NATIONAL HEART, LUNG, AND BLOOD ADVISORY COUNCIL
February 13, 2008
I. CALL TO ORDER AND OPENING REMARKS - Dr. Elizabeth G. Nabel
Dr. Elizabeth G. Nabel, Director of the National Heart, Lung, and Blood Institute (NHLBI), welcomed members to the 229th meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC).
Dr. Nabel recognized Dr. Andrew Marks and Dr. C. Noel Bairey Merz, as Council members attending their first NHLBAC meeting. Dr. Marks is Professor and Chair of Physiology and Cellular Biophysics and Medicine and Director of the Center for Molecular Cardiology at the College of Physicians and Surgeons, Columbia University. Dr. Bairey Merz is the Medical Director, Women’s Health Program at the Cedars-Sinai Medical Center.
Dr. Nabel recognized Dr. Marvin Konstam, who officially joined the Institute in January as Senior Advisor to the NHLBI Director in Cardiovascular Diseases.
Dr. Nabel also recognized Dr. Gail Weinmann who was recently selected as Deputy Director of the Division of Lung Diseases, NHLBI. Dr. Weinmann is a board-certified pulmonary and critical care physician/scientist who had a productive academic career at Johns Hopkins University prior to joining the Institute in 1995. While at the NHLBI, she has managed a wide range of extramural lung research programs, and most recently served as Chief of the Lung Division's Airway Biology and Disease Branch.
Dr. Nabel introduced Dr. Christopher O'Donnell, Senior Advisor to the NHLBI Director for Genome Research and Associate Director of the Framingham Heart Study and and Ms. Linda Avery, Co-Founder and President of 23andMe, Inc.
II. REVIEW OF CONFIDENTIALITY AND CONFLICT OF INTEREST - Dr. Elizaeth G. Nabel
The Council was reminded that under 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. A notice of this meeting was published in the Federal Register indicating that it would not be open to the public. 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
Dr. Nabel updated the Council on two recent Institute activities:
- The Heart Truth the Institute's successful heart health awareness campaign for women continues to raise awareness about the risks of heart disease for women. On National Wear Red Day (February 1st), The Heart Truth once again partnered with the fashion industry to present the Red Dress Collection 2008 Fashion Show, which featured well-known women in one-of-a-kind designer red dresses. Subsequently, First Lady Laura Bush, ambassador of the The Heart Truth® for several years, held a reception at the White House to honor everyone involved in Heart Truth® activities.
- This year, under the leadership of the NHLBI, the NIH Combined Federal Campaign (CFC), which offers NIH employees an opportunity to contribute to over 3,000 charitable organizations, raised over $2.2 million, exceeding its goal by $400,000. Dr. Nabel thanked NHLBI's CFC leaders, Mr. Don Christoferson and Mr. Tim Wheeles, as well as all the NIH CFC coordinators and keyworkers, for their efforts in the successful campaign.
Dr. Nabel reviewed the Institute's budget. The FY 2009 President's Budget contains $2,924,942,000 for the Institute, an increase of only $2.8 million (0.1 percent) over the FY 2008 Enacted Budget. Dr. Nabel acknowledged the trade-off between competing and noncompeting research project grants (RPGs) that occurs in tight budgetary times. The FY 2009 President's Budget includes an increase of $24.5 million for noncompeting RPGs and a decrease of $26.7 million for competing RPGs over the FY 2008 budget. With the astute management of the Institute's Budget Office, the NHLBI is able to continue its practice of funding competing grants at their full requested cost as approved by the study sections (i.e., not participating in the process known as "downward negotiation").
Select Pay Process
During times of fiscal constraint, Select Pay is used to enable the Institute to fund a limited number of additional meritorious applications in areas of greatest need and opportunity. Dr. Nabel summarized the Institute's Select Pay criteria and process. Three of the nine criteria that can be used for select pay decisions are: high risk/high impact research; highly innovative research; and research in areas highly relevant to the Institute's Strategic Plan, but with limited support. A portion of funds set aside for Requests for Applications (RFAs) will be used to fund Select Pay actions. In May, the Extramural Division Directors will develop a prioritized list of proposed Select Pay actions that will be sent to the Director, NHLBI, for consideration. In September, a summary of Select Pay actions will be provided to Council in closed session.
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IV. AWARD PRESENTATION TO DR. NABEL - Dr. Francis Collins
Dr. Francis Collins, Director, National Human Genome Research Institute (NHGRI), NIH, presented Dr. Elizabeth G. Nabel with the "NHGRI Special Recognition Award" for her leadership in areas important to the NHGRI, such as integrating genomics into research about heart, lung, and blood diseases and developing a trans-NIH policy for sharing data obtained in NIH-supported or -conducted genome-wide association studies.
