National Heart, Lung, and Blood Advisory Council June 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

June 12, 2018

The 277th meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC) was convened on Tuesday, June 12, 2018, in Building 35A, the Porter Neuroscience Center Conference Center, National Institutes of Health (NIH), Bethesda, Maryland. It was open to the public from 8:10 a.m. until 12:30 p.m. Closed session began at 12:50 p.m. and ended at 2:50 p.m. Dr. Gary H. Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI), presided as Chair.

Council Members attending

Dr. E. Dale Abel
Dr. Donna K. Arnett
Dr. Michael R. DeBaun
Dr. Karen Glanz
Dr. M. Luisa Iruela-Arispe
Dr. Diane J. Nugent
Dr. Robert C. Robbins
Dr. Kim M. Smith-Whitley
Dr. Sally E. Wenzel
Dr. Phyllis C. Zee

Council Members attending via teleconference

Dr. Richard S. Schofield (ex officio)

Council Members unable to attend

Dr. Nancy J. Brown
Dr. Serpil C. Erzurum
Dr. Pilar N. Ossorio

Ad Hoc Members attending

Dr. Garth Graham
Ms. Grace A. Dorney Koppel
Dr. Monica Kraft
Dr. Dean Sheppard
Dr. Andrew S. Weyrich

Public attending

Ms. Anne Berry, Association of American Medical Colleges
Mr. Philip Goglas II, Health and Medicine Counsel of Washington
Ms. Kay Khosbayar, McAllister & Quinn
Ms. Nuala Moore, American Thoracic Society
Dr. Gabriella Ryan, American Society of Hematology
Ms. Kirstie Saltsman, IQ Solutions
Dr. Collin Stultz, Massachusetts Institute of Technology

NHLBI employees attending

A number of NHLBI staff members were in attendance.

Other NIH Institute employees attending

Julia McInenny, OGC, NIH
Breahna Blakely, OD, NIH

I. CALL TO ORDER AND OPENING REMARKS

Dr. Gary H. Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI), called the 277th 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 (DERA), 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. Dr. Moen noted that the open session was being recorded. Beginning in FY2019 we are planning to webcast the open sessions of Council meetings. She then summarized the meeting agenda.

III. REPORT OF THE DIRECTOR

New Council Members. Dr. Gibbons began by introducing the new Council members (pending final clearance), Grace Dorney Koppel, J.D., COPD Foundation and Dorney-Koppel Foundation; Garth Graham, M.D., University of Connecticut and the Aetna Foundation; Monica Kraft, M.D., University of Arizona; Dean Sheppard, M.D., University of California San Francisco; and Andrew S. Weyrich, M.D., University of Utah.

Board of External Experts (BEE). This working group of the NHLBAC is charged with ensuring that the NHLBI’s research priorities remain dynamic and responsive to the evolving scientific landscape and emerging opportunities. The Institute is inviting new expertise to the group, and new members will be introduced in September 2018.

NHLBI’s 70th Anniversary. As part of the anniversary celebration there is an ongoing lecture series. The lectures are focused on the NHLBI’s legacy of excellence in translating discoveries to improve health.

Women’s Health. The NHLBI is leveraging momentum and continuing to build its women’s health research agenda. NHLBI staff and Council and BEE members held a dialogue in September 2017 focused on research on women’s health, and Barbara Streisand gave the J. Edward Rall Cultural Lecture on May 15, 2018, where she called for gender equity in research on cardiovascular disease.

FY2018 Appropriations. Congress passed an omnibus budget, which was generous to the NIH, so the NIH is no longer operating under a continuing resolution. The FY2018 omnibus allotted $3.38 billion to the NHLBI, a 5.4 percent increase ($173 million) over FY2017. NHLBI priorities with this additional money are Research Project Grants (RPGs), Early Stage Investigator (ESI) awards, and Strategic Vision (SV) opportunities.

