July 3, 2018

DEPARTMENT OF HEALTH AND HUMAN SERVICES
PUBLIC HEALTH SERVICE
NATIONAL ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES ADVISORY COUNCIL

MINUTES OF THE 94th MEETING
February 7, 2018
9:00 a.m. to 3:00 p.m.

February 7, 2018 Council Webcast

I.   CALL TO ORDER

The 94th meeting of the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council (NAMSAC) was held on February 7, 2018, at the National Institutes of Health (NIH) Campus, Building 31, Conference Room 10. The meeting was chaired by Dr. Stephen I. Katz, Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

Attendance

Council members present:

Dr. Joan E. Bechtold, Professor, Orthopaedic Surgery, University of Minnesota
Ms. Magdalena Castro-Lewis, former Vice President for Programs, National Alliance for Hispanic Health
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. Michael Holers, Professor, Department of Medicine, University of Colorado Denver School of Medicine
Dr. Judith A. James, Chair and Member, Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation
Dr. Sundeep Khosla, Dr. Francis Chucker and Nathan Landow Research Professor; Director, Mayo Clinic CTSA/Center for Clinical and Translational Science; Dean for Clinical and Translational Science, Mayo Clinic College of Medicine
Dr. Gary A. Koretzky, Dean, Weill Cornell Graduate School; Senior Associate Dean for Research, Weill Cornell Medical College
Dr. Ethan Lerner, Associate Professor of Dermatology, Massachusetts General Hospital
Ms. Rosemary J. Markoff, Co-Chair, Scleroderma Foundation National Advocacy Committee
Mr. William Mulvihill, The Mulvihill Advisory Group
Dr. Amy Paller, Professor, Dermatology, Feinberg School of Medicine
Dr. Grace Pavlath, Senior Vice President — Scientific Program Director, Muscular Dystrophy Association; Professor, Department of Pharmacology, Emory University School of Medicine 
Dr. Christy I. Sandborg, Professor of Pediatrics, Stanford University (via teleconference)
Mr. Richard F. Seiden, Foley & Lardner LLP (via teleconference)
Mr. Alexander Silver, Chairman, Jackson Gabriel Silver Foundation
Dr. Stephen J. Tapscott, Professor, Fred Hutchinson Cancer Research Center
Dr. Gwendolyn L. Powell Todd, Patient, Health Advocate, and Educator 
Dr. Michael Yaszemski, Professor, Orthopaedic Surgery and Biomedical Engineering, Mayo Clinic

Staff and Guests

The following NIAMS staff and guests attended:

Staff
 
Ms. Gema Souto Adeva
Dr. D. Lee Alekel
Ms. Pamela Beheler
Ms. Elizabeth Bouras
Dr. Amanda Boyce
Mr. Gahan Breithaupt
Dr. Nakia Brown
Ms. April Brundidge
Dr. Stephanie Burrows
Dr. Robert Carter
Ms. Cindy Caughman
Dr. Faye Chen
Ms. Jennifer Chi
Dr. Ricardo Cibotti
Dr. Jonelle Drugan
Ms. Barbara Footer
Dr. Nancy Garrick
Mr. Andrew Jones
Dr. Stephen I. Katz
Ms. Shahnaz Khan
Dr. Tony Kirilusha
Ms. Stephanie Kreider
Ms. Anita Linde
Dr. Kan Ma
Dr. Marie Mancini
Dr. Kathryn Marron
Dr. Joan McGowan
Ms. Leslie McIntire
Ms. Melinda Nelson
Dr. Van Nguyen
Dr. Kristy Nicks
Dr. John O‘Shea
Dr. Heiyoung Park
Dr. Carol Parsons
Ms. Andree Reuss
Ms. Trish Reynolds
Mr. Neil Roberts
Dr. Kathy Salaita
Dr. Susana Serrate-Sztein
Ms. Robyn Strachan
Dr. Hung Tseng
Dr. Fei Wang
Dr. Xibin Wang
Dr. Yan Wang
Dr. Chuck Washabaugh
Dr. James Witter
Dr. Xincheng Zheng
 
Guests 

Dr. Lauren Brodd, American Association of Immunologists
Dr. Jon Lorsch, National Institute of General Medical Sciences, NIH
Dr. David Murray, Office of Disease Prevention, NIH


II.   CONSIDERATION OF MINUTES

A motion was made, seconded, and passed to approve the minutes of the 93rd NAMSAC meeting, held on September 6, 2017.


III.   FUTURE COUNCIL MEETING DATES

Future Council meetings are currently planned for the following dates:

June 12, 2018
September 5, 2018
February 5, 2019
June 5, 2019
September 10, 2019


IV.   DIRECTOR’S REPORT AND DISCUSSION

Dr. Katz reminded Council members that the open session of this NAMSAC meeting was being videocast and will be archived on the NIH website. Roughly 150-200 people have been viewing the videocasts of recent Council meetings (about half have been viewing the proceedings in real time). Dr. Katz invited members to encourage their colleagues to view the proceedings of this meeting online at https://videocast.nih.gov/PastEvents.asp.

Dr. Katz thanked Drs. Koretzky, Pavlath, Todd, and Sandborg as well as Mr. Silver for extending their terms as Council members through this meeting and for their many contributions to the group’s deliberations. It is expected that new Council members will be officially approved soon. 

