DEPARTMENT OF HEALTH AND HUMAN SERVICES
PUBLIC HEALTH SERVICE
NATIONAL ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES ADVISORY COUNCIL
MINUTES OF THE 101st MEETING
June 9, 2020
10 a.m. to 2:30 p.m.
I. CALL TO ORDER
The 101st meeting of the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council (NAMSAC) was held on June 5, 2020, at the National Institutes of Health (NIH) Campus, Building 45, Conference Rooms E1/E2. The meeting was chaired by Dr. Robert H. Carter, Acting Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).
Attendance
Council members present:
Ms. Karen M. Ball, President and CEO, The Sturge-Weber Foundation
Dr. Joan M. Bathon, Professor and Chief of the Division of Rheumatology, Columbia University College of Physicians and Surgeons
Dr. Jill P. Buyon, Director, Division of Rheumatology, Department of Medicine, New York University School of Medicine, and Director, NYU Lupus Center
Dr. Elizabeth H. Chen, Professor, University of Texas Southwestern Medical Center
Mr. Vincent Del Gaizo, Patient Advocate and Founding Member and Past Chair, Friends of Childhood Arthritis and Rheumatology Research Alliance
Dr. Michael Econs, Glenn W. Irwin, Jr., Professor of Endocrinology and Metabolism; Director, Division of Endocrinology and Metabolism; and Professor of Medicine and Medical and Molecular Genetics, Indiana University School of Medicine
Dr. Said A. Ibrahim, Vice Chair for Strategy and Development and Chief, Division of Healthcare Delivery Science and Innovation, Department of Healthcare Policy and Research, Weill Cornell Medicine
Dr. Judith A. James, Chair and Member, Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation
Ms. Rosemary J. Markoff, Co-Chair, Scleroderma Foundation National Advocacy Committee
Dr. Anthony Oro, Eugene and Gloria Bauer Professor of Dermatology, Associate Director and Professor, Center for Definitive and Curative Medicine, Department of Dermatology, Stanford University School of Medicine
Dr. Jennifer J. Westendorf, Margaret Amini Professor of Orthopaedic Regenerative Medicine Research, Mayo Clinic
Dr. Michael J. Yaszemski, Professor, Orthopaedic Surgery and Biomedical Engineering, Mayo Clinic
Staff and Guests
The following NIAMS staff and guests attended:
Staff
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Dr. Nandini Arunkumar |
Dr. Aron Marquitz |
II. CONSIDERATION OF MINUTES
A motion was made, seconded, and passed to approve the minutes of the 100th NAMSAC meeting, held on February 3, 2020.
III. FUTURE COUNCIL MEETING DATES
Future Council meetings are currently planned for the following dates:
September 1, 2020
January 26, 2021
May 18, 2021
August 31, 2021
IV. DIRECTORS REPORT
Dr. Carter welcomed members to the first Advisory Council meeting held entirely via videoconference. NIH’s primary concern during the ongoing Coronavirus Disease 2019 (COVID-19) pandemic is the safety and health of its employees and stakeholders, which has necessitated shifting in-person gatherings to virtual meetings for the foreseeable future.
Personnel Changes
Dr. Carter began by briefly noting some recent personnel changes that have taken place at NIAMS. Dr. Gayle Lester has been named the Director of the Division of Extramural Research and Dr. Robert Colbert has been named the Clinical Director for the Intramural Research Program. Both had been serving in those positions in an acting capacity for some time, and the Institute is pleased that these appointments have been made official.
Dr. Tom Cheever has left NIAMS for a new position at the National Institute of Neurological Disorders and Stroke (NINDS). Dr. Emily Carifi has been hired to replace Dr. Cheever as the Muscle Disorders and Therapies Program Director.
Dr. Carter also briefly updated the Council on the search for the next NIAMS Director. A leading candidate has been identified and negotiations are ongoing. Dr. Carter is hopeful an announcement will be made in the coming few weeks. NIAMS is also looking to hire Extramural Medical Officers. This is an important role with the responsibility of administering extramural research grants and evaluating funded clinical projects. Dr. Carter asked Council members to bring any potential candidates for this position to the attention of Dr. Lester.
NIH and NIAMS Activities
Dr. Carter described recent efforts by the Institute to improve stakeholder and community outreach regarding NIAMS funding opportunities. The goals of this initiative are to increase overall awareness of funding opportunities, reach investigators with expertise outside the traditional NIAMS purview, and encourage new ideas and collaborations to advance and accelerate research. The outreach campaign will consist of a new NIAMS funding e-newsletter, email blasts to highlight specific announcements, and a new dedicated NIAMS funding Twitter account. This effort is being led by Science Communications and Outreach Branch in partnership with the Division of Extramural Research.
