DEPARTMENT OF HEALTH AND HUMAN SERVICES
NATIONAL INSTITUTES OF HEALTH
NATIONAL HEART, LUNG, AND BLOOD ADVISORY COUNCIL
February 10, 2015
The 261st meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC) was held Tuesday, February 10, 2015, in Building 31, Conference Room 6, National Institutes of Health (NIH), Bethesda, Maryland. It was open to the public from 8:06 a.m. until the open session ended at 12:12 p.m. The closed session began at 1:12 p.m. and adjourned at 1:46 p.m. Dr. Gary H. Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI) presided as chair.
Council Members attending
Ms. Coletta C. Barrett
Dr. Ivor J. Benjamin
Dr. James D. Crapo
Dr. Pamela S. Douglas
Dr. Jonathan A. Epstein
Dr. Ron G. King
Dr. Barbara A. Konkle
Dr. Naomi L.C. Luban
Dr. Polly E. Parsons
Dr. Bruce M. Psaty
Dr. Véronique Lee Roger
Dr. Anna Maria Siega-Riz
Council Member attending via videoconference
Dr. Bradford C. Berk
Council Members attendingvia teleconference
Dr. George Q. Daley
Dr. Gilbert C. White
Council Members unable to attend
Mr. Jonathan R. Alger
Dr. Robert Jesse (ex officio)
Dr. Fernando D. Martinez
Dr. Jeffrey A. Whitsett
Ms. Peggy Binzer, Polsinelli PC
Mr. Glenn Crater, Aerocrine
Mr. Jeffrey Cooper, CooperSoft
Ms. Tracy Hammond, Polsinelli PC
Ms. Claudia Louis, American Heart Association
Mr. Joseph Stewart, Health and Medical Council of Washington
NIH Center for Scientific Review attending
Dr. Larry Boerboom
Dr. Kathy Malinda
NHLBI Staff attending
A number of NHLBI staff were in attendance.
- CALL TO ORDER
Dr. Gary H. Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI), welcomed members to the 261st meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC).
- THE VIEW FROM THE NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
Dr. Jon Lorsch, Director of the National Institute of General Medical Sciences (NIGMS) presented an overview of his Institute’s pilot programs and approaches to increase the efficiency, productivity, and sustainability of the fundamental biomedical research enterprise. NIGMS’ overarching missions are to promote fundamental research on living systems in order to lay the foundation for advances in disease diagnosis, treatment, and prevention; and to enable the development of a highly trained, innovative, and productive biomedical research workforce. One strategic goal is to refocus its portfolio on investigator-initiated fundamental research. In the early 1990s, nearly 99% of the research portfolio was investigator-initiated and the current number is roughly 80%, which Dr. Lorsch believes is too low given the Institute’s mission.
In response, the NIGMS began rebalancing its portfolio in fiscal year 2014. By decreasing funding to centers and the number of targeted funding opportunity announcements, the Institute’s success rate rose from 20% to 25% in in just one fiscal year.
Dr. Lorsch believes one problem is how biomedical research is funded. The current model of project-based research funding, in which an investigator identifies both a specific question and specific set of experiments is not compatible with how scientific inquiry and discovery works. He believes investigators should have the ability to change their research focus as opportunities arise and the science evolves.
Dr. Lorsch presented direct costs data that showed the top 5% of NIGMS grantees were 24% of the funding and that the top 20% of grantees held 50% of NIGMS awards. Data was presented that showed this distribution trend held true across the NIH. Dr. Lorsch reported data indicating that the current distribution of funding was not as efficient in delivering high-quality science as it could be. A better metric for funding should be the number of investigators supported instead of NIH’s current metric of the number of grants awarded. Such a shift would maximize the breadth and diversity of investigators and the questions they are asking. NIGMS used this metric and is giving a single research grant per investigator to fund his or her research program instead of awarding multiple grants to fund individual projects. A “research program” is defined as the collection of projects in an individual’s lab that is relevant to the NIGMS mission.
