National Heart, Lung, and Blood Advisory Council October 2019 Meeting Summary

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

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

October 29, 2019

The 285th meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC) was convened on Tuesday, October 29, 2019, in Building 35A, the Porter Neuroscience Center Conference Center, National Institutes of Health (NIH), Bethesda, Maryland. It was open to the public from 8:30 a.m. until 12 noon. Closed session began at 12:48 p.m. and ended at 1:50 p.m. Dr. Gary H. Gibbons, Director ofthe National Heart, Lung, and Blood Institute (NHLBI), presided as Chair.

Council Members attending

Dr. E. Dale Abel
Dr. Donna K. Arnett
Dr. Jennifer Devoe
Dr. Martha U. Gillette
Dr. Karen Glanz
Dr. M. Luisa lruela-Arispe
Dr. Monica Kraft
Dr. Mohandas Narla
Dr. Diane J. Nugent
Dr. Robert C. Robbins
Dr. Dean Sheppard
Dr. Kim M. Smith-Whitley
Dr. Kevin Thomas
Dr. Sally E. Wenzel
Dr. Andrew S. Weyrich

Council Members attending via Teleconference

Dr. Garth Graham
Dr. Richard Schofield

Council Members unable to attend

Ms. Grace Dorney Koppel

Public attending

Ms. Sheila Harley, BETAH Associates
Ms. Regina James, 2M Research

NHLBI employees attending

A number of NHLBI staff members were in attendance

Other NIH Institute employees attending

Mr. Edmond Keane - Tribal Health Research Office
Ms. Tori Mends-Cole - Tribal Health Research Office
Dr. Maria Jamela Reviler - Tribal Health Research Office
Mr. Shawn Thomas - Tribal Health Research Office
Dr. David Wilson - Tribal Health Research Office

I. CALL TO ORDER AND OPENING REMARKS

Dr. Gary H. Gibbons called the 285th meeting of the National Heart, Lung, and Blood Advisory Council to order and welcomed members and other attendees.

II. ADMINISTRATIVE ANNOUNCEMENTS

Dr. Laura K. Moen, Director, Division of Extramural Research Activities, NHLBI, recognized the NHLBAC members who are retiring after 4 years of service on the Council: Diane Nugent, M.D.; Robert Robbins, M.D.; and Kim Smith-Whitley, M.D.

Dr. Moen reminded Council members of conflict of interest requirements and noted that the meeting would be publicly broadcast and archived on videocast.

Dr. Moen also recognized committee management officer Kay Valeda, who is retiring from NHLBI.

III. REPORT OF THE DIRECTOR

Dr. Gibbons summarized NHLBl's financial investments for fiscal year (FY) 2019 and projected investments for FY 2020. In particular, he noted the dedicated effort to support early-stage investigators. The institute embraces opportunities for flexibility, such as providing funding advantages for early-stage investigators and additional funding for highly meritorious P0l {Research Program) proposals that include an early-stage investigator. R56 Bridge Awards can help support both early-career and at-risk investigators. Recent results show that this nimble approach has helped more early-stage investigators transition to R0l {Research Project) support.

Demographics and Bias

Dr. Gibbons considered the demographics of NHLBI awardees. He noted that past research has shown differences in R0l awards by race with lower funding rates for R0l applications from African American scientists. Recent research suggests that one barrier may be the research topics proposed. In a recently published analysis, African American scientists were more likely to submit applications on topics with a community and population focus, which had lower funding success in study sections compared with applications that had a fundamental and mechanistic focus. Dr. Gibbons noted that grantees of the cardiovascular programs within the NHLBl's Programs to Increase Diversity Among Individuals Engaged in Health-Related Research (PRIDE) where there is an intense focus on mentoring, have a 63 percent success rate for achieving NIH awards. Programs such as this may serve to provide insights for achieving success.