Sickle Cell Disease. Emerging opportunities are making a difference in finding cures for sickle cell disease (SCD). The “Nucleotides to Neighborhoods” approach, which considers both biological and sociological factors in developing therapeutic strategies, will set the stage for future advances. The Institute has been leveraging resources in the Division of Intramural Research, the Clinical Center, and the extramural program to advance SCD research. Dr. Gibbons outlined the Cure Sickle Cell Initiative, which aims to accelerate promising genetic therapies for scalable cures within five years and noted that there is significant support for the initiative across the Health and Human Services family.

Data Science—Setting the Stage. The NIH has released a data science strategic plan, a roadmap for modernizing the NIH-funded biomedical data science ecosystem. Dr. Gibbons also mentioned the NHLBI Data STAGE (Storage, Tools, Analytics for biG-data Empowerment) initiative, which is a cloudbased platform for tools, applications, and workflows that is integrated with the NIH Data Commons ecosystem. He also announced the NHLBI Big Data Analysis Challenge prize, which aims to stimulate ideas for novel analysis tools from diverse sectors.

Precision Medicine Transformative Impact. Another area of great interest is in growing the potential of precision medicine, in part through collaboration with the NIH All of Us research program. Dr. Gibbons noted that gender is the highest order of precision medicine. The TOPMed genome-phenome resource and advances in deep phenotyping are helping to propel an innovative women’s health 2.0 agenda.

IV. ACCELERATING PRECISION HEALTH FOR ALL OF US

Dr. Eric Dishman, Director, All of Us Research Program, NIH, provided an update on the program. It has progressed significantly since he last spoke to the NHLBAC in October 2016, enrolling 70,000 individuals, collecting 1 million samples in the biobank, and forming a nationwide consortium. The resource will include a rich dataset of environmental, biological/clinical, social, and behavioral information. Participants will be asked to enroll, authorize access to their electronic health records (EHRs), complete surveys, and provide physical measurements and biosamples, and in the future, data from wearables and digital applications. Dr. Dishman briefly described the plans for the portal from a researcher’s perspective and noted that access to the data, then access to samples and cohorts for ancillary studies, will begin in 2019. He also indicated that there are two paths of engagement for the ICs: investment (pilots and ancillary studies) and influence (base platform and protocol). He mentioned the support of the Liaisons Coordinating Team, which consists of representatives from the ICs.

Dr. Dishman said that there would be additional opportunities to contribute new ideas through the crowdsourcing tool. He plans to open the tool about once per year. In response to a question about diversity, he noted that the program aims to include a broad diversity of participants, both in terms of health status, and race and ethnicity. He was encouraged to partner with Historically Black Colleges and Universities and other organizations that are already there and have deep entrenched relationships in the Deep South, an area that is generally medically underserved, in order to capture this difficult-toreach population.

Dr. Gina S. Wei, Associate Director of the Division of Cardiovascular Sciences, NHLBI, highlighted the close association between the NHLBI and the All of Us program. All of Us grew out of an earlier initiative, the Precision Medicine Initiative Cohort Program. The NHLBI was critically involved in leading this earlier initiative and continues to play a major role. Dr. Wei discussed the Institute’s efforts to engage stakeholders. NHLBI leadership and staff encouraged research idea submission during a crowdsourcing push from December 2017 to February 2018, and NHLBI stakeholders were well represented at the March 2018 workshop. The NHLBI is planning a follow-up workshop in July 2018 to discuss ways to advance the Institute’s research priorities using the All of Us platform. Dr. Wei closed by saying that the NHLBI remains a committed partner of All of Us in achieving the common goal of realizing the promise of precision medicine.

V. INTRODUCTION TO THE DIVISION OF INTRAMURAL RESEARCH

Dr. Robert S. Balaban, Scientific Director, Division of Intramural Research, NHLBI, explained that he would forego a review of Division activities as he had described them in detail at the last Council meeting. He then introduced the next speaker, Dr. John F. Tisdale who has a long-standing interest in finding curative therapies for sickle cell disease. He has been a senior investigator at the NHLBI since 2007 and leads the Cellular and Molecular Therapeutics Laboratory.

