National Heart, Lung, and Blood Advisory Council February 2021 Meeting Summary

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTES OF HEALTH NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NATIONAL HEART, LUNG, AND BLOOD ADVISORY COUNCIL MEETING SUMMARY

February 2, 2021

The 291st meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC) convened virtually on Tuesday, February 2, 2021. The meeting began in closed session at 10:05 a.m. and was open to the public between 2:04 p.m. until adjournment at 5:10 p.m. Dr. Gary H. Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI), presided as chair.

NHLBAC Members Attending

E. Dale Abel, M.D., Ph.D.
Donna K. Arnett, Ph.D., M.S.P.H.
Jennifer DeVoe, D.Phil., M.D.
Grace Anne Dorney Koppel, J.D.
Martha U. Gillette, Ph.D.
Karen Glanz, Ph.D., M.P.H.
Garth Graham, M.D., M.P.H.
David H. Ingbar, M.D.
M. Luisa Iruela-Arispe, Ph.D.
Monica Kraft, M.D.
Kiran Musunuru, M.D., Ph.D.
Mohandas Narla, D.Sc.
Julie A. Panepinto, M.D., M.S.P.H.
Richard S. Schofield, M.D. (Ex Officio)
Dean Sheppard, M.D.
Kevin L. Thomas, M.D.
Sally E. Wenzel, M.D.
Andrew S. Weyrich, Ph.D.
Zachariah P. Zachariah, M.D.

NHLBI Employees Attending

A number of NHLBI staff members were in attendance via Zoom.

NIH Employees and Public Attending

The total number watching/participating online was reported by NIH Videocast to be 218.

CLOSED SESSION

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.

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 recommended 3,520 applications requesting $7,612,609,871 in total costs. For the record, it is noted that secondary applications were also considered en bloc.

OPEN SESSION

I. CALL TO ORDER

Dr. Gibbons reconvened the NHLBAC meeting at 2:04 p.m. in Open Session. He welcomed Council members, NHLBI staff and public attendees to the Open Session of the meeting.

II. ADMINISTRATIVE ANNOUNCEMENTS

Dr. Laura K. Moen (Director, Division of Extramural Research Activities, NHLBI) provided guidance on participating, reminding Council members of conflict of interest requirements. She noted that the meeting would be publicly broadcast and archived on videocast.

III. REPORT OF THE DIRECTOR

Dr. Gibbons announced the recent appointments of Amy Patterson, M.D., as Deputy Director for Clinical Research and Strategic Initiatives in the NHLBI Office of the Director; and Marishka Brown, Ph.D., as Director of the National Center on Sleep Disorders Research (NCSDR).

Accountable Stewardship. Dr. Gibbons provided an update on NHLBI’s appropriations . The FY 2021 budget is 1.09 percent higher than the budget allocated in FY 2020, not including the additional FY 2020 allocation to respond to COVID-19. Investigator-initiated studies remain NHLBI’s highest priority, along with the strategic opportunities embarked upon with the advice of the Council. Dr. Gibbons noted that the rising average costs of investigator-initiated R01s create challenges in maintaining the number of R01 (Research Project) grants , but NHLBI is committed to predictable success rates for R01 grants and high success rates for grants to early-stage investigators and those eligible for career development (K awards).

NHLBI strives to maintain inclusive excellence in biomedicine and tracks sex/gender and race/ethnicity distributions in its awards. Dr. Gibbons highlighted two recent programs at the National Institutes of Health (NIH) level that promote diversity—the Maximizing Opportunities for Scientific and Academic Independent Careers (MOSAIC) program and NIH Faculty Institutional Recruitment for Sustainable Transformation (NIH FIRST) program. The FIRST program is a Common Fund initiative which supports the creation of cultures of inclusive excellence at the institutional level.

Dr. Gibbons acknowledged the challenges posed by the COVID-19 pandemic for the next generation of researchers. He noted that the Institute has been working with the NIH Office of the Director and other NIH Institutes and Centers (ICs) to develop NIH-wide guidance to mitigate the effects of the pandemic on researchers.

Public Health. NHLBI has long supported research that changes clinical practice and recently revised procedures for developing trustworthy clinical practice guidelines. The revised procedures emphasize transparency, systematic review, and communication. In the past, the Council recommended that the Institute develop guidelines on asthma within the framework of the National Asthma Education and Prevention Program (NAEPP), and work on updated guidelines would be presented later in the meeting.

A high-priority area for the Institute is addressing health inequities. Dr. Gibbons described some of the NIH programs that are addressing equity. He stated this effort is particularly timely in the context of the COVID-19 pandemic, which has disproportionately affected communities of color, particularly in the African-American communities, who have also had relatively low rates of vaccine uptake.

A trans-NIH effort has been under way to develop treatments for COVID-19 across its clinical course. NHLBI is supporting a wide range of studies to address both the near and long-term impacts of COVID-19. NHBLI-funded research recently found definitive evidence supporting the use of anticoagulation treatment in those with moderate COVID. Studies have found that monoclonal antibody treatment had no benefit to patients whose disease had progressed, that hydroxychloroquine has no benefit, and that colchicine reduces the risk of complications. Some patients have long-term effects of COVID-19 after viral clearance. This condition is still being defined and clarified, and it is not yet clear who is most at risk. The NIH Director has charged NHLBI, among others, to lead a trans-NIH effort to understand and treat post-acute COVID-19 sequelae.

