NATIONAL HEART, LUNG, AND BLOOD ADVISORY COUNCIL

MEETING MINUTES
June 11, 2008

I. CALL TO ORDER AND OPENING REMARKS - Dr. Elizabeth G. Nabel

Dr. Elizabeth Nabel, Director of the National Heart, Lung, and Blood Institute, welcomed members to the 230th meeting of the National Heart, Lung, and Blood Advisory Council.

Member Updates:

Dr. Nabel introduced a new Council member: Dr. Marlene Rabinovitch, Research Director, Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University School of Medicine.

New Staff:

Dr. Nabel welcomed Dr. Stephan Bour, who joined the Institute on May 11th as the Director of the Center for Biomedical Informatics. Previously, Dr. Bour served as Head of the Bioinformatics Core Facility at the National Institute for Allergy and Infectious Diseases (NIAID) Laboratory of Molecular Microbiology, and in 2004, he created and subsequently led the NIAID Bioinformatics and Scientific IT Program.

Dr. Nabel announced two other changes in personnel:

  • Dr. Chris O'Donnell, Senior Advisor to the NHLBI Director for Genetics and Genomics, has agreed to serve concurrently as Scientific Director of the Institute's SNP Health Association Resource (SHARe) Program. In this new position, Dr. O'Donnell will oversee the implementation of the new NIH Data Sharing Policy for data obtained in NIH supported or conducted genome-wide association studies (GWAS). He will also play a key role in steering the scientific direction of the SHARe program and coordinating with other NHLBI genome programs.
  • Dr. Keith Hoots will join the Institute in January as Director of the Division of Blood Diseases and Resources. Dr. Hoots is currently Professor of Pediatrics and Division Head, Pediatric Hematology, The University of Texas Medical School at Houston; Section Head, Pediatric Hematology, The University of Texas M.D. Anderson Cancer Center; and Medical Director, Gulf State Hemophilia and Thrombophilia Treatment Center. Dr. Hoots is a past president of the Hemophilia Research Society of North America.

Invited Guests:

  • Dr. Thomas Kodadek, Director of the University of Texas, Southwestern Center for Proteomics
  • Dr. Garry P. Nolan, Director of the Stanford University NHLBI Proteomics Center

r. Jennifer Van Eyk, Director of the Johns Hopkins University NHLBI Proteomics Center

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II. REVIEW OF CONFIDENTIALITY AND CONFLICT OF INTEREST Dr. Elizaeth G. Nabel

The Council was reminded that u nder Public Law 92-463, the Federal Advisory Committee Act, a portion of the meeting would be closed to the public, for the consideration of grant applications. Dr. Nabel also reminded the Council members that they are Special Government Employees and are subject to Departmental conduct regulations.

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III. REPORT OF THE DIRECTOR Dr. Elizabeth G. Nabel

Budget Update:

Dr. Nabel reported that no changes have been made to the Institute's FY 2009 budget since it was presented to Council in February, and little change is expected until the new Administration is in place. The Institute's FY 2009 President's Budget is $2,924,942,000, essentially the same as the FY 2008 budget (a 0.1 percent increase). The Institute's payline for traditional research project grants (R01s) is now at the 15th percentile; at the 25th percentile for new investigators' R01s (if expedited administrative review resolves summary statement comments); and at the 20th percentile for first-time renewal R01 applications from new investigators.

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IV. UPDATE ON ENHANCING PEER REVIEW – Dr. Elizabeth G. Nabel

Dr. Nabel updated the Council on the recent NIH-led effort to study the NIH peer review system and determine ways to enhance it. First-rate peer review is a cornerstone of the NIH, but new challenges for peer review are being created by the increasing breadth, complexity, and interdisciplinary nature of biomedical science and exacerbated by tight budgetary times.