Dr. Katz also thanked Dr. Bechtold for leading the Council Agenda Working Group, noting that this NAMSAC meeting’s agenda was influenced by direct input from this group.

  • Dr. Jon Lorsch, Director of the National Institute of General Medical Sciences (NIGMS), described the framework for the new NIH Strategic Plan for Data Science (Drs. Katz and Lorsch co-chair NIH’s Scientific Data Council, which is overseeing the Plan’s development).
  • Dr. David Murray, NIH Associate Director for Prevention and Director, Office of Disease Prevention (ODP), provided an update on the next ODP Strategic Plan. Dr. Katz reminded Council members that Dr. Murray wrote a Guest Director’s Letter on Advancing Prevention Research at the NIH that appeared in the October issue of the NIAMS Update. 
  • NIAMS Deputy Director Dr. Robert Carter presented some of NIAMS’ experiences with public-private partnerships. 

Budget and Congressional Activities

The NIAMS (and the NIH overall) is operating under a Continuing Resolution through midnight on February 8, 2018. An interim funding plan has been developed and posted on the Institute’s website. President Trump is expected to release his fiscal year (FY) 2019 budget proposal on February 12, 2018. 

This fall, both the House Committee on Energy and Commerce’s Subcommittee on Health and the Senate Committee on Health, Education, Labor, and Pensions held hearings on the implementation of the 21st Century Cures Act. NIH Director Dr. Francis Collins testified for the NIH at both hearings and provided updates on NIH efforts to: (1) balance data sharing needs with privacy concerns; (2) include people of all ages and from all racial and ethnic backgrounds in clinical trials; (3) strengthen the biomedical workforce; (4) reduce the administrative burdens placed on researchers, and (5) advance the NIH Innovation Fund, the Precision Medicine Initiative, the BRAIN® Initiative, the Cancer Moonshot, and the Regenerative Medicine Innovation Project.

As part of the Regenerative Medicine Innovation Project, the NIH held a workshop to explore the challenges surrounding the development of safe and effective products from adult stem cells. Dr. Katz and National Institute of Dental and Craniofacial Research Director Dr. Martha Somerman co-chaired one of the sessions at the December workshop, which was intended to shape the next set of Regenerative Medicine Innovation Project Funding Opportunity Announcements (FOAs). Dr. Katz commented that these FOAs are unusual in that they require a 50-50 partnership between government funds and non-government funds, and that arthritis, musculoskeletal, and skin research were well represented at the meeting. One grant was awarded to a group of skin researchers who are working on gene therapy for epidermolysis bullosa.

Personnel Changes

The Department of Health and Human Services (HHS) is now being led by Dr. Alex Azar, who was sworn in last week. Dr. Azar served as the HHS General Counsel and Deputy Secretary under President George W. Bush, in addition to being a former President of the American Division of Eli Lilly and Company.

At the NIH level, Dr. Norman Sharpless was officially sworn in as the 15th Director of the National Cancer Institute (NCI) on October 17, 2017. Dr. Sharpless served as the Director of the University of North Carolina Lineberger Comprehensive Cancer Center prior to joining the NIH. Dr. Roderic Pettigrew has stepped down as Director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB). At Dr. Collins’ request, Dr. Katz is chairing the search committee and NIBIB Deputy Director Dr. Jill Heemskerk is serving as the Institute’s Acting Director while this nationwide search is underway. Dr. Katz is also serving on the search committee for a new Director of the National Center for Complementary and Integrative Health (NCCIH) following Dr. Josie Briggs’ departure last fall. He asked Council members to provide him with any suggestions for candidates who may serve in the capacity of Director for either the NIBIB or the NCCIH. 

At the NIAMS, Dr. Joan McGowan will be retiring this spring after three decades of government service. Dr. McGowan has directed the NIAMS Division of Musculoskeletal Diseases since 2008 and helped train many of the Institute’s current senior program staff. She has been very active in osteoporosis and women’s health activities at NIH, having been a project officer for the Women’s Health Initiative and the Senior Scientific Editor of the Surgeon General’s Report on Osteoporosis and Bone Health that was published in 2004. Dr. McGowan co-chairs the Federal Working Group on Bone Diseases with Dr. Katz, represents the NIAMS as one of the NIH Common Fund’s Molecular Transducers of Physical Activity Consortium leaders, and is a valued member of the NIAMS Executive Group. 

After 30 years of NIH service, Dr. Bernadette Tyree, who most recently led the Institute’s Cartilage and Connective Tissue program within the Division of Musculoskeletal Diseases, retired in December.

The NIAMS Extramural Research Program (EP) welcomes Dr. Heiyoung Park as a Health Science Administrator in the Division of Skin and Rheumatic Diseases. Dr. Park originally joined the NIAMS as a Senior Research Fellow under the direction of Drs. John O’Shea (NIAMS Scientific Director and Chief of the Molecular Immunology and Inflammation Branch) and Richard Siegel (NIAMS Clinical Director and Chief of the NIAMS Autoimmunity Branch) and moved to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in 2009. The NIAMS EP also welcomes April Brundidge as a Clinical Research Manager; Ms. Brundidge spent the last 7 years at the NIAMS working as a Nurse Specialist, where she cared for research participants and supported protocol implementation, data collection and research participant protection.