Vision for Future Research

In the NHLBAC meeting in September, presentations from David Asch, M.D., and Eric Topol, M.D., put a spotlight on behavioral choices, the social determinants of health, and how new technologies could be used to improve health. Dr. Gibbons thanked the Council for the bold ideas offered in breakout sessions after the talks, particularly the ideas of using multidimensional data sets to assess and track outcomes and to leverage machine learning and artificial intelligence to deliver more precise interventions.

Dr. Gibbons reminded the Council that NHLBI is focused on building a communal discovery platform for multidisciplinary open science in support of systems biology research. In the near future, researchers should be able to log into this cloud resource and use state-of-the-art tools to perform complex analyses. This platform builds on investments that NHLBI made in the Trans-Omics for Precision Medicine (TOPMed) program. The NHLBI DataSTAGE (Storage, Toolspace, Access, and analytics for biG data Empowerment) platform is being renamed BioData Catalyst.

Dr. Gibbons offered examples of important research aligned with NHLBl's mission:

• Data-driven machine learning technologies can improve prediction of cardiovascular disease (CVD) risk. Computational approaches can help address complex problems such as population disparities. CVD mortality is particularly high in African Americans and Native Americans.
• A recent publication demonstrated that CVD mortality rates are increasing among American Indian/Alaska Native individuals aged 25-49 years. This speaks to the importance of nurturing strong partnerships with tribal nations. Since 1988, NHLBI has supported the study of CVD risk in at least 13 tribes across the country in the Strong Heart Study.
• He highlighted the work of Amanda Fretts, Ph.D., who started as a T32 (Training) grantee and is now a principal investigator of the Strong Heart Study, helping develop culturally contextual interventions for American Indian communities.
• The prevalence of vaping and e-cigarette use is another area of concern and a growing public health threat. Research needs to address what is causing vaping-related deaths and morbidity. NHLBI is helping develop an NIH-wide response. A notice of special interest is expected to be published in the coming weeks.
• For sickle cell disease (SCD), NHLBI is working toward development of curative genetic therapies. The NHLBI is working collaboratively with the National Institute of Allergy and Infectious Diseases (NIAID) and the NIH Office of the Director which has launched a new collaboration to develop gene-based cures to be available globally for both HIV and SCD with the Bill & Melinda Gates Foundation. The curative strategies developed for SCD may pave a path for cures for other rare diseases such as hemophilia and hypertrophic cardiomyopathy.

IV. TRIBAL HEALTH RESEARCH OFFICE INTRODUCTION AND UPDATE

David R. Wilson, Ph.D., Director, Tribal Health Research Office, Office of the Director, NIH, provided an overview of the work of his office, which was founded in 2015. He was appointed as its director in 2017. The Tribal Health Research Office (THRO) works with all 27 NIH institutes and centers (ICs). THRO has its own council of advisors, which comprises tribal leaders who guide investments in tribal health research. Dr. Wilson travels frequently to reservations for meetings.

Indian communities understand the importance of biomedical research, Dr. Wilson said, but trust is a problem. THRO serves as an intermediary and a resource for the community. The office communicates regularly with tribal communities. Providing training opportunities for students from Indian nations can be a helpful way to engage communities. THRO has helped administer summer internships, giving students an opportunity to work at NIH and visit Congress. Dr. Wilson emphasized the importance of community health representatives. As key members of their communities, they can provide guidance and insights for collaboration.

Dr. Wilson highlighted the following activities of THRO:

• THRO developed a strategic plan with four goals: communication and collaboration; building research capacity; expanding research; and enhancing cultural competency and community engagement.
• The office released an overview of funding to advance American Indian and Alaska Native (Al/AN} health for 2017. Early next year, the office will release a portfolio showing funding efforts for 2018.
• THRO brought together three agencies within the Department of Health and Human Services-NIH, the Indian Health Service (IHS}, and the Substance Abuse and Mental Health Services Administration (SAMHSA)-for a listening session on the opioid crisis in Indian Country. Tribal communities were very responsive. The meeting served as an opportunity to discuss the mission of NIH, which is research, versus that of IHS, which focuses on the delivery of health care.
• Indian communities have asked for better access to NIH data. With the help of summer interns from tribal nations, THRO created an Al/AN health research grant finder.
• In collaboration with the National Human Genome Research Institute (NHGRI), THRO created a briefing document on genetic research. The Navajo Tribe had previously issued a moratorium on genetic research. After a workshop and ongoing dialogue, members of the Navajo Nation are discussing lifting the moratorium.
• Tribal communities have expressed concern about how research data could be used to stigmatize their community as well as concerns about intellectual property. Dr. Wilson's office has been helping develop webinars about how data are stored, shared, and protected.
• In May, the Navajo Nation and NIH ratified the Environmental Influences on Child Health Outcomes (ECHO} data-sharing and use agreement. This agreement, which followed more than 2 years of discussion and negotiation, will address Navajo community concerns about exposure of children and mothers to uranium. Dr. Wilson suggested ECHO can serve as a model for agreements with other tribal nations.

V. NHLBI INITITATIVES

The NHLBI staff presented 15 initiatives. Members generally expressed support for these initiatives during the discussions. They asked for clarification on certain details and offered recommendations for some of the initiatives. Dr. Gibbons will consider their recommendations as well as other budgetary and programmatic issues in determining which, if any, of the proposed initiatives to implement.

Title: Production Assistance for Cellular Therapies (PACT} (N0l)

Objectives: This renewal aims to provide cell manufacturing services that will facilitate investigator-initiated pre­ clinical and first-in-human (Phase 1/11} clinical trials for regenerative medicine research. This is especially important because of the 21st Century Cures Act {2016} and intended contributions by NHLBI PACT for this Act.

Title: Renewal of the Atherosclerosis Risk in Communities (ARIC) Cohort Study (N0l}

Objectives: The proposed renewal continues the ARIC study as a resource for ongoing epidemiologic research on cardiovascular (CV}, lung, blood, sleep, and related diseases. This initiative will follow the 2016 recommendations of the NHLBI Population Research Strategy Group (PRSG) and will support the operations and follow-up of clinical events for the ARIC study with support for a basic core exam if ancillary study grants are funded.

Title: Sudden Death in the Young Initiative- Research Component Renewal (RFA: U01 / NOSI: R01)

Objectives: The sudden, unexpected loss of a child is a tragic event with significant impact on families and communities. The Sudden Death in the Young (SDY) Case Registry is a collaboration between the National Institutes of Health (NHLBI and NINDS) and the Centers for Disease Control and Prevention (CDC). It was designed to address critical knowledge gaps in the epidemiology and causes of SDY and to develop a resource for research that will enhance the evidence base to inform prevention efforts. The purpose of this renewal is to continue support mechanistic, genetic, and other studies to evaluate causes of and risk factors for SDY.

Title: HeartShare: Next-Generation Phenomics to Define Heart Failure Subtypes (U01)

Objectives: This initiative is a revision of the original HeartShare proposal (ID#1321) reviewed by the BEE in the Fall of 2018. There remains a large gap in clinical research on heart failure with preserved ejection fraction (HFpEF). Therefore, this initiative was revised to focus on understanding the heterogeneity of HFpEF patients through deep phenotyping in order to stratify them into subgroups with different underlying disease processes.

Title: National Health and Nutrition Examination Survey (NHANES) HLBS Component: 2021-2024 (Y01)

Objectives: The purpose of this initiative is to renew the lnstitute's participation in the National Health and Nutrition Examination Survey (NHANES), and thereby gather nationally representative data on prevalence and trends of heart, lung, blood and sleep disorders and disease, and their risk factors.

Title: Technology Resource Center for Aging Research in HLBS Conditions (P30)

Objectives: This initiative is designed to address the growing needs of aging Americans to assist them in remaining in their private homes for as long as possible by facilitating the needs of the elderly including in-home monitoring of heart, lung, blood, and sleep (HLBS) conditions. The overall goal of the initiative is to facilitate clinical validation and adoption of in-home technologies for seniors within the NHLBI mission.