Four core priorities emerged from the study, along with suggested actions for achieving related goals. The identified core priorities are:

  • Engage the best reviewers.
  • Improve the quality and transparency of reviews.
  • Ensure balanced and fair reviews across scientific fields and scientific career stages and reduce burden on applicants.
  • Develop a permanent process for continuous review of peer review.

The NIH is currently beginning the phased implementation of selected actions. Dr. Zerhouni is reviewing the proposed actions and is expected to announce his recommendations soon.

Related NHLBI Policy Issue:

In an effort to reduce the burden currently imposed on applicants, reviewers, and NHLBI staff by the large number of amended applications submitted each year, the NHLBI is exploring various strategies, such as setting different paylines for original applications (i.e., A0s), first amendments (i.e., A1s), and second amendments (i.e., A2s). Since a large percent of original applications with good scores are ultimately awarded, the process of submitting and reviewing revised applications for these projects seems an unnecessary burden. Dr. Nabel presented Institute data showing the number of unpaid A0s and A1s that could have been paid in FY 2007 from the dollars that would have been freed up by raising the payline for A2s for R01 and Exploratory/Developmental Research Grant (R21) applications.

Dr. Nabel requested input from Council on this potential policy change. Council members discussed the issue, raised questions, and offered numerous suggestions. The NHLBI plans to formulate a series of options, ask Council to review them over the summer, and raise the topic again at a Fall 2008 Council meeting.

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V. REPORT ON THE PUBLIC INTEREST ORGANIZATION (PIO) MEETING Ms. Paula Polite

Ms. Paula Polite, Council member and Manager of Quality Programs, Division of General Services for the City of Memphis, Memphis, Tennessee, reported on the NHLBI Ninth Annual PIO Meeting held June 9-10 in Bethesda, Maryland. Ms. Polite acknowledged that the PIO meetings are always a useful opportunity for attendees to learn how their organizations and the NIH can work together for their mutual benefit. Several PIO representatives also attended the Council meeting.

Dr. Nabel conveyed the Institute's pleasure in hosting members of the PIOs each year.

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VI. SCIENTIFIC AND CLINICAL IMPACT OF THE NHLBI CENTERS FOR PROTEOMIC INNOVATION Dr. Susan Old

Dr. Susan Old, Acting Deputy Director, Division of Cardiovascular Diseases, NHLBI, reviewed the history and purpose of the NHLBI Proteomics Initiative. In FY 2002, the Institute established a consortium of 10 highly interactive, multi-disciplinary Proteomics Centers to enhance and develop innovative proteomic technologies and apply them to relevant biological questions to advance knowledge of heart, lung, blood, and sleep health and disease. The Centers are entering their final year of support.

Directors of three Centers discussed highlights of their research:

  • Dr. Jennifer Van Eyk, Director of the Johns Hopkins University NHLBI Proteomics Center
  • Dr. Garry P. Nolan, Director of the Stanford University NHLBI Proteomics Center
  • Dr. Thomas Kodadek, Director of the University of Texas (UT) Southwestern Center for Proteomics Research

They emphasized that the NHLBI Proteomics Initiative has revolutionalized the field of proteomics.

A booklet providing an overview of the NHLBI Proteomics Initiative, including summaries of Center activities, news articles, and metrics on the productivity of the program, was distributed. The specific objectives of the 10 Centers are:

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VII. ACTIVITIES OF THE BOARD OF EXTERNAL EXPERTS (BEE) Dr. Elizabeth G. Nabel

The Board of External Experts (BEE), an advisory working group to the NHLBI Council, is charged with assisting the Institute in implementing its Strategic Plan, discussing and prioritizing program ideas and potential initiatives, serving as an incubator for new ideas and recommendations, recommending improvements in the Institute's business operations, and providing advice on a program's effectiveness on an ad hoc basis.

At its meeting on May 7, 2008, the BEE discussed and prioritized a number of proposed initiatives. Because the NHLBI Idea Forum provides an opportunity for scientific staff to present ideas and receive and incorporate input from their colleagues early in the initiative development process, initiatives are mature and well-defined when they are presented to the BEE.

