National Heart, Lung, and Blood Advisory Council June 2016 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 15, 2016

The 267th meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC) was
convened on Wednesday, June 15, 2016, Building 35A, Room 620/630/640 at the National
Institutes of Health (NIH), Bethesda, Maryland. It was open to the public from 8:07 a.m. until
1:19 p.m. Closed session began at 1:42 p.m. and ended at 2:57 p.m. Dr. Gary H. Gibbons,
Director of the National Heart, Lung, and Blood Institute (NHLBI), presided as Chair.

Council Members attending
Dr. Bradford C. Berk
Dr. Nancy J. Brown
Dr. James D. Crapo
Dr. George Q. Daley
Dr. Michael R. DeBaun
Dr. Jonathan A. Epstein
Dr. Serpil C. Erzurum
Dr. Fernando D. Martinez
Dr. Bruce M. Psaty
Dr. Véronique Lee Roger
Dr. Anna Maria Siega-Riz
Dr. Jeffrey A. Whitsett
Dr. Phyllis C. Zee

Council Members attending via teleconference
Dr. Pilar N. Ossorio

Council Members unable to attend
Dr. Richard Schofield (ex-officio)

Ad Hoc Members attending
Dr. Diane Nugent
Dr. Kim Smith-Whitley

NIH Center for Scientific Review Employees attending
Dr. Noni Byrnes
Dr. Denise Wiesch

Members of the Public attending
Ms. Danila Cariello, Decision Lens
Ms. Carol Gersten, Decision Lens
Ms. Jade James-Gist, Lewis-Burke
Ms. Alice Kuaban, American Society of Hematology
Dr. Jennifer McCulley, IQ Solutions
Ms. Nuala Moore, American Thoracic Society
Ms. Haley Payne, Health and Medicine Counsel of Washington
Dr. Eric Schadt, Icahn School of Medicine, Mount Sinai
Ms. Taylor Swankie, Research Triangle Institute

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

I. WELCOME

Dr. Gary H. Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI), welcomed
members and attendees to the 267th meeting of the National Heart, Lung, and Blood Advisory Council
(NHLBAC) and thanked them for their service to the Institute.

II. ADMINISTRATIVE ANNOUNCEMENTS

Dr. Jodi B. Black, Acting 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. They 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 introduced his report, saying that he would update the Council on a number of topics,
including personnel transitions, budget projections, and research activities, and close his report with a
look forward.

Personnel: Dr. Black will be the next deputy director of the Office of Extramural Research, NIH.
Dr. Gibbons expressed both his sense of loss that she was leaving the NHLBI and his pride in her work
for the Institute. Dr. Valerie Prenger has agreed to serve as the acting director of the NHLBI Division of
Extramural Research Activities.

He announced three new Council members: Dr. Diane J. Nugent, the Director and Chief of Hematology
at the Children’s Hospital of Orange County and is in the Department of Pediatrics at the University of
California, Irvine; Dr. Kim M. Smith-Whitley, the Medical Director of the Sickle Cell Clinical Program, the
Clinical Director of the Division of Hematology, and Elias Schwartz, MD, Endowed Chair in Hematology
at the Children’s Hospital of Philadelphia; and Dr. Robbins, the President and Chief Executive Officer of
Texas Medical Center, who was not in attendance. Dr. Gibbons spoke briefly about each of the new
members’ backgrounds.

Budget: Dr. Gibbons updated the Advisory Council on the budgetary outlook, noting that there were
encouraging signs from Congress for the fiscal year 2017 budget. The President’s fiscal year 2017 NIH
budget is $33.1 billion, $3.1 billion for NHLBI. He itemized several management strategies for multiyear
modeling and process changes. These included a shift away from paylines and toward zones of
consideration for strategic investments, with selective pay as an adjunct approach, and with input from
the Council to help direct it. NHLBI is also working to reduce the time between the funding decision and
the award.

