National Heart, Lung, and Blood Advisory Council June 2017 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 6, 2017

The 272nd meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC) was convened on Tuesday, June 6, 2017, in Building 35A, the Porter Neuroscience Center Conference Center, National Institutes of Health (NIH), Bethesda, Maryland. It was open to the public from 8:07 a.m. until 12:59 p.m. Closed session began at 1:44 p.m. and ended at 2:59 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 Arnett 
Dr. Bradford Berk
Dr. Nancy Brown 
Dr. James Crapo 
Dr. George Daley 
Dr. Serpil Erzurum 
Dr. Karen Glanz 
Dr. Diane Nugent 
Dr. Pilar Ossorio 
Dr. Kim Smith-Whitley 
Dr. Sally Wenzel 

Council Members attending via teleconference 

Dr. Michael DeBaun
Dr. Richard Schofield (ex officio) 

Council Members unable to attend

Dr. Fernando Martinez
Dr. Robert Robbins
Dr. Phyllis Zee

Ad Hoc Member attending 

Dr. M. Luisa Iruela-Aripse 

Public attending

Mr. Jeffrey Cooper, CooperSoft
Ms. Alison Evans, Lewis-Burke
Mr. Sean Ginty, Decision Lens
Mr. Ifeanyi Okechukwu, McAllister & Quinn
Dr. Yuk Fai Leung, Purdue University
Ms. Haley Payne, Health and Medicine Council
Ms. Sydney Sawyer, Decision Lens
Dr. John Greene, CSRA, Inc. 
Dr. Joe Selby, PCORI
Dr. Thomas Sors, Purdue University
Dr. Evelyn Whitlock, PCORI

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

Other NIH employees attending

Dr. John Bowers, CSR
Dr. Gene Carsteae, CSR
Dr. Gniesha Dinwiddie, CSR
Dr. Kathy Malinda, CSR

I. CALL TO ORDER AND OPENING REMARKS – Dr. Gary H. Gibbons

Dr. Gary H. Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI), called the 272nd meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC) to order and welcomed members and other attendees.

II. PATIENT-CENTERED OUTCOMES RESEARCH INSTITUTE (PCORI) AT 6 YEARS: LOOKING TO PARTNER

Dr. Joe V. Selby, Executive Director of the Patient-Centered Outcomes Research Institute (PCORI), provided an overview of his organization’s current activities and partnership opportunities.

PCORI has five national priorities for research; assessment of prevention, diagnosis, and treatment options; improving health care systems; communication and dissemination research; addressing disparities; and accelerating patient-centered outcomes research and methodological research.

To date, PCORI has distributed approximately $1.3 billion for research. The largest amount is for studies of mental or behavioral health, followed by cardiovascular disease (CVD) and cancer. Many early PCORI studies focused on systems questions, such as care transitions, use of community health workers, and health coaching.

Targeted research funding awards have addressed such topics as: treatment options for African Americans and Hispanics/Latinos with uncontrolled asthma (with involvement from the NHLBI), hypertension control in African American and rural populations (administered by the NHLBI), and care transitions for emerging adults with sickle cell disease.

PCORnet: The National Patient-Centered Clinical Research Network. PCORnet is PCORI’s largest investment to date. Much of clinical research does not answer specific questions that matter most to patients, does not generate the needed evidence to support clinical decisionmaking by patients and physicians, and is too slow and expensive. PCORnet is designed to make clinical research faster, easier, and less costly by harnessing the power of large amounts of electronic health data and patient partnerships.

PCORnet comprises 20 Patient-Powered Research Networks and 13 Clinical Data Research Networks. Each network is driven by electronic medical record data, and PCORI works with the networks to obtain claims data. A common data model codes data elements in a unified way. PCORnet has records on more than 110 million patients who have had a medical encounter in the past 5 years. The patients represent diverse racial/ethnic, socioeconomic status, age, and gender groups.

