National Heart, Lung, and Blood Advisory Council February 2017 Meeting Summary

DEPARTMENT OF HEALTH AND HUMAN SERVICES
NATIONAL INSTITUTES OF HEALTH
NATIONAL HEART, LUNG, AND BLOOD ADVISORY COUNCIL

MEETING SUMMARY OF THE
NATIONAL HEART, LUNG, AND BLOOD ADVISORY COUNCIL

February 7, 2017

The 271st meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC) was convened on Wednesday, February 7, 2017, in Building 35A, the Porter Neuroscience Center Conference Center, National Institutes of Health (NIH), Bethesda, Maryland. It was open to the public from 8:05 a.m. until 11:46 a.m. Closed session began at 12:37 p.m. and ended at 1:35 p.m. Dr. Gary H. Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI), presided as Chair.

Council Members attending

Dr. E. Dale Abel 
Dr. Donna Arnett 
Dr. Nancy Brown 
Dr. James Crapo 
Dr. George Daley 
Dr. Michael DeBaun 
Dr. Serpil Erzurum 
Dr. Karen Glanz 
Dr. Diane Nugent 
Dr. Pilar Ossorio 
Dr. Bruce Psaty 
Dr. Robert Robbins 
Dr. Kim Smith-Whitley 
Dr. Sally Wenzel 
Dr. Phyllis Zee 

Council Members attending via teleconference 

Dr. Bradford Berk 
Dr. Richard Schofield (ex officio) 

Council Members unable to attend

Dr. Fernando Martinez

Ad Hoc Member attending 

Dr. M. Luisa Iruela-Aripse 

Public attending

Ms. Debby Berlyne, IQ Solutions 
Ms. Meghan Calabro, RTI International
Ms. Julie Croxford, RTI International 
Dr. John Greene, CSRA, Inc. 
Dr. David Hall, Rho 
Ms. Melissa King, Nestat 
Dr. Steven Murphy, WebMD 
Dr. Todd Pihl, CSRA, Inc. 
Dr. David Pot, CSRA, Inc. 
Dr. Gabriella Ryan, American Society of Hematology 

NHLBI employees attending 
A number of NHLBI staff members were in attendance.

Other NIH employees attending

Dr. Vivien Bonazzi, OD, NIH 
Dr. Irwin Feuerstein, OD, NIH 
Dr. Anthony Kerlavage, NCI 

I. CALL TO ORDER AND OPENING REMARKS – Dr. Gary H. Gibbons

Dr. Gary H. Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI), welcomed members and called the 271st meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC) to order. 

II. REVIEW OF CONFIDENTIALITY AND CONFLICT OF INTEREST – Dr. Valerie L. Prenger

Dr. Valerie Prenger, Acting Director, Division of Extramural Research Activities (DERA), NHLBI, welcomed the following new members to the NHLBAC: Dr. E. Dale Abel, Dr. Donna K. Arnett, Dr. Karen Glanz, and Dr. Sally E. Wenzel. She also welcomed Dr. M. Luisa Iruela-Arispe, an ad hoc NHLBAC member, who is completing the clearance process to become a full member. 

Dr. Prenger made the required announcements for the Council meeting, which included: that a notice of the meeting was published in the Federal Register, that Council members may not engage in lobbying activities while attending Council meetings or sponsored events, and that the open session was being recorded. 

III. REPORT OF THE DIRECTOR

Heart Health Month. Dr. Gibbons began his report by noting that February is Heart Health Month. Activities at the NHLBI during this month included a “power of community” panel, an NHLBI healthy heart champions forum, a Red Dress Collection® fashion show, and Heart Valve Disease Awareness Day on Capitol Hill. Through these and other activities, the NHLBI planned to focus on the intersection between women’s health and cardiovascular health. The Institute also planned to reach out to various populations to make the transition from awareness to action to prevent heart disease in women.  

Leadership Transitions. Dr. Gibbons welcomed Dr. David C. Goff, who became the new Director of the Division of Cardiovascular Sciences at the NHLBI in November 2016. Dr. Goff is a renowned cardiovascular scientist who has been at the forefront of cardiovascular disease prevention. Dr. Laura K. Moen is the new Director of the DERA at the NHLBI. Dr. Gibbons thanked Dr. Prenger for her dedication and service as the acting director of the DERA during this transition. Finally, Dr. Gibbons welcomed the new NHLBAC members, acknowledging their talent, experience, and expertise. 

