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
September 12, 2023
The 304th meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC) convened as a hybrid meeting via videoconference on Tuesday, September 12, 2023. In addition to NHLBAC members, the meeting included the ad hoc Board of External Experts (BEE), scientists with research expertise in National Heart, Lung, and Blood Institute (NHLBI) mission areas, who were recruited for this meeting as a special NHLBAC working group. The Council meeting began at 9:12 a.m. and ended at 4:34 p.m., EDT. The meeting was open to the public between 9:12 a.m. to 12:45 p.m. and 3:30 p.m. to 4:34 p.m. to hear reports and recommendations from each working group.
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.
Merritt Raitt, M.D., Ex Officio
Lynn Schnapp, M.D.
Martha Sola-Visner, M.D.
Zachariah P. Zachariah, M.D.
BEE Members Attending
Michelle A. Albert, M.D., M.P.H.
Judy L. Aschner, M.D.
Timothy S. Blackwell, M.D.
Joanne Chikwe, M.D.
Randi Foraker, Ph.D.
Annetine A. Geliujns, Ph.D., J.D.
Nadia Hansel, M.D.
Bertha Hidalgo, Ph.D., M.P.H.
Hans-Peter Kiem, M.D.
Darrell N. Kotton, M.D.
Elizabeth McNally, M.D., Ph.D.
Brian S. Mittman, Ph.D.
Matthias Nahrendorf, M.D., Ph.D.
Ellis J. Neufeld, M.D., Ph.D.
Laura Kristen Newby, M.D.
Herman Taylor, M.D.
Griffin M. Weber, M.D.
Kenneth Wright, Jr., Ph.D.
Members of the Public Attending
The total number watching online was reported to NIH Videocast to 380.
NHLBI Employees Attending
Several NHLBI staff members were present and in attendance via Zoom.
I. CALL TO ORDER
Dr. Gary H. Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI), called the meeting to order at 9:12 a.m. He welcomed members of the National Heart, Lung, and Blood Advisory Council (NHLBAC) and the ad hoc Board of External Experts (BEE) to this joint meeting.
II. ADMINISTRATIVE ANNOUNCEMENTS
Dr. Laura K. Moen, Director of the Division of Extramural Research Activities at NHLBI, made the required announcements for the Council meeting, including the publication of a notice in the Federal Register as well as reminders to Council members regarding conflict of interest and lobbying activities.
In addition, Dr. Moen stated that the meeting objective is to engage the NHLBAC and BEE, as representatives of the NHLBI research community, to advise the Institute on thought-provoking opportunities to allow a more comprehensive discussion of the NHLBI Strategic Vision.
III. DIRECTOR’S REMARKS
Dr. Gary Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI) gave his opening remarks. This year’s combined meeting was intended to address a refresh of the NHLBI Strategic Vision, so he emphasized addressing key questions and developing bold cross-cutting ideas to advance heart, lung, blood, and sleep (HLBS) health. Priorities for this refresh of the Strategic Vision included understanding human biology, reducing human disease through preemptive measures, and identifying strategies for translation and implementation. These priorities were highlighted to address inequities and reduce the burden of disease across heterogenous populations.
Dr. Gibbons emphasized better use of predictive modeling and data science strategies which incorporate artificial intelligence (AI) and machine learning (ML). Such practices would enable the leveraging of data to prevent disease and begin interventions earlier. Additionally, fuller understanding of human biology would enable the identification of more precise risk factors and targets for treatment and prevention of specific HLBS diseases and disorders. Collective collaboration and competition through team science was encouraged to drive innovation and develop new technologies for precision medicine and health equity.
IV. DIVISION UPDATES
Division of Lung Diseases – James P. Kiley, Ph.D., M.S.
Dr. James Kiley provided the update from the Division of Lung Diseases (DLD). He presented programs that have been successful under the guidelines of the current Strategic Vision as well as certain lessons learned and how the DLD plans to move forward to over the next 5-10 years.
Precision medicine is a key focus of the DLD to better understand and manage lung disease and sleep-disordered breathing. Using powerful tools to identify biomarkers and develop pathobiology approaches is key to earlier detection and treatment. The model developed during the Severe Asthma Research Program (SARP) integrated data with other programs to push precision medicine. This model was then used to build out the research and treatment infrastructures for other diseases and the heterogeneity among the diseases. The Precision Interventions for Severe and/or Exacerbation-Prone Asthma (PrecISE) Network was developed as the first adaptive trial design. This led to the selection of specific antibodies as predictive biomarkers through combining predictive methods with pathobiology to develop tailored therapies.