Strategic Visioning: Dr. Gibbons reviewed the NHLBI’s visioning. A draft has been out for public
comment and is being refined in preparation for a communication launch. It is time to pivot to decide
how to operationalize the vision by determining the most pressing research priorities for the next two
fiscal years and issuing funding announcements. Dr. Gibbons and NHLBI staff will delve much more
deeply into this process this summer to prepare the programmatic elements that will underpin this work
for presentation to Council in the fall.

A couple of areas inspired by the strategic visioning process were noted: 1) Preparing the biomedical
workforce of the future is one of NHLBI’s strategic goals and vital to NHLBI’s mission. Some compelling
questions that were discovered include how to attract students into emerging fields, such as data
science, and how to incorporate interdisciplinary and team science in training and career programs, 2)
NHLBI’s visioning process also revealed some critical ongoing challenges. Clinician-scientists make up
a shrinking pool. This is particularly troubling in the era of precision medicine, perhaps the most
propitious time to get clinician-scientists into the pipeline. How to develop them and help them
incorporate the multiple skills needed for this type of research is an area that the Institute asks that the
Council help think through. It is vital that this be done and done efficiently and effectively.

NHLBI is also challenged to help facilitate transitions between career stages. Some of NHLBI’s
mechanisms and processes are clearly isolated, whereas from the perspective of the trainee or the
early-stage investigator (ESI), this is actually a continuous process. The fragmented support makes
their transitions more difficult. To have a robust biomedical workforce for the emerging science of the
future, careful attention is needed to help bridge two difficult transitions: that between the postdoctoral
or residency phase and the early career phase and that between the early career phase and the
established career phase. NHLBI is seeking ways to build these vital bridges for clinician-scientists’
career trajectories.

Research Activities: Substantial investment in T32 training grant programs was an important goal to
Dr. Gibbons, especially because he was a product of the T32 program, but there is a challenge in the
difficulty of getting new grants funded. Only a fraction of the total T32 and T35 grants awarded to new
investigators, and there has been a decline in the number supported. Dr. Gibbons stressed the need to
look at the return on investment in these programs, to see if they can function better and serve as a hub
for launching the next generation of investigators.

Dr. Gibbons discussed the idea of a partnership between academia and NIH, one in which NIH is a coinvestor
or venture partner in investing in new faculty to help ensure that those doing research in
NHLBI’s space will have the firm foundation needed to start their careers. Another possibility would be
for NHLBI to extend residency clinical fellowship programs, developing mechanisms to allow M.D.,
Ph.D. students to get their clinical practice but then come in and reboot their research capabilities to
help them launch a research career. Dr. Gibbons asked the Council to think about such flexible
mechanisms. Dr. Gibbons spoke of refashioning the Clinical and Translation Science Awards to more
effectively leverage the training environments created in specific disease area contexts.

A final opportunity on the horizon, one on which Dr. Gibbons seeks input from the Council, is leveraging
opportunities in data science. It is imperative that NHLBI’s scientific resources be aligned with notions
of data integration, creating an infrastructure that emphasizes the importance of investigators’ ability to
move across data sets. What NHLBI funds and creates must be amenable to the data integration
process and to leveraging systems to create virtual registries as part of the digital age transformation of
medicine. It is clear that biomedicine is in an age of tsunami-like data generation, with varying
complexity and dimension. These data will be part of asking and answering questions over the next 5 to
10 years. Dr. Gibbons envisioned NHLBI as a steward of this new knowledge-generation process,
ensuring that these data are generated, used, and reused to facilitate discovery.

Dr. Gibbons envisioned a future state in which researchers from all disciplines have user-friendly but
controlled, responsible access to the integrated platforms of advanced digital services, scientific
instruments, data, knowledge, and expertise they need to collaborate and innovate to advance
biomedicine. Dr. Gibbons noted that this vision was recommended by this Council and embraced by
NHLBI in the visioning process. He wishes to move forward in developing a strategy to pursue and
facilitate this open science approach. It is time to make the transition to a secure cloud-based approach
rather than the old siloed, multi–data set dissemination-and-download model. This requires data
standardization, harmonization, and interoperability as well as development of data-sharing policies and
practices. NIH is well situated to promote this kind of data sharing and to ensure that responsible
access is available and that the different pieces work together seamlessly. This will facilitate data
sharing policies and practices and promote team science that can bring disciplines together and create
synergies.