Several benefits are expected from this model: increased funding stability should enhance investigators’ willingness to undertake ambitious projects with a creative approach and to follow new research directions as opportunities arise. The new funding approach could reduce the time spent writing grant applications and increase the time doing research. The peer review system would also benefit due to the reduced number of grant applications. A new award to test this approach is the “Maximizing Investigators Research Award,” or MIRA, which uses the R35 mechanism.
The first funding opportunity announcement was released in January 2015. A moderate number of applications must be received to test the overall concept and develop the proper peer review procedures. Lorsch explained that this should not create an elite class of NIGMS awardees, because the Institute will ask that the investigators forgo some of their current funding in exchange for the increased stability and flexibility. The money given up will go back into the system to support more researchers or increase the amount of funding for underfunded investigators.
The floor was opened to discussion and several Council members had questions about metrics and accountability.
- ADMINISTRATIVE ANNOUNCEMENTS
Dr. Stephen C. Mockrin, Director, Division of Extramural Research Activities, made the standard administrative announcements and outlined the agenda for the Council meeting. He also thanked recently retired members, Ms. Coletta Barrett, and Drs. Ivor Benjamin, Naomi Luban, Polly Parsons, and Gilbert White for attending a final Council meeting.
- REPORT OF THE DIRECTOR
Dr. Gibbons began his Report by outlining its three sections: 1) accountable stewardship and fiscal management, 2) investing in the next generation, and 3) emerging scientific opportunities and the strategic visioning process.
Dr. Gibbons reported a dip in the number of R01 awards funded from 2008 to 2012. Since 2012, the NHLBI increased its payline for R01s, which resulted in some benefits for the success rate. Although the Institute’s fiscal year 2015 budget of $2,995,865,000 is still under the pre-sequester budget of 2012, the R01 payline will be increased to the 13th percentile and the Early Stage Investigator payline will be increased to the 23rd percentile. The NHLBI will continue to make R56 Bridge awards in fiscal year 2015.
Dr. Gibbons spoke about the need to expand and sustain the Institute’s investigator pool and highlighted this challenge by looking at the decline in the investigator pool of the blood research community in the NHLBI Division of Blood Diseases and Resources. He believes it is critical for the NHLBI to maintain its higher success rates for Early Stage Investigators because of the anxiety among those just entering the field about whether research is a sustainable career path.
Dr. Gibbons described the heavy debt burden facing physician-scientists and stated hope that the NHLBI will continue to use the loan repayment program to invest in the next generation of scientists. He spoke about the usefulness of the career development K awards and presented data on the high rate of K awardees who went on to get research project grant funding. He would like to see those success rates rise to more than 30 percent.
He reported that while the R56 Bridge Award is still being assessed by the Institute, it has been extended to Early Stage Investigators, who received 15 R56 awards in FY14.
Dr. Gibbons addressed Dr. Lorsch’s presentation on the NIGMS’s use of the R35 mechanism with the MIRA, and raised the question of whether there was an opportunity to introduce it to the NHLBI portfolio. He reported that the NHLBI has a working group looking into the feasibility and appropriateness of the Institute introducing the R35 mechanism and their findings would be provided to Council.
Dr. Gibbons reminded the Council that February is Heart Month and that the Institute has an ongoing commitment to women’s health. He stated that the NHLBI has taken part in the NIH-wide effort to take a more substantive look at gender-specific differences across its portfolio.
Dr. Gibbons suggested there may be a renaissance in thinking about systematic characterization and classification because of the new tools and capabilities associated with systems biology and precision medicine. He gave an example of a group that is trying to create an atlas of perinatal lung maturation that includes both a developmental component as well as various model systems. The group hopes to characterize the 40 different cell types in the lung in a systematic way that will bridge the preclinical space with humans. Dr. Gibbons stated this work could lynchpin the fundamental basis of understanding the development and maintenance of human health with its implications in disease states, whether it’s the different populations of progenitor cells or immune cells that may then occur in various models of human disease.
