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
June 6, 2023
NHLBAC Members Attending
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 Morrisey, Ph.D.
Kiran Musunuru, M.D., Ph.D.
Lynn M. Schnapp, M.D.
Martha C. Sola-Visner, M.D.
Zachariah P. Zachariah, M.D.
Members of the Public Attending
The total number watching online was reported by NIH Videocast to 331.
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 3,304 applications requesting $10,370,150,147 in total costs. For the record, it is noted that secondary applications were also considered en bloc.
OPEN SESSION
I. CALL TO ORDER
Dr. Gary H. Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI), called the meeting to order at 11:44 a.m. He welcomed Council members, NHLBI staff, and public attendees to the Open Session of the meeting.
II. ADMINISTRATIVE ANNOUNCEMENTS
Dr. Laura K. Moen (Director, Division of Extramural Research Activities, NHLBI) informed attendees that the meeting would be publicly broadcast and archived on videocast. She reviewed the agenda.
III. REPORT OF THE DIRECTOR
Accountable Stewardship. Dr. Gibbons gave an update of NHLBI’s budget status for fiscal year (FY) 2023, an increase of 4.6% over 2022. For the FY 2024 appropriations hearings, the NIH has highlighted several topics, including next generation approaches, health disparities, inclusive excellence/workforce diversity, rural health, diabetes and Down Syndrome. All those topics are relevant to NHLBI’s portfolio and priorities, he noted. Nonetheless, FY 2024 is expected to bring leaner budget increases than in the past 5-6 years, due to economic and political factors, placing some tension on NHLBI’s programs. For example, applications for investigator-initiated programs and projects have been rising, as have grant costs, making it more challenging to hit award targets and maintain the success rates of recent years.
Dr. Gibbons welcomed new Deputy Directors, Dr. Cara Lewis and Ms. Cindy Caughman, and new Division of Lung Disease (DLD) leadership, Dr. Gustavo Matute-Bello and Dr. Sumita Khatri.
As part of ongoing adaptations to its organizational structure, the NBLBI has proposed the reorganization of its DLD. The agency remains mindful of evolving scientific needs and aims to respond accordingly. This includes the alignment of expertise, science knowledge translation, effective leadership oversight, operational sustainability and succession planning.
Dr. Gibbons also mentioned the NBLBI’s intramural program and its exceptional research, which complements and extends the work undertaken in the extramural portfolio. The diversity of tenure- track investigators has been increasing, as part of inclusive excellence across the Institute.
Lastly, Dr. Gibbons thanked the Council for supporting the NHLBI’s 75th anniversary and welcomes its participation in the agency’s 2016 strategic vision document reexamination this fall. He added that he hopes stakeholders will help determine the best path forward for the next 5-10 years, to enhance and advance the NHLBI’s science portfolio and accelerate discoveries to improve public health.
A key focus of the strategic refresh will be persistent health disparities across NHLBI’s portfolio, for instance, geographical disparities in rates of hypertension, chronic obstructive pulmonary disease (COPD), obesity, diabetes and maternal mortality. Tackling these persistent problems will probably necessitate novel, multi-dimensional approaches. The strategic vision refresh will also study how to leverage the tools, analytics and capacity to understand science at a basic level and in an integrated way. Overall, the refresh is an opportunity to reflect on investments in research platforms and how to incorporate different models and paradigms to address health disparities on many levels, including individual, family, community and environment.
Dr. Gibbons reviewed the NIH Community Engagement Alliance (CEAL) program, which is pivoting focus from Covid to a trans-NIH platform, to enhance community engaged research relevant to health equity, including outreach to indigenous populations.
Several programs are underway to address maternal care deserts, including the Maternal Health Community Implementation Project and Enhancing Nutrition Services to Improve Maternal and Child Health in Africa and Asia (ENRICH) program, and efforts in precision medicine and data science to reduce adverse pregnancy outcomes.
In conclusion, Dr. Gibbons said a key element of the strategic vision refresh for the next 5 years will be devising how to harnessing diverse data resources leverage new capabilities, to fulfill the NHLBI mission and preempt heart, lung, blood and sleep disorders. The Council will play a critical role in discussions with its creative energy, commitment and sustained participation.
IV. NHLBI/DIVISION OF LUNG DISEASE (DLD), PROPOSED REORGANIZATION
Dr. James Kiley (Director, DLD) presented on his Division’s proposed reorganization. Significant growth has occurred in pulmonary and critical care research as new science has emerged, increasing the need for the Division to collaborate and integrate broader research. This has also produced challenges in areas such as staff development, promotion and retention.
The DLD plan proposes four branches dealing with the lung: Acute and infectious lung diseases; Lung development and pediatric diseases; Obstructive lung diseases; and Restrictive and vascular lung diseases, in addition to the current National Center for Sleep Disorders Research branch. The Division currently has three branches on airwaves, lung and sleep.
The new structure would allow the Division to align disease areas with disease agnostic areas and meet administrative requirements. The plan makes sense scientifically and administratively. The changes would be incremental and foster expanded communication within and across all branches.
