National Heart, Lung, and Blood Advisory Council October 2018 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 30, 2018

The 280th meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC) was convened on Tuesday, October 30, 2018, in Building 35A, the Porter Neuroscience Center Conference Center, National Institutes of Health (NIH), Bethesda, Maryland. It was open to the public from 8:00 a.m. until 1:10 p.m. Closed session began at 1:25 p.m. and ended at 2:15 p.m. Dr. Gary H. Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI), presided as Chair.

Council Members attending

Dr. Donna K. Arnett 
Dr. Nancy J. Brown 
Ms. Grace A. Dorney Koppel 
Dr. Serpil C. Erzurum 
Dr. Garth Graham 
Dr. M. Luisa Iruela-Arispe 
Dr. Monica Kraft 
Dr. Diane J. Nugent 
Dr. Pilar N. Ossorio 
Dr. Dean Sheppard 
Dr. Kim M. Smith-Whitley 
Dr. Sally E. Wenzel 
Dr. Andrew S. Weyrich 
Dr. Phyllis C. Zee

Council Members unable to attend

Dr. E. Dale Abel
Dr. Michael R. DeBaun 
Dr. Karen Glanz 
Dr. Richard S. Schofield (ex officio)
Dr. Robert C. Robbins

Public attending

Ms. Maria Ryan, Decision Lens 
Dr. Anthony Cristillo, Social & Scientific Systems 
Ms. Jenee Bevett-Rose, Social & Scientific Systems 
Ms. Nuala Moore, American Thoracic Society

NHLBI employees attending

A number of NHLBI staff members were in attendance.

Other NIH Institute employees attending

Dr. Katherine Malinda, CSR, NIH
Dr. Larry Pinkus, CSR, NIH

I. CALL TO ORDER AND OPENING REMARKS

Dr. Gary H. Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI), called the 280th meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC) to order and welcomed members and other attendees.

II. ADMINISTRATIVE ANNOUNCEMENTS

Dr. Laura K. Moen, Director, Division of Extramural Research Activities, NHLBI, announced that this meeting would be webcast to the public and 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.

Dr. Moen announced that the following council members were retiring: Dr. Nancy J. Brown, Dr. Michael R. DeBaun, Dr. Serpil C. Erzurum, Dr. Pilar N. Ossorio, and Dr. Phyllis C. Zee. She thanked them for their service on the Council.

Council members were asked to make a note of the upcoming Council meeting dates in 2019: February 5, June 4, August 27 (teleconference), September 10 (with the Board of External Experts), and October 29. She then reviewed the meeting agenda.

III. REPORT OF THE DIRECTOR

Decision to Pause the CONCERT-HF Trial. Dr. Gibbons explained that recent calls for the retraction of journal articles in cell therapy research have raised concerns about the scientific foundations of the CONCERT-HF trial. Although none of the articles in question derive from the CONCERT-HF trial, the NHLBI convened the CONCERT-HF’s Data and Safety Monitoring Board (DSMB) out of an abundance of caution. Based on the DSMB’s recommendations on October 29, 2018, the NHLBI decided to pause enrollment and treatment.

Fiscal Stewardship. The NHLBI’s fiscal year (FY) 2019 budget, at $3.29 billion, is 3.1% higher than in FY 2018. This is the fourth year in a row that the NHLBI’s appropriation has increased. The additional funding will allow the NHLBI to increase its paylines for R01 awards and for early-stage investigator (ESI) awards. The NHLBI continues to fund awards for meritorious science that address important scientific priorities.

Dr. Gibbons presented data on NHLBI-initiated requests for applications (RFAs) and program announcements as well as the 22 FOAs that the NHLBI is cosponsoring with other National Institutes of Health (NIH) Institutes and Centers (ICs). In FY 2018, the NHLBI’s funding for research program grants totaled $560.2 million. Dr. Gibbons also summarized the Institute’s initiative development process, which begins with strategic visioning priorities, includes concept development and review by the NHLBAC and BEE, and continues through development and publication of the FOAs.

Seizing Unprecedented Opportunities. The NHLBI is participating in the Helping to End Addiction Long-term Initiative led by the National Institute on Drug Abuse and National Institute of Neurological Disorders and Stroke, to speed the development of scientific solutions to stem the national opioid crisis.

The NHLBI is also collaborating with other NIH ICs in the Investigation of Co-occurring Conditions Across the Lifespan to Understand Down Syndrome (INCLUDE) Project. People with this condition often have congenital heart disease, obstructive sleep apnea, and other conditions that fall within NHLBI’s mission.