Title: Reflung: A publicly available reference of molecular and cellular maps that describe the normal human lung across the lifespan (N01)

Objectives: To construct a single-cell omics-based reference of the normal human lung (Reflung), reflecting dynamic spatio-temporal changes across entire lifespan from early development to late stage of aging. Reflung will provide healthy control data needed for research of many different lung diseases, enabling and greatly increasing the efficiency of pulmonary pathobiological research.

Title: Competitive Supplement for Implementation Science {ISupp) (Clinical Trial Optional) (R33,UH3)

Objectives: To enhance existing NHLBI funded research through supplements to support integrated and coordinated research programs that emphasize the multilevel factors associated with the successful implementation of evidence-based interventions and guidelines within clinical and community settings (e.g., worksites, communities, health systems/practitioners or schools).

Title: Secondary Participation for 4DN Transition to Primary Cells, Organoids, Tissues and Model Organisms to Explore Nuclear Architecture in Human Health and Disease - U01for ESls

Objectives: To, as part of the 4D Nucleome Common Fund Program, develop and apply tools to investigate the role of nuclear organization during development and lifespan in human health and disease. To support the careers of Early Stage Investigators in this important research area.

Title: Secondary Participation Reissue of Common Fund RFA-RM-17-027 entitled "Tissue Mapping Centers for the Human BioMolecular Atlas Program (U54 Clinical Trial Not Allowed)"

Objectives: The vision for the Human BioMolecular Atlas Program (HuBMAP) is to catalyze development of a framework for mapping of the human body at high resolution to transform our understanding of tissue organization and function.

Title: Secondary Participation Reissue of Common Fund RFA-RM-17-025 entitled "Transformative Technology Development for the Human BioMolecular Atlas Program (UG3/UH3 Clinical Trial Not Allowed)"

Objectives: The objective behind the reissuance of this Common Fund FOA (Funding Opportunity Announcement), RM-17-025 (https://grants.nih.gov/grants/guide/rfa-files/rfa-rm-17-025.html), is to solicit additional transformative technologies that will significantly expand throughput, multiplexing and discrimination of biomolecules in human tissues for comprehensive mapping of individual cells and their context in human tissues.

Title: Pediatric HIV/AIDS Cohort Study (PHACS) Secondary Sign-on, Clinical Trials not included (P01)

Objectives: The objectives of this co-funding opportunity is to contribute to understanding of long-term safety of antiretroviral therapy (ART) among HIV exposed but uninfected infants (SMARTT study) and HLBS outcomes among adolescent and young adults living with perinatally acquired HIV infection (AMP studies).

Title: NHLBI Secondary Participation in the Native American Research Centers for Health (NARCH) Program (S06)

Objectives: The objective of this proposal is to request secondary participation for the Native American Research Centers for Health (NARCH) Program, a program that funds grants focused on the research and development needs and health priorities of American Indian/Alaska Native (Al/AN) communities (https://www.nigms.nih.gov/Research/DRCB/NARCH). The program FOA will be re-issued in spring 2020 and spring 2021(NARCH 11 and 12).

Title: Secondary Participation PA-18-932: Increasing Uptake of Evidence-Based Screening in Diverse Adult Populations (R01 Clinical Trial Optional)

Objectives: The FOA calls for research grant applications that seek to test and/or understand strategies to reduce disparities in the uptake of evidence-based screening across the adult lifespan. This FDA was published September 21, 2018 with standard application receipt dates. Two receipt dates have now passed, and expedited sign-on will indicate NHLBl's interest in this important area and allow acceptance of applications for the next available receipt dates, which go through January 2022.

Title: Secondary Participation in PAR-Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) (R01)

Objectives: The objectives of this Trans-NIH PAR are to stimulate new research on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and to encourage an interdisciplinary approach to the research.

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 552b(c)(6), Title 5, U.S. Code and Section lO(d) of the Federal Advisory Committee Act, as amended.

VI. 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 2817 applications requesting $6,688,995,986 in total costs. For the record, it is noted that secondary applications were also considered en bloc.

ADJOURNMENT

The meeting was adjourned at 1:50 p.m.