HHS and NIH Activities

As part of an HHS-wide effort called Reimagine HHS, the NIH is making changes to increase the efficiency and effectiveness of its administrative functions. As a corollary to the overall Reimagine HHS program, this activity is named Optimize NIH. Initial efforts will focus on improving NIH operations, business processes, and coordination. NIAMS Executive Officer Gahan Breithaupt is serving as the NIAMS representative to Optimize NIH, and Council members will be kept informed of any changes that are likely to impact the Institute’s extramural research activities.

In collaboration with the National Institute of Neurological Disorders and Stroke (NINDS); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); and the National Heart, Lung, and Blood Institute (NHLBI); the NIAMS is assembling an external working group to examine the Senator Paul D. Wellstone Muscular Dystrophy Research Centers program, which is now in its 15th year. Dr. Katz noted that biomedical research has changed dramatically since the program was established, and these four Institutes feel it is time to examine how the program could be adjusted to better support the muscular dystrophy community. Some NAMSAC members will be asked to participate in the evaluation as part of a working group led by Dr. Bechtold. The goal is to complete the evaluation and resulting report within 12 months so that any recommendations can be considered for the next Wellstone FOA.

The NIAMS also is examining how its Extramural Research Program could be restructured to better underpin the goals of investing in the best science, enabling a robust and thriving investigator community, and being responsible stewards of taxpayer dollars. It has been more than 10 years since the Institute examined this aspect of its organization. Feedback from interviews with each of the NIAMS Program Directors and with other staff regarding how to improve the program has been obtained. Dr. Katz presented a draft proposed structure, noting that the operational details are still being worked on and that further discussion would take place during the closed session of this NAMSAC meeting.

Dr. Katz noted that the Institute is also about to develop another long-range plan to guide its scientific efforts, with Council input, over the next 5 years.

During a number of previous NAMSAC meetings, Council members have been updated on NIH’s Next Generation Researchers Initiative, which would prioritize funding for R01-equivalent applications from early-stage investigators and from early-established investigators who are at risk of losing all NIH funding or who have only one active award. The Advisory Committee to the NIH Director (ACD) established a working group that is examining the policy, its projected impact, and ways that it should be improved. Specific recommendations are expected to be unveiled at the June ACD meeting. The recommendations will focus on prioritizing funds to ensure support for investigators who are at risk for losing all funding support, with the general goals of: (1) protecting junior investigators for the future of the research workforce, (2) protecting and stabilizing career trajectories of successful and productive mid-career investigators, (3) developing rigorously vetted and evidence-based policies, and (4) recognizing and mitigating unintended consequences of these actions. 

Dr. Katz reminded the Council of its lengthy discussions about how changes to the NIH’s clinical trial policy would affect how arthritis, musculoskeletal, and skin-related applications for basic biologic or behavioral mechanisms would be reviewed if they meet the NIH definition of a clinical trial. To ensure that all of the applications the NIAMS receives are reviewed by the most relevant study sections, participation in the parent NIH clinical trial FOAs are being limited so that only applications to explore behavioral or biological processes, the pathophysiology of a disease, or the mechanism of action of an intervention will be reviewed by an NIH Center for Scientific Review (CSR) study section. As before, applications for studies of an intervention’s safety, tolerability, efficacy or effectiveness will be reviewed by NIAMS’ internal AMSC study section. In other words, investigators who are proposing clinical trials of interest to the NIAMS will continue to submit their applications in response to the NIAMS-specific FOAs unless their proposed study meets the definition of a mechanistic clinical trial.

Council members were also reminded of NIH’s policy of making the Project Outcomes sections of all Interim and Final Research Performance Progress Reports submitted on or after October 1, 2017, available to the public via NIH RePORTER. As emphasized in a special announcement sent to NIAMS investigators, the NIH will publish outcomes exactly as they are submitted by the grantee. 

The NIAMS website was redesigned to better meet the needs of the nearly 2 million people who visit the site each month. Dr. Katz thanked all who provided input regarding how the site is structured, including more than 70 members of NIAMS Coalition organizations who provided formal feedback on the site’s organization. Council members were provided with a 1-page overview of the key components of the redesigned website.

Since the last Council meeting, the sixth Biennial Coalition Outreach and Education Meeting was held and attended by more than 55 representatives from 38 different patient and professional organizations. Dr. Katz expressed appreciation for the efforts of the Coalition Steering Committee and others who helped plan this event, particularly NIAMS Coalition Co-Chair Ms. Stephanie Hazlett of the American Association of Orthopaedic Surgeons, Mr. Robert Riggs of the Scleroderma Foundation, whose term as Co-Chair ended in December, and incoming Co-Chair Ms. Anna Hyde of the Arthritis Foundation. The meeting provided Coalition members with opportunities to expand their understanding of the NIH and the NIAMS, to meet and network with NIAMS staff and fellow Coalition members, and to share experiences and strategies through breakout sessions and poster presentations.

Dr. Katz drew Council members’ attention to the brochure NIH: Turning Discovery Into Health, which Dr. Collins shared recently when he visited Capitol Hill. Several topics to which NIAMS investigators are contributing are featured in the brochure, which is available online (click here for additional information). NIAMS-funded studies also have been featured in four of Dr. Collins’ recent blog posts. Dr. Collins’ blog can be viewed at https://directorsblog.nih.gov/.