This is a dynamic space with many players amassing data and data systems in ways that could be
enriching or could impose more silos. This is something of which NHLBI needs to be aware as it
asserts its public good-stewardship role. It is essential to assert the security and safety of these data as
well as broad access to them. NHLBI hopes to move forward to create a communal discovery platform
that can enable multidisciplinary team science. What NHLBI supports and leverages to create this
discovery “sandbox” will include things done as legacy efforts, cohorts, and clinical trials—all
investments that could be reused, particularly if they include biospecimens as part of the studies. Those
investments do not need to stop with primary journal publications. They can continue to add to scientific
advances. This may be mediated through resources like the Biologic Specimen and Data Repositories
Information Coordinating Center. This has promise, and it will be exciting to see such resources in the
cloud, with harmonized data sets and the capacity to move across these different populations and
clinical research. There are registry data and data linked to biological samples such as the National
Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions.

Dr. Gibbons hopes that in addition to phenotype and genotype data, NHLBI will create a resource
space where investigators can go from those data sets across various mouse and human models. That
is part of the vision to move forward and create a cloud-based data commons for discovery science.
This vision would leverage a great legacy of investments and make it possible in the digital age to find,
share, and access quality data with the necessary tools and analytics to facilitate discovery. These
resources would be linked to other NIH resources, including the NIH National Center for Biotechnology
Information’s Cloud, the NIH Precision Medicine Initiative’s Cloud, and/or the MVP UK Biobank,
creating interoperability between them.

Dr. Gibbons closed with acknowledgements and thanks to the strategic visioning effort; the tremendous
effort made on clinical trials in a short period; the Program Project Grants Working Group, whose
recommendations will be presented later; and the TOPMed Employee Assistance Program for input on
phenotypes, data storage, analysis, and data commons. He congratulated the OCTET Funding
Opportunity Announcement Team and the Clinical Trials Optimization Working Group, who worked
tremendously hard with staff on the multi-site, investigator-initiated clinical trials collaborative
(UG3/UH3) PAR-16-300.

IV. INTEGRATING WEARABLE DEVICE, ELECTRONIC MEDICAL RECORDS (EMR), AND
LARGE-SCALE PANOMICS DATA TO BETTER UNDERSTAND, TREAT, AND PREVENT
DISEASE

Dr. Eric E. Schadt, Director of the Icahn Institute for Genomics and Multiscale Biology at Mount Sinai
gave a presentation on integrating electronic medical data to better understand, treat, and prevent
disease. He indicated it was eye opening to see how medicine works in a big system. It used to be
many tests were run just to create revenue, but Medicine is undergoing a fundamental transformation.
With the Patient Protection and Affordable Care Act placing cost pressures on medical systems, that
model is fundamentally changing to one in which hospitals do not want to keep patients. The future of
hospital systems means pushing care into the home, with more routine monitoring and longitudinal
monitoring of patients. In terms of digital health, three major components are mobile health, the
quantified self, and health information technology to manage all the information. Dr. Schadt’s mission at
Mount Sinai is to use big data and analytics to integrate many kinds of data and build models of
disease. The question now is how to transform these big medical systems to become more efficient and
to do better for the patients.

One of the big challenges is how to acquire and manage all the data. A big investment made at Mount
Sinai was the hardware and software needed to manage Web-scale data. This included bringing
experts to Mount Sinai to help develop the Web-scalable infrastructure needed for acquiring data on a
daily longitudinal basis. Mount Sinai was also one of the first groups to partner with Apple in developing
the HealthKit, a research platform to monitor patients in a routine way. Dr. Schadt considered this
fundamentally transformative as a means of engaging individuals in research. It became possible to
enroll them in institutional review board (IRB)–approved protocols, collect biological samples for testing,
have the results returned to the subjects, and enable the subjects to share their data. All of those
elements were possible electronically.

