Bethesda, MD
Description
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 24, 2023
The 305th meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC) convened hybrid on Tuesday, October 24, 2023. The Council meeting began with a closed session that started at 8:02 a.m. and ended at 9:57 a.m. The open session convened from 10:18 a.m. and ended at 2:01 p.m. Dr. Gary H. Gibbons, Director of NHLBI, presided as chair.
NHLBAC Members Attending
Victoria L. Bautch, Ph.D.
Kirsten Bibbins-Domingo, M.D., Ph.D.
Mercedes R. Carnethon, Ph.D.
Amanda Mae Fretts, M.D., M.P.H.
Tina V. Hartert, M.D., Ph.D.
David H. Ingbar, M.D.
Edward E. Morrisey, Ph.D.
Kiran Musunuru, M.D., Ph.D.
Merritt Raitt, M.D., Ex Officio
Lynn M. Schnapp, M.D.
Martha C. Sola-Visner, M.D.
Zachariah P. Zachariah, M.D.
Ad Hoc Members Attending
Olveen Carrasquillo, M.D., M.P.H.
Allison King, M.D., M.P.H., Ph.D.
Eldrin Lewis, M.D., M.P.H.
Solomon Ofori-Acquah, Ph.D.
Susan Redline, M.D., M.P.H.
Susan Spencer
Members of the Public Attending
The total number watching online was reported by NIH Videocast to 316.
NHLBI Employees Attending
Several NHLBI staff members were in-person and virtually via Zoom.
CLOSED SESSION
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 10(d) of the Federal Advisory Committee Act, as amended.
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 2,974 applications requesting $8,428,407,375.00 in total costs. For the record, it is noted that secondary applications were also considered en bloc.
OPEN SESSION
I. CALL TO ORDER
Dr. Laura K. Moen (Director, Division of Extramural Research Activities, NHLBI) called the meeting to order 10:18 a.m. and welcomed Council members, NHLBI staff, and public attendees. She recognized people retiring from the Council: Drs. Ingbar, Musunuru and Zachariah.
II. ADMINISTRATIVE ANNOUNCEMENTS
Dr. Moen informed attendees that the meeting would be publicly broadcast and archived on videocast. She reviewed the agenda.
III. REPORT OF THE DIRECTOR
Dr. Gibbons acknowledged three departing Advisory Council members: Dr. David Ingbar, University of Minnesota; Dr. Kiran Musunuru, University of Pennsylvania; and Dr. Zachariah Zachariah, University of Miami Health System. He thanked them for their service and contributions.
Accountable Stewardship. Dr. Gibbons reported that NHLBI fiscal year 2024 (FY 2024) appropriations proposed by Congress are unchanged from FY 2023 at $3.98 billion, and the President’s FY 2024 proposed budget is lower, at $2.8 billion. For the NIH as a whole, Dr. Gibbons indicated that the President’s proposed FY 2024 funding allocation was up 3 percent from FY 2023, but the House proposed an 8 percent reduction and the Senate a 2 percent increase. Dr. Gibbons noted that funding in the upcoming year could be very challenging in many ways.
Dr. Gibbons briefly discussed the Other Transaction Authority (OTA) Research, a mechanism that is neither a grant nor strictly a contract, but involves other, nontraditional entities. The OTA is intended to promote agility in discovery and translation, including through unique partnerships. Examples include BioData Catalyst and Cure Sickle Cell.
Dr. Gibbons noted that the September retreat to discuss the re-envisioning of the Strategic Vision for the next 5 to 10 years produced important insights and ideas along the various domains of NHLBI’s strategic goals and objectives, and a report will be forthcoming. He reviewed the Strategic Vision’s three key elements: Understanding Human Biology, Reducing Human Disease, and Translation and Implementation.
Understanding Human Biology. In discussing the transformative potential of basic science discoveries, Dr. Gibbons cited work by Dr. Robert Lefkowitz, who was awarded the 2012 Nobel Prize in Chemistry for his work on G-protein-coupled receptors. Dr. Lefkowitz came to NIH first as an intramural program fellow and later received NHLBI support. The impact of his discoveries has significantly influenced the NHLBI portfolio and benefited patients, and other transformational innovations could catalyze in the next 5 to 10 years, Dr. Gibbons said.