In an effort to become self-sustaining, PCORI launched The People-Centered Research Foundation on March 21, 2017. This foundation will sponsor and coordinate PCORnet in the future.

Collaboration with NIH Institutes and Centers (ICs). The Affordable Care Act requires PCORI to contract with appropriate federal agencies, giving preference to the Agency for Healthcare Research and Quality and the NIH. An example of this type of collaborative study is a comparison of second-line treatments for type 2 diabetes for patients whose glycemic control can no longer be maintained with metformin alone.

III. ADMINISTRATIVE ANNOUNCEMENTS

Dr. Laura K. Moen, Director, Division of Extramural Research Activities (DERA), NHLBI, made the required announcements for the Council meeting, including: a notice of the meeting was published in the Federal Register, Council members may not engage in lobbying activities while attending Council meetings or sponsored events, and the open session was being recorded.

IV. REPORT OF THE DIRECTOR

NHLBI Budget. Dr. Gibbons reported that he accompanied Dr. Francis Collins, NIH Director, and other IC directors to a recent House appropriations hearing focused on FY2017 activities. In the current fiscal year, the NIH received an increase of approximately $2 billion, including an additional $98 million for the NHLBI. Congress continued to express bipartisan support for NIH funding. This meeting explored such topics as broadening the NIH understanding of health disparities to include geographic disparities, the future of the Framingham Heart Study, and activities focused on chronic lung diseases, especially chronic obstructive pulmonary disease (COPD).

Congress recently passed the 21st Century Cures Act, which provides investments in the Cancer Moonshot, the All of Us Research Program, and the Regenerative Medicine Innovation Fund. The act emphasizes early-stage investigators (ESIs), the NIH Loan Repayment Programs, and the inclusion of women and minorities in clinical research.

Grant Stewardship. The NHLBI continues to conduct its business as efficiently and economically as possible as it expedites its grant approval process and nurtures the next generation of research. The Institute has increased success rates for ESIs. NHLBI has also increased its investment in the NIH Loan Repayment Programs and its stipends for physician scientists.

Support for Research on Heart, Lung, Blood, and Sleep Disorders. The NHLBI has worked collaboratively with its federal partners and broader community to develop the national COPD Action Plan in accordance with the request by Congress. This plan is very timely because this disease is the third leading cause of death in the United States and a major health burden. Mortality in women surpasses that of men, while hospitalizations and costs continue to rise. The hope is to make the same progress in COPD that has previously been made in CVD, which has seen over 70% decline in mortality over approximately the last 50 years. Much of this success is due to a better understanding of the drivers of disease and the development of targeted therapies. However, the rapid progressive decline in heart-related deaths is slowing down, and some groups are experiencing a slight rise. These data are a call to action for the NHLBI to redouble its efforts in heart disease, especially with respect to disparities by race/ethnicity, gender, and geography.

A priority is to bend the curve and return to the steep slope of declines in heart disease throughout every community in this country. Some intriguing data to inform next steps come from the recent Coronary Artery Risk Development in Young Adults (CARDIA) study. In black participants of the CARDIA study, participants who lived in areas with decreases in racial segregation over 25 years also experienced reductions their systolic blood pressure over that time. The reasons for these declines are not yet known, but these data can help the NHLBI move toward bending the curve for all communities in this nation. The NHLBI is collaborating with the PCORI on a program to test multilevel interventions to improve blood pressure control in minority racial/ethnic, low-socioeconomic-status, and/or rural populations.

The NHLBI strategic vision aligns with the trans-NIH priorities for HIV-related research, which include mitigating comorbidities. Some reports anticipate that by 2030, over 80% of people with HIV infection will have at least one comorbidity, and over 75% of patients will be diagnosed with CVD. The NHLBI plans to leverage existing HIV/AIDS cohorts focused on HIV pathogenesis for 4 studies on comorbidities. This research will provide an opportunity to understand the relationship between HIV infection and age-related disorders and determine how to influence this natural history.