The Institute recently launched the Cure Sickle Cell Initiative, which will leverage the assets developed by the NHLBI and a broad range of stakeholders (including biotechnology and pharmaceutical companies, other federal agencies, professional societies, academic institutions, and patients and patient advocacy groups). The initiative’s purpose is to seize the scientific opportunity to use new therapies and new technologies (e.g., gene transfer, gene editing) to cure sickle cell disease in the next 5 years. The NHLBI is committed to ensuring that evidence-based technologies and therapies are implemented in ways that promote high-quality care for as many patients as possible.

The NHLBI will issue the FOA, Rare Disease Cohorts in Heart, Lung, Blood and Sleep Disorders (UG3/UH3), in December 2018, and applications will be due in February 2019. This research will support the discovery and deeper understanding of the biological pathways and genetics of rare disease (including hypertrophic cardiomyopathy, idiopathic pulmonary fibrosis, and sickle cell disease and other hemoglobinopathies) to improve diagnosis and development of new and better treatments.

The NHLBI plans to seize on the scientific opportunities in rare and complex disease research offered by multidimensional, multiscale data and new technologies, including environmental and cohort datasets, -omics and machine learning technologies, and big data integration in the cloud. The Institute will leverage the capabilities of machine learning and artificial intelligence to seek novel patterns in these data.

IV. RECAP FROM SEPTEMBER COUNCIL/BOARD OF EXTERNAL EXPERTS (BEE MEETING)

Dr. David Goff, Director of the Division of Cardiovascular Sciences (DCVS) at the NHLBI, summarized the recommendations from the breakout sessions at the September 5, 2018, joint NHLBAC and BEE meeting.

During the discussion of the recommendations, NHLBAC members emphasized the need to create research mechanisms that support the acquisition of large data resources. Dr. Gibbons explained that the NIH Data Commons and Data STAGE will use a central institutional review board to facilitate addressing the specific issues of data use with the development of new technologies and platforms.  Dr. Goff reported that the NHLBI continues to support efforts through cohort studies to validate and ascertain methods for integrating data from Electronic Health Records and other phenotype measures. The NHLBI believes that such challenges need to be overcome because of the value of these data.  Dr. Gibbons mentioned the All of Us Research Program, which is building a very large cohort based on new capabilities, as a potential resource.  Dr. Goff’s presentation and Council discussion was followed by summaries that gave a brief overview of the information that was presented at the open session of the September meeting.

V. NHLBI INITIATIVES

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: Trans-Agency Blood Brain Interface Program (R33, R61)

Objectives: The goal of this initiative is to support research on the blood component and regulation of the neurovascular blood unit (aka. Blood Brain Barrier; BBB) in normal and pathological states. This initiative will also serve to stimulate the development of a new field of science and re-define the neurovascular unit to include the blood component to identify targets for diagnostics and potentially regulation of the Blood Brain Interface.

Title: Computational Approaches to Cardiovascular Developmental Biology (U01)

Objectives: To apply basic science and -omics knowledge of cardiovascular development toward the interpretation of human congenital heart disease (CHD) datasets.

Title: Pediatric Cardiac Genomics Consortium Renewal (UM1)

Objectives: The objective of this initiative is to improve the outcomes of patients with congenital heart disease (CHD) by translating discoveries of the genetic architecture of CHD into optimized diagnosis, management, and therapeutic strategies.

Title: The Women’s Health Initiative (WHI) Renewal Initiative (N01)

Objectives: The overall goal of the Women’s Health Initiative (WHI) Renewal is to continue to serve as a resource for innovative epidemiological research and to expand knowledge about the determinants of cardiovascular disease among older women, successful aging in the absence of cardiovascular disease, and maintaining quality of life in the presence of cardiovascular disease.

Title: Next generation of mammalian animal models for Vascular Contribution to Cognitive Impairment and Dementia (VCID) (R61, R33)

Objectives: This initiative is to support the development, characterization and validation of Vascular Contribution to Cognitive Impairment and Dementia (VCID) animal models that recapitulate key vascular pathologies underlying dementia etiology to facilitate basic and translational research on VCID and mixed etiology dementias (MED).