The lung health cohort may use such tools and strategies to examine diseases in utero and early childhood to determine which factors might impact health and influence disease later in life. Predictive models and precision medicine would be of further importance to develop genotype stratified trials that are designed to determine how to get the correct treatment to the right people at the right time. By using adaptive clinical pathways, significant therapeutic interventions can be identified within heterogenous disease populations.
As part of the strategic refresh, the DLD aims to better incorporate communities in the discovery process to implement discoveries and improve translation of interventions. Technology and large data sets should be leveraged more effectively through new data science tools to discover novel phenotypes and explore heterogeneity among populations. By better understanding human biology and disease mechanisms, the DLD aims to identify risk factors and prevent lung disease in as many populations as possible, while also identifying targeted treatments and effective interventions.
Division of Blood Diseases and Resources – Traci Heath Mondoro, Ph.D.
The Division of Blood Diseases and Resources (DBDR) has focused on cell and gene therapies for all blood disorders. Systems blood science has been embraced to establish a more holistic approach to prevention, diagnosis, and treatment of blood diseases which involves investigating the roles played by human biology, social determinants of health (SDOH), environmental stressors, and more. Understanding the mechanisms of mutations that drive clonal expansion in healthy humans has been useful in determining how these mutations affect diseases. Progress has been made in better understanding of the mechanisms of sickle cell disease (SCD) and thalassemia by focusing on mutations, as well as the development of gene therapy vector techniques to support clinical trials. Such techniques are important in developing precision medicine approaches.
Precision medicine and systems science are important tools to optimize clinical trials, leverage opportunities with new partners, and engage predictive modeling more effectively. Leveraging data sets from both public and private settings can lead to better understanding of blood disorders and subgroups across heterogeneous populations. Improved data analyses can then expand the capabilities of predictive modeling to identify better therapeutic targets and determine which patients would most benefit from curative therapy.
To implement all of these methods, a diverse workforce must be trained and retained as part of the multi-disciplinary teams that are key to driving innovation. The Pride Mentorship Program was established as a 15-year program to increase representation and retention within the area of blood science. Programs such as this, combined with partnerships in industry and other agencies, are vital to building multi-disciplinary teams with broad impacts. Greater engagement and partnership with community input panels are also needed to understand barriers to care and which resources are needed to address disparities. Community input panels provide a better opportunity for investigators to understand what a positive outcome (“positive health”) means to different disease populations versus what investigators deem a positive outcome.
The DBDR emphasized translation of innovations from the bench to bedside and vice versa. Understanding SDOH plays a vital in translation and implementation since multiple factors and stressors, including those from the environment in which one lives, can affect disease patterns. SDOH also influence how treatments and innovations reach communities. Potential barriers to care, participation, and information access must be considered for the implementation process in blood health interventions. SDOH are among many stressors, including sleep health and environmental factors, that contribute to inflammatory responses which negatively impact blood health. There is a great need to better understand inflammation and its contribution to disease profiles for the future of preventative care and therapeutic treatments of blood diseases.
Division of Cardiovascular Sciences – David C. Goff, Jr., M.D., Ph.D.
The Division of Cardiovascular Sciences (DCVS) accomplished much over the past several years while supporting NHLBI’s priorities such as workforce development, precision medicine, and COVID response. Multiple programs and cohorts were engaged to drive innovation and promote equity in cardiovascular health across lifespans. Programs such as HeartShare and the Accelerating Medicines Partnership (AMP) have leveraged data from multiple sources and utilized precision medicine to identify new treatment targets for specific endotypes. Partnerships with other agencies and private industry have also enabled innovation.
Cardiovascular health (CVH) across the lifespan has been promoted through programs such as the Early Intervention to Promote Cardiovascular Health of Mothers and Children (ENRICH), and the RURAL and Asian American-Pacific Islander-Native Hawaiian (AAPINH) cohorts. These programs all have a focus on addressing SDOH in various populations to promote early interventions and close health equity gaps.
Over the next several years, DCVS aims to continue collecting data across the spectrum to understand mechanisms of CVH and identify specific targets for intervention and therapeutics. This data should include cardiovascular sensor and mobile health data, as well as SDOH, imaging, phenotype, clinical, and molecular data. The application of AI, ML, and other data science methods to these large data sets should allow for better understanding of cell-specific omics, phenotypes, and endotypes to develop more effective and equitable interventions. Overall, the Division’s goal is to reestablish the decline in cardiovascular disease mortality by expanding the size of the cohorts, engaging with more partners, and working with communities to close health equity gaps and develop more effective interventions.