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V. NHLBI GENETICS AND GENOMICS UPDATE - Dr. Christopher O. Donnell
Dr. Christopher O'Donnell, Senior Advisor to the NHLBI Director for Genome Research and Associate Director of the Framingham Heart Study, updated Council on the Institute's activities in the field of genetics and genomics. In September 2005, the NHLBI held a Working Group on Genome-wide Association in NHLBI Cohorts, which recommended that the Institute proceed with large-scale genome-wide association studies (GWAS) and resequencing projects, use existing cohorts with large collections of phenotypic and exposure data, and make the genotype-phenotype data immediately available to other researchers in a centralized data repository. (A GWAS is any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits such as blood pressure or weight, or the presence or absence of a disease or condition.)
Since 2005, GWAS have proliferated, resulting in a substantial increase in the number of strongly replicated associations between genes (or chromosomal loci) and disease. Currently, the NHLBI is supporting a number of large-scale genetic association studies (see NHLBI Genetics and Genomics Programs). Due in part to the efforts of the NHLBI leadership, the NIH Policy for Sharing of Data Obtained in NIH Supported and Conducted GWAS was developed and implemented in January 2008, to realize the full potential of GWAS by making data derived from them available as rapidly as possible to a wide range of scientific investigators, with appropriate safeguards for participant confidentiality.
The Framingham Heart Study SNP Health Association Resource (Framingham SHARe) is a comprehensive effort by the NHLBI, the National Center for Biotechnology Information (NCBI) at the National Library of Medicine, and the Boston University School of Medicine to pinpoint genes underlying cardiovascular and other chronic diseases. The Framingham Heart Study has collected an extensive array of phenotype and clinical data on its participants over the past 60 years. Framingham SHARe, which builds on the Framingham Heart Study, examined 550,000 genetic variants in over 9,000 study participants across three generations. The linked genotype-phenotype data are now stored in a database known as dbGaP, which was developed by the NCBI, and are available, with appropriate safeguards for participant confidentiality, to authorized investigators around the world who meet requirements outlined in the NIH GWAS policy. Since October 2007, twelve applications for Framingham SHARe data have been approved. The NHLBI plans to add data from several of its other large cohorts to SHARe, thereby providing opportunities to perform GWAS in over 20,000 participants.
Recently, an interest in genome-wide resequencing has developed and the NHLBI has responded by issuing an initiative in collaboration with the NHGRI to develop new approaches to enable resequencing of genome-wide medical targets (functional regions of the genome) that could be used to sequence thousands of DNA samples in well-phenotyped populations cost-effectively. As research moves along the continuum from gene discovery to personalized medicine, carefully developed procedures for informed consent and notification, along with national laws to prevent discrimination based upon genetic status, will be needed.
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VI. CONSUMER ENABLED RESEARCH THROUGH PERSONAL GENETICS - Ms. Linda Ave
Ms. Linda Avey, co-Founder and President of 23andMe, Inc., a privately held personal genetics company founded in 2006, discussed the objectives and services of her company. One of several companies now offering direct-to-consumer personal genetic services, 23andMe seeks to help individuals understand their own genetic information. Customers provide a saliva sample using an at-home kit and can then use web-based interactive tools to learn more about their distant ancestors and family inheritance, and receive an individual risk assessment (increased, decreased, or average risk) for various diseases. Ms. Avey noted that 23andMe considers itself a research company, not a genetic testing company. Once customers have received their genetic information, they will be asked to respond to Web-based questions about their health and medication experiences. Ms. Avey considers this the beginning of a new research model, which she hopes will help accelerate the realization of personalized medicine.
Following the presentation, Council members asked questions about how 23andMe communicates risk to customers, what procedures are in place to uphold rigor in data collection, and how the company handles confidentiality concerns.
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VII. RAPID ACCESS TO INTERVENTION DEVELOPMENT (RAID) - Dr. Sonia Skarlato
Dr. Sonia Skarlatos, Deputy Director, Division of Cardiovascular Diseases, NHLBI, explained the Institute's plan to partner with the National Cancer Institute (NCI), NIH, to expand the NCI RAID program for use by NHLBI-supported investigators. The goal of the RAID program is to remove common barriers between laboratory discoveries and clinical trials of new molecular entities (agents such as small molecules and biological therapeutic agents including vaccines).
Dr. Skarlatos explained that NCI-RAID is not a grant program. NCI contractors, under the NCI/Developmental Therapeutics Program (NCI/DTP), perform the services for the principal investigators. Outputs of the program include GMP synthesized material, acquisition of bulk supply, formulation research, pharmacological methods, or IND-directed toxicology. Since it began in 1998, the productive NCI-RAID program has led to the licensing of 32 agents and the approval of 32 INDs (investigational new drugs). Since an NIH-wide RAID Pilot Program was initiated in 2005, four of its ten approved projects have been for NHLBI investigators.
On February 15th, the NHLBI was scheduled to release a Request for Information (RFI), entitled NHLBI/NCI RAID Program for Heart, Lung, and Blood Disorders, to determine the level of interest among the extramural community and assess the types of resources and services needed. The proposed schedule is to release a notice of funding opportunity in April 2008, with funding to commence in the Fall 2008.