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VIII. PRESENTATION OF INITIATIVES Dr. Elizabeth G. Nabel

NHLBI staff presented 18 new initiatives, all of which had been reviewed and ranked by the BEE. The Council was supportive of the initiatives but made a number of specific recommendations for consideration prior to their release. Dr. Nabel will consider the recommendations of the BEE and the Council and other budgetary and programmatic issues in determining which of the proposed initiatives, if any, to implement.  

INITIATIVES RELATED TO SICKLE CELL DISEASE

Exploratory Studies in the Neurobiology of Pain in Sickle Cell Disease, RFA

To investigate pain syndromes in sickle cell disease by using techniques that have been applied to the elucidation of the nociceptive system in non-human and human studies of acute and chronic pain.

Council recommended this initiative.

NHLBI-CDC Registry and Surveillance System in Hemoglobinopathies (RuSH), RFP

To develop and implement a national data system (surveillance component and registry system) and biospecimen repository that will provide data to describe the epidemiologic and clinical characteristics of people with all genotypes of sickle cell disease, thalassemias, and other hemoglobinopathies. This initiative will conduct the first phase of the project, comprising pilot studies in 7 to 10 states to test specific data collection methods, procedures, and organizational structures, and to determine the feasibility of implementing RuSH on a national level.

Council recommended this initiative.

INITIATIVES RELATED TO TRANSLATIONAL SCIENCE

Translational Program Project Grants (tPPG), PAR

To encourage collaborative, translational science that will help foster a research continuum from basic to applied biomedical research to improve diagnosis and treatment. A two-cycle program project is proposed: the first cycle requires a small clinical research component, while the second cycle shifts to a program with a significant clinical research component.

Council recommended this initiative.

Phase II Clinical Trials for Evaluation of Novel Therapies for Lung Diseases and Sleep Disorders, RFA

To support phase II clinical treatment trials (i.e., proof of concept, interventional studies) of innovative and novel agents for lung diseases and sleep disorders, along with one or more closely related, smaller ancillary mechanistic studies linked to the clinical question.

Council recommended this initiative.

Cardiac Translational Research Implementation Program (C-TRIP), RFA

To accelerate translation of promising new fundamental research discoveries for the treatment and prevention of heart failure and arrhythmias through well-designed clinical trials that demonstrate efficacy and safety; a two-staged program to support (1) study development and trial planning, and (2) clinical trials of new therapeutic interventions.

Council recommended this initiative.

INITIATIVES RELATED TO STRATEGIC PLAN GOAL I

Airway Smooth Muscle Function and Targeted Therapeutics in Human Asthma, RFA

To investigate the complex role of airway smooth muscle functions in the development of human asthma and to identify new therapeutic targets.

Council recommended this initiative.

Characterizing the Blood Stem Cell Niche, RFA

To develop approaches to dissect the cellular components and factors involved in the hematopoietic stem cell niche, such as the use of conditional genetic knock-out models to test the role of factors from specific cell lineages, along with cellular imaging.

Council recommended this initiative.

Crosstalk between Platelets and Immune-competent Cells during Inflammation, RFA

To improve understanding of the pathophysiological mechanisms of immune cell and platelet interactions that lead to thrombosis, and to use new technologies and research methodologies to identify common regulatory pathways for cellular components of immune and coagulation systems to develop targeted therapeutic interventions for thrombotic events and inflammation.

Council recommended this initiative.

Microbiome of the Lung and Respiratory Track in HIV-infected Individuals and Controls, RFA

To characterize the microbiome in the lung alone, or in combination with the microbiome of one of the nasal and/or oropharyngeal cavities, in HIV-infected individuals and matched uninfected controls, by using molecular techniques to identify bacteria and possibly other organisms such as viruses, cell wall deficient organisms, protozoa, and fungi.

Council recommended this initiative.