This matters because within a couple of weeks of putting the application up in the App Store, 50,000
users downloaded it. Entry criteria were straightforward and included being diagnosed with asthma and
being on treatment, so 9,000 of those 50,000 met the criteria for enrollment in the study. In 2 weeks, it
was possible to assemble one of the largest asthma cohorts ever in the United States at practically no
cost, although it cost about $150,000 to build the app and get it into the App Store. This gives an idea
of how clinical trials could be transformed. The data included global-positioning-system tagging linked
to many other data, such as pollution levels, temperatures, and other environmental data, routinely
sampled hundreds of times a day. Data can be collected from anything that is Bluetooth enabled,
including activity monitors, scales, blood pressure monitors, and validated survey instruments as well,
such as the Asthma Assessment Test.

Dr. Schadt showed a visual representation of data after just a few weeks. He compared this to a classic
study, in which it would take several years to get a few hundred subjects, constrained by geographic
region. This study had subjects from all 50 states and could look at all the different types of asthma
medications. The app made possible the measurement of huge environmental variability, to see the
exacerbation of symptoms due to fires in the northwest, for example.

The ultimate aim of all the data collection is to be able to interpret individual patients based on many
types of data. The goal is to understand what systems or networks are disrupted and what interventions
to assign, given the disruption. That is the model toward which medicine is moving, using health graphs
to develop predictive models so that all these data can be used. On the research side, this can lead to
new targets; in the clinic, this can lead to decisions of what diagnosis is best for a patient and how the
patient should be treated. Dr. Schadt believes that the largest health systems in the world will soon own
no hospitals. The monitoring of patients where they live, where they work, and so on will be good
enough that instead of physicians with stethoscopes, there will be a big National Aeronautics and
Space Administration (NASA)–style control system monitoring all this information in real time.

Genetics is necessary but not sufficient to diagnose and treat disease, but systems biology appears to
be the path to understanding. It integrates all the dimensions of data, not just a single dimension like
DNA. The Icahn Institute for Genomics and Multiscale Biology at Mount Sinai attempts to look at all
levels, from the molecular all the way up to the ecosystem. Information flows within and across those
domains. The mission is more than understanding a disease; it is the ability to track and predict a
patient’s health course trajectory.

One of the first computational models of a living system was published by Jonathan Karr, titled Toward
whole-cell models for science and engineering. This model included every aspect of a primitive
bacterium—every gene, transcription, translation, and reactions to different environments—so that it
was possible to simulate the activity of the cell in a particular growth medium and then perturb the
genes in silico to see what they produced. Being able to perturb all the genes in a matter of seconds on
the supercomputer can enable an understanding of what is regulating cell growth, for example, and
make it possible to come up with novel hypotheses that can be tested and validated. This is a glimpse
of the future of biological research, which will be more like how physics and climatology are today.

The ultimate objective is to have predictive models to navigate a person’s health trajectory throughout
the life course. The beauty of modeling is the ability to have knowledge of which genes to be pushed to
move from a disease state to a normal state or vice versa. We are very keen to have this as the future.

Dr. Schadt concluded by acknowledging the many key partners and staff members who have made it
possible to build the ability to do this work at Mount Sinai.

V. COMPARISON OF R01s AND P01s AND PROGRAM PROJECT GRANT (PPG) WORKING GROUP UPDATE

Comparison of R01s and P01s

Dr. Michael Lauer, Deputy Director for Extramural Research, NIH gave a presentation comparing R01
grants to P01 grants. He started by indicating that there has been a fair amount of discussion on how to
measure scientific output. Dr. Lauer briefly explained the PQRST mnemonic method, P = productivity
as measured by publications and highly cited papers, Q = quality, R = replication, S = sharing, and T =
translation. He explained that the use of publications and citations for evaluating impact is called
bibliometrics. This technique is somewhat controversial because raw citations do not really tell much of
a story. One important problem is that fields vary greatly in how frequently papers are cited. For
instance, papers in the field of cardiology are cited much more frequently than papers in mathematics.

