NATIONAL HEART, LUNG, AND BLOOD ADVISORY COUNCIL

I. CALL TO ORDER AND OPENING REMARKS

Dr. Gibbons called the meeting to order at 8:07 a.m.  He told members that they would be engaged in priority setting during the meeting in a very substantive way that would create a more data-driven approach to resource allocation and return on investments.

II. ADMINISTRATIVE ANNOUNCEMENTS

Dr. Stephen C. Mockrin, Director, Division of Extramural Research Activities (DERA), made the standard administrative announcements and outlined the agenda for the Council meeting.

Three new members were introduced and joined the meeting as ad hocs because their clearance is still in progress.  It is hoped all will cleared by the September meeting:

• Dr. Bradford Berk, Professor of Medicine, Cardiology, and Pharmacology; Senior Vice President for Health Sciences and CEO; University of Rochester Medical Center
• Dr. James Crapo, Professor of Medicine, Division of Pulmonary Critical Care and Sleep Medicine, National Jewish Medical and Research Center
• Dr. Fernando Martinez, Swift-McNear Professor of Pediatrics, Director of Arizona Respiratory Center, University of Arizona

III. REPORT OF THE DIRECTOR

Dr. Gibbons provided an update of the June 2013 Council meeting discussion about NHLBI’s role in systematic evidence reviews and clinical guidelines. The transition to a collaborative model with the American Heart Association, American College of Cardiology, and other professional societies has already resulted in the release of the cardiovascular guidelines, which are accessible on the NHLBI website.

Fiscal Update:  Dr. Gibbons reviewed the impact of the partial government shutdown, sequester and the current budget compromise.  The sequester resulted in an approximately 5% cut to the 2013 budget and a residual 2% cut in the non-competing budget line relative to fiscal year 2012.  Although the compromise increased the 2014 budget by approximately 2.5% over 2013, it is still below the 2012 baseline. The Institute has tried to mitigate the impact on new competing awards, and although tentative, the anticipated R01 payline will be at least at the 11^th percentile, an improvement over the 2012 baseline. Young researchers will be protected in two ways:  Early Stage Investigators’ payline will be held at the 21st percentile and the Institute will try to maintain the Career Development Mechanism (K awards) success rates in the 20s.

Strategic Planning:  Dr. Gibbons spoke about actively engaging Council as the Institute moves toward a more prospective, strategic approach. It will integrate a five-year modeling approach to account for all out-year commitments. Council will be actively involved in balancing the Institute’s portfolio ─ maintaining as large an investigator-initiated R01 pool as possible and achieving a balance of investigator-initiated science and Institute initiatives.  A five-year budget model would provide a way to make out-year commitments and provide some predictability going forward.  Dr. Gibbons spoke of the need to make strategic, short-term investments with this one-year spike of funds, which could present a strategic opportunity to invest in resources requiring short-term seed capital that promote investigator-initiated science over the long term.

Research Portfolio: Dr. Gibbons outlined several opportunities to reshape what science will be for the NHLBI over the next five to 10 years.  The NHLBI is poised to integrate heart, lung, blood, and sleep clinical phenotypes with a systems approach to leverage clinician expertise with in-depth omics analytics, other phenotype capabilities, and imaging.  The growth of digital technology and big data will enable the layering of multidimensional elements into integrated datasets to create what the Institute has dubbed “systems medicine data commons” ─ taking basic clinical and population science and integrating it in new ways; having cellular and animal models, human subjects, and datasets that cross traditional boundaries using omic technologies and creating a resource using advances in computational science.  The capabilities that systems biology and systems medicine represent are good opportunities to tap into resources that have already been opened up by the NIH Common Fund, including analyzing biological function and going beyond mapping loci and identifying markers to identifying mediators and linking those mediators to heart, lung, blood, and sleep phenotypes.