The NHLBI’s strategic vision also aligns with efforts to develop cures for sickle cell disease. Genetic and cell therapies hold promise for this disease and other hemoglobinopathies. Some opportunities might be available for the NHLBI to work with the NIH Common Fund to promote the advance and implementation of new technologies in this context. The NHLBI is also investing in many extramural research resources (including the Center for International Blood & Marrow Transplant Research, Production Assistance for Cellular Therapies, BioLINCC, and Sickle Cell Implementation Program) in order to push curative therapies for hemoglobinopathies over the finish line.

Precision Medicine. The NHLBI precision medicine portfolio fits into the Institute’s strategic research priority of identifying factors that account for individual differences in pathobiology and responses to treatments. Trans-Omics for Precision Medicine (TOPMed) currently has 120,000 study participants from various cohorts. This rich data source represents diverse heart, lung, blood, and sleep phenotypes and populations. It can be used by the scientific community for multi-omics research to define the mediator pathways of these disorders and discover novel therapies. The NHLBI and the NIH are developing a community discovery platform for multidisciplinary open science. TOPMed will be a pilot for the creation of this platform, an NIH Data Commons.

V. NIH UPDATES

Dr. Lawrence Tabak, Principal Deputy Director, NIH discussed the new efforts to promote a stronger and more stable biomedical research workforce. The effort to enhance grants stewardship at the NIH is grounded in the NIH strategic plan, which calls for enhanced stewardship through, among other strategies, recruitment and retention of an outstanding research workforce and enhancement of workforce diversity.

After presenting a recent analysis that indicated research project grants (RGP) awards to midcareer investigators are declining Dr. Tabak noted the NIH has established several objectives for increasing the number of funded early-career scientists.

1. Expand the prioritization of ESIs. Because of the current NIH policy, ESI success rates are similar to those of more experienced investigators.
2. Provide new support systems to nurture investigators with 10 or fewer years of experience as NIH principal investigators who seek support for their first competitive renewal.
3. Provide new support systems to nurture investigators with 10 or fewer years of experience as NIH principal investigators who seek support for their second RPG.

All the ICs have made commitments to providing additional support for highly meritorious earlystage and mid-career investigators.

VI. NHLBI PROGRAM PROJECT APPLICATIONS (P01s)

Dr. Melissa Nagelin, Scientific Review Officer, Division of Extramural Research Activities, NHLBI explained that the program project grants (PPGs) at the NHLBI support integrated, collaborative research programs with a well-defined central research focus or objective. PPG applicants must include in their applications at least three distinct projects that investigate a complex biomedical theme or question and are led by an independent investigator or the project leader. The projects should be interrelated and synergistic. Each PPG application also includes an administrative core and may include one or more scientific cores.

There are challenges to administering the PPG portfolio. Many PPGs are long lived, and most applications submitted to NHLBI are for competitive renewals (not new programs) giving the impression that new applications are unlikely to be successful. PPGs are costlier than most other NHLBI-supported mechanisms, so the aggregate costs of this portfolio are high. Finally, many application scores cluster, making it difficult for NHLBI to make funding decisions.

To address these challenges, the NHLBI formed the PPG Working Group, chaired by NHLBAC member Dr. James Crapo, Professor in the Division of Pulmonary, Critical Care, and Sleep Medicine at National Jewish Health, and consisting of members from NHLBI’s Council and Board of External Experts. The group’s recommendations were to: continue the PPG program at the NHLBI, retain the two-tiered PPG review system but modify the tailored review scoring, increase the flexibility of multi-investigator applications research, and offer opportunities for ESIled projects in PPG applications.

The internal group proposed changes to address the recommendations in the new FOA. While reviewers will not be asked to give higher priority to PPG applications that include an ESI, ESI involvement is encouraged by the Institute.