Dr. Lauer compared the productivity of NIH-funded R01 and P01 grants by looking at these types of
grants’ association with the production of highly cited papers. He used data from all type 1 grants
funded between 2000 and 2010 and followed these grants throughout their lifetimes. If they were
renewed, he continued to follow them. All of the data came from the internal NIH IMPAC II (Information
for Management, Planning, Analysis, and Coordination) system, and the papers were matched to the
grants through SPIRES+ (Scientific Publication Information Retrieval & Evaluation System). These are
publicly available databases containing every known paper linked to an NIH grant back to 1985. The
citation statistics were obtained from Thomson Reuters.

In the first analysis, the median for P01 papers is the 75th percentile and that for R01 papers is
somewhat less. This means that half of the P01 papers were cited more often than 75% of the same
type of paper in the same year, whereas the median of the R01 papers is a bit less. A large proportion
of papers produced by both types of grants are cited more often than others of their type, but the P01
mechanism does a bit better. Dr. Lauer noted that it would be cause for concern if the picture did not
look something like this because the P01s receive more money.

The second analysis looked at impact per $1 million spent. When looked at this way, the median
citation impact of the two types of grants is about the same. However, the P01 distribution is very
narrow, meaning that there are few grants with low impact by this measure, whereas many R01s are
not very productive by the same measure. It is also noteworthy that few R01s have high impact when
looked at this way. A problem with this analysis is that these two types of grants are not the same. A
P01 is a collection of projects, each with a budget similar to an R01. The data available link papers to
grants, so it is impossible to link papers to specific subprojects within a P01. As an approximate
adjustment for this, the next analysis estimated that a P01 is six times an R01, so each P01 grant was
divided into six “units,” with each unit equivalent to an R01. When these data are plotted in the same
way as before, P01 grants are still marginally better.

Dr. Lauer summarized, noting that P01s are more expensive, have better-established investigators,
have a history of funding, and are more likely to be reviewed favorably. By these analyses, using
papers as the unit of analysis, P01s are a bit better in that they have a higher citation impact. They may
have a slightly higher impact per unit of money as well. There are many caveats to be considered;
R01s and P01s are not the same. They have different structures and a different type of investigators.
These analyses have been an attempt to adjust for the various confounders. They show that the overall
productivity of the two mechanisms is largely comparable, but if anything, P01s have less spread and
are somewhat higher in their productivity.

Program Project Grant (PPG) Working Group Update

Dr. James Crapo, Professor, Division of Pulmonary, Critical Care, and Sleep Medicine, National Jewish
Health presented an update on the PPG Working Group. The Working Group’s charge was to
recommend (1) criteria by which the value of the PPG program could be assessed, (2) policies that
would optimize the PPG peer review process, (3) new approaches for stimulating or promoting multiinvestigator
science, (4) ways to enhance support for early-stage investigators (ESIs), and (5)
improvements concerning solicitation and funding of PPG applications.

Currently, PPGs have a funding cap of $1.515 million, or 105% of the prior year’s funding for renewals.
Each PPG must have a minimum of three subprojects along with needed cores. In review, the
individual subprojects are scored as standalone grants, and the cores are approved but not given a
score. The PPG peer review process consists of essentially three tiers. The first is a tailored review
committee, which includes two members of the Parent Committee and a number of ad hoc reviewers.
This group scores the subprojects and discusses the overall PPG’s synergy. Applications then go to the
Parent Committee. Some are withdrawn, and the Parent Committee reviews about 30 to 40 per year.
This group gives each application a final Impact Score. Then applications go to the Council and staff for
funding decisions.