Dr. Carter next discussed the NIAMS Roundtable on Subset Analysis in Clinical Studies, which was held on March 11th. NIAMS holds roundtables to seek input from the scientific and lay communities to assist the Institute in planning and to signal interest in a specific topic and hopefully spur research. The goal of the subset analysis roundtable was to foster discussion on clinical study alternatives to traditional randomized controlled trials (RCTs). Most clinical trials funded by NIAMS use traditional RCT designs, which measure the difference in average outcome between participants assigned to one intervention or another. However, it would be more clinically useful to understand who would likely benefit more from (or be harmed by) either intervention in a given population. Ultimately, the goal at the clinical level is to identify “whom to treat, when, with what?” The meeting on March 11th was well attended and the conclusions were that, while RCTs are still the gold standard for medical research, other supplemental and targeted analyses are worth exploring.
Dr. Carter announced that NIH’s All of Us Research Program has entered its beta phase and has begun opening up more parts of its database to researchers via its Research Workbench. The program’s overall goals are to establish a diverse database of one million U.S. participants and to maintain those relationships longitudinally, thereby creating the largest research cohort in the world. Importantly, the database will be free to access for the research community at large. Thus far, over 348,000 participants have been enrolled and 271,000 have completed the initial phases of the program. Access will be granted to researchers through a tiered system. The three initial tiers will be the public tier, registered tier, and controlled tier. The public tier provides basic access to summary statistics and aggregate data only. This tier is already active and requires no login or registration. The Research Workbench is now available in the registered tier where users will have to complete a registration process. At this level, researchers will have access to deidentified electronic health records (EHRs), physical measurements, and survey data. The Workbench also provides tools for running data analysis, although Python coding expertise is needed for some of the more advanced analyses. The privacy controls will be more stringent than required under the Health Insurance Portability and Accountability Act (HIPAA). Later on, the controlled tier will potentially grant access to genomic data, full text clinical records, and other more granular data types. This tier will include further registration requirements that have yet to be defined. Other tiers of access may be established in the future as the database grows.
NIAMS Budget Update
Dr. Carter began by presenting the FY 2020 NIAMS funding plan. Dr. Carter highlighted that the R01 and R21 funding level has decreased to the 11th percentile. This is a decline from the 12th percentile in FY 2019 and the 13th percentile levels of FYs 2016-2018. This decline has occurred as NIAMS’ overall budget has increased in recent years. Dr. Carter presented data from NIH and NIAMS to put the NIAMS payline in context and help explain how this decline in the R01/R21 payline came to be. Overall at NIH, the average cost of research project grants (RPGs) has steadily increased since FY 2013, along with the number of applications. However, the same graph for NIAMS shows that applications have held steady since FY 2016 and the average cost of RPGs has only increased 2 percent. At the same time, NIAMS’ noncompeting RPG commitments have increased steadily since FY 2015, to the level of $308 million in FY 2020. These funds are committed for up to 5 years after the grant is issued and thus cannot be used for new applications. In other words, as the commitments for noncompeting RPGs increase, funds available for new awards decrease. It had been hypothesized that this increase in noncompeting commitments was an after-effect of the FY 2013 budget sequestration, but any grants made at that time have now expired and thus are not the cause of current increases. The growth of noncompeting RPGs is the main factor that limits the funds available for competing RPGs. This growth is generally driven by the cost of commitments that are ending compared to the cost of new commitments from last fiscal year’s competing awards. Other factors that can affect competing and committed funds include changes to NIAMS’ budget, the size of savings from unobligated balances and how those savings are utilized, the impact of long-duration grants (R01) versus short duration grants (R56), and the effects of hardship pay grants awarded at September Council. With regard to hardship pay, the Institute used to follow a more expansive definition and was more generous in its hardship grants. In FY 2016, the Institute awarded $9.6 million, and that number fell to $2.4 million in FY 2019. Notably, the budget impact of these hardship awards is reflected in the following fiscal year and results in a somewhat artificial boost in the payline. Despite NIAMS’ decision to tighten the hardship definition and the decrease in percentile, the actual monetary amount for competing RPGs and the number of awards granted has held relatively steady over the past three years. In other words, a decreasing payline has not translated into a decrease in total money granted or applications approved. Dr. Carter believes this adjustment in reporting and hardship approvals provides a more accurate reflection of the payline as a percentile of grants received in the fiscal year and will allow for more accurate success rate calculations. Dr. Carter cautioned that this discussion does not take into account the effects of the COVID-19 pandemic, which are exceedingly hard to predict given the number of variables at play.
