This is a brief summary of the October 21, 2008, meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC). It will be replaced by the full minutes of the meeting when they become available.

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OPENING REMARKS AND REPORT OF THE DIRECTOR

Dr. Elizabeth Nabel, Director of the National Heart, Lung, and Blood Institute (NHLBI), welcomed members to the 232nd meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC).

Dr. Nabel welcomed representatives of two NHLBI Advisory Committees:

• Dr. Robert Wise, representing the Heart, Lung, and Blood Program Project Review Committee
• Dr. Pamela Ouyang, representing the Clinical Trials Review Committee

Dr. Nabel announced two changes at the NIH:

• The NIH became a tobacco-free campus on October 1st.
• Dr. Elias Zerhouni, Director of the NIH for the past 6 years, will be leaving the NIH at the end of October. A tribute to him will be held on October 30th. Dr. Zerhouni brought important reforms to the NIH during challenging times. Dr. Raynard Kington, currently Deputy Director of the NIH, will assume the duties of Acting Director.

Dr. Nabel also announced two upcoming changes in NHLBI personnel:

• Dr. Marvin Konstam, Senior Advisor to the Director for Cardiovascular Diseases, is returning to Tufts University to serve as Chief Physician Executive at the new Tufts Medical Center Cardiovascular Center. While at the NHLBI, Dr. Konstam provided invaluable advice and strategic guidance for the Institute's national research programs on the causes, prevention, and treatment of cardiovascular diseases.
• Dr. Keith Hoots will join the Institute in January as the 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. Nabel acknowledged the extraordinary efforts of Dr. Susan Shurin, Deputy Director, NHLBI, who has been serving as Acting Director of the Division of Blood Diseases and Resources.

Dr. Nabel recognized five Council members who are retiring:

• Dr. Charles Esmon
• Dr. Katherine High
• Ms. J. Hoxi Jones
• Dr. Jeffrey McCullough
• Dr. Patricia Wahl

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Budget Update

The NIH is currently operating under a Continuing Resolution, in effect through March 6, 2009. Consequently, the NHLBI must operate at its FY 2008 budget level, which was $2,922,654,000 (not including the $15 million end-of-year supplement received in FY 2008). Dr. Nabel cautioned that the NIH may have to operate under the Continuing Resolution for the entire fiscal year, but assured Council that the Institute will do its best to continue its support of research project grants as well as other innovative programs.

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New and Early Stage Investigators

The NIH is developing new policies related to New and Early Stage Investigators in a continuing effort to encourage new investigators early in their research careers to make the transition from training (e.g., postdoctoral programs) to positions of independent research.

NIH definitions:

New Investigator: A principal investigator (PI) is considered a New Investigator if he/she has not yet competed successfully as a PI for a significant NIH independent research award.

Early Stage Investigator: An individual who is classified as a New or First-Time Investigator and is within 10 years of completing his/her terminal research degree or is within 10 years of completing medical residency (or the equivalent) is considered an Early Stage Investigator.

• Triaging — Review committees will discuss and score the same proportion of applications from New Investigators as from Established Investigators.
• Clustering at Review — Review committees will cluster applications from New and Early Stage Investigators, thereby permitting committees to develop score metrics based on applicants at the same stage in their careers.
• Encouraging Traditional Research Project Grant (R01) Applications — New Investigators will be discouraged from submitting Exploratory/Developmental Grant (R21) applications. The NHLBI is already doing this.
• Setting Targets for New and Early Stage Investigators
• Success rates for Early Stage Investigators will be equivalent to success rates on Type 1 (i.e., new) R01 applications from established investigators.
• NIH Institutes/Centers will use this approach to make R01 awards to approximately 1,650 New Investigators in FY 2009.
• At least 60 percent of the New Investigator pool will be Early Stage Investigators (proportion will increase to 75 percent over future years).

The NHLBI will begin implementing the new policy on success rate targets and composition of the New Investigator pool immediately. Based on an analysis of applications considered at a recent Council round, the success rate of Early Stage Investigators was already slightly higher than that of Established Investigators on Type 1 R01 applications under existing NHLBI New Investigator policies.

Dr. Nabel requested input from Council on the new policies. The Institute will analyze data from this Council round (October 2008) and report to Council.

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New NIH Policy Regarding Amended Applications

Beginning with the January 2009 application receipt date, all original (i.e., unamended) new applications and competing renewal applications will be permitted only a single amendment (A1). The new policy (resulting from the recent review of the NIH peer review system) was established to facilitate earlier funding of high-quality applications and improve efficiencies in the peer review system.

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Enhancing Peer Review at the NIH: Implementation of Recommended Actions

Dr. Nabel updated the Council on progress in implementing recommended actions resulting from the recent NIH-led study of the NIH peer review system. First-rate peer review is a cornerstone of the NIH, but new challenges for peer review have been created by the increasing breadth, complexity, and interdisciplinary nature of biomedical science and exacerbated by tight budgetary times. Recommendations and plans for implementation can be found at Enhancing Peer Review at NIH. The study identified four priority areas:

• Priority Area 1: Engage the best reviewers
• Priority Area 2: Improve the quality and transparency of review
• Priority Area 3: Ensure balanced and fair reviews across scientific fields and career stages, and reduce administrative burden
• Priority Area 4: Ensure continuous review of Peer Review.

