical education and clinical practice to allow patients to realize the benefits of targeted therapies. He outlined four major goals for the next five to ten years: (1) establish standards of quality for the research enterprise, (2) establish robust systems for more rapid evidence generation, (3) harmonize regulatory and reimbursement standards and (4) develop innovative partnerships to accelerate the overall agenda.

Panel Discussion: Current Clinical Applications of Personalized Approaches to Cardiovascular Medicine. Three applications that are primed for widespread clinical use were described: (1) the use of pharmacogenomic algorithms to guide the dosing of warfarin therapy; (2) the use of blood cell gene expression profiles to detect or rule out cardiac transplant rejection; and (3) the resequencing of genes implicated in long QT syndromes to identify causal mutations in affected individuals and to screen family members for the same mutations.

Panel Discussion: Shaping the Future of Cardiovascular Care: Emerging Technologies and Needed Evidence: Part I: Emerging Technologies. After a presentation on the types of evidentiary frameworks needed to evaluate personalized medicine applications, several new technologies with the potential to result in new tests were discussed, including deep sequencing of DNA and RNA, biomarker panels, polymerase chain reaction technology, proteomics, and metabolomics. Several potential shortcomings of the new technologies were addressed, including the danger of premature adoption of a test before it has been fully replicated and validated.

Genetics, Your Heart and Your Future. In this keynote address by Jack Lewin, MD, of the ACC, the focus was on proactive medical care, improved patient outcomes, and clinical adoption of evidence-based personalized approaches to cardiovascular medicine. He described survey data that indicated that very few cardiologists feel knowledgeable with respect to personalized medicine, highlighting the particular need for education aimed not only at patients but also at providers. He also stressed the need for funding of innovative study designs to evaluate and implement personalized medicine applications.

Panel Discussion: Shaping the Future of Cardiovascular Care: Emerging Technologies and Needed Evidence: Part II: Emerging Diagnostics and Treatments. Much of the discussion centered on the so-called “valley of death” between basic science discoveries and development of successful drugs, with a high failure rate of drugs in Phase II clinical trials. Proposed strategies to reduce this failure rate included the use of genomics data to establish the relevance of drug targets in humans before starting large scale clinical trials, the use of intermediate biomarker or imaging endpoints to make the decision to proceed with or terminate drug candidates early in the development process, and early identification of subpopulations most likely to benefit from therapy.

Panel Discussion: Clinical and Regulatory Barriers to Personalized Cardiovascular Care. The panel addressed a number of issues, including the education of providers in principles of basic science that are relevant to personalized medicine; integrating personalized medicine practices into the clinical workflow using electronic platforms; the utility of “real-world” studies to assess whether personalized medicine improves outcomes when employed in a clinical practice context; and possible incentives for providers and patients to improve adherence to personalized medicine practices.

Cardiovascular Genomic Medicine: Time for a Systems Approach. In the final keynote address, Susan Shurin, MD, Acting Director of the NHLBI, outlined the NHLBI’s interest in personalized medicine, describing the types of work the agency is currently funding and plans to fund in the future, as well as its efforts to improve patient outcomes through personalized medicine. In particular, she highlighted the need for systems-based approaches, both with respect to research as well as to healthcare delivery.

Recommendations

Establish standards of quality for the research enterprise. This would include achieving consensus on the “best practices” for the use of biostatistics and cost-effectiveness analyses in personalized medicine studies, establishing cross-compatible institutional standards for data provenance, and training investigators in the skills needed for personalized medicine studies, including clinical pharmacology, genetics, biostatistics, informatics, epidemiology, and clinical trial design.

Establish robust systems for more rapid evidence generation. This can be done by building intra-institutional research infrastructure that directly connects to clinical data systems, as well as by fostering collaborations between many institutions and healthcare networks.

Harmonize regulatory and reimbursement standards. The same weight of evidence should be necessary and sufficient for both regulatory approvals of personalized medicine tests as well as acceptance of the tests as reimbursable healthcare expenses by payers.

Develop innovative partnerships between academia, industry, and other stakeholders. These stakeholders include academic medical centers, pharmaceutical and biotechnology companies, funding agencies, regulatory agencies, payers, providers, patients, and communities.

Devise and fund innovative clinical trial designs. An example is to compare outcomes between community practice groups that adopt a personalized medicine strategy and groups that maintain the usual practices. Such trial designs will require cooperation among various stakeholders, some of who are not traditionally involved in clinical trials.

Invest in emerging technologies to develop new personalized medicine applications. These technologies include deep sequencing of DNA and RNA, biomarker panels, polymerase chain reaction technology, proteomics, and metabolomics.

Target education to both the patients and the providers. In order for personalized medicine tests to be used widely, not only do patients have to be educated about the tests in layperson terms, but providers also need to be made knowledgeable about the availability of the tests and their utility for patient management.

Integrate personalized medicine into the clinical workflow. This can be done through the use of information technology, e.g., incorporating personalized medicine-related reminders into a computerized order entry system.

The Joint NHLBI-PMC-ACC-AMA-GWU Conference, “New Frontiers in Personalized Medicine: Cardiovascular Research and Clinical Care”

Executive Summary

Discussion

Recommendations

Publication Plans

Participating Division, Institute, and Organizations

Co-Chairs

Panel Members and Keynote Speakers

NHLBI Staff

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