National Heart, Lung, and Blood Advisory Council October 2016 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

October 26, 2016

The 270th meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC) was convened on Wednesday, October 26, 2016, in Building 35A, the Porter Neuroscience Center Conference Center, National Institutes of Health (NIH), Bethesda, Maryland. It was open to the public from 8:02 a.m. until 12: 51 p.m. Closed session began at 1:12 p.m. and ended at 3:13 p.m. Dr. Gary H. Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI), presided as Chair.

Council Members attending

Dr. Nancy Brown
Dr. James Crapo
Dr. Fernando Martinez
Dr. Diane Nugent
Dr. Bruce Psaty
Dr. Véronique Lee Roger
Dr. Richard Schofield (ex officio)
Dr. Anna Maria Siega-Riz
Dr. Phyllis Zee

Council Members attending via teleconference

Dr. George Daley
Dr. Michael DeBaun
Dr. Kim Smith-Whitley

Council Members unable to attend

Dr. Bradford Berk
Dr. Jonathan Epstein
Dr. Serpil Erzurum
Dr. Pilar Ossorio
Dr. Jeffrey Whitsett

Public attending

Ms. Julie Croxford, RTI International
Dr. Ulyana Desiderio, American Society of Hematology
John Greene, CSRA, Inc.
Ms. Haley Payne, Health and Medicine Counsel of Washington
Ms. Sydney Sawyer, Decision Lens
Winfield Swanda, AFYA, Inc.

NHLBI employees attending

A number of NHLBI staff members were in attendance.

Other NIH Institute employees attending

Dr. Eugene Carstea, CSR
Dr. Nara Gavini, NINR
Dr. Chee Lim, CSR

I. CALL TO ORDER AND OPENING REMARKS

Dr. Gary H. Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI), welcomed members and called the 270th 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, Acting Director, Division of Extramural Research Activities (DERA), NHLBI, made the required announcements for the Council meeting, including: a notice of the meeting was published in the Federal Register, Council members may not engage in lobbying activities while attending Council meetings or sponsored events, and the open session was being recorded.

III. REPORT OF THE DIRECTOR

Dr. Gibbons reported on NHLBI’s recruitments for directors of the Division of Cardiovascular Science (DCVS) and the Division of Extramural Research Activities (DERA). David Goff, Jr., MD, PhD has accepted the appointment of DCVS director and will begin his tenure in November 2016. NHLBI is continuing its search for the DERA director.

Retiring Council members are: Dr. Jonathan Epstein, Dr. Bruce Psaty, Dr. Veronica Roger, Dr. Anna Maria Siega-Riz, and Dr. Jeffrey Whitsett. Dr. Gibbons also congratulated Dr. George Daley on his appointment as Dean of Harvard Medical School (effective January 1, 2017).

Dr. Gibbons reported that the NIH is operating under a continuing resolution. During this time, NHLBI will continue to expedite payline decisions and fund grantee awards. Preliminary estimates reveal that NHLBI exceeded its fiscal year (FY) 2016 goal for R01 awards: funding 710 R01 awards, including 136 Early Stage Investigator (ESI) awards. This corresponds to a payline of the 25th percentile for ESIs, and the 15th percentile for R01s. Final numbers will be available after end-of-year closing activities have been completed.

Regarding funding of the next generation, the Institute will continue to use its flexibility in funding career (K) awards and R01s for ESIs. Zones of consideration will be used to maintain an appropriate balance and will continue to be used for P01 applications, training grants (T32s), and R21s.

The first round of applications for the NHLBI R35 program has been received and reviewed. These applications focus on funding the research program of an outstanding individual rather than funding a specific project. There are two R35 opportunities: one focused on outstanding established investigators, the other is focused on outstanding emerging investigators.

In order to align Institute-initiated science with the Strategic Vision, NHLBI convened a brainstorming retreat in September 2016 with members of the Advisory Council and BEE, during which three areas of importance were discussed: early translational research, data science (including the reuse of scientific data), and the physician-scientist workforce. The Institute anticipates shaping recommendations from that retreat into concrete next steps and activities.

NHLBI’s TOPMed program links heart, lung, blood, and sleep (HLBS) phenotypes with genomics data to create a genome-phenome resource. This approach has been deliberately inclusive of diverse participants and advanced collaboration with the Genome Institute. TOPMed efforts are complementary to the NIH Precision Medicine Initiative, or All of Us research program.