VII. STIMULATING PATHWAYS TO RESEARCH CAREERS (SPARC): RESEARCH RESIDENCY TO FELLOW TRANSITION AWARD

Dr. Helena Mishoe, Associate Director for research training and diversity, NHLBI explained that the Advisory Committee to the Director directed the NIH to identify gaps and develop pilot programs to increase and strengthen the physician-scientist workforce across the career continuum. The committee identified opportunities for research in residency as a significant gap for this group.

The NHLBI proposes to join other ICs in support of SPaRC, a pilot program designed to encourage and retain outstanding health professionals who have shown potential and interest in pursuing a clinician-investigator career. Representatives of professional societies and licensing boards have expressed enthusiasm for NIH support for a research-in-residency program because funding for such programs is limited. Six of 24 specialty boards have research pathways, and evidence shows that participants are much more likely to enter researchpathway programs in academic medicine.

The program will be open to individuals with an M.D., an M.D. and Ph.D., or a nursing Ph.D. The initial phase of this two-phase award will provide institutional support for 1 to 2 years for research in residency, depending on the specialty. The second, transition phase will be open to participants whose promise for a career as a clinician-investigator receives a positive review. This phase will provide support for individual plans for up to 2 years of research during the participant’s fellowship.

The program emphasizes mentorship and career sponsorship, and participants may conduct any type of biomedical research, from basic to translational. The program is unlikely to lengthen the duration of participants’ residency programs, but this will depend on the program.

VIII. NHLBI INITIATIVES

NHLBI staff presented 14 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. 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 to implement.

Title: Renewing BioLINCC: Advancing Science by Building on Past Success (N01)

Objectives: This renewal will strengthen and expand the existing Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) platform to improve access to the NHLBI Biorepository and Data Repository, thereby maximizing their scientific value and utilization by the research community. BioLINCC makes available online data from over 140 clinical studies and biospecimens from 49 study collections (4.0 million vials) from NHLBI funded studies. These resources are invaluable in allowing researchers to probe the mechanisms that underpin diseases and gain new insights through secondary analyses of existing data and biospecimens, as was highlighted at the recent New England Journal of Medicine summit on sharing clinical trial data.

Title: Center for International Blood and Marrow Transplant Research (CIBMTR) Renewal: Data Resource for Analyzing Blood and Marrow Transplants (U24)

Objectives: To improve survival and quality of life (QOL) of patients with non-malignant hematologic diseases receiving hematopoietic stem cell transplants (HCT) and/or cell therapy (CT) by: prospectively collecting short term and long-term research-grade clinical outcomes data; providing the biomedical community with a high quality database and state-of-art statistical support to address important research questions; expanding the resource to include patient-reported outcomes; gathering and disseminating data necessary for health services; and collaborating with national and international networks and related fields.

Title: NHLBI Clinical Ancillary Studies (R01)

Objectives: This initiative will support investigator-initiated applications for heart, lung, blood and sleep focused ancillary studies to large ongoing clinical trials/cohorts to capitalize on the infrastructure of the parent study and expand the scientific impact.

Title: Technologies for Healthy Independent Living (R44)

Objectives: The objectives of this initiative are to improve the effectiveness of heart, lung, blood, and sleep (HLBS) disease prevention, to improve access to healthcare, and to sustain healthy independent living through home and mobile digital health technologies specifically designed for use by aging adults.

Title: Renewal of the Sudden Death in the Young Initiative (N01)

Objectives: The Sudden Death in the Young (SDY) Initiative is a collaboration between the National Institutes of Health (NHLBI and NINDS) and the Centers for Disease Control and Prevention (CDC). It was designed to address critical knowledge gaps in the epidemiology and causes of SDY and to develop a resource for research that will enhance the evidence base to inform prevention efforts.

