National Heart, Lung, and Blood Advisory Council October 2015 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 28, 2015
 
The 265th meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC) was
convened on Wednesday, October 28, in Building 31, Conference Room 6C6 at the National
Institutes of Health (NIH), Bethesda, Maryland. It was open to the public from 8:08 a.m. until
12:00 p.m. Closed session began at 12:24 p.m. and ended at 1:48 p.m. Dr. Gary H. Gibbons,
Director of the National Heart, Lung, and Blood Institute (NHLBI), presided as Chair.

Council Members attending
Dr. James D. Crapo
Dr. Pamela S. Douglas
Dr. Serpil C. Erzurum
Dr. Ron G. King
Dr. Barbara A. Konkle
Dr. Fernando Martinez
Dr. Pilar Ossorio
Dr. Bruce M. Psaty
Dr. Véronique Lee Roger
Dr. Jeffrey A. Whitsett
Dr. Phyllis C. Zee

Council members attending by teleconference
Dr. Bradford C. Berk
Dr. Nancy J. Brown
Dr. Michael R. DeBaun
Dr. Jonathan A. Epstein
Dr. Anna Maria Siega-Riz

Council Members unable to attend
Dr. George Q. Daley

NIH Center for Scientific Review attending
Dr. Larry Boerboom
Dr. John Bowers
Dr. Eileen Bradley
Dr. Jan Li
Dr. D. Scott Wright

Members of the public attending
Dr. Patrick Cooke, IQ Solutions
Dr. Nicole Garcia, IQ Solutions
Dr. Phillips Goglas II, Health and Medicine Counsel of Washington
Dr. Madeline Halpern, ICF
Dr. Jennifer McCulley, IQ Solutions
Dr. Nancy R. Moy, SRI, International
Dr. Taylore Swankie, RTI International
Dr. Jennifer Tripp – Muscular Dystrophy Association
Dr. Robert Yates, A-Tek
Ms. Debbie Yu, DecisionLens

NHLBI employees attending
A number of NHLBI staff members were in attendance.

I. CALL TO ORDER

Dr. Gary H. Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI),
welcomed members to the 265th meeting of the National Heart, Lung, and Blood Advisory
Council (NHLBAC).

II. ADMINISTRATIVE ANNOUNCEMENTS

Dr. Stephen C. Mockrin, Director, Division of Extramural Research Activities (DERA), NHLBI,
made the standard administrative announcements and outlined the agenda for the Council
meeting. A notice of the meeting was published in the Federal Register. Members were
reminded about conflicts of interest and the need to absent themselves during review of any
application if their presence would constitute or appear to constitute a conflict of interest.
Members may not engage in any lobbying activities while attending Council meetings or
sponsored events. Members were reminded to sign and return a conflict of interest form at the
end of the meeting.

III. REPORT OF THE DIRECTOR

Dr. Gibbons began by noting Dr. Michael Lauer’s departure as Director of the Division of
Cardiovascular Sciences (DCVS) to assume the role of Director of the Division of Extramural
Research at the National Institutes of Health (NIH). Dr. Gibbons remarked that it will be difficult
to replace Dr. Lauer and thanked Dr. George Mensah for filling in as Acting Director of DCVS.
He then remarked on the following topics:

Capitol Hill Developments—Dr. Gibbons noted recent signals that Congress would like an NIHwide
strategic plan. He also reflected on Congressional interest in Alzheimer’s disease
research, noting that the NHLBI can play a role in this area because evidence suggests that
vascular disease, heart health, and sleep may all affect the development of Alzheimer’s
disease.

NIH HIV/AIDS Priorities—The NIH is re-examining how it invests funds in HIV and AIDS
research, and Dr. Gibbons stated that such a re-examination may present an opportunity to the
NHLBI to continue to invest in HIV-related research related to comorbidities associated with the
condition, such as heart disease. Individuals infected with HIV have an increased risk for
cardiovascular disease.

R56 Awards—Dr. Gibbons commented on the success of the R56 bridge awards in sustaining
the research funding of meritorious established laboratories and early-stage investigators who
would otherwise suffer a gap in funding. Dr. Gibbons described analysis showing that those who
received the bridge awards largely went onto success in receiving R01 funding.

Balanced Approach to Funding—Dr. Gibbons indicated that the Institute is developing a new
approach to funding researchers that balances a respect for the peer review scoring system
with greater flexibility to award grants to those projects that do not meet the score cutoff but
nonetheless would advance the NHLBI mission by, for example, stimulating needed research.
The Institute is developing criteria that would guide funding decisions for those applications
below the minimum score, and these criteria will be made clear to grant applicants.