Division of Intramural Research, NHLBI

Dr. Robert Balaban, Scientific Director, Division of Intramural Research (DIR), NHLBI, discussed efforts in the DIR to raise public awareness of the mission and activities of the Division. As such, the DIR has created videos every year that highlight scientists and research programs with high impact publications and contributions to the scientific community. Dr. Balaban shared the latest video with the meeting participants.

IV. PRECISION MEDICINE INITIATIVE AND NHLBI

Mr. Eric Dishman, Director of the Precision Medicine Initiative (PMI) Cohort Program, Office of the Director, NIH, began his tenure with the PMI by rebranding it to “All of Us,” in response to feedback from community groups and potential participants. The initiative focuses on how to better use a range of technologies for early detection and cure of disease in diverse groups. Mr. Dishman stated that “Regardless of priorities, approaches, and participants, the initiative could not have gotten off the ground without NHLBI.”

The initiative’s approach begins with collecting data that is meaningful to large volumes of people across a diverse sector. It could begin with something as simple as mobile heart health, an app which uses a smartphone. The Initiative offers an opportunity for volunteers to provide data on an ongoing basis across a wide range of health conditions. The approach includes diverse groups, various health statuses, data types, geographies, as well as a transformational approach to participation (i.e., what data are collected, what lab analyses are done, what research is conducted, and how data are returned).

All of Us is currently developing new methodologies to facilitate a large number of users and participants. Approximately 5,000 people are helping to test the systems. This transformational approach to data access will level the playing field for diverse researchers. Data sharing will be swift for both researchers and participants alike, while privacy and security will adhere to the highest standards. If a researcher cannot return data to the subjects, he or she is encouraged not to participate.

The major building blocks of the research program are: a Data and Research Support Center, BioBank, Participant Technologies Center, and Health Care Provider Organizations. A launch of the first version is being prepared as well as the protocol, including consent language and an initial set of questionnaires. Other activities include holding webinars and workshops on outreach and community engagement; testing an enrollment website, smartphones, and a data center; building IT interfaces; creating one of the world’s largest biobanks; and obtaining feedback from more than 5,000 potential participants. The following five modules are ready for presentation to an institutional review board: health care access and utilization; personal habits; overall health, including mental health; sociodemographics; and sleep. All of Us is currently building a framework for research questions and requirements. Opportunities for NHLBI collaboration include program planning as staff grows, helping to define and execute the research roadmap for the next decade, educating NHLBI researchers, and exploring recruitment potential.

Members remarked that the presentation was excellent. They had some questions about the work being done, such as concern about representative sampling, including groups like children or young adults, and how to get participation by those groups that generally do not participate. Mr. Dishman indicated that they are currently trying to collect as many samples as possible, while at the same time working to collect samples from missing geographic areas and populations. At this point they are just including participants 18 years and over, while simultaneously working on the complex issues of consent for children and recruitment of families. He also welcomed the suggestions of the group.

V. TRANSMURAL CARDIOVASCULAR INTERVENTIONS AT THE NHLBI DIVISION OF INTRAMURAL RESEARCH (DIR)

Dr. Robert Lederman, Senior Investigator, Cardiovascular Intervention Program, NHLBI presented his work that has the goal of inventing new catheterization procedures and disseminating them to clinical practices. Magnetic resonance imaging (MRI) catheterization is a technique ready for platform development and dissemination. It enables real- time image guidance, measures flow and volume more accurately, avoids radiation, and is versatile. His work includes MRI myocardial chemoablation (a completely new approach to cardiac electrophysiology, which uniquely provides immediate and certain depiction of irreversible damage); MRI endomyocardial biopsy; MRI-guided cavopulmonary shunt; and MRI percutaneous superior vena cava syndrome imaging. The technique enables screening for pulmonary hypertension and has an acceptable workflow. However, training is difficult, long, and expensive.

Dr. Lederman presented 30-day data from the NHLBI Transcaval Investigational Device Exemption (IDE) Trial, which showed treatment to be successful in 99 of 100 cases, with no adverse events. Imaging allows safe tissue traversal for nonsurgical transmural catheter procedures. Now is a fertile time to develop new image-guided and structural catheter interventions.