Center for Translational and Implementation Science – George Mensah, M.D., FACC
Implementation science is required to get innovations to communities so that they can thrive and meaningful community-engaged research is important to successfully implement innovations. The Community Engagement Alliance (CEAL) exists to drive meaningful community engagement in a bi-directional manner. Listening to community needs and challenges helps to build trust while also developing pathways for effective implementation. Funding implementation science awards has increased to aid in developing more tools and methods to bring effective and meaningful research to communities.
Telehealth has been an important tool for implementation, particularly in geographic or socioeconomic areas that cannot easily access health care or innovations. Partnerships in non-traditional settings have been useful for various implementation strategies, including establishing programs in schools for children and in faith-based settings for some areas. Training and career development opportunities have been an additional focus of the Center for Translational and Implementation Science (CTRIS) through building partnerships and developing training and career opportunities.
The strategic vision of CTRIS for the next several years includes continuing to build workforces and accelerate the implementation of discoveries for improved health. New areas of science include the examination of how implementation science and SDOH intersect, and how this knowledge can be leveraged by investigators to make the best use of theories and frameworks. The Gravity Project is a program currently developing standards for the sharing of SDOH data to assist investigators. By centering communities, research can be better implemented for those who need it most and reduce disease burdens. On a global scale, the infrastructure established through the Fogarty study can be leveraged to build a global workforce that reinforces the NHLBI Strategic Vision through a focus on non-communicable diseases and community health worldwide.
V. DIRECTOR’S CHARGE TO THE NHLBAC AND BEE
Charge: Refreshing Key Priorities of NHLBI’s Strategic Vision
Group A: Understanding Human Biology
- How can we feed the knowledge gained from complex genetics, omics, and cohorts back into hypothesis-driven research on basic mechanisms of disease?
- To which fundamental underlying mechanisms that regulate biological processes may we expand our currently disease-specific cohort and data studies and how can we leverage these to move HLBS science forward?
- How can we generate data-driven hypotheses for understanding biological mechanisms through data science or epidemiological studies such as new cohorts?
- What emerging scientific areas may benefit from novel cohort studies?
Group B: Reducing Human Disease
- What new directions can we take to approaches of human disease given the newer understanding/treatments developed over the past 5 years?
- What new directions and approaches can we take to reverse the trend of widening health inequities in many areas of HLBS diseases and related risk factors?
- What new approaches and desired changes in the strategic plan can capitalize on changes in the research ecosystem in the past 5 years, such as increased AI/ML capabilities, or increased access to other new technologies?
- What applications and implementation of AI technologies could be developed to reduce human disease?
Group C: Translation and Implementation
- In HLBS mission areas where successful implementation of scientific advances have occurred, what have been the primary facilitators and drivers of success and how can NHLBI disseminate and scale these successes?
- What barriers still exist to implementation of scientific advances and how can we address and remove them to speed translation?
- How can we best support meaningful community engagement, especially in underserved minority populations, to grow a trust in science and accelerate translation and implementation of HLBS scientific advances?
- How can we best measure translation and implementation processes in HLBS research and evaluate their outcomes and impact?
VI. REPORTS FROM THE WORKING GROUP DISCUSSIONS
Group A: Co-Facilitators: Bertha Hidalgo, Ph.D., M.P.H. and Gustavo Matute-Bello, M.D.
The focus of this breakout group was to identify strategies that advance the understanding of human biology. There was a great emphasis on team science spanning multiple disciplines to drive innovation. Optimizing team science mechanisms and encouraging funding models to incentivize multi-disciplinary teams were highlighted as keys to driving greater understanding of human biology. Additionally, grant reviewers must also be trained to eliminate bias and follow the NHLBI vision and mission to encourage team science. Cross-training between disciplines is another way to push innovation forward and partially address the current bottleneck in research and data science due to the lack of data scientists. Through the proper utilization of data scientists, enormous data sets can be leveraged to identify targets for next steps in research and innovation.
Encouraging partnerships with Historically Black Colleges and Universities (HBCUs) as leaders of science can also drive recruitment of diverse researchers and participant populations. Partnerships with non-traditional partners can further drive innovation through the development of regional and cross-regional incubators of knowledge. Improving communication across disciplines will also encourage forward thinking in the design of critical trials. The inclusion of biospecimens and variables from other studies will increase data sets available for use by other investigators. In future clinical trials, the ability to tease out factors related to race from other SDOH, as well as environmental, geographic, and climate factors will be important to advance the understanding of human biology and effects of real-world settings.