He cited the example of work by Dr. Patrick T. Ellinor and his team to amass all the transcriptome data that exist publicly and identify and characterize the state of each cell in the human body over the lifespan in health and disease.
Dr. Gibbons also mentioned the complex, cross-disciplinary work underway on heart failure with preserved ejection fraction (HFpEF). The HF Accelerating Medicines Partnership (AMP) approach involves nine groups of stakeholders and provides an opportunity to optimize discovery with team science, he noted.
Reducing Human Disease. Dr. Gibbons commented on the potentially transformative research in tackling human disease, citing work by Dr. Justin Cosentino and his team to use machine learning (ML) to identify chronic obstructive pulmonary disease (COPD) phenotypes from electronic health records (EHRs). This work, he said, could lead to improved disease prediction and genomic discovery.
Dr. Gibbons said that ensuring health equity in this era of precision medicine is essential. This means robust testing, cross-validations, population diversity, and other steps to ensure that AI systems used are free from bias and discrimination.
Translation and Implementation. Establishing the most appropriate research agenda requires a multilevel approach and extensive engagement with communities, essentially an integrated holistic approach at scale, Dr. Gibbons said. This involves building on community partnerships, addressing misinformation, increasing trust in science, and accelerating the uptake of beneficial interventions.
Dr. Gibbons showed a conceptual model to advance health equity through transformed systems for health, which could be employed across the NHLBI portfolio. He mentioned the DECIPHeR program, which has adapted the CEAL approach to test multilevel interventions to reduce or eliminate cardiovascular health disparities. Another example is the Alliance for Community Engagement on Climate and Health, which is promoting climate resilience and adaptive capacity in indigenous populations in Alaska.
Dr. Gibbons concluded that NBLBI will continue to look for opportunities for synergies and collaborations and advance its strategic priorities.
IV. PRESENTATION: “ALL OF US” RESEARCH PROGRAM OVERVIEW
Dr. Joshua C. Denny, Chief Executive Officer, “All of Us” Research Program, NIH
Dr. Denny gave an overview of the All of Us program, which has a mission to accelerate health research and medical breakthroughs enabling individualized prevention, treatment, and care for everyone. To date, more than 719,000 participants have enrolled, representing a broad range of race and ethnicity; 80 percent reflect groups that are underrepresented in biomedical research.
Dr. Denny described how All of Us has met participants in their localities to encourage engagement, using outreach vans and mobile units, employing Spanish as well as English, and enabling virtual enrollment as well.
The data types collected from All of Us participants include annual survey responses, physical measurements, biosamples, and EHRs, if authorized. A broad range of data is collected via wearable devices, including more than 30,000 FitBits supplied to participants. The teams also record participants’ social determinants of health, such as neighborhood safety, loneliness, and food security.
An essential part of All of Us is to give participants feedback where feasible—for instance, genetic information, comparative survey data, EHR data, ongoing study updates, scientific findings, and other information.
Dr. Denny cited examples of results in genomic health, including one study analyzing seven genes that can affect how bodies metabolize medicines. Among the more than 66,200 participants, 27 percent had an actionable result for a drug they had been exposed to. All of Us now has nearly 250,00 whole-genome sequences intended to advance precision medicine, the world’s largest such set widely available for research, he noted.
Dr. Denny described the public data browser and researcher workbench access, usage, and diversity, and cited some of the publications and projects based on All of Us data. For example, he mentioned a study by Dr. Patrick K. Wu repurposing drugs using gene expression signatures and EHR data and another study on APOL1 genetic variants and their link to end-stage kidney disease in people of African ancestry.
In conclusion, Dr. Denny briefly described All of Us ancillary studies, which include randomized-controlled trials, observational trials, devices, new biospecimen collection, and biospecimen access. He added that All of Us plans to include pediatric participants soon.