Dr. Gibbons spoke about the Institute’s interest in categorizing disorders to be more precise about what is being diagnosed and treated. One opportunity is to create knowledge exchange networks based on creating a data commons with multi-level and multi-dimensions of data. Standard clinical signs and symptoms would be entered and layered on new imaging capabilities and –omic technologies to provide a new age of clinical taxonomy and phenomics.
Dr. Gibbons reviewed some of the ideas that emerged from the genomics workshop, including creating an NHLBI data commons to integrate phenotype and –omics data that reflect the diversity of the nation by race, ethnicity, and sex. The Institute began pursuing the vision of an NHLBI data commons in 2014, and efforts in precision medicine to leverage existing cohorts by making some seed investments. Internal conversations were initiated with many cohorts to potentially create a consortium of cohorts.
Precision medicine was mentioned in the January 2015 State of the Union address when President Obama spoke about launching a Precision Medicine Initiative. The President’s proposed budget included $130 million for NIH to develop a volunteer national research cohort. If passed by Congress and implemented, it would be carried out as a collaborative partnership, with the NHLBI and the National Human Genome Research Institute serving as co-leads in a trans-NIH effort.
Finally, Dr. Gibbons provided the Council with an update on the Institute’s strategic visioning process. The combined work of the Board of External Experts, the Council, and Institute staff has generated 333 compelling questions and 127 critical challenges. Goal number two, dealing with clinical studies, had more than 150 suggestions and so he anticipated that the Council might be brought in to take a deeper look at those contributions. Dr. Gibbons noted that the strategic visioning process would soon enter the public phase, during which the Institute would solicit public input via announcements on the website and in specialty journals.
Dr. Gibbons opened the floor to discussion and Council members were given the opportunity to comment and ask questions. There was further discussion about K awardees, as well as the reported decline in blood researchers.
- INCLUSION OF FEMALES AND MINORITIES IN CLINICAL STUDIES
Dr. Lenora E. Johnson, Director, Office of Science Policy, Engagement, Education, and Communications, presented the biennial report of inclusion of women and minorities in clinical studies.
NIH policy calls for appropriate representation of women and minorities in its studies and to account for that representation. Council’s responsibility is to review the implementation procedures and determine if the Institute is in compliance with the Revitalization Act.
Internal NHLBI review groups evaluate all enrollment plans proposed by investigators to ensure women and minorities are included in the studies. If NHLBI Program Officials find there is not appropriate representation, the concerns are communicated to the investigator so modifications can be made. If concerns are not addressed, the issue would come to Council. Dr. Johnson reported that all projects had been compliant and nothing was brought to Council for resolution.
Dr. Johnson presented FY 13 data showing an increase in Hispanic representation and a decrease in Asian representation in Phase III clinical studies. She also noted relatively low Native American and Hispanic representation in intramural studies.
Investigators are not currently required to report gender differences for preclinical data, although that could change in the future.
The floor was opened and there were discussions about the increasing difficulty in meeting reporting requirements, concerns with how the U.S. Census collects and characterizes demographic information given the increasingly diverse nature of the population, and how to address the emerging issue of gender identification.
Dr. Mockrin called for a motion from the Council to adopt the report, which would then be submitted as a part of the NIH’s report on how Institutes and Centers comply with the inclusion policy. The Council proposed and approved a motion.