Dr. Lederman showed short videos that illustrated this new technique and he emphasized his desire to develop procedures that are clinically meaningful and more importantly, that leverage the precious national resource that is the DIR - to do things that are unlikely to be done anywhere else, but have the potential to become revolutionary treatments.

VI. NHLBI INITIATIVES

NHLBI staff presented 23 initiatives, all of which had been reviewed in September by the Board of External Experts (BEE), a working group of Council. Initiative development at the NHLBI is a two-cycle process. First, extramural program staff develop ideas and potential initiatives, which they present to the trans-NHLBI Idea Forum. Sufficiently developed initiatives are subsequently considered by the BEE, which provides advice to Council.

Members were generally supportive during detailed discussions, but had a number of questions and recommendations for consideration. The Director, NHLBI, will consider the recommendations of the Council, as well as other budgetary and programmatic issues in determining which of the proposed initiatives to implement.

Title: New Epidemiology Cohort Studies in Heart, Lung, Blood, Sleep Diseases and Disorders (U01)

Objectives: The goal of this initiative is to fund infrastructure, participant examination, and innovative hypotheses for NEW epidemiology cohort studies with the intention to convert a successful R01 application to a cooperative agreement.

Title: RENEWAL of Grant Based Epidemiology Cohort Studies in Heart, Lung, Blood, Sleep Diseases and Disorders (U01)

Objectives: The goal of this initiative is to fund infrastructure, and a brief core clinical examination for RENEWAL of grant based epidemiology cohort studies with the intention to convert successful R01 applications to cooperative agreements.

Title: Notices to Invite Innovative Grant Applications for Ancillary Studies to Cohort Study Exams (R01)

Objectives: The objective of this initiative is to provide official communications to the research community about opportunities and timing for submission of grant applications proposing components to scheduled upcoming cohort study participant examinations.

The next four initiatives propose renewal of some of the existing NHLBI research cohorts. Simultaneous consideration of these cohort renewals are the direct result of implementation of recommendations from the NHLBI Population Research Strategy Group (PRSG) released in February 2016 and endorsed by NHLBI leadership.

Title: Renewal of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (N01)

Objectives: The objectives of the proposed renewal of funding for the HCHS/SOL are: continuing the annual follow-up of study participants to enhance the statistical power for analyses of predictors of clinical events by Hispanic/Latino heritage group; measure and characterize changes in cardiovascular and pulmonary health and disease and their risk factors to determine the putative causes and consequences of these changes in Hispanics/Latinos; and serve as a platform for investigator-initiated ancillary studies.

Title: Renewal of the SHS and SHFS Cohort Studies (N01)

Objectives: This is a proposal that incorporates recommendations from the NHLBI Population Research Strategy Group (PRSG) released in February 2016 and endorsed by NHLBI leadership. It was developed in collaboration with the NHLBI Population Research Initiative Working Group, which was formed in response to recommendations from the PRSG. This proposal aims to develop and release a RFP to renew the Strong Heart Study (SHS) and the Strong Heart Family Study (SHFS) core support as resources for ongoing epidemiologic research on cardiovascular, pulmonary, blood diseases, and sleep disorders, and related diseases or risk factors in American Indians (AIs). As recommended by PRSG, this renewal will support basic core operations of the cohort, including maintaining contact with participants, maintaining and distributing datasets and biological specimens, and ascertaining clinical endpoints. This basic follow-up examination would include an update of family and personal medical history, anthropometry, resting blood pressure, blood collection and storage, and the measurement of blood lipids and glucose (HbA1c).

Title: The Coronary Artery Risk Development in Young Adults (CARDIA) Study Renewal (N01)

Objectives: This is an initiative that incorporates recommendations from the NHLBI Population Research Strategy Group (PRSG) released in February 2016 and endorsed by NHLBI leadership. It was developed in collaboration with the NHLBI Population Research Initiative Working Group, which was formed in response to recommendations from the PRSG. This initiative will develop and release an RFP to renew core support for the Coronary Artery Risk Development in Young Adults (CARDIA) Study as a resource for ongoing epidemiologic research on cardiovascular, pulmonary, blood diseases, and sleep disorders, and related diseases or risk factors. As recommended by PRSG, this renewal will support basic core operations of the cohort, including maintaining contact with participants, maintaining and distributing datasets and biological specimens, and ascertaining clinical endpoints. Limited support for a basic follow-up examination during the contract cycle will be included if independent ancillary study grants to the examination are funded.