Before concluding his Director’s Report, Dr. Katz noted that the meeting’s agenda also featured an update from Dr. O’Shea on work taking place within the NIAMS IRP.

Highlights of Selected Recent Scientific Advances

Dr. Katz described several scientific advances of interest to the Council. 

  • Work by Dr. Peter Grayson, Head of the NIAMS Vasculitis Translational Research Program, is providing data to end the controversy surrounding the use of positron emission tomography (PET) for assessing inflammatory diseases such as large vessel vasculitis. He demonstrated that the PET imaging marker 18F-flurodeoxyglucose (FDG), which is rapidly absorbed by inflammatory cells that infiltrate patients’ arteries, can be useful in combination with clinical assessment to distinguish between patients who have large vessel vasculitis or other diseases with similar symptoms. FDG-PET may also help clinicians predict the likelihood of disease relapse in these patients (Arthritis Rheumatol. 2018 Mar;70(3):439-449. doi: 10.1002/art.40379. Epub 2018 Feb 6. PMID: 29145713).
  • To determine whether any changes in a patient’s blood could predict the development of interstitial lung disease, a group of researchers including Drs. Shervin Assassi and Maureen Mayes at the University of Texas Health Science Center at Houston and Dr. Sandeep Agarwal at Baylor College of Medicine examined samples and data collected through two studies of scleroderma patients—the Genetics versus Environment in Scleroderma Outcome Study and the Canadian Scleroderma Research Group. Analysis of both groups independently revealed an association between higher blood levels of the chemokine C-C motif ligand 2 (CCL2), and faster declines in lung function, suggesting that CCL2 can be used to identify patients who are at highest risk of rapidly progressing interstitial lung disease (Arthritis Rheumatol. 2017 Sep;69(9):1871-1878. doi: 10.1002/art.40171. Epub 2017 Aug 8. PMID: 28575534).
  • Building on work showing that a protein called FLIP is necessary for the differentiation and survival of inflammatory macrophages, the laboratory of Dr. Richard Pope at Northwestern University Feinberg School of Medicine determined that FLIP also impacts inflammation and bone erosions in rheumatoid arthritis (RA). When the researchers developed a mouse model that produces lower than normal levels of FLIP, they observed that these mice experienced joint swelling sooner than controls during the early phase of arthritis, but had lower peak disease scores and significantly less severe disease during the late phase (Arthritis Rheumatol. 2017 Sep;69(9):1762-1771. doi: 10.1002/art.40151. Epub 2017 Aug 1. PMID: 28511285).
  • Investigators at the University of California, San Francisco, including NIAMS grantee Dr. Ann Schwartz, studied 30 obese women to address whether changes in glucose metabolism and fat depots following bariatric surgery affect bone. They examined changes in bone marrow fat, which is a dynamic and unique fat depot thought to regulate both bone and fat. Data from diabetic and non-diabetic women suggest that glucose metabolism and weight loss may influence marrow fat, which in turn seems to influence bone mineral density (J Bone Miner Res. 2017 Nov;32(11):2239-2247. doi: 10.1002/jbmr.3212. Epub 2017 Aug 9. PMID: 28791737).
  • Dr. Yi-Ping Li and colleagues at the University of Texas Health Science Center at Houston demonstrated that tumor-secreted extracellular vesicles that are coated with heat shock proteins play a role in cachexia (the significant loss of skeletal muscle mass due to increased breakdown of muscle protein and reduced protein synthesis that cannot be halted through nutritional intervention or exercise) independent of their effects on the immune system (Nat Commun. 2017 Sep 19;8(1):589. doi: 10.1038/s41467-017-00726-x. PMID: 28928431).
  • Investigators from the laboratory of Dr. Brian Kim at Washington University School of Medicine in St. Louis outlined the mechanisms by which IL-4 induces itch and demonstrated that the IL-4R-alpha-JAK1 signaling pathway is a promising target for the treatment of chronic itch. They showed that sensory neurons are directly activated by the type 2 cytokine IL-4, and that this activation results in scratching behavior. They also deleted the receptor IL-4R-alpha in sensory neurons and discovered that chronic itch depends on the signals transmitted by this receptor via the JAK1 signaling pathway. Finally, the researchers demonstrated that treatment with the JAK inhibitor tofacitinib (which was developed by Pfizer in collaboration with Dr. O’Shea’s laboratory) ameliorates chronic itch in chronic idiopathic pruritus patients who had not responded to other immunosuppressive treatments (Cell. 2017 Sep 21;171(1):217-228.e13. doi: 10.1016/j.cell.2017.08.006. Epub 2017 Sep 7. PMID: 28890086). 
  • Current arthritis estimates rely on a single National Health Interview Survey (NHIS) question asking participants whether they remember being ever told by a health professional that they have arthritis, although more arthritis related information is also collected in the course of the survey. Drs. Reza Jafarzadeh and David Felson at Boston University School of Medicine recalculated the arthritis prevalence using a method they developed that incorporates a person’s responses to two additional questions related to presence and duration of joint symptoms. When applied to data from the 2015 NHIS, the investigators’ model revealed a substantial fraction of young-to-middle-aged adults with arthritis symptoms are currently misclassified as healthy based on a physician-diagnosed arthritis criterion alone, but are captured by the addition of questions on joint pain, aching or stiffness and the timeframe of these symptoms. This research provides a revised profile that reflects the occurrence of arthritis in younger individuals and an updated estimate of the national prevalence of this disease in the overall population (Arthritis Rheumatol. 2018 Feb;70(2):185-192. doi: 10.1002/art.40355. Epub 2018 Jan 3. PMID: 29178176).