Dr. Kiley noted that DLD is seeking community feedback, which it will incorporate before submitting the final proposal for NIH approval. Implementation of the reorganization is expected to take at least a year.
V. PRESENTATION: “REDEFINIG ACUTE REJECTION TO IMPROVE TRANSPLANT OUTCOMES: INSIGHTS TO DIAGNOSIS AND TREATMENT”
Dr. Sean Agbor-Enoh (Lasker Clinical Research Fellow, NIH Distinguished Scholar, DIR, The Laboratory of Applied Precision Omics, NHLBI) presented his research in novel approaches to detect and prevent transplant rejection, which is a major contributor to the high mortality of lung transplant patients.
Specifically, Dr. Agbor-Enoh described his work on plasma levels of cell-free DNA (cfDNA), or DNA fragments that are continuously shed into body fluids. Spiking levels of these fragments can signal organ rejection months before routine, more invasive bronchoscopy screening is conducted. Dr. Agbor-Enoh aims to exploit this finding to develop novel and better diagnostic tools for organ failure. In the future, he hopes to redefine acute rejection and more rapidly identify patients needing treatment.
Dr. Agbor-Enoh told the Council about the work of the Genomic Research Alliance for Transplantation (GRAfT) consortium, sponsored by NHLBI. GRAfT embarked on two studies in heart and in lung, to assess the cfDNA tool’s effectiveness. The initial approach was to standardize sample collection, assign adjudication committees to characterize transplant conditions, and test 130,000 samples from 690 patients.
The studies found that cfDNA detected organ dysfunction 2-4 months before biopsy screening. Bronchoscopy identified only a quarter of clinically relevant elevations of cfDNA. However, the cfDNA test is currently non-specific, unable to distinguish if a fragment spike is due to rejection or an infection. To bring more clarity, researchers are investigating the epigenetic fingerprints of cfDNA, which are distinct from the DNA sequence.
Current outcomes from Dr. Agbor-Enoh’s work:
- GRAfT research has discovered that molecular injury often occurs before lung transplant, raising the risk of early allograft failure. The team is profiling injury states to identify optimal times to treat patients.
- The cfDNA protocol has been added to routine clinical care in many places around the world to identify rejection, even as the team moves toward Phase II intervention studies.
VI. NHLBI CONCEPT CLEARANCE
NHLBI staff presented 16 concepts for clearance. Members of the Advisory Council were asked to rate the concepts on six criteria using Decision Lens.
Title: Short-Term Research Education Program to Increase Diversity in Health-Related Research (R25)
Description: This concept supports short-term research education activities that enhance the diversity of the biomedical, behavioral and clinical research workforce. The NHLBI aims to enrich the pool of individuals from nationally under-represented groups who will be available to compete for research opportunities in topics of interest to the NHLBI. Up to nine meritorious awards a year would be approved, each lasting up to 5 years.
Title: Secondary Participation in Multi-sectoral preventive interventions that address social determinants of heath in populations that experience health disparities. (UG3/UH3, PAR)
Description: This concept supports an NIH-wide initiative to test prospective, multi-sectoral, preventive interventions that address social determinants of health. Each project must focus on health equity in communities. Projects will be part of a research network that will share approaches, data and methods, to facilitate the generation of research evidence on preventing common risk factors for multiple health conditions across different populations. Seven NIH institutes/centers are participating.
Title: Secondary Participation in Fogarty HIV Research Training Program for Low- and Middle-Income Country Institutions (D43 Clinical Trial Optional)
Description: This concept supports the goal of strengthening human capacity at institutions in low- and middle-income countries conducting HIV-related research. It is designed to leverage the HIV-AIDS investments and capacity built by other funders, to train in-country experts on the science of heart, lung and blood comorbidities. This is a trans-NIH-wide initiative led by the Fogarty International Center and is open to in-country or U.S. institutions.
Titles: Data Coordinating Center for Cardiovascular Risk Reduction in Type 1 Diabetes Clinical Trial (Collaborative U24 Clinical Trial Required). Efficacy and Implementation of Cardiovascular Risk Reduction in Type 1 Diabetes Mellitus (UG3/UH3)
Description: These concepts support a collaborating Data Coordinating Center for an investigator-initiated, multi-site clinical trial. This trial will test interventions to reduce cardiovascular disease (CVD) risk in people with Type 1 diabetes (T1D) and fill evidence gaps, ultimately contributing to CVD prevention guidelines for T1D. NIDDK is leading the initiative.
Title: Multi-Ethnic Study of Atherosclerosis (MESA) Renewal (N01)
Description: This concept renews support of the MESA study infrastructure as a publicly available resource for Precision Health and novel epidemiologic research on heart, lung, blood, sleep, and related disorders. The MESA cohort is a diverse NHLBI initiative established 23 years ago. This renewal would support regular contact with study participants and other key needs.
Title: Secondary Participation in Understanding Chronic Conditions Understudied Among Women (R01 Clinical Trial Optional)
Description: This concept supports research aims to increase knowledge about chronic conditions that are understudied among women or those that disproportionately affect women who are understudied, under-represented and under-reported in biomedical research. The initiative is led by the Office of Research on Women’s Health.