Fiscal Year (FY) 2017 Budget Update. The NHLBI, like the rest of the National Institutes of Health (NIH), is operating under a continuing resolution.  Notable for this fiscal year was that Congress passed the 21st Century Cures Act, and President Obama signed this bill into law in December 2016. This act carved out funding for the Cancer Moonshot, All of Us (the branded name of the Precision Medicine Initiative), a new Regenerative Medicine Program, and the new Cures Innovation Fund. The Act also provides additional funding for the NIH Loan Repayment Programs.   

The NHLBI has published its funding and operating guidelines, which include the anticipated paylines for R01 and other award mechanisms in the current fiscal year. The NHLBI is proceeding with a zone of consideration (a range of priority scores within which the Institute will consider competing applications for funding) for certain types of applications, which enhances its flexibility to respond to scientific opportunities. The NHLBI has steadily increased the number of R01 grants it funds by 53 percent since the lowest point in 2012. Success rates are now more than 20 percent for established investigators and more than 30 percent for early stage investigators.
 
Portfolio Highlights. The NHLBI has funded the first round of R35 grants, including 24 Outstanding Investigator Awards and eight Emerging Investigator Awards. These awards support research across all heart, lung, blood, and sleep research programs.  

The NHLBI issued new funding opportunity announcements this year to respond to the recommendations of the NHLBAC Working Group on Clinical Trials. Applications requesting clinical trial funding from the NHLBI will need to respond to one of the new announcements. With support from the NHLBAC, the NHLBI has been at the vanguard of the transformation to the new NIH approach to clinical trials oversight..  

Sickle Cell Disease. The time is right to address the needs in sickle cell disease, and the NHLBI is engaged in a multipronged, comprehensive effort in this area. Activities include basic discovery research, clinical trials, and implementation science research. The NHLBI is also considering the use of gene-editing and gene-transfer technologies to develop a cure for the disease.  
Precision Medicine. The NHLBI is developing one of the largest and most diverse genome/phenome resources in the world through its Trans-Omics for Precision Medicine (TOPMed) Program. This program grew out of workshops that involved the NHLBAC. TOPMed currently has 72,000 participants and is well on its way to meeting its goal of 100,000 to 150,000 participants. TOPMed, which aligns with the NHLBI strategic vision, represents a prudent long-term investment and helps position the NHLBI at the leading edge of population science and precision medicine.  

IV. MILLION VETERANS PROGRAM

Dr. J. Michael Gaziano, Director, Massachusetts Veterans Epidemiology Research; Information Center Professor of Medicine, Harvard Medical School; and Chief, Division of Aging, Brigham and Women’s Hospital, started his presentation with an overview of the history of epidemiology. 

The Department of Veterans Affairs (VA) is an ideal setting for state-of-the-art population science. It has an outstanding electronic medical records system that is fully integrated into clinical care, a research structure with diverse areas of expertise, and a population of 8 million users a year. The goal of the Million Veteran Program (MVP) is to enroll up to one million Veterans Health Administration users into an observational mega-cohort to collect health and lifestyle information as well as blood samples.  

The program recruits most participants in person, but it plans to do additional recruitment by mail or on the Web. Participants who agree to join the MVP complete a baseline survey and informed consent form. A blood specimen is collected, and participants receive an MVP pin. To date, approximately 540,000 veterans have consented to join the study, which is open at 58 sites around the country. The program collaborates with the Department of Energy, which will provide supercomputing capacity to conduct most of the MVP data analyses. In addition to survey and molecular data, the MVP will use clinical data from numerous VA sources and data from non-VA sources (such as the Centers for Medicare & Medicaid Services).  

The MVP is building an interface for investigators with query tools. Investigators who have a grant and institutional review board approval will be able to set up a study data mart that meets their specifications. An early version of this system is available now, and it will be refined with assistance from the Department of Energy. The data are only accessible to VA investigators at present, but Dr. Gaziano hopes to offer access to investigators outside the VA, although they will first need to complete the VA’s certification and credentialing process. The MVP will join the All of Us cohort study, and it plans to collaborate with other large cohort studies in the United States and other countries

V. NHLBI TRANS-OMICS IN PRECISION MEDICINE (TOPMED) PROGRAM UPDATE

Dr. Cashell Jaquish, Program Director, Division of Cardiovascular Sciences, NHLBI, reported that TOPMed, which grew out of a 2014 NHLBI workshop on future genomic strategies, has the following components: 