Discussion

In response to a question from Mr. Silver, Dr. Katz explained that the chronic itch findings from Dr. Kim’s laboratory represent one of many potential pathways to target, although it has yet to be determined whether the IL-4R-alpha-JAK1 signaling pathway plays a role in all forms of itching (e.g., itching related to wound healing). Dr. Lerner noted that he participated in a NIAMS Roundtable discussion 8-10 years ago during which it was noted that a number of stakeholders (patient advocacy groups, industry, etc.) were becoming increasingly aware of the importance of itch-related research. Since that time, there have been significant advances in the understanding of itch—Dr. Lerner asked about whether itch could be considered a disease, rather than a symptom, noting that this would be useful in terms of drug approvals.

Dr. Paller agreed with the need to begin considering itch as its own disorder, particularly in terms of examining inflammatory pathways and moving forward to create classes of drugs specifically to treat itch. Dr. Katz commented that there is difficulty in considering itch a disease because of the assumed many different pathways associated with itch from wound healing, itch from renal disease, itch from atopic dermatitis, etc. Dr. Koretzky noted that hypertension is similar to itch in that it has many different causes and/or underlying mechanisms, yet it is considered a disorder unto itself. Dr. Katz commented that if patient-reported outcomes become more embraced by the U.S. Food and Drug Administration, it may facilitate easier approval of medications specifically for treating itch. Dr. Paller commented on the need for the field to move beyond simply quantifying the intensity of a person’s itch to explore the quality of a person’s itch and comparing that to what is seen in biomarker studies and responses to different agents. She also agreed that a greater emphasis on patient-reported outcomes would be helpful. Mr. Silver noted that in a small, anecdotal survey of the epidermylosis bullosa community, itch ranked highest (even higher than pain) as the issue that troubled patients most.
 

V.   DEVELOPING AN NIH STRATEGIC PLAN FOR DATA SCIENCE 

Dr. Lorsch described the framework for an NIH-wide strategic plan for data science. This plan was requested by Congress and will focus on:

  • Modernizing the data resource ecosystem to increase its utility for researchers and other stakeholders and to optimize its efficiency of operation
  • Enhancing data sharing, access, and interoperability
  • Improving the ability to use electronic health record (EHR), clinical, and observational data for research while ensuring data confidentiality
  • Modernizing infrastructure and increasing capacity.

The Scientific Data Council has agreed on the following working definition for the term data science: “An interdisciplinary field of inquiry in which quantitative and analytical approaches, processes, and systems are developed and used to extract knowledge and insights from increasingly large and/or complex sets of data.” Dr. Lorsch explained that the data housed in NIH-supported repositories should be “FAIR” (i.e., Findable, Accessible, Interoperable, and Reusable). Five domains of data science have been identified as part of the plan’s development: (1) data infrastructure; (2) data resources; (3) advanced management, analytics, and visualization tools; (4) workforce development; and (5) policy, stewardship, and sustainability. 

Dr. Lorsch described the organization of the NIH-wide strategic plan for data science, with overarching goals tied to the domains of data science and supported by strategic objectives, implementation tactics, and milestones and performance measures. The plan’s overarching goals and strategic objectives include:

  • Overarching Goal 1: Support highly efficient and effective data infrastructure for biomedical research
    • Strategic Objective 1-1: Optimize data storage, access, and security
    • Strategic Objective 1-2: Connect NIH data systems.
  • Overarching Goal 2: Promote the modernization of the data resources ecosystem
    • Strategic Objective 2-1: Modernize the data repository ecosystem
    • Strategic Objective 2-2: Support the storage and sharing of individual datasets
    • Strategic Objective 2-3: Leverage ongoing initiatives to better integrate clinical and observational data into biomedical data science.
  • Overarching Goal 3: Support the development and dissemination of advanced data management, analytics, and visualization tools
    • Strategic Objective 3-1: Support useful, generalizable, and accessible tools and workflows
    • Strategic Objective 3-2: Broaden use of specialized tools
    • Strategic Objective 3-3: Improve discovery and cataloging resources.
  • Overarching Goal 4: Enhance workforce development for biomedical data science
    • Strategic Objective 4-1: Enhance the NIH workforce
    • Strategic Objective 4-2: Expand the national research workforce
    • Strategic Objective 4-3: Engage a broader community.
  • Overarching Goal 5: Enact appropriate policies to promote stewardship and sustainability
    • Strategic Objective 5-1: Develop policies for a FAIR data ecosystem
    • Strategic Objective 5-2: Enhance stewardship.

As he described the overarching goals and strategic objectives, Dr. Lorsch made the distinction between databases and “knowledge bases.” Databases are data repositories that store, organize, validate, and make accessible the core data related to a particular system or systems. For example, the core data for a model organism database might include genome, transcriptome, and protein sequences and functional annotations of gene products. Knowledge bases accumulate, organize, and link growing bodies of information related to core datasets. An example is information about expression patterns, splicing variants, localization, protein-protein interaction and pathway networks related to an organism or set of organisms, and publication information. Dr. Lorsch also explained why the NIH-wide strategic plan for data science separates the support of databases, knowledge bases, and tool development. NIH-funded data resources historically have been evaluated and funded as research grants, and that database and knowledgebase functions, needs, and uses are not the same. Furthermore, there is a need for usage, utility, impact, and efficiency metrics for each kind of research and for tools. 