IV. UPDATE OF THE ASTHMA GUIDELINES

Dr. James P. Kiley (Director, Division of Lung Diseases, NHLBI) provided the background for an overview subsequently presented by Dr. Michelle Cloutier, professor emerita of the University of Connecticut School of Medicine. He noted that the publication of the December 2020 NHLBI update to asthma guidelines began with a recommendation from the NHLBAC in 2014. After an assessment of which areas of asthma management in particular needed systematic review, an NAEPP Coordinating Committee (NAEPPCC) expert panel working group led by Dr. Cloutier was convened in 2018. In a highly inclusive process, more than 650 members of the asthma community provided input. Dr. Kiley pointed out that the 2020 update is a focused update, not a complete revision, as done in 2007. Instead, the update provides new guidance in six key areas and offers 19 recommendations.

In her overview, Dr. Cloutier indicated that the update addressed the four cornerstones of asthma care: assessment and monitoring, therapy, environmental factors, and education. For each new recommendation, the 2020 update provides a section on implementation guidance, providing clinicians with practical suggestions on when they should implement each recommendation and how. Each recommendation is specific for an age group and level of asthma severity. The expert panel included people with diverse expertise—including primary care providers, health policy experts, and those with experience in information dissemination. Focus groups included patients and caregivers. The panel used a transparent method for integrating data so that anyone who disagrees with recommendations can see exactly how they were developed. The panel applied rigorous conflict-of-interest policies. Dr. Cloutier concluded that she believes the end result is a set of “guidelines we can trust.”

Among the recommendations is to use a single inhaler both for daily prevention and acute relief of symptoms for people with moderate, persistent asthma. Preferred and alternative treatments were offered in different contexts. In several cases, the preferred therapies are new recommendations. Fractional exhaled nitric oxide was recommended for use as an adjunct test for asthma diagnosis and management. The panel recommended against using fractional exhaled nitric oxide to assess control, exacerbation severity, or to predict the future development of asthma. Immunotherapy was recommended as an add-on to standard therapy. Allergen mitigation can have small benefits, and the panel did not recommend allergen mitigation as part of routine asthma care, but it did recommend multicomponent mitigation strategies targeted to specific allergens for individuals who are sensitive to specific exposures.

For future directions, the expert panel recommended developing a mechanism for making ongoing guideline updates in a way that is efficient, adheres to the highest standards, and engages a broad range of stakeholders. Moving forward, the panel expects better identification of subpopulations based on their biological characteristics, which will help personalize the management of asthma. The panel would like to encourage researchers to use standardized and validated outcome measures with minimally important differences. One of the challenges the panel faced was the variety of measures used in studies. The panel recommended considering patient preferences in recommending sustainable treatments; for example, many patients say they prefer therapies they can use daily.

Dr. Kiley said that NHLBI will disseminate the guidelines on its own and with partners, including other NIH ICs, other federal agencies, and with representatives from scientific, professional, and voluntary health organizations. NHLBI has prepared materials that are available on its website, including the panel’s full report, a clinicians’ guide, and an at-a-glance guide. In addition, the working group’s report was published in the December 2020 issue of the Journal of Allergy and Clinical Immunology.

V. LOAN REPAYMENT PROGRAM

Dr. Kiley provided an update on NIH’s Loan Repayment Programs (LRPs), which are intended to help individuals pursue research careers. LRPs repay up to $100,000 of researchers’ educational loan debt over 2 years. The 2-year contracts can be competitively renewed. NIH funds approximately 1,300 researchers through LRPs each year. NHLBI is a leading funder of loan repayment recipients among NIH ICs.

Dr. Kiley noted that the LRP was expanded under the 21st Century Cures Act, which gave the NIH Director the authority to increase the maximum repayment amount and to expand eligibility based on workforce and scientific priorities. A working group was convened in the spring of 2018 to make recommendations for revising the program, which led to increasing the maximum loan repayment amount from $35,000 to $50,000 per year. Greater support is also being provided to underrepresented groups. Across NIH, the success rate for applicants to the program has increased from 21 percent to 36 percent.

A new LRP is in development that will focus on emerging and gap areas of research, with awards scheduled to begin in FY 2022. Dr. Kiley welcomed feedback from the Council on how to structure the new LRP. NHLBI also welcomes feedback on benchmarks to use to track the success of the new program and LRPs in general.

Dr. Kiley presented data on the numbers of applications, awards, and success rates of NHLBI LRPs over the last decade. Overall, about 43 percent of all applicants and awardees for the program were female over FY 2011-2019. Success rates for female researchers were initially lower than for male researchers but have recently been higher. About 11 percent of both applicants and awardees to LRPs over FY 11-19 have been underrepresented minorities (URMs). The success rates for URMs have increased in recent years.