Title: Biorepository of Human Induced Pluripotent Stem Cells for Cardiovascular Diseases (N01)

Objectives: The objective of this initiative is to support an expanded biorepository of induced pluripotent stem cells (iPSCs) derived from healthy individuals and patients with cardiovascular diseases (CVDs). The initiative will focus on the development, sequencing, and distribution of cardiac iPSC lines, as well as their differentiated progeny, to facilitate understanding of disease mechanisms and development of therapeutic approaches.

Title: National Sleep Research Resource (N01 Contract)

Objectives: Prepare intensely utilized community-based sleep-specific phenotype and physiological signal data resources to be inter-operable and reusable by developing the required deep annotation of these datasets. This development is a fundamental requirement under FAIR Data Principles and transition of the data-sharing resource to NHLBI Data Stage and NIH Data Commons.

Title: A National Biorepository for Lung Disease-Specific iPS Cells (N01)

Objectives: The objective of this initiative is to support and grow a critical national biorepository of normal and lung disease-specific induced pluripotent stem cells (iPSCs) as well as their differentiated progeny to serve the lung research community. The initiative will focus on the development, characterization, and distribution of lung iPSC lines and associated progeny to facilitate the understanding of both normal human lung development and disease pathobiology. This initiative will be a limited competition.

Title: Disease Modifying Therapies for Chronic Lung Diseases (U24; R61/R33)

Objectives: In this renewal, the Pulmonary Trials Cooperative will focus exclusively on trials that test new therapeutic approaches that seek to modify (either arresting or reversing) the course of chronic lung diseases.

Title: Pulmonary Cell Resource (N01)

Objectives: This program will support a resource to harvest human lung specimens from well characterized donor subjects with pulmonary diseases and to distribute the living tissues to pre-approved researchers.

Title: Programs - Outstanding Investigator Award (OIA) and Emerging Investigator Award (EIA) (R35) Renewal

Objectives: The purpose of the NHLBI OIA and EIA R35 awards are: To provide a stable funding environment for NHLBI-supported investigators, thereby improving productivity and facilitating ambitious, creative research in Heart, Lung, Blood Diseases, and Sleep Disorders (HLBS); To increase scientific innovation by enabling flexibility in pursuing new research directions as they arise; and To reduce the time researchers spend writing grant applications and managing multiple grant awards, thereby allowing more time for conducting research, mentoring junior scientists, and producing the next generation of well-trained researchers and physician-scientists.

Title: Bold New Bioengineering Research for Heart, Lung, Blood Diseases and Sleep Disorders (R21)

Objectives: To encourage proof-of-concept research projects that are needed for the advancement of bioengineering approaches for heart, lung, and blood diseases and sleep disorders.

Title: Integrative Omics Analysis of NHLBI TOPMed Data (R01)

Objectives: The objective of this initiative is to address the continued need for support of TOPMed trans-omics data analysis. The ultimate goal is to realize the potential of TOPMed to inform precision medicine approaches to HLBS diseases.

Title: Resource to Assay the Functional Impact of -Omics Candidates (N01)

Objectives: To support medium- to high-throughput functional assays of candidate variants and molecules discovered through -omics technologies.

Title: SEARCH: Stimulating ExplorAtory Research on HIV/AIDS Contribution to Heart, Lung, Blood and Sleep Comorbidities (R01, Clinical Trial Not Allowed)

Objectives: The objective of this PA is to support exploratory and innovative research on HIV-related heart, lung, blood, and sleep (HLBS) comorbidities in order to bring new insights and deeper understanding of the pathobiology of HIV-related HLBS comorbidities in the antiretroviral therapy (ART) era. We also intend to promote productive interdisciplinary research collaborations between established and junior investigators, and reinforce interactions and communication between NHLBI and the HIV/AIDS research communities with a focus on HLBS comorbidities.

Dr. Moen explained that 13 additional initiatives from other ICs in which NHLBI plans to participate were included in the electronic council book. She also reported that the NHLBI will reissue its clinical trials FOAs so that it can continue accepting applications for clinical trials.

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 10(d) of the Federal Advisory Committee Act, as amended.

VI. REVIEW OF INTRAMURAL RESEARCH

A report prepared by the Board of Scientific Counselors (BSC), NHLBI, on NHLBI staff and intramural laboratories was presented to the Council by Dr. Douglas Wallace (former BSC Chair), University of Pennsylvania.

VII. 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 2,905 applications requesting $7,089,157,213 in total costs.  For the record, it is noted that secondary applications were also considered en bloc.

ADJOURNMENT

The meeting was adjourned at 2:15 p.m.

CERTIFICATION

I hereby certify that the foregoing minutes are accurate and complete.