V. NHLBI CONCEPT CLEARANCE
NHLBI staff presented 24 concepts for clearance. Members of the Advisory Council were asked to rate each concept on six criteria using Decision Lens.
Title: Continuation of NHLBI Secondary Participation in the Native American Research Centers for Health (NARCH) Program (S06)
Description: This concept proposes renewed support for secondary participation in NARCH, a program that funds grants focused on the research and development needs and health priorities of American Indian/Alaska Native communities. This NIH-wide initiative, led by NIGMS, partners 19 NIH Institutes and Centers with federally recognized tribes and tribal organizations. NHLBI participated in 2021 and 2022.
Title: Framingham Heart Study (FHS) Contract Renewal (N01)
Description: This concept supports continuation of an NIH-wide initiative on novel epidemiological research covering heart, lung, blood, sleep, and other diseases. The objectives of this renewal are to continue participant retention, follow-up, and clinical event adjudication, as well as core study functions. FHS has an astounding collection of multigenerational data, Dr. Goff noted.
Title: Secondary Participation to Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Centers
Description: This concept proposes renewed support publicizing a competition for centers researching this understudied group of hereditary, progressive degenerative disorders, which have a particular impact on heart and lung health. NHLBI began co-funding this NIH-wide initiative in 2008.
Title: T32 Training Program for Institutions that Promote Diversity
Description: This concept proposed continued support of institutions to train individuals from nationally underrepresented backgrounds in cardiovascular, pulmonary, hematologic and sleep disorders, thereby expanding diversity in research capacity. NHLBI has supported this program since 1992.
Title: NHLBI Secondary Participation in the Intervention Research to Improve Native American Health (IRINAH) Program (R01)
Description: This concept proposes renewed support of the IRINAH program to support intervention research to enhance the health of Native American populations and reduce disparities. NHLBI expects to make two to three new awards per year. This NIH-wide program is led by NIDA.
Title: Jackson Heart Study (JHS) Renewal (N01)
Description: This concept proposes renewed support for novel epidemiological research on HLBS diseases in a cohort of multigenerational African Americans. The program was launched in 1999 to examine factors behind the high prevalence of cardiovascular disease in African Americans living in Jackson, and it continues to provide opportunities to discover novel indications.
Title: NHLBI Career Transition Award for Intramural Postdoctoral Fellows and Research Trainees (K22)
Description: This concept proposes renewed support for highly qualified NHLBI intramural postdoctoral fellows to facilitate their transition to independent faculty positions and develop their own research. The goal of this NIH-wide program is to prepare a diverse pool of individuals to impact the health of the nation.
Titles: Phased Multi-Site Clinical Trial: Testing Prevention of Cardiovascular Disease in Young Adults With High Lifetime Risk Using Surrogate Outcomes (U24); Phased Multi-Site Clinical Trial: Testing Prevention of Cardiovascular Disease in Young Adults With High Lifetime Risk Using Surrogate Outcomes (UG3/UH3)
Description: These concepts propose trans-NHLBI focus on a clinical trial testing whether earlier pharmacological intervention on cardiovascular risk factors can reduce or delay the onset of related clinical disease in adults with a high lifetime risk. The focus of Phase I is on screening, and Phase II is on testing the effectiveness of select interventions.
Title: Risk Underlying Rural Areas Longitudinal (RURAL) Study (N01)
Description: This concept proposes renewed support for an ongoing program to enroll—via a mobile examination unit—6,600 participants in the US South, including from Hispanic/Latin populations, to facilitate studying the rural health penalty. This is an NIH-wide program.
Title: NHLBI R35 Programs – Outstanding Investigator Award (OIA) and Emerging Investigator Award (EIA) (R35) Renewal
Description: These concepts propose continued support for the NHLBI R35 programs, which aim to allow NHLBI-supported investigators stable long-term funding and the flexibility to pursue new research directions as they arise. The goal is to promote productivity and facilitate ambitious, creative HLBS research. NHLBI established this initiative in 2017 and has approved an average of 68 OIA and 19 EIA applications annually.