VI. THE LONG AND WINDING ROAD TO CURATIVE THERAPIES FOR SICKLE CELL DISEASE

Dr. John F. Tisdale, Senior Investigator, Molecular and Clinical Hematology Branch, NHLBI began by presenting some background on Sickle Cell Disease (SCD), which was first described more than 100 years ago, and is the first disease to have been described at a molecular level. It stems from a single 4 substitution in the ß-globin chain, which leads to abnormal hemoglobin polymerization upon deoxygenation. Current therapy is limited and largely supportive, so the development of curative strategies for SCD, along with clinical trials to test them, are urgently needed.

Dr. Tisdale described bone marrow transplantation, which is a curative strategy for SCD. There are two types: (1) allogeneic, in which the transplant is from a healthy HLA-matched individual; and (2) autologous, in which a patient’s own bone marrow cells are removed, engineered to express a normal ß-globin chain, then reintroduced into the patient. He described the activities that his laboratory is working on with both types of transplantations and the encouraging results.

There are currently both bone marrow transplantation and gene therapy trials that are open and accruing patients. Dr. Tisdale closed by saying that the NHLBI Cure Sickle Cell Initiative launched in 2018 will help to accelerate progress and increase participation in clinical trials which should ultimately improve the outlook for patients.

VII. NHLBI INITIATIVES

Title: BLOODSAFE: Research to enhance blood availability and safety for patients with severe anemia and hemorrhagic conditions in low and lower-middle income countries (LMICs) (UG3/UH3 and U24)

Objectives: To support research that will enhance blood transfusion availability and safety in patients with severe anemia and hemorrhagic conditions who reside in low and lower-middle income countries (LMICs).

Title: Renewal of the Mortality Disparities in American Communities (MDAC) Study (Y01)

Objectives: The Mortality Disparities in American Communities (MDAC) Study is a linked dataset for secondary analyses of social, economic, demographic, and occupational differentials affecting health and mortality in the United States. The MDAC is available to investigators to advance the high-priority scientific interests of NHLBI and other co-funding Institutes and Centers (ICs). Co-funding ICs include the National Institute of Aging, National Cancer Institute, the Census Bureau, FDA Center for Tobacco Products and CDC National Center for Health Statistics.

Title: A Statin Primary Prevention Trial in Individuals Age 75 and Older

Objectives: This initiative proposes a joint RFA between NHLBI and NIA for a 7-year pragmatic placebo-controlled randomized clinical trial to determine the benefits versus harms of statin treatment for two composite endpoints in individuals age 75 and older who do not have clinical atherosclerotic cardiovascular disease (ASCVD). The trial would have two major composite endpoints: 1) a primary outcome of all-cause mortality, persistent disability, and dementia and 2) a major secondary outcome of a composite cardiovascular outcomes (MACE). The hypothesis is that statin treatment will reduce both composites.

Title: Multi-Ethnic Study of Atherosclerosis (MESA) Renewal (N01)

Objectives: The overall objective of the Multi-Ethnic Study of Atherosclerosis (MESA) renewal is to continue serving as a resource for novel epidemiologic research on heart, lung, blood, sleep (HLBS), and related diseases. Specific objectives are to 1) continue participant follow-up and classification of 5 cardiovascular (CV) events to increase statistical power for analyses, 2) continue core study functions, including maintaining and enabling continued access to existing data, image, and biospecimen repositories by qualifying researchers, and 3) perform a basic research examination as a platform for independently-funded ancillary studies to implement new hypothesis-driven exam components in the MESA cohort.

Title: Cardiovascular Health Study (CHS) (N01)

Objectives: This initiative is to re-establish the Cardiovascular Health Study (CHS) as a unified contract, to better align with NHLBI’s policies and Institute Leadership’s recommendation regarding stewardship of data and specimens originating from our epidemiologic studies. This contract will support infrastructure activities and maintenance of the database and biorepository. Specifically, support would be provided for (1) core functions including maintenance of various databases and data management and sharing; administrative activities; tracking of ancillary studies and publications; semiannual telephone calls to collect health-related information on participants; events ascertainment of outcomes and total mortality; limited mentoring and analytic support for scientific working groups using CHS data and (2) maintenance and sharing of bio-specimens. The contract would help support access to CHS data and specimens in order to pursue new research directions via ancillary study opportunities.