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REBALANCING SUCCESS RATES

Dr. Carl Roth, Associate Director for Scientific Program Operation, NHLBI, presented a potential funding policy which was developed by an NHLBI committee charged with developing policies and procedures to restructure success rates among submissions—initial applications (A0s), first amendments (A1s), and second amendments (A2s)—in order to reduce the number of resubmissions necessary to receive an award, and thereby improve the efficiency of the peer review system and reduce the associated burdens on applicants, reviewers, and NIH staff.

Based on its analysis of recent NHLBI funding, the Committee concurred with the NIH decision to eliminate A2s. (Note: The Committee commenced its work prior to the NIH decision.) NHLBI funding data from the post-doubling era (FY 2004 - FY 2007) show that a large proportion of applications with an A0 percentile score fairly far down the percentile ranking were eventually funded, often as A1s or A2s. For example, about 80 percent of applications from established investigators (85 percent from new investigators) with an A0 score at the 20th percentile were eventually funded. The data also indicate a marked shift toward A2s and away from A0s. Furthermore, the data show substantial improvement in percentile scores between A0 applications and their A1s, and likewise between A1 applications and their A2s, for new investigators as well as established investigators. Based on these data, the Committee recommended eliminating A2s.

Next, the Committee considered percentiling A0s separately from A1s. FY 2007 data show this policy would have substantially lowered the percentile scores of A0s and substantially raised the scores of A1s. A retrospective model that re-percentiled NHLBI R01s and R21s by amendment status (and excluded A2s) showed that 267 resubmissions could have been avoided in FY 2007, 199 resubmissions avoided in FY 2006, and 31 resubmissions avoided in 2005. Therefore, the Committee proposed the following funding policy for consideration by Council:

For applications funded starting in FY 2010 (received January 2009 and thereafter):

• Re-percentile by:
• Amendment status (A0, A1)
• Investigator status (Early Stage Investigator, Established Investigator)
• Pay by new percentile to equivalent success rates

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UNDERSTANDING SUPERORGANISM BIOCHEMISTRY IN HEALTH AND DISEASE

Dr. Jeremy Nicholson, Head of the Department of Biomolecular Medicine, Imperial College, London, and author of many articles and patents on the development and application of new spectroscopic and chemometric approaches to studying disturbed metabolic processes in complex organisms, described some of his extensive research.

Dr. Nicholson described his model of the complex human biological system, which comprises several components including genetics, environment, diet, and the microbiome (i.e., the entire set of microbes living in a person’s body). These components interact in complicated ways that affect human metabolism and ultimately influence health and disease. The model provides a new paradigm for personalizing medicine. Dr. Nicholson studies microbial metabolic factors (i.e., the metabolic activity of the microbes found in a person’s body) as well as human metabolic factors. He proposed the idea (and presented supportive data) that various diseases (e.g., hypertension and obesity) could be, in part, related to activity of the human microbiome. Dr. Nicholson’s research suggests that the human microbiome is a potential new target for drugs (in addition to the genetic targets being sought via genome-wide association studies).

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CHARACTERIZATION OF HUMAN EPIGENOMES

Dr. Keji Zhao, Senior Investigator, Laboratory of Molecular Immunology, NHLBI Division of Intramural Research, discussed his research. Dr. Zhao's productivity at the NIH illustrates the opportunities inherent in supporting young investigators with exciting, new ideas.

Dr. Zhao's research is in the area of epigenomics—a field that involves the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence. Epigenetic mechanisms are affected by factors such as development in utero and in childhood, environmental chemicals, drugs and pharmaceuticals, aging, and diet, and they are thought to sometimes affect people's health, possibly resulting in illnesses such as cancer, autoimmune disease, mental disorders, and diabetes. (See NIH Roadmap for Medical Research for more information on epigenomics.)

Dr. Zhao presented results from his research, which focuses on how the chromatin structure (chromatin is the complex combination of DNA and proteins that makes up chromosomes) of eukaryotic DNA (i.e., DNA in organisms like the human body in which the cells have membrane-bound nuclei) is modified during cellular development and how those changes determine the expression potential of a specific genomic locus.

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REPORT OF THE BOARD OF EXTERNAL EXPERTS
AND INITIATIVES AND IDEAS FOR FISCAL YEARS 2009 AND BEYOND

NHLBI staff presented 7 new initiatives and 8 renewals, 2 ideas, and 2 requests by other ICs for secondary support, all of which had been reviewed in October by the Board of External Experts (BEE). Initiative development at the NHLBI is a two-cycle process. First, staff within each extramural Division develop ideas and potential initiatives, which they present to the trans-NHLBI Idea Forum. Sufficiently developed initiatives are subsequently considered by the BEE, which ranks each and provides accompanying advice. The BEE also considers ideas that are not developed to the level of an initiative, but does not rank them.

The Council was mostly supportive of the initiatives presented, but made a number of specific recommendations for consideration prior to their release. The Director, NHLBI, 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 and Ideas related to Strategic Plan Goal I: To improve understanding of the molecular and physiological basis of health and disease, and to use that understanding to develop improved approaches to disease diagnosis, treatment, and prevention

Initiatives related to Strategic Plan Goal II: To improve understanding of the clinical mechanisms of disease and thereby enable better prevention, diagnosis, and treatment

Initiatives related to Strategic Plan Goal III: To generate an improved understanding of the processes involved in translating research into practice and use that understanding to enable improvements in public health and to stimulate further scientific discovery

Requests for Secondary Support