Title: The Jackson Heart Study (JHS) Renewal Initiative (N01)

Objectives: The overall objective of the renewal for the Jackson Heart Study (JHS) is to support novel epidemiologic research on cardiovascular (CV) and related diseases in this cohort, and to provide a resource to the scientific community for future research.

Title: HLB SIMPLe: Heart, Lung, and Blood Co-morbiditieS Implementation Models in People Living with HIV (U01)

Objectives: The goal of the initiative entitled, “Heart, Lung, and Blood Co-morbiditieS Implementation Models in People Living with HIV (HLB SIMPle)” is to facilitate delivery of prevention and treatment of heart, lung, blood, and sleep (HLBS) comorbid diseases and disorders in people living with HIV/AIDS (PLWHIV) in low-resource settings, using T4 translation research to study models, theories, and strategies. Moreover, this initiative will also address implementation research training in low-resource settings by requiring goals for training and dissemination of T4 translation research methodologies to address the HIV epidemic.

Title: Centers of Excellence for Training in Glycosciences (K12)

Objectives: The objective of this RFA is to create centers of excellence for training the next generation of biomedical investigators in the glycosciences. The ultimate goal will be to transform and democratize glycoscience from a super- specialized research domain into the mainstream of biology and clinical translation such that glycans become an integral component of their scientific thinking, thus creating a pathway for major scientific breakthroughs specifically in heart, lung, blood and sleep (HLBS) science.

Title: The Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P) (N01)

Objectives: The goal of this public health research initiative is to continue to evaluate and improve the safety and effectiveness of transfusion therapies with an additional specific focus on vulnerable populations including neonates and children. This will be accomplished by using a comprehensive, multi-targeted strategy involving translational and clinical research to proactively address potential emerging threats to the nation’s blood supply, evaluate how to enhance the effectiveness and safety of transfusions, and serve as a resource for ongoing work in transfusion research.

Title: Establishment of Research Centers to Investigate the FVIII Immune Response in Patients with Hemophilia A (U54)

Objectives: The primary objective of the “Centers for the Investigation of Factor VIII (FVIII) Immune Response in Patients with Hemophilia A” program is to utilize cross-disciplinary science and novel technologies to define the basic mechanisms involved in the development of anti-FVIII neutralizing antibodies, also known as FVIII inhibitors, in patients with congenital hemophilia A. To accomplish this, our U54 initiative will support multidisciplinary Centers that will investigate and define the mechanistic and translational mechanisms involved in the formation, suppression or elimination of anti-FVIII antibodies. We are specifically requesting investigators to apply an interdisciplinary “out of the box”, or non-traditional approach to understanding the triggering mechanisms of FVIII neutralizing antibodies. In addition to the disciplines already working in this field (biochemistry, immunology, molecular biology, genetics) Centers are required to include sciences not currently exploited in this research area (e.g. microbiology, glycobiology, biophysics, computational biology, in silico chemistry), among others.

Title: Consortium Linking Oncology with Thrombosis (CLOT) (U01)

Objectives: To establish a collaborative NHLBI - NCI program that will advance translational research in cancer related thrombosis.

Title: Programs to Increase Diversity among Individuals Engaged in Health Related Research (PRIDE) Renewal (Summer Institutes (R25); Coordination Core (R01)

Objectives: This initiative seeks to renew the Programs to Increase Diversity among Individuals Engaged in Health-Related Research (PRIDE) (R25/R01) which aims to increase diversity and research independence among biomedical research scientists focused on heart, lung, blood, and sleep (HLBS) disorders.

Title: Human Cell Based Functional Annotation of Novel Genetic Variants (R01)

Objectives: The Next Gen Program successfully produced a resource consisting of iPSC lines from 1,500 diverse, deeply phenotyped and genotyped study participants for “disease in a dish models”. This initiative will build upon work performed in Next Gen and utilize the Next Gen resource to further refine differentiation protocols, use of gene editing technology, and multiple cell type models to facilitate human functional genomics research. The initiative will fill the gap between variant discovery in programs such as TOPMed and translation to prediction and treatment by elucidating gene function and mechanism of action in human cells. This initiative maps to Strategic Visioning Objectives #2 and #4: to investigate newly discovered pathobiological mechanisms important to the onset and progression of HLBS disorders and to identify factors that account for individual differences in pathobiology and in responses to treatments.