The NIH-wide strategic plan for data science will be delivered in final form to Congress in May this year. Before then, stakeholder feedback will be obtained through a Request for Information (RFI) and presentations at Institute advisory council meetings; short-, medium-, and long-term priorities will be identified; and performance measures and milestones will be identified.

Discussion

Dr. Katz pointed out that the NIH on its own cannot support all of the datasets and knowledge bases it needs to access. Dr. Lorsch explained that the amount of data being generated and stored is increasing exponentially, and the associated costs are rising as well. There will come a point at which the cost of storing the data will exceed the cost of generating it; therefore, it is critical to: (1) identify what data need to be stored and for how long, and (2) find more efficient ways to store data and provide access to the community. The current model, which dates back at least 30 years, is not the most efficient or the most useful for the research community.

Dr. Yaszemski discussed patient data in an EHR and interoperability. He asked about the prospects of involving Epic and Cerner, two of the largest private companies in this space. Dr. Lorsch responded that ideally, Epic, Cerner, and the many other private enterprises developing electronic EHRs will be engaged and that promoting research that leads to improved communication across different platforms is an important need. Dr. Katz discussed utilizing EHR data in research efforts, noting that the NIH may be able to enhance the knowledge base, but that utilization of EHRs to help facilitate research efforts is not a primary goal at this point.

Dr. Koretzky asked about potential partnerships with other public agencies, such as the National Science Foundation (NSF), noting that the NSF and certain other federal groups have expertise in managing big data issues. Dr. Lorsch (who is the NIH liaison to the NSF) agreed; noting that the NIH-wide strategic plan for data science specifically lays out the need to work with other federal and private funding agencies, both nationally and internationally.

Dr. James asked about making NIH intramural data more accessible to the extramural community. Dr. Lorsch agreed that this would be helpful and asked Council members for suggestions regarding any intramural datasets that the community at large would benefit from being able to access.

Dr. Econs noted that the Indiana Health Information Exchange serves as an example of participating hospitals sharing EHR data across platforms and systems. The Exchange is not perfect, but its experiences, challenges, and lessons learned may be of interest to the Scientific Data Council.

Dr. Sandborg asked about measures being taken to ensure quality, especially in terms of tool validation. Dr. Lorsch agreed that data quality is a key issue; moving the community towards agreed-upon standards that are put in place will be challenging but is essential.

Dr. Katz closed the discussion session by noting that there is an NIH Data Commons pilot project that in many ways represents a microcosm of the challenges and opportunities described by Dr. Lorsch. This pilot is using a series of datasets that will serve as test cases for the principles, policies, processes, and architectures that need to be developed to access and share the data. Dr. Koretzky will be joining the NIH Council of Councils and may be asked to provide an update at a future NAMSAC meeting.

VI.   DEVELOPING A STRATEGIC PLAN FOR THE NIH OFFICE OF DISEASE PREVENTION (ODP)

ODP’s mission is to: improve the public health by increasing the scope, quality, dissemination, and impact of prevention research supported by NIH; and (2) provide leadership for the development, coordination, and implementation of prevention research in collaboration with NIH Institutes and Centers (ICs) and other partners. Dr. Murray outlined a few of the Office’s key current activities, such as managing the $100 million Tobacco Regulatory Science Program, serving as the liaison to other HHS activities and partners like the U.S. Preventive Services Task Force, offering evidence-based assessment programs such as Pathways to Prevention (the next Pathways to Prevention workshop will be in October and led by the NIAMS, and will be on the subject of the appropriate use of drug therapeutics for osteoporotic fracture prevention), training and education activities, and co-funding NIH projects that support prevention research.

ODP’s current 5-year strategic plan is set to expire this year, and so the Office is developing a new plan for 2019-2023. Dr. Murray described ODP’s proposed strategic priorities and associated objectives for the next 5 years as follows:

  • Systematically monitor NIH investments in prevention research and the progress and results of that research.
    • Characterize and report on the NIH prevention research portfolio based on the taxonomy for prevention research developed by the
    • Regularly assess the progress and results of NIH investments in prevention research.
    • Partner with NIH ICs and Offices to disseminate ODP portfolio analysis tools and related data.
  • Identify prevention research areas for investment or expanded effort by the NIH.
    • Work with a variety of stakeholders to identify needs in prevention research.
    • Compare identified needs in prevention research with the current NIH portfolio to identify gaps in prevention research.
    • Work across the ODP and with NIH ICs and Offices to identify the most promising/feasible prevention research gaps for investment or expanded effort.
  • Promote the use of the best available methods in prevention research and support the development of better methods.
    • Provide resources for review staff to identify experts in prevention research methods for recruitment to review panels.
    • Provide training in prevention science methods to NIH program and review staff, to NIH investigators, and to investigators external to NIH.
    • Serve as a resource to other ICs on prevention science.
    • Collaborate with other ICs and Offices to strengthen NIH policies and procedures to encourage the use of the best available methods.
  • Promote collaborative prevention research projects and facilitate coordination of such projects across the NIH and with other public and private entities.
    • Coordinate and support the development of collaborative prevention initiatives to address gaps in prevention research and practice.
    • Develop a triennial State of Prevention Conference highlighting research progress, gaps, and opportunities focused on a specific prevention gap of cross-cutting relevance across NIH.
  • Advance the understanding of prevention research, increase the availability of prevention research resources and programs, and enhance ODP’s stakeholder engagement.
    • Increase the visibility of information about prevention research.
    • Engage and collaborate with stakeholders to coordinate and enhance communications about disease prevention research.
    • Support the communications-related efforts of all ODP strategic priorities including the promotion of ODP activities, events, and resources.