Title: Advancing Novel Research Models to Study Idiopathic Pulmonary Fibrosis (U01)

Objectives: To establish a set of complementary model systems that reproduce essential diseasedefining features of human idiopathic pulmonary fibrosis (IPF). This collection of models will advance our understanding of the pathogenesis of IPF from inception through disease progression and serve as a resource for the broader research community, including investigators developing and testing novel therapies to treat this fatal disease.

Title: Characterization of Patients with Obstructive Lung Disease that Is Not Well-Described as Asthma or COPD (U01)

Objectives: The purpose of this initiative is to characterize the overall population of adults who have obstructive lung disease, specifically including those who would be ineligible for most studies and trials of asthma or COPD because of their “atypical” disease presentation. Knowledge of the clinical characteristics of these patients and of the treatments they now receive empirically is needed to support the design of future studies that will investigate how these patients should be managed.

Title: Implementation of shared decision making for HLBS diseases and conditions (R01)

Objectives: The objective of this initiative is to support implementation research of shared decision making (SDM) strategies to improve patient-centered care for HLBS diseases and conditions. Other objectives are to understand the barriers and facilitators related to SDM strategies used to improve quality of care, adherence, informed consent, reduce health disparities, and deliver treatments best suited for individual patients.

Title: Addressing Hypertension in Low and Middle-Income Countries (UG3/UH3)

Objectives: The objective of this initiative is to take the next steps in reducing hypertension-related cardiovascular disorders by determining whether evidence-based strategies implemented at nationalor regional-levels substantially reduce blood pressure levels in low- and middle-income countries (LMICs).

Title: New Research Directions that Advance the NHLBI Strategic Vision – Normal Biology (R21)

Objectives: This FOA will support pilot studies by R01-funded investigators in areas of research that: 1) advance high priority studies of normal biology and resilience as described by Objective 1 of the NHLBI Strategic Vision; and 2) represent a new scientific direction for the Principal Investigator (PI).

Title: NHLBI Clinical Trial Pilot Studies (R34)

Objectives: To support studies that are critical, yet also sufficient to inform and complete the protocol design of Phase II or beyond clinical trials which have as their primary intent testing the efficacy, safety, clinical management, or implementation of intervention(s) in the prevention, treatment and management of heart, lung, blood, and sleep disorders.

Title: Opportunities for Collaborative Research at the NIH Clinical Center (U01)

Objectives: The goal of this initiative is to support the national translational research agenda through collaborative partnership between extramural researchers and intramural scientists and leverage the exceptional resources of the NIH Clinical Center.

Title: NHLBI Big Data Analysis Challenge Prize (N01)

Objectives: To test the effectiveness of the Challenge Prize mechanism to spread awareness of TOPMed and other NHLBI health data beyond our typical academic investigators and institutions and to promote innovative, out-of-the-box analysis approaches to address specific HLBS disease questions. In this pilot phase, the Challenge will solicit computational analyses that develop more useful diagnostic categorizations of heart failure.

Title: Rare Disease Cohorts in Heart, Lung, Blood and Sleep Disorders (UG3/UH3)

Objectives: The objective of this initiative is to establish cohorts in rare heart, lung, blood, and/or sleep (HLBS) diseases that enable multidisciplinary teams to conduct natural history and mechanistic studies that provide the evidence base for future clinical trials and improved diagnostics. These studies will help to advance fundamental insights into key molecular, genomic, environmental and lifestyle determinants of rare HLBS diseases and their outcomes leading to diagnostic and therapeutic strategies.

Title: Catalyze - Preclinical (CatPC): Advancing Development of Novel Technologies for HLBS Disorders (OT3)

Objectives: The goal of the NHLBI Catalyze Program is to provide a comprehensive suite of support and services to facilitate the transition of basic science discoveries into viable diagnostic and therapeutic candidates that have been cleared for human testing, and to develop a translational research workforce fluent in product development and entrepreneurship. Specifically, the Catalyze Preclinical initiative (CatPC) will facilitate and accelerate the development of novel technologies for the prevention, diagnosis, and/or treatment of heart, lung, blood, and sleep (HLBS) disorders from late optimization through regulatory approval filing.