Title: Integrative Computational Biology for Analysis of NHLBI TOPMed Data (R01)

Objectives: To support the data analysis that will be generated thru the NHLBI’s TOPMed program. The analysis approach will focus on using computational and systems approaches to maximize the biological information and insight that can be gained from analysis of large genomics datasets. This initiative maps to Strategic Visioning Objectives #2 and #3: to investigate newly discovered pathobiological mechanisms important to the onset and investigating factors that account for differences in health among populations.

Title: NHLBI’s secondary participation in the NIBIB Point-of-Care Technology Research Network (U54)

Objectives: The overall goal of the initiative is to facilitate clinical validation and adoption of point-of-care (POC) technologies within the NHLBI mission. It proposes to fund one center to help validate POC technology in real world settings by serving as a “clinical laboratory” to provide clinical resources for in-house testing, or as a “matchmaker” to connect POC technologies with ongoing/future clinical studies.

Title: Secondary participation in PA-16-167 “Diet and Physical Activity Assessment Methodology (R01)" (reissue of PAR-15-170)

Objectives: To support research to develop better instruments, innovative technologies, and advances in statistical and analytic techniques that will lead to improved and objective measures of dietary intake and physical/sedentary behavior assessment.

Title: NHLBI Secondary Participation in PA-16 -169 Understanding Factors in Infancy and Early Childhood (Birth to 24 months) that Influence Obesity Development (R01)

Objectives: The objective of this initiative is to stimulate research to elucidate the mechanisms and factors in children 0-24 months that contribute to childhood obesity.

Title: Enhancing Use of Cardiac and Pulmonary Rehabilitation in Traditional and Community Settings (R01)

Objectives: The objective of this proposed FOA is to test strategies that will lead to increased use of cardiac rehabilitation (CR) and pulmonary rehabilitation (PR) in the US population who are eligible based on clinical guidelines. A related objective is to test strategies that will lead to reduced disparities in the use of CR and PR based on age, gender, race/ethnicity, and socioeconomic status (SES). Another objective is to demonstrate that increased use of CR or PR, whether traditional center-based CR/PR or new models, is associated with improvements in relevant clinical and patient-centered variables.

Title: Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases Renewal (U24)

Objectives: The objective of this initiative is to renew the NHLBI Center for Fetal Monkey Gene Transfer (CFMGT) in Heart, Lung, and Blood Diseases. The CFMGT supports the work of NHLBI-funded researchers by providing expertise, resources and services to evaluate the safety and efficacy of gene transfer in rhesus monkeys. This write-up describes the features and achievements of the current CFMGT to highlight the types of services needed for a resource program such as this. However, please note that this renewal solicitation would be an open competition.

Title: Multi -Level Interventions Addressing Obesity to Improve Markers of Cardiovascular and Blood Health (UH2/UH3)

Objectives: The objective of this initiative is to advance obesity research among children and their caregivers to improve markers of cardiovascular health, including improved ardiometabolic risk factors, reduction in adiposity, physical inactivity, and sedentary behaviors. Subgroups of the population shown in national statistics to have a high burden of overweight or obesity and those with special chronic diseases (e.g., overweight or obese patients with hemophilia, sickle cell or sleep disorders) are the target of this initiative. The ultimate goal is to change the trajectory toward cardiovascular disease by reducing obesity disparities and improving cardiovascular health among children and their caregivers.

Title: Implementation Research for HLBS Diseases in the Inpatient Setting (U34, U01)

Objectives: The goal of this initiative is to support implementation research in the acute care hospital setting that will lead to increased translation of evidence-based practices for inpatients with HLBS diseases.

Title: Managing Asthma in Primary Care (MAP) (UM2)

Objectives: To identify best clinical practices currently in use by primary care providers for the care of asthma patients and to prospectively compare best practices in the care of the entire spectrum of U.S. based asthma patients seen by primary care providers (PCPs).

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 INTRAMURAL RESEARCH

Reports prepared by the Board of Scientific Counselors (BSC), NHLBI, on the NHLBI intramural laboratories reviewed during FY 2016 were presented to the Council by Dr. Robert Balaban, Director, Division of Intramural Research, NHLBI; Dr. Sharona Gordon (BSC Chair), University of Washington; and Dr. Collin Stultz (BSC Member), Massachusetts Institute of Technology.

VIII. 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 2,755 applications requesting $ 6,070,070,485.