Another opportunity is to bring in the domain expertise of the NHLBI research community to begin linking deep omic analytics (genomics, transcriptomics, proteomics, microbiomics) with deep clinical phenotypes.  This will allow the research community to drive both the scientific questions and the nature of the resource itself, enabling investigator-initiated discovery science. Dr. Gibbons noted a need for a common repository for all of the information that could enable an investigator to mine and connect the dots in a way that no one person could.  NHLBI could facilitate this by creating a community of data-sharing, a common library that investigators can share and can contribute to collectively.  In the next five to ten years, the NHLBI should move beyond GWAS mapping of loci to categorizing disease mediators and the molecular biology of human disease in ways that give investigators insights into novel clinical applications.

Council’s advice was requested and their input will help determine the best approach for moving forward. A working group may be convened with Council members and those with domain expertise on the clinical phenotyping side and omic technology applications. The group would consider how to create a heart, lung, blood, and sleep systems medicine data commons network. Council will also be involved in an overall process of strategic priority-setting to map out the Institute’s future for the next five to 10 years.

Council will meet with the NHLBI Board of External Experts in September to outline the Institute’s long-term strategic priorities to guide the scientific priorities and resource allocation decisions.  Several process principles were outlined, including sustaining an investigator-initiated science driven portfolio and establishing a collaborative iterative process with the NHLBI research community to identify critical knowledge gaps and compelling questions.

Dr. Gibbons wants this to be a “living GPS” to provide feedback on a real-time basis and to influence what the Institute develops as workshops and think tanks, what programs no longer address compelling questions, as well as the Institute’s initiative development process and Council itself.

Council members had questions and comments about the data commons concept, such as how to quickly prepare a pipeline of information, needs for communication and interaction across research areas, and for pilot projects that develop partnerships with new organizations and that bring in younger investigators.

IV. NHLBI INITIATIVE CONCEPTS

Dr. Melissa Antman, Office of Extramural Policy and Training, reviewed the criteria that Council would use to score and prioritize Initiatives.  Those criteria were defined by the Council/BEE Working Group and Institute staff.

NHLBI staff presented 11 new initiatives, seven renewals, and one request to partner on an established initiative.  Following the initiative concept presentations, Dr. Antman presented the rating scores as determined by Council members voting using the Decision Lens software, led a discussion about the results, and displayed the initiative rating results from the May BEE meeting.

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

INITIATIVES: NON-HIV/AIDS, NON-SBIR/STTR

Initiative:  Mentored Career Development Award to Promote Faculty Diversity/Re-Entry in Biomedical Research (K01) – Renewal
Purpose:  To increase the number of highly trained junior faculty, from diverse backgrounds or from those who wish to re-enter their research careers after a hiatus due to family circumstances.

Initiative:  T32 Training Program for Institutions That Promote Diversity (T32) – Renewal
Purpose:  To: (1) enhance research training capabilities and foster institutional environments conducive to professional development in the biomedical sciences, (2) contribute to the expansion of the future pool of individuals from diverse backgrounds underrepresented in the biomedicine science enterprise, (3) enable trainees to increase their competitiveness for peer-review research funding, and (4) strengthen publication record of trainees.

Initiative:  Short-Term Research Education Program to Increase Diversity in Health-Related Research (R25) – Renewal
Purpose:  To support educational activities that enhance the diversity of the biomedical and behavioral research workforce.

Initiative:  Test Multilevel Interventions to Improve Blood Pressure Control in Minority and Low Socioeconomic Status Rural Populations (UH2/UH3)
Purpose:  To test multilevel interventions to improve blood pressure control in health care facilities or organizations serving patient populations that have high CVD risk and inadequate blood pressure control.

Initiative:  Ancillary Studies in Clinical Trials (R01) – Renewal
Purpose:  To leverage the research contribution of ongoing clinical trials and other prospective studies by soliciting investigator-initiated, time-sensitive, ancillary studies to these programs in heart, lung, blood diseases and sleep disorders.

Initiative:  Exosomes as Paracrine Signal Mediators in Cardiovascular, Lung, and Blood Disease (R01)
Purpose:  To explore the role of exosomes in cardiovascular, lung, and blood diseases.