In fiscal year 2014, there were 63 applications, 13 were funded and of those, 9 had a perfect score. In
fiscal year 2015, 17 of 60 were funded, but only 1 of those 17 did not have a perfect score. Virtually all
of the funded grants had a perfect score.

What seems to have caused this problem was that an application would come to the Parent Committee
from the first-tier review with an average score of 1.5 for the subprojects. The Parent Committee must
give a single overall score, and because they can only give an integer score, they can only give
applications a score of 1 or 2 in such cases. They all wish they could use a tenth-point scale, allowing a
final score of 1.3 or 1.7, for example. The current funding problem seems directly related to this lack of
ability to discriminate between grants in a fine-grained manner.

Dr. Crapo moved on to a series of recommendations.

Recommendation 1 is a unanimous endorsement of the PPG program’s unique value. It enables largescale
science and ambitious projects, has high productivity, and does much more. The PPGs are a
unique asset to NHLBI. They provide training environments and enhance the credibility of host
institutions. They change investigators’ ability to obtain resources at the local institution and they
change the national and international reputation of both the host institution and NHLBI.

Recommendation 2 concerns ways to tackle the difficult problem of changing the scoring system. The
group recommends that no score be given by the tailored review committee for the subprojects. They
recommend modifications to the two-tier review system, including the following: the first-tier review will
discuss the subprojects and give a scoring range for each. In addition, the review group will give a
written summary of the overall PPG applications potential innovation, impact, value, and importance.
This will allow the Parent Committee to use a broader scoring range. These changes will help the
scores to be more naturally spread. The minimum cutoff score for funding should not be made public.
This will restore the community’s confidence in being able to compete. Another question is how to
improve communication between the tailored review group and the Parent Committee. Possibilities
include adding an additional Parent Committee member to the tailored committee, adding an ad hoc
expert, and possibly reinstating reverse site visits to enhance communication in the review process.
This should be a primary goal. The Working Group also recommends an obligation for the Parent
Committee to rank applications that end up with tied scores.

Recommendation 3 is to increase the flexibility of multi-investigator applications. As one example of
how this might happen, the Working Group proposes what it calls a Horizon Award. Instead of a PPG
consisting of three separate subprojects, this award would be for one integrated initiative whose
“subprojects” would not be separate, but would instead be components essential to the topic, none of
which could stand by itself. The proposal is for a funding cap of $2 million/year direct. This award is an
attempt to recognize where science is today. This would not just be three projects with a similar theme,
but instead a single interesting and powerful award that could focus multiple cutting-edge disciplines on
a single important question. The proposal is that this would be in addition to the current PPG program,
not replace it.

Recommendation 4 concerns the need for greater support for ESIs in the PPG program. The idea is to
offer the option of supplemental awards for ESIs. If submitted with the initial application, these
supplemental awards would be reviewed with the PPG application but would not count in its score. The
funding cap for one of these supplemental awards would be $200,000. Because this would be a
supplemental award, it would not take away a person’s ESI status, but it would put the investigator on
the PPG team. This is a novel and potentially successful way to support new investigators.

Recommendation 5 is a series of policy recommendations. First, the group recommends a limit on the
number of renewals for which a PPG can apply, they should be funded for no more than 10 or 15 total
years. The investigators could assemble a new team and project and compete with other new
applications. Secondly, the cores, including the administrative core, should not be mandatory and
should be evaluated on the basis of being essential to the projects and not duplicating resources
already available at the institution. Cores can be very important for some PPGs, but not all PPGs need
them. Finally, the group believes strongly that there should be no fixed ratio of funded heart, lung,
blood, or sleep applications. The most meritorious applications should be funded, regardless of
scientific area.

Dr. Crapo invited other Working Group members to add their thoughts to the recommendations and
thanked the group and NHLBI staff whose work made the report possible.