Clinical Trial Funding—Dr. Gibbons described the work of an internal group, which includes
Council members, that is re-examining how the Institute funds clinical trials. The goal of the
group is to identify policies and practices that enable Institute-supported clinical trials to be more
effectively run and to result in greater value to the public.

NHLBI-Supported Science—Dr. Gibbons closed his report by discussing exciting NHLBIsupported
scientific developments, including the recently closed SPRINT trial and the
developing TOPMed program.

IV. DIVISION OF INTRAMURAL RESEARCH PRESENTATION: FETAL HEMOGLOBIN –
FROM GENETICS TO MOLECULAR MECHANISMS AND TARGETED THERAPY

Dr. Robert Balaban, Scientific Director of the NHLBI Division of Intramural Research (DIR),
introduced the next presenter, Dr. Swee Lay Thein, who recently started a new sickle cell
disease research program in DIR. Dr. Thein discussed the genetics of hemoglobinopathies,
recent research discoveries, and promising genetic targets for new therapeutic approaches.

The beneficial effect of fetal hemoglobin (HbF) in thalassemia and sickle cell disease has been
a major driving force for the study of hemoglobin switching and therapeutic approaches for its
reactivation. The globin chains that make up the hemoglobin proteins are encoded by genes
found in two separate clusters. These genes are arranged in the order of their developmental
expression pattern.

The transition from fetal to adult hemoglobin production, referred to as hemoglobin switching, in
humans, occurs around the time of birth but it is not complete because variable residual
amounts of HbF continue to be produced throughout adult life. Persistent expression of the
endogenous γ globin genes has major beneficial effects on the clinical severity of β thalassemia
and sickle cell disease, disorders with substantial morbidity and mortality worldwide. Clinical and
twin studies have shown that HbF persistence in adults is largely genetically controlled.

Applications of the “new” genetic, genomic, transcriptomic and proteomic approaches have
provided new insights into the developmental regulation of the fetal and adult globin genes, and
identified specific transcription and epigenetic regulators modulating HbF variation in adults as
potential molecular targets for therapeutic modulation of fetal hemoglobin.

As always, however, substantial hurdles remain in achieving specificity of effect and adequate
therapeutic window. Optimal HbF modulation may well involve a combination of different
strategies and molecular targets.

V. NHLBI INITIATIVE CONCEPTS

NHLBI staff presented 14 initiatives, all of which had been reviewed in September by the Board
of External Experts (BEE), a working group of Council. Initiative development at the NHLBI is a
two-cycle process. First, extramural program staff develop ideas and potential initiatives, which
they present to the trans-NHLBI Idea Forum. Sufficiently developed initiatives are subsequently
considered by the BEE, which provides advice to Council.

Members were generally supportive during detailed discussions, but had a number of questions
and recommendations for consideration prior to their approval. The Director, NHLBI, will
consider the recommendations of the Council, as well as other budgetary and programmatic
issues in determining which of the proposed initiatives, if any, to implement.

Title: Small Market Awards: SBIR Phase IIB Competing Renewals for Heart, Lung, Blood, and
Sleep Technologies with Small Commercial Markets (R44)

Objectives: The purpose of the NHLBI SBIR Phase IIB Small Market Award is to support
technology development for rare HLBS diseases and/or pediatric populations. There are two
primary goals: to fill a gap in early-stage funding for technologies with these small commercial
markets; and to create public-private partnerships that enhance the return on the NHLBI
investment in the small business program.

Title: New Methods to Assess Cardiotoxicity of Therapeutic Agents (R41/42, R43/44)

Objectives: The goal of this initiative is to develop new and improved methods to assess,
monitor, or predict the cardiovascular toxicity of therapeutic agents. Improving cardiovascular
toxicity-risk assessment methods will a) improve safety and efficacy of therapeutics; b)
accelerate translation of research findings into clinical applications; and c) enable development
of new and more effective cardioprotective measures for existing therapies that are effective at
treatment but are known to pose significant cardiovascular risk.

Title: NHLBI Exploratory Bioengineering Research Grants (R21)

Objectives: The goal of this initiative is to encourage basic, translational, and clinical proof-ofconcept
research projects that are needed for the advancement of bioengineering approaches
for heart, lung, and blood diseases.

Title: Secondary Participation in PAR-15-346: Time-Sensitive Obesity Policy and Program
Evaluation (R01)

Objectives: The objective of this initiative is to join the renewal of NIDDK’s PAR 15-346 Time-
Sensitive Obesity Policy and Program Evaluation (R01) (http://grants.nih.gov/grants/guide/pafiles/PAR-15-346.html).
This PAR supports a review/award process to fund time-sensitive research to evaluate a new policy or
program expected to influence weight outcomes and/or obesity-related behaviors (e.g., dietary intake, physical
activity, or sedentary behavior) in an effort to prevent or reduce obesity.