- ASTHMA EXPERT PANEL WORKING GROUP REPORT
Dr. James Kiley, Director, Division of Lung Diseases, presented the recommendations of the Asthma Expert Panel Working Group. NHLBI produced its first asthma clinical practice guidelines in 1991 and an update was done in 2007. In 2011, the National Asthma Education and Prevention Program (NAEPP) concluded another update was needed and Council determined in 2012 that a needs assessment be conducted prior to engaging in any guideline activity. In 2014, Council convened the Asthma Expert Panel Working Group to conduct a needs assessment. Dr. Kiley summarized the three questions the Working Group addressed and the information sources used to develop the needs assessment. He reviewed the draft report that was presented to the NHLBAC in June 2014. It recommended that an update should be made to the 2007 clinical practice guidelines; identified five priority topics for immediate systematic review and update; and recommended that the NHLBI maintain the NAEPP structure, coordinate the systematic reviews, and update the report. After public comments of the draft needs assessment report were received and reviewed, the Working Group recommended adding a sixth priority topic to the report.
Those topic areas are: (1) Adjustable medication dosing in recurrent wheezing and asthma (“intermittent therapy”), (2) long acting anti-muscarinic agents in asthma management as add-on to inhaled corticosteroids, (3) bronchial thermoplasty in adult severe asthma, (4) fractional exhaled nitric oxide (FeNO) in diagnosis, medication selection, and monitoring treatment response, (5) remediation of indoor allergens (house dust mites/pets), and (6) the role of immunotherapy in the treatment of asthma.
The Working Group recommended that several emerging topic areas be acknowledged and monitored, but did not yet merit systematic review. When the floor was opened for discussion, members spoke about the positive impact of the previous guidelines, and the need to evaluate and incorporate current high-quality research into the guidelines. They asked whether any public policy issues such as insurance reimbursement rates would be addressed as a part of the guideline process, and why the NHLBI was moving forward with the asthma guidelines when the recent cardiovascular disease prevention guidelines were shifted to the American Heart Association and the American College of Cardiology.
The Council proposed and accepted a motion to accept the report.
- STRATEGIC PLANNING IN THE DIVISION OF INTRAMURAL RESEARCH
Dr. Robert S. Balaban, Scientific Director, Division of Intramural Research (DIR), presented a report on the Division’s strategic planning efforts. The DIR is comprised of five clinical branches, five basic science centers, and 14 scientific support cores. The majority of staff are post-doctoral fellows and one key function is to train the next generation of scientists and clinicians. Therefore, all of the mentoring and training programs are geared toward post-doctoral fellows, which is unique to the DIR.
Its budget of $192 million is roughly 6% of the overall Institute budget. Approximately $119 million goes to the Office of the Scientific Director to support Board of Scientific Counselors (BSC)-reviewed science and the remaining $73 million goes to help run the NIH campus and the NIH Clinical Center. Increasing operating costs are proportionally decreasing the money available for research operations. The majority of the DIR funding goes to personnel costs, and 20% goes to the research budget.
Dr. Balaban described how the BSC process functions as the quality control system in the DIR. Every four years, the DIR principal investigators and research cores are retrospectively reviewed by the BSC in terms of impact of an individual on the field or in a program, based on productivity, use of DIR resources, mentoring, and publications. Dr. Balaban reported that on average, 23% of DIR labs are reduced or closed as a result of the review process.
The BSC review process was evaluated and preliminary results indicate a strong correlation between receiving a good BSC score and subsequently being very productive, based on bibliometric measurements. This evaluation is being expanded across the NIH DIR.
The DIR budget has become significantly tighter because research costs have increased and rising hospital costs. To manage a flat budget over the last decade, DIR has focused on smaller labs, shifted resources into central cores so they can be shared, and partnered the clinical program with regional hospitals to leverage third-party payment systems. The biggest decrease has been to the number of post-doctoral fellows.
Dr. Balaban reviewed the NHLBI DIR faculty recruitment philosophy and process, and the 10-year strategic planning process initiated by the NIH Director for all Institutes or Centers with Intramural Research Programs. The Advisory Committee to the Director integrated the strategic plans from across the NIH into a trans-NIH DIR strategic plan, which was released in December 2014.
Recommendations of its Long-Term Intramural Research Program (IRP) Planning Working Group Report included refocusing the mission and function of the Clinical Research Center, encouraging team science and promoting more synergistic intramural and extramural collaborations, accelerating efforts to identify solutions for pending data and computer issues, increasing diversity throughout all levels of the NIH DIR, and identifying the most sustainable size of the IRP workforce.