VI. NHLBI INITIATIVES

NHLBI staff presented 17 initiatives, all of which had been reviewed in April 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: Integrated Approaches to HIV-related Cardiovascular, Pulmonary, and Hematological
Diseases (R01)

Objectives: The objective is to support coordinated “systems biology” approaches using clinical
samples from HIV-infected patients to elucidate the biological perturbations underlying HIV-related
heart, lung, and blood (HLB) disorders.

Title: Sleep Health and Circadian Biology in HIV-Related Comorbidities (R01)

Objectives: To elucidate sleep and circadian mechanisms implicated in the etiology of prevalent HIV
comorbidities, complications, and failure to sustain medical health.

Title: NHLBI Research Career Development Program in HIV-Related Heart, Lung, Blood and
Sleep Research (K12)

Objectives: The overall goal is to encourage institutions to develop and sustain programs that support
inter-disciplinary, intensive mentored research training and career development for junior Ph.D.s and
M.D.s in AIDS comorbidities as well as cell and gene therapies for HIV cure and prevention of HIV
transfusion transmission.

Title: imPlementation REsearCh to DEvelop interventions for people living with HIV (PRECluDE)
(U01)

Objectives: The goal is to stimulate implementation research in the delivery of proven effective
interventions for comorbid heart, lung, blood, and sleep (HLBS) diseases and conditions in people living
with HIV/AIDS (PLWHIV) domestically. This initiative will support collaborative research teams
composed of multidisciplinary partners, (e.g. public health researchers, policy makers, academic and
health system delivery researchers and others) to conduct locally or regionally identified high priority T4
implementation research focused on addressing HLBS comorbid diseases and conditions for PLWHIV.
For this proposal, T4 implementation research for the prevention, treatment, and control of HLBS
diseases and conditions in PLWHIV using proven effective interventions will be encouraged.

Title: Secondary Dataset Analyses in Heart, Lung, and Blood Diseases and Sleep Disorders
(R21)

Objectives: This funding opportunity aims to stimulate the use of existing human datasets for wellfocused
secondary analyses to test innovative hypotheses concerning the epidemiology,
pathophysiology, prevention or treatment, and implementation of evidence-base interventions for HLBS
diseases/conditions relevant to the NHLBI mission. Analyzing existing datasets provides a cost
effective method to address research questions and generate preliminary data for subsequent research
proposals.

Title: Small Research Grants for Analyses of Gabriella Miller Kids First Pediatric Research Data
(R03)

Objectives: To catalyze discovery of new genetic variants underlying structural birth defects or
childhood cancer by supporting analyses of whole genome sequence datasets that are being generated
as part of the Gabriella Miller Kids (Kids First) Pediatric Research Program. Another important goal of
the initiative is to generate preliminary data that can be used to support larger, investigator-initiated
projects focused on functional studies. This initiative is a trans-NIH funding announcement, led by
NICHD, and will involve a partnership of multiple Institutes.

Title: Basic and Translational Research in Calcific Aortic Valve Disease (R01)

Objectives: To extend our knowledge of the pathobiology of calcific aortic valve disease (CAVD) to
improve therapy and diagnosis.

Title: Addressing the Barriers and Challenges Related to Cardiovascular Research in the Prison
Population (R21/R33)

Objectives: This initiative focuses on two areas: 1) Research that explores the barriers to data
collection on cardiovascular disease (CVD) and CVD risk factors in the prison population via a planning
grant (R21) and 2) Research comparing subjective data collection (survey questions) on CVD and CVD
risk factors to objective measurements such as height, weight, blood pressure, cholesterol and glucose
in the prison population via a demonstration project (R33).

Title: Circadian Mechanisms of Obesity Underlying Heart, Lung, and Blood Disorders (R01)

Objectives: To elucidate circadian-dependent mechanisms contributing to the risk of obesity and
identify potential therapeutic targets associated with heart, lung, blood and sleep disorder morbidity.