Initiative:  Mobilizing Research: A Research Resource to Enhance mHealth Researchers (U2C)
Purpose:  To support, maintain, and upgrade the Mobilizing Research resource and activities that enable its transition to become a sustainable resource to accelerate research enrollment that can function after NIH funding ends and translate into practice.

INITIATIVE: SBIR/STTR

Initiative:  Stem Cell-Derived Blood Products for Therapeutic Use: Technology Improvement (R41, R42, R43, R44)
Purpose:  To support the development of better techniques and tools to improve the manufacturing process and enhance the production of clinically-relevant, functional stem cell-derived red blood cells or platelets more efficiently and at reduced costs.

INITIATIVES: NON-HIV/AIDS, NON-SBIR/STTR

Initiative:  Stem Cell-Derived Blood Products for Therapeutic Use (R01)
Purpose:  To support research addressing remaining scientific questions to enable and accelerate the use of stem cell-derived blood products as therapeutics.

Initiative:  Production Assistance for Cellular Therapies (PACT) (N01) – Renewal
Purpose:  To provide services that will greatly facilitate investigator-initiated translational cell therapy research and human efficacy studies.

Initiative:  Maintenance of the NHLBI Biologic Specimen Repository (N01) – Renewal
Purpose:  To: (1) maximize the return on the NHLBI investment in clinical studies by storing biospecimen collections that have high scientific utility potential and are not otherwise available to the scientific community, and (2) continue the NHLBI Biologic Specimen Repository (Biorepository) mission in a cost-effective manner by implementing strategies to efficiently maintain, acquire and distribute quality and scientifically highly valuable biospecimens from NHLBI-funded clinical studies to a wide range of investigators.

Initiative:  Vascular Dysfunction in the Pathogenesis of Severe Malaria (R01)
Purpose:  To: (1) support basic and translational research addressing the role of vascular alterations in the pathogenesis of severe malaria, a disorder that remains a significant cause of morbidity and mortality world-wide, and (2) promote multi-disciplinary science to elucidate the cellular and molecular mechanisms underlying vascular dysfunction that contribute to the pathogenesis of severe malaria.

Initiative:  Asthma Empowerment Collaborations to Reduce Childhood Asthma Disparities (U34, UH2/UH3)
Purpose:  To address two key research questions: 1) will a community based system of care that integrates multi-sector interventions for high risk children improve asthma outcomes and reduce disparities?; and 2) what are the critical components of such systems that would enable implementation in other communities or diseases?

Initiative:  Collaborative Projects to Accelerate Research in Organ Fibrosis (R01, R21)
Purpose:  To collaboratively: 1) characterize and compare mechanisms of aberrant fibrogenesis and fibrosis resolution in heart, lung, bone marrow and other organ systems; 2) develop novel therapeutic strategies aimed to lessen organ fibrosis; and 3) develop novel technologies to study fibrosis in different organ systems.

Initiative:  Lung Tissue Research Consortium Renewal (N01)
Purpose:  To continue operations of the Lung Tissue Resource Consortium (LTRC) but with substantial modifications intended to maximize the utility of this resource and prepare it for termination in FY 2019.

Initiative:  Use of Novel In Vitro Cellular Models to Predict Responses to CFTR-Directed Therapeutics (R01)
Purpose:  To test the ability of human cellular models to predict individual responses to CFTR-directed therapeutics for CF lung disease.

Initiative:  Primary Prevention of Chronic Lung Diseases: Definition of Resilience and Pre-Symptomatic Disease in Lung Health and Disease (R01)
Purpose:  To prospectively define and/or validate pulmonary or immune system attributes associated with pre-symptomatic disease states or resilience that will inform the development of primary prevention strategies for chronic lung diseases.

Initiative:  Primary Prevention of Chronic Lung Diseases: Pre-Symptomatic Profiles of Chronic Lung Disease(s) from Retrospective Cohorts (R21)
Purpose:  To identify pre-symptomatic profiles of chronic lung disease(s) using existing clinical research datasets.

Initiative:  Primary Prevention of Chronic Lung Diseases: Primary Prevention Trials for Chronic Lung Diseases (R01)
Purpose:  To encourage and promote testing of primary prevention interventions for chronic lung diseases in high risk and/or general populations where it is possible to assess intervention efficacy and pre-clinical disease states.