Group B: Co-Facilitators: Mercedes Carnethon, Ph.D., M.S. and Larry Fine, M.D., Ph.D.
One way to reduce human disease is to prevent it from ever developing. This breakout group focused on strategies including treatments that don’t require constant follow up or medication, policy changes to support interventions from birth through childhood, and a special focus on preventative approaches that begin with families and infants. Focusing on the origins of disease and healthy behaviors in early life is also a priority to reduce and even prevent human disease. When developing patterns for prevention efforts, investigators must also be conscious of the environments in which people live so ensure access and reduce inequities.
Leveraging big data is key to achieving big goals. As many subgroups as possible must be included in data sets and the uncommon occurrences should be examined more closely, rather than discarded or ignored. Better strategies are needed for working with data, including responsible use of AI and machine learning so that disparities are not worsened through bias. To continue this work, the next generation of data scientists is needed, and user interfaces should be designed for non-experts to effectively use data mining tools. Leveraging surveillance data from wearable medical devices can also help with timing studies to determine when interventions may be most effective in regards to circadian rhythms and lifespan.
Team science approaches were emphasized to drive innovation by bringing together ideas and expertise from different fields. Through partnerships with schools, community organizations, prenatal care providers, and federally qualified health centers, interventions can reach populations where they are and at earlier life stages. A desire to distribute grant money in a more equitable and efficacious manner was indicated to further close equity gaps and reduce disease.
Group C: Co-Facilitators: Judy Aschner, M.D. and Patrice Desvigne-Nickens, M.D.
Examining and addressing barriers to translation and implementation of scientific advances were the priorities of this breakout group. Breaking down silos and focusing on team science were proposed to translate findings from research to the real world. However, not all researchers speak the same language and may be resistant to collaboration. Incentivization of team science and cross-training through funding opportunities could encourage more team science frameworks. An opportunity for the future would be to study the science of team science and to optimize such collaborative strategies.
The future of translation and implementation may require leveraging social media and AI to drive participant recruitment and facilitate dissemination of information and innovations. Barriers to access and underrepresentation in clinical trials are contributing factors that exacerbate inequities in health. However, working with communities can further increase participation and determine which scientific questions are most important to improve health outcomes. Mandating dissemination and implementation plan within funded research can help address some barriers and encourage communities to participate further.
Building and maintaining partnerships with non-traditional partners can also drive innovation in translation and implementation strategies. Professional society databases can be used to find investigators, build teams, and gather research data while also leveraging electronic health records and developing harmonization strategies. Developing adequate funding models to incentivize team science and implementation, while also de-incentivizing harmful practices, are key strategies to break down barriers to translation and implementation of scientific advances across various populations.
VII: COMBINED SUMMARY OF REPORTS FROM THE WORKING GROUP DISCUSSIONS
Throughout the division presentations and breakout working groups, there were common themes to be included in the strategic refresh – encouraging team science, increasing the data science workforce, and prioritizing community engagement to close health equity gaps. Team science must be encouraged with funding models reflecting the importance of such multi-disciplinary workforces. Fostering collaboration within and between teams encourages the breaking of silos and exchanging information. Investigators with different experiences and areas of expertise can build on each other’s strengths, facilitate new discoveries, and drive innovation to improve health outcomes.
The field of data science is important to all divisions, however, there is a great need for data scientists and cross-training opportunities. Without a workforce that knows how to analyze and leverage data, significant bottlenecks in innovation and discovery will persist. The influx of data from EHRs, wearable devices, clinical data, imaging, and more must be analyzed in a responsible and effective way that minimizes bias and maximizes utility. Reducing human disease requires a more preventative mindset that accounts for a variety of factors across heterogeneous populations. New tools and technologies such as AI and ML can facilitate advanced prediction models through expanded access to data and inclusion of more data sources, but this must be done in an appropriate way that does not exacerbate inequities.
Addressing the specific needs of communities is important to address health disparities and ensure that they can thrive. Improved community engagement is one way to develop interventions that close equity gaps and improve health in a culturally relevant manner. Community-based cohorts can identify what communities consider positive health, understand specific challenges, and develop implementation strategies that can be optimized and tailored to populations to have the best positive impact. Moving forward, there needs to be a collective commitment to advance health equity, driven by multi-disciplinary team science, expanded use of data science, and greater engagement with communities and subpopulations.
CLOSING REMARKS AND ADJOURNMENT
Dr. Gibbons thanked everyone for the rich dialogue and discussion.
Dr. Moen thanked everyone and adjourned the meeting at 4:34 p.m.