Title: Placental Determinants of Early Lung Health and Disease (R01)

Objectives: The primary purpose is to determine the role of the placenta in early lung health and
disease. Experts in pregnancy, the placenta, and offspring will be essential. Investigators will test
hypotheses of biological mechanisms that influence early postnatal lung structure and function by
analysis of human placentas. The ultimate goal is to develop novel approaches for the detection and
modulation of placental function and dysfunction that could improve lung health and the prevention of
lung disease.

Title: Using Electronic Health Records to Better Understand Sarcoidosis: A Pilot Study (U01)

Objectives: The goal of this pilot project is to integrate and analyze clinical data from diverse medical
centers across the U.S. to more comprehensively and accurately assess sarcoidosis disease burden in
this country as well as to better understand various sarcoidosis complications and “real world”
treatment practices. This line of research is expected to provide information needed to reduce health
disparities and improve patient outcomes in sarcoidosis.

Title: Cardiopulmonary Research on E-Cigarettes (R01)

Objectives: The goal of this initiative is to stimulate research on the effects of e-cigarette aerosols and
constituents on the cardiovascular and/or pulmonary systems.

Title: Renewal of SPIROMICS Genomics and Informatics Center and Biorepository (N01)

Objectives: To maintain basic functions of the SPIROMICS Genomics and Informatics Center,
including: 1) data storage and dissemination; 2) biorepository maintenance and biospecimen
dissemination; 3) minimal contact required to maintain the SPIROMICS cohort; and 4) data analysis
and biostatistics support for investigators.

Title: Secondary participation in PAS-16-033 and PAS-15-168: Stimulating Hematology
Investigations and New Directions in Hematology Research (R01)

Objectives: The objective of this initiative is to join NIDDK’s two closely related FOAs in an effort to
increase the number of hematology research applications and grants at NHLBI on key scientific topics.

Title: Maximizing the Scientific Value of the NHLBI Biologic Biospecimen Repository: Scientific
Opportunities for Exploratory Research (R21)

Objectives: The objective of this RFA renewal is to continue to maximize the scientific value of the 44
unique biospecimen collections (12 heart, 12 lung, and 20 blood) stored in NHLBI Biologic Biospecimen
Repository (NHLBI Biorepository) and to promote use of this resource by investigators early in their
career. The RFA will provide two years of funding through the R21 mechanism for meritorious
applications utilizing the stored biospecimens in NHLBI Biorepository and encourage applications from
Early Stage Investigators (ESI) by taking ESI status into consideration, thereby supporting the
development of the HLBS scientific workforce.

Title: Perinatal Stroke (R01)

Objectives: The proposed initiative supports basic and translational research addressing normal
neurovascular development, and the blood related etiologies and outcomes of perinatal stroke. Its
ultimate intent is to stimulate research that identifies non-neuronal therapeutic targets in perinatal
stroke.

Title: Sex Hormone Induced Thromboembolism in Women (R61/R33)

Objectives: The primary objective of this initiative is to understand the mechanisms by which female
sex-hormones and hormone-based therapies increase the risk of venous and arterial thromboembolism
(TE) in premenopausal women. This knowledge will strengthen our understanding of the mechanisms
underlying thrombus formation under conditions of endogenous hormonal perturbation (e.g.,
pregnancy), and, separately, under conditions of exogenous hormonal supplementation, e.g.oral
contraceptive (OCA) use. This initiative focuses on pre-menopausal women, rather than on postmenopausal
women, to better discriminate hormone-induced mechanisms of thrombus formation from
those more likely related to the presence of other comorbid conditions that increase with age. The
mechanistic knowledge gained from this initiative could inform the development of biomarker-driven
thrombotic risk assessment and individualized strategies for risk-minimizing therapeutic intervention, as
well as guide the identification of novel female sex-hormone therapeutics with significantly decreased
potential for TE in premenopausal women.

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 3,293 applications
requesting $5,017,778,910.

ADJOURNMENT

The meeting was adjourned at 2:57 p.m.