Discussion
Dr. Carter invited questions from Council members on the budget. Dr. Westendorf asked if Dr. Carter had data on non-RPG grants, such as grants to research program centers and SBIR/STTR, and if he could comment more generally on how NIAMS balances funding for centers with funding for individual investigators. Dr. Carter said that last question was perhaps the biggest challenge the Institute faces. Overall, NIAMS has tried to keep the budget for centers stable. There has been an increase in high budget clinical studies and managing those requests has been a challenge. A general discussion of the centers is a good topic for discussion at a future Council meeting, but Dr. Carter noted that team science is one of the focuses of the Accelerating Medicines Partnership (AMP) Lessons Learned Work Group. Ultimately, Dr. Carter sees the centers as supporting and maintaining individual investigator-led studies, which remain the heart of NIAMS’ research.
Dr. James asked if K awards are staying stable. Dr. Carter confirmed that they are. He added that NIAMS puts a slightly greater focus on training awards than other ICs and NIAMS always strives to keep that payline steady.
Dr. Oro asked Dr. Carter to discuss how NIAMS balances the more expensive clinical studies versus basic science. Dr. Carter said clinical studies are the mechanism through which NIAMS has the most direct impact in the short term. Dr. Oro asked whether this might be an area where the Institute can explore partnerships with industry to potentially increase funding. Dr. Carter says investigators can explore partnerships via advocacy groups but that is not something NIAMS does directly. The Institute’s partnerships with pharmaceutical companies have historically been based on drugs rather than monetary support. Very few of NIAMS’ studies are new drug efficacy trials. But Dr. Carter acknowledged these were potential pathways worth exploring and were one of the topics at the Subset Analysis in Clinical Studies Roundtable discussed previously. Cost, clinical applicability, and discovery potential are all considerations that the Institute must weigh when allocating funding.
Dr. Econs asked how many at-risk investigators NIAMS is funding. Dr. Carter said he would get back to Dr. Econs with that number. Dr. Buyon asked if NIAMS has considered bringing back the Hyperaccelerated Award for clinical trials for subset analyses. Dr. Carter said NIAMS’ current ancillary studies mechanism is designed to serve that purpose for time-sensitive study opportunities.
SARS-CoV-2 Response
Dr. Carter briefly highlighted NIH efforts in response to the COVID-19 pandemic. The NIH campus in Bethesda has been closed except for coronavirus-related activities. The National Institute of Allergy and Infectious Diseases (NIAID) drafted a Strategic Plan for COVID-19 Research and COVID-19 Treatment Guidelines. There are a number of NIH initiatives underway supported by supplemental funding from Congress. Accelerating COVID-19 Therapeutics Interventions and Vaccines (ACTIV) is a public-private partnership to help identify and accelerate the study and development of potential interventions. The Rapid Acceleration of Diagnostics (RADx) initiative is a similar effort focused on identifying and supporting innovative testing concepts all the way through regulatory approval and scaling. In general, the international research community’s response to the pandemic has been remarkable and has had a secondary effect of improving data sharing and availability of pre-print studies. Dr. Carter asked the Council to think about long-term changes to research models that might emerge as a result of the global response to the pandemic and what NIH’s role might be in this new era.
Discussion
Dr. Ibrahim said it has been remarkable to see the entire clinical research community in New York shift over to COVID-related research and the amount of study proposals that are being submitted. This has led to a rush of research that has not always stood up to rigorous scrutiny. Dr. Ibrahim hopes that NIH can continue to serve as a backstop for sound science in a chaotic climate where everyone seems to be in a hurry to push out preliminary findings. Dr. Buyon said that some institutes have found ways to reorganize themselves effectively and efficiently, which could serve as models in the future. Overall, she feels the research community’s response has been positive and impressive. Dr. Bathon pointed out that non-COVID research has been shut down in many places, which has been very difficult for investigators in regard to career anxiety and economic concerns. The economic hit to medical institutions has also been massive and will likely have significant repercussions. Dr. Carter said NIAMS will use its authority to extend deadlines where possible.
Dr. James said the pandemic is likely to have a number of long-term impacts on NIH and the research community. There may be permanent changes in the way portions of clinical trials are conducted. Researchers have learned that some aspects of the clinical trial process that were previously believed had to occur in person can now be done remotely in a secure manner. The pandemic may also lead to researchers making better use of publicly available databases and could also encourage team science now that more researchers have experience in collaborative research.