Council members were enthusiastic about the program and offered a number of ideas and suggestions. Dr. Nabel encouraged them and their colleagues to respond to the RFI.
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VIII. THE ACTION TO CONTROL CARDIOVASCULAR RISK IN DIABETES (ACCORD) TRIAL - Dr. Denise Simons-Morton
Dr. Denise Simons-Morton, Chief of the Clinical Applications and Prevention Branch, Division of Prevention and Population Sciences, NHLBI, and ACCORD Project Officer, described the ACCORD trial and summarized the recently reported findings that led to the Institute decision to discontinue the intensive glycemic treatment arm of the study.
About 20 million people in the U.S. have diabetes (90-95 percent of whom have type 2 diabetes), which increases risk for cardiovascular disease (CVD) 2 to 4 times. CVD is the leading cause of death in diabetes patients. ACCORD was designed to test three separate research questions addressing strategies to reduce CVD in persons with type 2 diabetes who are also at an especially high risk for CVD events:
- Glycemia control: intensive treatment vs. standard treatment
- Blood pressure control: intensive treatment vs. standard treatment
- Lipid control: treatment with a fibrate and statin vs. a placebo and statin
Results from the glycemia control arm were reported earlier this month. Of the 10,251 ACCORD participants, 257 in the intensive treatment group have died, compared with 203 in the standard treatment group—a difference of 54 deaths, or 3 deaths per 1,000 participants per year, over an average of almost four years of treatment. Upon review, the NHLBI concurred with the recommendation of the independent Data Safety Monitoring Board to discontinue intensive glycemia treatment. All participants will be transitioned to standard glycemia treatment, and the blood pressure and lipid arms of the trial will be continued.
Dr. Simons-Morton explained that no clear cause of the difference in deaths has been found to date and that additional analyses are underway. She also assured Council members that the results should not affect current treatment for most people with diabetes because few diabetes patients are treated to the low glycemia level that was the goal of the intensive treatment arm of ACCORD.
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IX. FUTURE DIRECTIONS IN SICKLE CELL DISEASE (SCD) RESEARCH - Dr. Katherine High
Dr. Katherine A. High, Professor of Pediatrics at the University of Pennsylvania and Chair of the Council Subcommittee for Review of the NHLBI Sickle Cell Disease Program, presented the Subcommittee's findings and recommendations for future directions. Established in 1972, the NHLBI Sickle Cell Disease Program has been instrumental in a number of advances, including the use of prophylactic penicillin to reduce sepsis and mortality in young children with SCD and the use of hydroxyurea therapy to reduce symptoms in adults with SCD.
Informed by careful review including analysis of the NIH and NHLBI SCD research portfolio, review of the most highly cited SCD publications over the past 10 years, analysis of responses to an NHLBI Request for Information (RFI) on scientific opportunities for investment in research on SCD and other hemoglobinopathies, and other informative review activities—the Subcommittee developed a comprehensive set of recommendations for the future direction of the NHLBI SCD Program. Some illustrative examples of the Subcommittee's recommendations, organized by category, are:
- Basic Research - Encourage development of new treatments, such as drugs to increase fetal hemoglobin, use of hematopoietic stem cell (HSC) transplantation (allogeneic), and use of genetically modified autologous HSCs.
- Translational Research - Focus resources on conducting translational phase I clinical trials of novel therapeutic approaches.
- Clinical Research - Structure a clinical network that will create a larger pool of potential subjects for interventional trials; include investigators in geographic regions where the largest groups of patients reside.
- Practice Guidelines and Educational Materials - Develop programs to conduct health care education for physicians, other health care providers, and patients.
- Training and Career Development - Attract investigators into adult SCD research and care; inform SCD investigators about eligibility for NIH Loan Repayment Program for researchers in areas of health care disparities and in pediatrics.
- NHLBI SCD Program Structure - Provide appropriate structure for several kinds of clinical research studies, including pilot studies of early phase testing of new therapeutic approaches; larger studies of therapeutic interventions; and studies of standard interventions to prevent late complications of disease.
Dr. Nabel and Council members commended the Subcommittee for its valuable contribution. The resulting recommendations will be considered carefully by the Institute.
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X. ANNUAL REVIEW OF COUNCIL DELEGATED AUTHORITIES - Dr. Elizabeth G. Nabe
The Council reviewed and approved the existing "Delegated Authorities from the National Heart, Lung, and Blood Advisory Council", which allow NHLBI staff to perform specific functions without involving Council. Council members requested a yearly summary of the frequency and types of decisions made by NHLBI staff.
This portion of the meeting was closed to the public in accordance with the determination that it concerned matters exempt from mandatory disclosure 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).
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XI. REVIEW OF APPLICATIONS
The Council considered 1,054 applications requesting $1,396,096,861 in total direct costs. The Council recommended 1,053 applications with total direct costs of $1,393,775,791 . A summary of applications by activity code may be found in Attachment B.
The meeting was adjourned at 2:30 p.m. on February 13, 2008 .