The goals of the NHLBI DIR Strategic Plan are to: promote a vibrant community of scientists, serve as a global leader in human biology and clinical science, serve as an international resource for training the next generation of scientific leaders, enhance efforts in computational biology and medicine infrastructure that enable investigators to seize emerging scientific opportunities, and promoted sustained support for the IRP by demonstrating its value and complementary synergy with NIH extramural programs.
The objectives of the Clinical Research Strategic Plan are to: support investigator-initiated research; support first-in-human trials, especially with respect to safety, reporting, and regulatory standards; develop a sustainable infrastructure for clinical data and bio-specimens; hire, train, and mentor the next generation of physician-scientist leaders; and partner with regional clinical programs to expand the patient base and share clinical costs.
Dr. Balaban highlighted the Orloff Science Awards, which are awarded for outstanding scientific infrastructure achievements and emphasize the teamwork that made the achievements possible. The 2015 awardees, selected by Drs. Gibbons and Balaban, will give 10-minute “TED”-like talks to explain their research and why it is important. The talks will help improve oral communications and will also be posted to the website.
Council members were given the opportunity to ask questions about the future of post-doctoral fellows, the cost of running NHLBI DIR laboratories, and the logistics of partnering with local hospitals in terms of infrastructure and data management.
- LOAN REPAYMENT PROGRAM
Dr. James Kiley, Director, Division of Lung Diseases, presented an update of the NIH/NHLBI Loan Repayment Program (LRP). The LRP provides a way to encourage health professionals to pursue careers in biomedical research and is a way to help keep people in the research field. The program repays educational loan debt of up to $35,000 per year for performing NIH-relevant research at domestic, non-profit, or government entities. There are a total of eight NHLBI LRPs, including three intramural LRPs, but his update focused on the five extramural LRPs: clinical research, pediatric research, health disparity research, clinical research for individuals from disadvantaged backgrounds, and contraception and infertility research. He explained that specific Institutes cover the last three programs and the NHLBI primarily supports the clinical and pediatric research programs.
More than 1,300 LRP awards, totaling over $66 million, were awarded by the NIH in FY13. Data showed 77% of the new awardees had more than $50,000 in educational debt, 13% had more than $200,000; 55% of awardees were female; 75% of awardees were white, and 8% of awardees were African-American.
Dr. Kiley reviewed the success rate for the NIH LRPs, which averaged roughly 49% for all five extramural LRPs. He also reported that the NHLBI is the third leading Institute in supporting the NIH LRP, after the National Institute on Minority Health and Health Disparities and the National Cancer Institute.
For FY14, the NHLBI received 353 applications from 110 institutions. NHLBI had more male LRP awardees than at the NIH level, more M.D.-Ph.D. applicants than single-degree applicants, and more clinical research applications than pediatric research applications.
He concluded his report by summarizing the data that LRP applicants appear to need roughly 10 years for training and maturation before they become successful independent investigators; awardees are productive and many hold faculty positions at academic institutions; a combination of the LRP with individual research training through the F and K mechanism is the best predictor of subsequent R01 funding.
Based on the data presented in his report, Dr. Kiley proposed that Council consider and discuss whether there would be value in giving preferential funding consideration for LRPs to all junior investigators with NIH or NHLBI Career Development Awards or individual fellowships.
When the floor was open, there were questions about whether it is possible to know the true role that the LRP plays in securing subsequent R01 funding, whether the synergistic relationship between training grant programs and loan repayment needs formalization, and whether the Institute should explore maintaining its current LRP review but increase its support of the LRP as a whole. Council members said the program should be better publicized and the application process simplified.
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).
- 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 1,174 applications requesting $1,722,947,881 in total direct costs.
The meeting was adjourned at 1:46 p.m.