Title: Catalyze - Enabling Technologies and Transformative Platforms for HLBS Research (R21, R33)

Objectives: The goal of the NHLBI Catalyze Program is to provide a comprehensive suite of support and services to facilitate the transition of basic science discoveries into viable diagnostic and therapeutic candidates that have been cleared for human testing, and to develop a translational research workforce fluent in product development and entrepreneurship. This initiative, a key component of the Catalyze program, will develop new transformative technologies and platforms to enable faster development of next-generation diagnostic and therapeutic products for HLBS diseases and disorders.

Title: Catalyze Product Definition - Small molecule and biologic target identification and validation, assay development and screening (R61, R33)

Objectives: The goal of the NHLBI Catalyze Program is to provide a comprehensive suite of support and services to facilitate the transition of basic science discoveries into viable diagnostic and therapeutic candidates that have been cleared for human testing, and to develop a translational research workforce fluent in product development and entrepreneurship. This specific Catalyze Product Definition initiative will provide the early stage translational support needed for the activities required to identify and characterize potential therapeutic candidates to treat HLBS diseases and disorders. This initiative has a companion initiative that supports development of devices and diagnostics, and is also part of a suite of innovation grants to advance projects to the point where they can meet the entry criteria for the NHLBI Catalyze Preclinical Program.

Title: Catalyze Product Definition – Device prototype design/testing and Diagnostic disease target identification and assay development (R33, R61)

Objectives: The goal of the NHLBI Catalyze Program is to provide a comprehensive suite of support and services to facilitate the transition of basic science discoveries into viable diagnostic and therapeutic candidates that have been cleared for human testing, and to develop a translational research workforce fluent in product development and entrepreneurship. This specific NHLBI Catalyze Product Definition initiative will provide the early stage translational support needed for the activities required to design and test device prototypes and/or identify diagnostic disease targets and develop associated assays for use in the treatment of HLBS diseases and disorders. This initiative has a companion NHLBI Catalyze Product Definition initiative that supports development of small molecules and biologics, and their shared goal is to advance projects to the point where they can meet the entry criteria for the NHLBI Catalyze: Preclinical Program.

Title: Catalyze Workforce Development - Short-Term Translational Research Education (R25)

Objectives: The goal of the NHLBI Catalyze Program is to provide a comprehensive suite of support and services to facilitate the transition of basic science discoveries into viable diagnostic and therapeutic candidates that have been cleared for human testing, and to develop a translational research workforce fluent in product development and entrepreneurship. This initiative will promote the development of translational research workforce though short-term research education support in cardiovascular, pulmonary, hematologic diseases, and sleep disorders research.

Title: Catalyze Workforce Development - Entrepreneurship Training Initiative (R25)

Objectives: The goal of the NHLBI Catalyze Program is to provide a comprehensive suite of support and services to facilitate the transition of basic science discoveries into viable diagnostic and therapeutic candidates that have been cleared for human testing, and to develop a translational research workforce fluent in product development and entrepreneurship. This initiative will leverage existing entrepreneurial training programs to support the training of NHLBI innovators (both academic and small business awardees) in stakeholder requirement research. The results of this stakeholder research, sometimes called customer discovery activity, will be used to refine the innovators research plans for the continued development of their technology.

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.

VIII. REVIEW OF INTRAMURAL RESEARCH

Reports prepared by the Board of Scientific Counselors (BSC), NHLBI, on the NHLBI intramural laboratories reviewed during FY 2018 were presented to the Council by Dr. Robert Balaban, Director, Division of Intramural Research, NHLBI and Dr. Collin M. Stultz (BSC Chair), Massachusetts Institute of Technology.

IX. 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 3,345 applications requesting $6,592,456,670 in total costs. For the record, it is noted that secondary applications were also considered en bloc. There were applications considered by early concurrence.

ADJOURNMENT

The meeting was adjourned at 2:50 p.m.