V. CONCEPT CLEARANCE
Dr. Gayle Lester, Director, Division of Extramural Research, presented the concept clearances. This batch consists of five new concepts and three reissued funding opportunities. These concepts are presented to the Council to provide public notice of NIAMS’ activities and to give the Council a sense of NIAMS’ strategic trajectory.
Dr. Lester said she was excited by the new ideas proposed by the program directors and noted that many of the concepts have broad applicability across NIAMS’ mission areas. Dr. Lester encouraged Council members to contact the concept leads with any questions or suggestions after the meeting.
New Concepts:
- Exploring New Mammalian Models for Studying Tissue Regeneration
Lead: Dr. Alexey Belkin - Role of Inflammation Resolution in Chronic Inflammatory Disease within NIAMS Mission Lead: Dr. Heiyoung Park
- Accelerating Host Gene Microbiome Interactions Research in NIAMS Core Mission Diseases
Lead: Dr. Ricardo Cibotti - Evidence, Challenges, and Lessons Learned in Clinical Trials of Cell-based Therapies for Knee Osteoarthritis
Lead: Dr. Ted Zheng - Addressing Health Equity in Osteoarthritis
Lead: Dr. Kristy Nicks
Reissued Funding Opportunity Announcements:
- Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Centers
Lead: Dr. Emily Carifi - Core Centers for Clinical Research (CCCR)
Lead: Dr. Aron Marquitz - NIAMS Clinical Studies Operations Management and Support Contract
Lead: Ms. Shahnaz Khan
Discussion
Dr. Bathon asked why the fifth new concept, “Addressing Health Equity in Osteoarthritis,” is focused solely on osteoarthritis rather than a broader set of conditions. Dr. Lester said the idea was that this concept could establish a model for future efforts to address health equity across the broader NIAMS portfolio. Osteoarthritis (OA) was chosen because of the lack of treatment options and the increase in the number of people suffering from its effects. Dr. Lester invited Dr. Nicks, the concept lead, to respond further. Dr. Nicks confirmed that the idea was to develop this as a proof of concept that could later be applied across NIAMS program areas. A broader scope might have presented obstacles or complications that could be avoided by tackling one program area or specific condition at a time. Dr. Carter added that OA was a field with a great deal of established research on health equity and disparate outcomes. In addition, the initial work with the concept will look at examples and best practices across the medical research community before attempting to develop OA-specific interventions. OA was chosen because the need is so great and the inequities so stark that any progress could have a great deal of impact. Health equity is a massive project for NIAMS, but Dr. Carter feels now is the time to begin. Dr. Ibrahim agreed that the time is ripe to address health equity and lauded NIAMS for responding to rising national sentiment on the issue. He noted that health equity research generally goes through three generations: the first generation identifies and defines existing disparities, the second defines the etiology and targets for intervention, and the third develops the interventions. Dr. Ibrahim suggested that NIAMS was pointing to a fourth generation of health equity research: implementation science and how to disseminate interventions to the population at large. He added that NIAMS might also consider centers focused on population health and social determinants of health to spur team-based science to confront health disparities. Dr. Lester noted that NIAMS recently brought on an epidemiologist, Dr. Stephanie George, as a Health Science Administrator in the Division of Extramural Research, and she has been of great help as NIAMS shapes its health equity efforts. Mr. Del Gaizo pointed out that access to care is one of the major factors in health equity and suggested that NIAMS explore validation of remote rheumatologic assessment modalities as a way to help improve access to care.
Regarding the concept “Role of Inflammation Resolution in Chronic Inflammatory Disease within NIAMS Mission,” Dr. Oro asked whether there might be a way to connect this concept to COVID-19 and acute inflammatory diseases. Dr. Carter said that was an interesting idea and worth considering. Unfortunately, NIAMS has not received much in the way of COVID funding but has worked to identify plans if that funding does arrive.
VI. INTRAMURAL RESEARCH PROGRAM UPDATE
Dr. John O’Shea, NIAMS Scientific Director and Director of the NIAMS Intramural Research Program (IRP), presented the annual IRP update to the Council.
Dr. O’Shea began by giving a general overview of the NIAMS IRP. The IRP consists of approximately 275 staff members (including postdocs, postbacs, and graduate students) and 28 faculty level employees. Overall, the IRP represents 11% of NIAMS’ budget. Dr. O’Shea briefly noted the IRP’s faculty investigators, recent promotions and tenure news, and their areas of interest.