• Data generation: whole-genome sequence (WGS), proteomics, metabolomics, RNA sequencing, and other omics
• Data processing: Quality assurance/quality control, validation, and harmonization
• Data storage and access: GenPORT, National Center for Biotechnology Information, and the database of Genotypes and Phenotypes (dbGaP)
• Ethical, legal, and social implications: Consent limitations, data sharing restrictions, and return of results
• Data commons/cloud: Bioinformatics and high-performance computing
• Analysis and methods development

To date, TOPMed has completed WGS on approximately 20,000 phase 1 samples, and these data were added to database of Genotypes and Phenotypes (dbGaP) in October 2016. The 52,000 phase 2 sample analyses will be completed in March 2017, and WGS of the 47,000 phase 3 samples will start soon. The phase 1 and 2 participants have diverse phenotypes and ancestry, and the overall data quality has been very high. 

By 2018, TOPMed will complete WGS on 120,000 samples. It is anticipated that the final dataset will include 10,000 atrial fibrillation cases and controls, 12,000 chronic obstructive pulmonary disease cases and controls, 6,300 sickle cell disease cases, and 26,000 asthma cases and families. The program is well situated to produce novel findings in these diseases soon.

VI. TOWARDS AN NCI CANCER DATA ECOSYSTEM​

Dr. Anthony Kerlavage, Chief, Cancer Informatics Branch, National Cancer Institute (NCI), described several NCI genomics data resources. He described precision medicine as a grand challenge that requires deep biological understanding and advances in scientific methods, instruments, technology, and data management and computation. The data from cancer research and clinical care are critical to creating a national learning health system for cancer. 

The NCI began illuminating the underlying causes of primary untreated tumors using very deep omics characterizations in 2006 with The Cancer Genome Atlas (TCGA), which generated a comprehensive catalog of cancer genes and pathways. More recently, the Cancer Moonshot is injecting a great deal of energy and enthusiasm into efforts to accelerate progress in cancer from cutting-edge research to wider uptake of standard care. In 2015, NIH developed its genomic data sharing policy, and the NCI subsequently published its guidance for grantees on public sharing of genomic datasets.  

NCI Genomic Data Commons (GDC). The GDC was designed to unify the NCI’s fragmentary data repositories and support the receipt, quality control, integration, storage, and redistribution of standardized genomic datasets derived from cancer research. The GDC also uses state-of-the-art methods to provide the foundation for identifying high- and low-frequency cancer drivers, defining genomic determinants of responses to therapy, and digitally creating trial cohorts. 

NCI Cancer Genomics Cloud Pilots. The NCI Cancer Genomics Cloud Pilots are designed to help the research community to analyze high-quality, large-scale cancer genomic data and associated clinical information. The cloud pilots provide access to large genomic datasets without the need to download them as well as to pipelines and visualization tools. Researchers can also bring their own tools and pipelines to the data and analyze their own data in combination with the NCI’s genomic data. The Cloud Pilots offer many analysis pipelines and visualization tools not available in the GDC. 

A Cancer Research Data Ecosystem. The cancer research data ecosystem currently links the GDC, researchers, Web and application programming interfaces, and the NCI Cloud Pilots. In the coming year, the NCI plans to add copies of GDC content to several commercial cloud environments (including those of Microsoft, Amazon, and Google) to ensure the broadest use possible. The Cloud Pilots and other tools will be clients of the GDC in the cloud, and investigators will be able to apply the tool of their choice to one of these clouds. 

The NCI is now creating imaging, proteomics, clinical, and population (Surveillance, Epidemiology, and End Results program) data commons. The cancer research data ecosystem will ultimately include these resources as well as model organism and cell line data. Contributors and consumers will expand from researchers only to institutions, clinicians, and patients. The NCI wants to find ways for patients to contribute their data and benefit from the accumulated information gathered in this ecosystem to increase their control of their health care. 

CLOSED PORTION 

This portion of the meeting was closed to the public in accordance with the determination that it concerned matters exempt from mandatory disclosures under Sections 552b(c)(4) and 52b(c)(6), Title 5, U.S. Code and Section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. appendix 2). 

VII. REVIEW OF APPLICATIONS​

The session included a discussion of procedures and policies regarding voting and confidentiality of application materials, committee discussions and recommendations. Members absented themselves from the meeting during discussion of and voting on applications from their own institutions, or other applications in which there was a potential conflict of interest, real or apparent. Members were asked to sign a statement to this effect. The Council considered and recommended 2,943 applications requesting $3,906,775,947. 

ADJOURNMENT 
The meeting was adjourned at 1:35 p.m.