VI. ENHANCING REPRODUCIBILITY OF RESEARCH FINDINGS

Dr. Susan B. Shurin, Deputy Director, NHLBI, reported findings of the Enhancing Reproducibility of Research Findings initiative. She stated the NIH has been late to address the fact that many clinical studies cannot be reproduced. Reasons why so many promising drugs fail include efficacy, strategic, safety, and pharmacokinetic issues. Inherent flaws in the experimental system, the evaluation process, laboratory and professional practices can also lead to results that cannot be reproduced.

She spoke about a core set of reporting standards for rigorous study design that should be defined prospectively, including randomization, blinding of investigators, sample-size estimation, and statistical methods.  New author guidelines released by Science magazine earlier this year were also reviewed.  NHLBI is not aware of any extramural areas in which it has made substantial investments that have not paid off due to irreproducibility.  The Division of Intramural Research is already evaluating guidelines and considering how to implement changes.

Dr. Shurin reviewed some of the activities currently underway across the NIH, including evaluation of scientific premises and grant applications resulting in new funding opportunity announcements with additional review criteria, checklist and reporting guidelines, changes to the biosketch to place the emphasis on impact rather than number of publications, approaches to reduce “perverse incentives” such as exploring ways to provide longer periods of support to investigators, supporting replication studies, and training.

Dr. Shurin asked the Council to advise the Institute on recommendations for actions to address these issues.  The floor was opened up for comments and questions from Council members.

V. APPRECIATION OF DR. SUSAN B. SHURIN

Dr. Gibbons led an appreciation of Dr. Shurin, who is retiring at the end of the month.  She served as both Acting Director of NHLBI and the Eunice Kennedy Shriver National Institute of Child Health and Human Development in 2009, and has served as NHLBI Deputy Director since August 2012.  Council members also spoke about their experiences with Dr. Shurin and thanked her for her leadership and service.

VI. NATIONAL HEART, LUNG, AND BLOOD ADVISORY COUNCIL (NHLBAC) ASTHMA EXPERT WORKING GROUP REPORT

Dr. James P. Kiley, Director, Division of Lung Diseases, presented the needs assessment for potential updates of the 2007 Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma.  He reviewed the activities and role of the 25-year old National Asthmas Education and Prevention Program (NAEPP), which was initiated in 1989 to raise awareness of asthma as a major public health issue, ensure recognition of asthma symptoms, and achieve more effective control of asthma.  The last guidelines were released in 2007 and in 2011, the NAEPP made a recommendation to update them.  Based on the recommendations, the NHLBAC Asthma Expert Panel Working Group in 2014 was identified to oversee the needs assessment.

The Working Group found there have been enough scientific advances to warrant the review and possible update to the Guidelines.  He reported that the working group ranked the 2007 Guidelines in order of need for updating.  The Working Group held teleconferences and released a Request for Information, which resulted in 95 responses.  The Working Group identified five priority topic areas:  Adjustable medication dosing in recurrent wheezing and asthma (“intermittent therapy”); long acting anti-muscarinic agents in asthma management as add-on to inhaled corticosteroids; bronchial thermoplasty in adult severe asthma; fractional exhaled nitric oxide (FeNO) in diagnosis, medication selection, and monitoring treatment response; and remediation of indoor allergens (house dust mites/pets). Each of the five topics was put in the Institute of Medicine’s “PICO” format (Population, Intervention, Comparator, Outcome).

The Working Group has also identified other topics that should be monitored, but do not merit systematic review at this time.  The group recommended that the NHLBI continue to coordinate the Guidelines with the NAEPP; that NAEPP organizations submit an implementation plan for their organization as part of their partnership in the update; and that NAEPP partner organizations critically review drafts of the report before they are finalized.

Dr. Kiley reviewed the estimated timeline for a possible update.

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 approved 1,112 applications requesting $1,599,271,940 in total direct costs.

VIII. ADJOURNMENT

The meeting was adjourned at 3:56 p.m.