Title: NHLBI Stewardship of MACS/WIHS-CC Research on HIV Related Co-morbidities, FY19-25 (U01, UM1)

Objectives: The NIH Office of AIDS Research (OAR) is supporting the NHLBI to become the primary Institute for a trans-NIH initiative as of FY 2019, the Multicenter AIDS Cohort Study
(MACS) and Women’s Interagency HIV Study (WIHS) Combined Cohort Study (MACS/WIHS-CCS). The MACS/WIHS-CCS initiative will enable high-impact investigations of one of the highest priorities of HIV-infection research supported by NIH: the clinical epidemiology of heart, lung, blood and sleep (HLBS) and other HIV-related co-morbidities in the antiretroviral therapy (ART) era.

Title: Shedding light on the human dark genome: Long Non-coding RNA in Cardiovascular, Lung, Blood, and Sleep Research (R01)

Objectives: This initiative will support investigator-initiated applications that will develop and validate new tools and technologies to 1) delineate the role of human long non-coding RNAs (lncRNAs) in the normal biology and pathophysiology of Heart, Lung, Blood, and Sleep (HLBS) diseases, and 2) exploit advances in lncRNA knowledge and structural biology to identify and develop novel biomarkers and therapeutic interventions for HLBS diseases.

Title: Secondary Participation in RFA-OD-17-001: Research Resource for Human Organs and Tissues (Limited Competition U42)

Objectives: The purpose of this trans-NIH initiative is to support a Research Resource for Human Organs and Tissues for the continued availability of human tissue and organs to biomedical researchers in the United States. The research resource is expected to facilitate procurement, preservation, and distribution of human tissues and organs to qualified investigators. Co-funding from NHLBI will support tissue and specimen collection, storage, and distribution for HLBS research, with a particular emphasis on lymphangioleiomyomatosis (LAM) research.

Title: Intersection Between Aging Biology and Pathobiology of Lung Diseases (U01)

Objectives: Apply a multidisciplinary approach to improve our understanding of lung biology throughout the aging process and investigate the role of normal aging in the development and progression of lung diseases.

Title: Molecular Prognostics of Sarcoidosis Progression (U01, U24)

Objectives: The goal of this initiative is to identify molecular predictors of sarcoidosis progression that will pave the way for future early interventions aimed at altering the course of the disease among sarcoidosis patients most likely to benefit.

Title: Secondary Participation in PA-17-225: Advancing the Science of Geriatric Palliative Care (R01)

Objectives: The purpose of this trans-NIH initiative is to support research focused on palliative care in geriatric populations. Participation of NHLBI in this initiative will facilitate research on how best to integrate and implement palliative care into the management of patients with HLBS diseases.

Title: Secondary Participation in NIMHD’s Simulation Modeling and Systems Science PAR to Address Health Inequities (R01)

Objectives: To join NIMHD’s PAR as a secondary participating IC. This PAR will stimulate the use of simulation modeling and systems science approaches to address health inequities in HLBS diseases and conditions. Secondary participation in this initiative will promote interdisciplinary collaboration among health researchers and experts to use computational approaches, including simulation modeling, to further the development of systems science methodologies and their application to diseases relevant to the NHLBI mission.

Title: Strategies for Stimulating Implementation Research Studies (R01)

Objectives: To stimulate late-stage T4 translation research (T4TR) which is defined as research that identifies implementation strategies to enhance sustainable uptake of evidence-based interventions into current medical settings. T4 translation research primary outcomes include acceptability, affordability, appropriateness, cost, feasibility, fidelity, penetration, and sustainability of the intervention in specific contexts.

Title: Clinician-Scientist New Faculty Research Award for Early Stage Investigators (R01)

Objectives: The Clinician-Scientist New Faculty Research Award for ESIs is intended to promote the research career independence of clinician-scientist faculty committed to academic medicine research careers with an emphasis on heart, lung, and blood diseases, and sleep disorders and related implementation research.

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.

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 3,205 applications requesting $6,631,288,276 in total costs. 161 applications were considered by early concurrence. For the record, it is noted that secondary applications were also considered en bloc.  

ADJOURNMENT 
The meeting was adjourned at 2:59 p.m.