Title: Proposed Renewal of the National Gene Vector Biorepository (NGVB) Contact (N01)
Description: This concept renews support for the gene therapy resource, NGVB, which provides critical help to NHLBI investigators performing preclinical and clinical gene therapy research. NGVB has proactively anticipated the needs of gene therapy investigators over the past 15 years. This initiative would enable NGVB to continue operating as a cost-effective center of gene therapy excellence for NHLBI and other NIH teams.
Title: Proposed Renewal of the Gene Therapy Resource Program (GTRP) (N01)
Description: This concept renews the NHLBI’s GTRP, to continue providing resources to researchers and facilitate the translation of gene therapy discoveries into clinical advancements for heart, lung, blood, and sleep disorders. GTRP has made numerous contributions across the translational spectrum of gene therapy research since its launch in 2007. This renewal would support the existing three cores and additionally a new reagent core.
Title: National Ferret Resource and Research Center (N01)
Description: This concept renews support for existing, and some new, ferret animal models and tissues. This resource is valuable in the research of novel disease mechanisms and the testing of therapeutics for a variety of human health conditions, particularly of the pulmonary system but also of heart and blood. Historically, this model has been productive in the study of cystic fibrosis and is currently used to study respiratory disease and infections. It has potential for use in cardiovascular disease and other NHLBI research.
Titles: Secondary participation in Advancing Methods for 24-hour Behavioral Patterns: Diet, Physical Activity, and Sleep (U01). Secondary participation in Advancing Methods for 24-hour Behavioral Patterns: Diet, Physical Activity, and Sleep (U24)
Description: These concepts support research integrating the temporal patterns of diet, physical activity and sleep, to determine how the timing of these interconnected behaviors combine to affect health outcomes, trajectory and treatment across the lifespan. This holistic approach, suggested initially by the White House, includes cardiopulmonary and cardiometabolic disease risk, aligning with NHLBI’s objectives. The NCI is leading the initiatives, with support also from NIDDK and OBSSR.
Title: NHLBI Program Project Application (P01 Clinical Trial Optional)
Description: This concept renews, without changes, support for investigator-initiated program project grant applications to advance understanding of fundamental processes and disease in heart, lung, blood and sleep. The NHLBI encourages collaborative research efforts to accelerate the acquisition of knowledge in integrated research projects .This initiative also encourages the careers of junior investigators.
Title: NHLBI Clinical Trial Pilot Studies (R34 Clinical Trial Optional)
Description: This concept renews support for investigators planning to conduct a future Phase II or higher clinical trial, who need additional research to produce critical information necessary to complete the design, for instance, on efficacy, safety, clinical management or implementation of interventions. The NHLBI has used the R34 mechanism since 2010 and funds 20-25 grants per year.
Title: Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) (N01)
Description: This concept renews support for the long-standing NHLBI study to identify different subpopulations of individuals with COPD and ultimately define endotypes within this heterogenous disease that are responsive to mechanism-specific interventions. This renewal charges investigators to obtain additional longitudinal data from the existing cohort, to address three critical topics highlighted by recent research findings. A parallel study in younger smokers will be rolled into this study.
Title: Maintenance of Canine Models of Human Bleeding Disorders Program (N01)
Description: This concept renews support for maintaining the canine hemophilia model, to ensure this unique resource can continue to serve the research community studying inherited bleeding disorders. This model began in 1947 and has yielded strong predictive accuracy for successful translational research.
VII. OPEN DISCUSSION
Discussion was initiated by Council members about the areas of overlap between the two gene therapy programs, including the new Reagent core. Dr. Goff cited prior discussions about whether to bring those two programs under a larger umbrella, perhaps an overarching award with subawards, and reduce further the possibility of redundancy. Additional comments included that some needs are generic and apply across many different organs but others are organ-specific. Dr. Gibbons followed up, saying that the NHLBI must remain adaptive and nimble, keeping focus on what support the gene therapy community needs in the next 5-10 years. There are many commercial cores, vendors and biomanufacturers able to make products and NHLBI should assess, with the gene therapy community, when to adjust focus. Dr. Goff mentioned an increasing number of diversity-related R01 offerings from other NIH institutes and centers and asked if the NHLBI was planning more participation in this area. Dr. Moen replied that the NHLBI has participated in many of those initiatives and is continuing to develop its own potential new offerings. Dr. Gibbons added that the NHLBI are open ideas and concepts in this area and, like many NIH institutions, has led the field in inclusion. It is important to appreciate that executing these programs appropriately involves significant legal consultation to ensure the NIH is aligned with what is appropriately inclusive. Dr. Moen suggested that the diversity program be on the agenda for a future NHLBAC meeting.
Dr. Mensah suggested a discussion at the September joint sessions about the science of health disparities research, what could be approached differently to improve inclusion, not only as an institute but as a nation. Dr. Moen said that regarding the September meeting, the NHLBAC will have an opportunity to comment on proposed topics, including the strategic plan refresh and how to adapt programs to remain attractive.
VIII. CLOSING REMARKS
Dr. Gibbons adjourned the meeting at 2:59 p.m.