The program was originally intended to target graduates of medical school programs in order to encourage physicians to pursue careers in academic medicine rather than careers in private practice. Future directions have discussed the possibility of expanding the programs to include more support for research which does not involve direct patient contact. Some members of the Council agreed that expanding program access could be beneficial to the NHLBI mission.

VI. OPTIMIZING STEWARDSHIP OF EMERGENCY CARE RESEARCH CONDUCTED UNDER EXCEPTION FROM INFORMED CONSENT

Dr. Patterson, and two investigators from the Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN) (Dr. Robert Silbergleit, Department of Emergency Medicine, University of Michigan Medical School, and Dr. Neal Dickert, Division of Cardiology, Emory University) reported their findings about Exception from Informed Consent (EFIC) studies as part of an NIH response to a query from a member of Congress. Dr. Patterson noted that EFIC studies are intended to address major gaps in knowledge in how to administer emergency care. She explained that EFIC studies are restricted to settings where time constraints and the condition of the patient preclude obtaining informed consent for a medical trial and where subjects have life-threatening conditions. EFIC trials have helped improve the care of patients in critical condition. Dr. Patterson welcomed Council suggestions as these findings are shared with a broader research community.

Dr. Silbergleit explained that the work organized through the SIREN network was intended to contribute to NIH’s stewardship of emergency medicine research conducted under EFIC or in prehospital settings. Input was sought from stakeholder focus groups, as well as semi-structured telephone interviews, followed by a thematic analysis of the information gathered. More than half of the stakeholders were paramedics. Ultimately, agreement emerged in the themes:

• Paramedics would like to have more input in trial design
• Stakeholders agreed on the importance of engaging nonmedical leaders in striving to improve patient care
• Generational culture differences were observed, with rising professional standards among younger paramedics
• In-person training was considered important for paramedics

The investigators also undertook a robust review of policies, practices, and training related to EFIC studies, with the goal of delivering a thorough review and model operating procedures for NIH-sponsored multicenter clinical trials that use EFIC for emergency research.

Dr. Dickert noted that EFIC regulations are the only federal regulations that require formal community engagement, with community consultation (CC) required before studies are approved, and public disclosure (PD) required before studies are conducted and after they are finished. Heterogeneous practices have emerged for both CC and PD, but both CC and PD remain unfamiliar to many investigators and Institutional Review Boards (IRBs).

Much of the literature has focused on feedback from the general public through surveys. A number of surveys have asked if people who participate in CC would accept being enrolled in the discussed study. For public disclosure, a variety of methods were used: traditionally, print media, and more recently, internet-based approaches. Institution-based notifications such as flyers in hospitals were also common. Awareness among the public has tended to be low. Dr. Dickert said that it is difficult to know the right metrics for public disclosure beyond making a good-faith effort.

The group identified a consensus in the literature that community consultation should be a two-way process. It is common for researchers to use a combination of methods. Areas of debate are whether to aim for depth versus breadth of feedback, whether to focus on those with a connection to the condition as opposed to representing the geographic community, and how best to assess community acceptance.

For public disclosure, the literature showed consensus around needing a good-faith effort, but no ideal benchmarks were proposed on what a good-faith effort is. There is less focus in the literature on PD than on CC. Open questions include:

• the proper role of social media in the PD process,
• the importance of broad surveys versus targeting people with a stake in the condition,
• the role of central IRBs.

A manuscript about this work is currently under review, and a draft was circulated to the Council. Dr. Silbergleit pointed out that every trial has to be tailored to its particular context. The manuscript he and his colleagues developed is intended to be a useful tool and serve as peer-to-peer guidance rather than as regulatory guidance or a policy requirement of NIH.

Dr. Silbergleit ended the presentation by discussing the insights obtained in a workshop involving family members of patients with cardiac arrest or severe neurotrauma.

• Family members were involved after recovered patients noted that they had little insight to share about their experiences since they were often comatose. Four workshop cochairs decided to invite a small enough group to allow everyone to share their experiences while representing a diversity of experience. In the workshop, 58 themes emerged across five domains: information needs, communication needs, emotional needs, sociocultural needs, and physical needs.
  • As an information need, family members said they often were not sure whether they did not know what was happening with their family member because the information was not known or they were not told. For communication, family members would like clear, consistent, compassionate communication and appreciated when information was repeated since they were often overwhelmed. Many family members wanted to be able to communicate via text or social media.
  • Families expected to be respected no matter their sociocultural differences, and language-interpretation services when needed. Physical needs included wanting space to be close to the patient and care teams, as well as having basic needs met, such as access to toothbrushes and razors. Many family members wished to be able to touch the patient in critical care but refrained from doing so because of the tubing and equipment surrounding the patient and the fear of disturbing the apparatus or breaking rules. Cases where a provider encouraged family members to touch a patient can be very meaningful.

Dr. Silbergleit closed with the suggestion that perhaps there are ways to break the bubble of physical isolation around patients.

VII. DELEGATION OF AUTHORITY

Dr. Moen asked the Council to consider and confirm the delegated authorities for the Institute for 2021. No questions were raised, and delegated authorities were approved.

CLOSING REMARKS

Dr. Moen adjourned the meeting at 5:10 p.m.