The IRP has been highly productive considering its modest size compared to other ICs. Dr. O’Shea highlighted a few noteworthy publications released in the past year. Dr. Rafael Casellas’ lab has published a number of articles related to transcription, chromatin looping, and the 4D genome. Dr. Mariana Kaplan has an article forthcoming in PNAS on sex differences in neutrophils and interferon response. The study found that female neutrophils are more mature, have greater NET formation, greater IFN-I response, and reduced mitochondrial metabolism as compared to male neutrophils, among other noteworthy findings. Dr. Tim Bhattacharyya’s team contributed to a forthcoming article in the Journal of Experimental Medicine on somatic SMAD3-activating mutations and melorheostosis. Dr. Bhattacharyya has another article in press with JAMA Internal Medicine that shows that the decline in the number of hip replacements since 1990 is correlated with declines in smoking and drinking. Dr. Chris Nagao and Dr. Heidi Kong contributed to a case study in Nature Medicine looking at targeted therapy of single-cell transcriptomic analysis in drug-induced hypersensitivity syndrome.
Dr. O’Shea next reviewed IRP staff awards and career highlights that have occurred in recent months:
- Dr. Markus Hafner received tenure
- Dr. Bob Colbert was named Clinical Director
- Dr. Luis Franco was named a Tenure Track Investigator
- Dr. Tasha Morrison, a Post-Doctoral Fellow, applied for the Independent Research Scholar Program
- Dr. Danielle Chisolm and Dr. Rachael Philips were named Postdoctoral Research Associates as part of the National Institute of General Medical Sciences (NIGMS) PRAT program.
- Dr. Chen Yao applied for the NIAID New Innovators Award
- Dr. Maria Morasso received an NIH Bench-to-Bedside Award
- Dr. Kaplan was elected to the Council of the Association of American Physicians and named Deputy Editor of Arthritis & Rheumatology
- Dr. Kaitlin Quinn will be joining NIAMS in July as a Staff Clinician and was accepted to the American College of Rheumatology/European League Against Rheumatism exchange program
Dr. O’Shea next discussed the IRP’s efforts in support of NIH’s response to the COVID-19 pandemic. NIAMS’ labs on campus have been closed since March 13th and maximal teleworking was instituted on March 16th. Several labs have since been approved for COVID-related activities. Dr. Paul Wingfield’s lab has been working on ACE2 peptide antagonists, MAP30, and momordin. Dr. Casellas’ team has been researching anti-spike protein nanobodies from llamas and engineered “nanomice.” Dr. Vittorio Sartorelli’s lab is studying the epigenomic impact of SARS-CoV-2 proteins. Dr. Hafner’s team is conducting research on SARS-Cov-2 RNA-binding proteins. Dr. O’Shea’s lab has been working on baricitinib studies and developing a COVID-19 Portal.
On June 15th, NIAMS plans to begin returning more employees to campus under appropriate social distancing and Personal Protective Equipment (PPE) usage. The first group to return will be those most negatively impacted by telework. NIAMS’ governing principles for this return to work effort are: Safe, Voluntary, Flexible, Fair, Cooperative, and Respectful.
The NIAMS IRP’s Scientific Retreat, scheduled for June 10th, will take place virtually this year. Scheduled speakers include Dr. Amita Seghal, Department of Neuroscience, University of Pennsylvania; Dr. Brandon Brown, Department of Social Medicine, Population, and Public Health, University of California-Riverside; Dr. Lydia Lynch, Department of Immunology, Harvard University; Ms. Marsha Ivins, NASA Astronaut and Engineer (retired); and Dr. Rachael Clark, Department of Dermatology, Harvard University.
VII. SPECIAL ACTIONS
This portion of the meeting occurred during closed session.
The 101st National Arthritis and Musculoskeletal and Skin Diseases Advisory Council met virtually via Webex on June 9, 2020. Twelve council members attended via Webex. En bloc concurrence was unanimously approved for 746 primary and 274 secondary applications. The total cost requested in year -01 for all applications was $420,871,029.
VIII. ADJOURNMENT
The 101st National Arthritis and Musculoskeletal and Skin Diseases Advisory Council adjourned at 2:30 p.m. Proceedings of the public portion of this meeting are recorded in this summary.
I hereby certify that, to the best of my knowledge, the foregoing summary and attachments are accurate and complete.
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Melinda Nelson |
Robert H. Carter, M.D |