Summer Institute for Training in Biostatistics (SIBS) II, RFA

To support up to seven universities to teach summer courses in biomedical statistics for advanced undergraduates and beginning graduate students to encourage them to pursue careers in this area.

Council recommended this initiative.

The Role of Cardiomyocyte Mitochondria in Heart Disease: An Integrated Approach, RFA

To improve understanding of cardiomyocyte mitochondrial biology and its contributions to myocardial adaptations and disease progression by combining functional data with information derived from powerful new technologies, such as genomics, proteomics, metabolomics, and imaging.

Council recommended this initiative.

Ancillary Studies in Clinical Trials — Renewal, RFA

To conduct time-sensitive ancillary studies related to heart, lung, and blood diseases and sleep disorders in conjunction with ongoing large clinical studies. An accelerated review/award process will be an integral part of this initiative to support the crucial time frame in which these ancillary studies must be performed.

Council recommended this initiative.

 

INITIATIVES RELATED TO STRATEGIC PLAN GOAL II

 

PUMPs for Kids, Infants, and Neonates (PumpKIN) — Renewal, RFP

To translate the advances developed through the Pediatric Circulatory Support Program into clinical benefit for neonates, infants, and small children. The staged, milestone-driven process includes: (1) pre-clinical testing and analyses sufficient for FDA Investigational Device Exemption (IDE) approval; (2) development of an FDA-approved clinical trial design; (3) manufacturing of devices for the pre-clinical and clinical studies; and (4) clinical trials for the most promising advanced ventricular support devices for young pediatric patients.

Council recommended this initiative.

Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) — Renewal, RFP

To continue support for a data and clinical coordination center to manage INTERMACS (the established national registry of patients receiving mechanical circulatory support device therapy to treat advanced heart failure) and associated activities; extend the registry into pediatric populations; and continue to publish and disseminate results to the scientific, medical, and lay communities.

Council recommended this initiative.

Clinical Proteomics Program — Renewal, RFA

To encourage systematic, comprehensive, large-scale validation of existing and new candidate protein markers for use in predicting disease susceptibility, diagnosis, disease staging, assessing response to therapy, and assessing prognosis; and to develop an educational curriculum for physicians and scientists to gain expertise in the clinical application of proteomics.

Council recommended this initiative.

Diuretic-induced Dysglycemia in Treatment of Hypertension with Clinically Effective Doses of Diuretics: Potential for Prevention, RFA

To evaluate clinically feasible approaches to preventing diuretic-induced increase in serum glucose levels (and resulting new-onset diabetes) and to investigate mechanistic and genetic underpinnings of diuretic-induced dysglycemia and its prevention.

Council recommended this initiative.

Production Assistance for Cellular Therapies (PACT) — Renewal, RFP

To continue to support cellular therapy research in the areas of regeneration of damaged/diseased tissues, organs, and biologic systems, and targeted treatments for serious diseases without effective therapies; to continue to provide the current services of the three PACT cell-manufacturing facilities and to include other services, such as adding up to six geographically dispersed facilities to provide the consulting, manufacturing, and regulatory expertise essential for the development of cellular therapies for heart, lung, and blood diseases and disorders.

Council recommended this initiative.

INITIATIVES RELATED TO STRATEGIC PLAN GOAL III

 

Childhood Obesity Prevention and Treatment Research Networks, RFA

To support multiple controlled trials to test the efficacy of innovative interventions that address issues germane to the childhood obesity epidemic. The program would have two main foci: (1) prevention of excess weight gain in non-overweight youth and additional weight gain in obese youth, and (2) weight loss in obese youth.

Council recommended this initiative.

 

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IV. REVIEW OF APPLICATIONS

The Council considered 2,323 applications requesting $604,599,462 in total direct costs. The Council recommended 1,316 applications with total direct costs of $353,810,720. A summary of applications by activity code may be found in Attachment B.

ADJOURNMENT

The meeting was adjourned at 2:35 p.m. on June 11, 2008.

 

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