Title: Integration of Host-Pathogen Multidimensional Omics Data to Understand TB Latency and
Reactivation in the Lung (R01)

Objectives: This Topic of Special Interest (TOSI) is to support studies that integrate
computational and experimental approaches to address major questions in the lung biology of
tuberculosis, with a focus on host responses to the pathogen Mycobacterium tuberculosis (Mtb)
and the mechanisms that lead to latency and reactivation.

Title: Precision Interventions for Severe and Exacerbation-Prone (PrecISE) Asthma Network
(U10)

Objectives: The objective of this program will be to conduct early-phase clinical trials to test
the safety and/or efficacy of interventions in stratified patient populations for the treatment of
severe and exacerbation-prone asthma.

Title: The Impact of Microenvironment of Lung Progenitor Cell Function (R01)

Objectives: The goal of this initiative is to understand the impact of microenvironment on lung
progenitor cell function during development, homeostasis, injury repair and regeneration.

Title: The NHLBI’s Trans-Omics Precision Medicine (TOPMed) Program: Systems Approaches
for High Throughput Analyses of TOPMed Data (R21)

Objectives: The goal of this initiative is to support the development and application of novel
methods for analyzing extensive, high-dimensionality data like that generated in NHLBI’s
TOPMed program. These methods will use systems approaches to maximize the biological
information and insight that can be gained from analysis of large genomics datasets.

Title: The Role of Dysbiosis in Cardiovascular, Pulmonary, and Hematological Complications
During HIB Infection (R01)

Objectives: The goal of this initiative is to support studies that evaluate the role of HIV-induced
dysbiosis (microbial imbalance) and how it contributes to or affects the occurrence of heart,
lung, and blood co-morbidities in infected patients.

Title: Blood and Marrow Transplant Clinical Trials Network (BMT CTN) II (U10)

Objectives: The goal of this initiative is to advance hematopoietic cell transplantation (HCT) for
all patients, but particularly for patients with rare and difficult to treat blood diseases. This will be
accomplished by using novel cell and gene therapy approaches and through advances of
traditional HCT approaches.

Title: Human Parvovirus B19 Vaccine for Sickle Cell Disease (N01)

Objectives: The initiative’s long term objective is to develop a human parvovirus B19 vaccine
that will protect individuals with sickle cell disease from serious infection associated
complications. The intent of the RFP proposed herein is to help support early stage
development by facilitating the manufacture of clinical grade vaccine.

Title: Hypertension Outcomes for T4 REsearch within Lower Middle-Income Countries (Hy-
TREC) (UH2/UH3)

Objectives: The goal of Hypertension Outcomes for T4 REsearch within Lower Middle-Income
Countries (Hy-TREC) is to catalyze in-country T4 collaborative research teams that will study
strategies to broadly implement evidence-based interventions that can accelerate regional and
national hypertension treatment and control. These in-country collaborative research teams
composed of trans-disciplinary researchers, public health researchers, government
representatives (e.g. ministries of health), in-country academic and health institution
researchers and others, will conduct locally identified high priority T4 research for hypertension
control.

Title: NHLBI Research Career Development Programs in T4 Implementation Research (K12)

Objectives: The goal of this program is to build a new trans-disciplinary dissemination and
implementation (D&I) research workforce to investigate strategies that, when scaled up improve
health outcomes for NHLBI-related diseases and conditions and also reduce or eliminate health
inequities.

Title: NHLBI T4 Translation Research Initiative (T4TRI): Strategies to Enable ImPlementation
REseArch StuDies (SPREAD) (U01)

Objectives: The overarching goal of Strategies to Enable ImPlementation REseArch StuDies
(SPREAD) initiative is to serve as a catalyst for advancing T4 translation research (T4TR).
T4TR investigates approaches to promote sustained uptake of effective interventions in clinical
practice- and community-based settings. The SPREAD initiative will be implemented via two
linked Request For Applications (RFAs). One RFA will support the establishment of a Central
Management Core (CMCor), and the other will support three meritorious applications that
address hypertension treatment.

VI. LOAN REPAYMENT PROGRAM

Dr. James Kiley, Director, Division of Lung Diseases, provided the annual look at the Institute’s
support of the NIH Loan Repayment Program (LRP). NHLBI received 325 applications – 222 of
which were clinical and 103 were pediatric. More applications were funded in each area than in
previous years, which translated into an increased success rate. NHLBI committed $12.6 million
to the LRP.

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 (5 U.S.C. appendix 2).

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 1801 applications requesting $3,095,084,322.

ADJOURNMENT

The meeting was adjourned at 1:48 p.m.