Title: Mentored Career Development Award to Promote Faculty Diversity in Biomedical Research (K01)
Description: This concept proposes renewed support for an award designed to raise the number of highly trained junior faculty from diverse backgrounds, in an effort to address national and global health disparities. This NIH-wide program will support 20 awards per year.
Title: Secondary Participation in Renewal of Rare Diseases Clinical Research Network (RDCRN) (U54)
Description: This concept proposes renewed support for clinical research in 165 rare diseases and disorders, fostering collaborations between physicians, scientists, and their multidisciplinary teams in association with patient advocacy groups. This NIH-wide program is led by NCATS and aims to produce a robust pipeline of research in rare diseases.
Title: A National Lung Biorepository for Lung-Disease Specific iPS Cells (N01)
Description: This concept proposes renewed support, without change, for the national biorepository of normal and lung-disease-specific induced pluripotent stem cells and their derivatives. The goal is to facilitate research in this high-cost, technically complicated field.
Titles: NHLBI Early Phase CT for Therapeutics and/or Diagnostics for HLBS Disorders (R33 CT required);
NHLBI Early Phase CT for Therapeutics and/or Diagnostics for HLBS Disorders (R61/R33 CT required)
Description: These concepts propose renewed support for investigator-initiated, early-phase clinical trials in translational research, with the aim of accelerating the development of new clinical interventions to advance diagnoses and therapeutic interventions for HLBS disorders in both adults and children. NHLBI supported 33 awards over the past year.
Title: Developing a Pipeline of Cell and Gene Therapies for HIV Cure (U19)
Description: This concept would support translational research in innovative approaches beyond antiretroviral therapy, to cure HIV-1. Long-term adherence to, and side effects of, antiretroviral therapies can be problematic; and elimination of the virus in a few patients has laid the groundwork for further research. Two awards will be from NHLBI and two from NIAID.
Titles: Renewal of Secondary Participation: Stimulating Hematology Investigation: New Endeavors (SHINE) (R01 Clinical trial not allowed); Renewal of Secondary Participation: New Directions in Hematology Research (SHINE II) (R01) PAS21-150
Description: These concepts proposed renewed support for investigator-initiated grant applications in basic and translational hematology research, to encourage more research in nonmalignant hematology. Partnering in this program, initiated by NIDDK, are NHLBI and NIA.
Title: Advancing HIV Testing, Prevention, and Care Through Pharmacists and Pharmacies (R01)
Description: This concept would support expanding access to HIV testing, prevention, and care services through pharmacists and pharmacy settings, thereby reducing HIV-associated comorbidities, including in HLBS. Such settings are generally regarded non-stigmatizing, locally convenient, and offer expanded hours, thereby encouraging access to healthcare. This is an NIH-wide program.
Title: NHLBI Co-Funding Support for the World Health Organization’s WHO Science Council Genomics Report Activities (U01)
Description: This concept proposes support for WHO’s program to expand access to genomics for global health, especially in low- and middle-income countries (LMICs) and strengthen genomics capacity at the regional and country levels. The program is for 2 years, and eight NIH entities are participating.
Titles: Renewal of Secondary Participation in FIC Emerging Global Leader Award (K43 Clinical Trial Not Allowed); Renewal of Secondary Participation in FIC Emerging Global Leader Award (K43 Independent Clinical Trial Required)
Description: These concepts propose continued support for capacity building in LMICs. This initiative provides early-career scientists in those countries with protected time and funding for research, mentoring, and career development. This NIH-wide initiative is led by FIC.
Title: Secondary Participation in the Renewal of RFA-MD-22-003: Innovations for Healthy Living SBIR RFA (R43, R44)
Description: This concept proposes renewed support for the development, optimization, adaptation, and repurposing of new devices, digital health, and diagnostic tools to meet the health needs of underserved populations. This NIH-wide initiative supports small businesses and is led by NIMHD.
VI. CLOSING REMARKS
Dr. Gibbons adjourned the meeting at 2:01 p.m.