Dr. Murray and the ODP are obtaining input on the Office’s draft strategic plan from advisory councils such as the NAMSAC, IC Directors, and NIH staff. The draft plan was posted for public viewing in November 2017, at which time an RFI was issued. By the end of March 2018, the draft plan will be revised based on feedback, and milestones/timelines will be identified. The Office plans to prepare a staffing plan and resource request by the end of May, submit the package for approval by the end of June, and release the final plan on September 30, 2018. In concluding his remarks, Dr. Murray asked Council members to consider the following:

  • How can the ODP help the NIAMS advance prevention research?
  • Are there other strategic priorities the ODP should consider?
  • Are there cross-cutting themes that the ODP should consider, apart from the draft priorities?

Discussion

Dr. Khosla noted that several NAMSAC members have been involved in the Pathway to Prevention project on facture prevention and commented that from his perspective: (1) there is significant value being provided by this effort in the careful summary of the state of the science that will be provided, and (2) in those areas for which there is significant debate, having an agency that is external to the specialists that can provide an objective assessment is key. Dr. Murray agreed, explaining that the Pathways to Prevention activity is centered around an extensive evidence review and an independent panel of scientists who are not experts in the topic (but are expert in relevant general scientific areas) and do not have a personal/professional stake in it, such that they can evaluate the science independently and objectively. The panel’s final report is published in a peer-reviewed journal, and federal partners are engaged to identify what steps agencies can take to address the recommendations in the panel’s report.

Dr. Holers noted that autoimmune disease prevention cuts across many NIH ICs and there are a number of emerging common themes in areas related to autoimmune disease prevention. He encouraged the ODP to consider a Pathways to Prevention effort focused on this area.

Dr. James suggested that additional work is needed in the area of risk modeling and identifying timeframes when patients are most at risk for developing a disease. Dr. Murray explained that the ODP is not able to offer resources at this granular level for individual investigators, but it is well positioned to convene a group to discuss these issues and generate recommendations. Dr. James also asked about ODP integration efforts with the All of Us Research Program, the U.S. Centers for Disease Control and Prevention (CDC), and other groups building large consortia/cohorts. Dr. Murray noted that the ODP is involved in many of these activities. For example, he is a member of the All of Us Institutional Review Board and was a member of the All of Us planning team, and the ODP is the liaison office for the Community Preventive Services Task Force, which is supported by the CDC. Additionally, the ODP has been working with representatives from the NIH Environmental Influences on Child Health Outcomes (ECHO) Program.

In response to a question from Dr. Koretzky, Dr. Murray explained that the ODP does not have a fellowship program, but has considered establishing one if resources become available. The ODP does offer online courses and webinars that are available for NIAMS fellows and fellows from other ICs.

Dr. Katz clarified that although the Pathways to Prevention panel members are not experts on the topic being considered, these meetings are replete with other attendees who are experts on the topic and who can provide presentations, perspectives, and input for panel members’ consideration.

VII.   PUBLIC-PRIVATE PARTNERSHIPS: PAST AND FUTURE

The NIH depends on partnerships with academia, patient advocacy groups, professional organizations, other federal agencies, and the biotech and pharmaceutical industries, both for research efforts and for disseminating the results of that research. These partnerships are vital to the agency’s mission. Examples of NIAMS partnerships include those in the areas of: (1) committees and workshops (e.g., federal working groups, ancillary sessions during scientific meetings, roundtables); (2) communications (e.g., the NIAMS Coalition); (3) training (e.g., training and career development awards, career development bridge funding awards); and (4) research (e.g., pilot or bridge funding of meritorious research applications outside of the NIH payline, supplements to new or existing grants, public-private partnerships).

Dr. Carter described the genesis of the following examples of research-oriented NIAMS public-private partnerships:

  • The North American Rheumatoid Arthritis Consortium (NARAC). The NARAC focuses on genetics and began as a self-assembled group of investigators who joined with the Arthritis Foundation (AF) and subsequently the NIAMS, National Institute of Allergy and Infectious Diseases (NIAID), and Office of Research on Women’s Health (ORWH).
  • The Osteoarthritis Initiative (OAI). OAI was developed to create research resources to aid in the identification and evaluation of biomarkers as candidates for surrogate endpoints for OA. More than 450 publications have come out of this important initiative. The OAI grew out of broad NIH interest in biomarkers, with leadership of then NIH Director Dr. Harold Varmus, and developed with leadership from the NIAMS and National Institute on Aging (NIA). Through the OAI, the NIH serves a convener of researchers and industry. Initial funding through the NIH has been through the NIAMS, NIA, NCCIH, National Institute of Mental Health (NIMH), ORWH, and NIBIB. Initial funding through the Foundation for NIH (FNIH) has been through Pfizer, Merck, GlaxoSmithKline, and Novartis.  
  • The Accelerating Medicines Partnership (AMP) in Rheumatoid Arthritis/Systemic Lupus Erythematosus (RA/SLE). The AMP in RA/SLE is focused at examining -omics based on tissue from the site of disease in humans with RA or SLE, focusing mostly on single-cell -omics in these tissues. This partnership traces back to a meeting of the heads of research and development at major pharmaceutical companies and NIH leadership that is now held annually. Dr. Carter noted that even in this day and age, with all of the research that has been conducted, only about half of the drugs that make it to phase 3 late-stage studies are actually approved. Roughly two-thirds of those drugs that are not approved fail because they simply do not work. This partnership is intended to address this issue by better understanding disease mechanisms.
  • FNIH Biomarkers Consortium Bone Quality Project. This partnership was formed to advance the qualification of biomarkers for drug development and patient management with the goal of improving the ability to predict fracture. The project team includes the NIH, U.S. Food and Drug Administration, academic researchers, industry, the American Society for Bone and Mineral Research, and the Dairy Research Institute®. The group published the results of a review of biomarkers for bone quality in 2017 in the Journal of Bone and Mineral Research. The NIH functions as a convener of this group and provides staff support.

Dr. Carter characterized each of these research-oriented NIAMS public-private partnerships as extraordinarily important efforts. There are some questions that require a team science approach and a level of funding that the NIH cannot provide on its own—in some of these instances, partnerships are necessary. He noted that the NIAMS welcomes the opportunity to explore future partnerships that align with the Institute’s goals and budget.

Discussion

Dr. Castro-Lewis suggested that there is a need to more clearly identify how the NIAMS includes representation from ethnically diverse and underserved communities in its partnership efforts. Dr. Katz noted that careful attention was given to including minority populations in the cohort of 5,000 participants in the OAI. At that time, leadership from the National Center for Minority Health and Health Disparities (now the National Institute on Minority Health and Health Disparities, or NIMHD) was included in planning efforts. Both the National Center for Minority Health and Health Disparities and the ORWH have made very important contributions to the OAI. Dr. Katz explained that the NIAMS is well aware of the need to ensure that underserved communities are included in these types of partnership efforts as well as the need to engage with the NIMHD. Dr. Castro-Lewis suggested that the Institute present these inclusion activities to other interested/applicable groups in an effort to raise awareness of the Institute’s inclusion efforts and to emphasize their importance.

Mr. Mulvihill asked about NIAMS’ role moving forward in terms of initiating public-private partnerships as well as facilitating their development and progress. He also asked about the amount of money that NIAMS Coalition member organizations spend on research and whether their efforts leverage what the NIAMS and others are doing. Dr. Katz noted that the Rheumatology Foundation was one of the first groups to supplement the Institute’s K Awards, and those K awardees were found to perform better in a subsequent competitions. The NIAMS shared this information and as a consequence, the National Psoriasis Foundation and Alopecia Areata Foundation have also started to supplement NIAMS K awardees. Asking these types of organizations to invest in research that is not necessarily focused on their disease areas, however, is a much more challenging prospect. Mr. Mulvihill suggested that it may be helpful to present the totality of funds being spent on research in the disease areas of interest to the NIAMS to help begin these types of discussions and potentially accelerate discoveries.

Mr. Silver asked if there were lessons learned from existing NIAMS public-private partnerships that can be used to help inform both the NIAMS and its stakeholders in terms of what has worked and what has not been successful. Dr. Katz described unsuccessful partnership attempts with the American Skin Association and the American Orthopaedic Research and Education Foundation. In both instances, the challenge was the lack of research in the area of prevention, clinical studies, epidemiology, etc. Dr. Carter suggested that there are different tensions between groups that the NIH organizes itself compared with existing, coherent groups that enter into partnerships with the NIH. Dr. Katz agreed and referenced the Childhood Arthritis and Rheumatology Research Alliance (CARRA) as an existing group that has been supported by the NIAMS—CARRA came to the NIAMS having already identified high-priority research questions and clinical studies. Dr. Serrate-Sztein, Director of the NIAMS Division of Skin and Rheumatic Diseases, noted that the NIH has had to work within the context of uncertainties and instability within industry and non-profit partners—these uncertainties and instabilities can be extremely challenging and can threaten the stability of the partnership.

In response to a question about ensuring the sustainability of partnerships, Dr. Carter used AMP as an example and explained that the creation of a product or deliverable that is useful and valuable to the community at large is an important consideration (in the AMP example, a database will be generated and used to test hypotheses for new, investigator-initiated studies). The importance of partnership outcomes relates to the sustainability issue. For AMP, the goal is to change the way research is conducted.  

VIII.   NIAMS STATE OF THE IRP 2018

Dr. O’Shea provided Council members with an overview of NIAMS IRP activities, noting that the IRP represents approximately 10.4% of the total NIAMS budget. The IRP has 23 core faculty members as well as 21 clinical faculty members. The IRP includes the Office of Science and Technology and a Training and Outreach Branch, and is reviewed by the Board of Scientific Counselors (BSC).

Last year, the Dermatology Branch was added to the NIAMS IRP (previously, the Branch was housed within the NCI). Dr. O’Shea provided a brief overview of the research interests and areas represented by the investigators within the Branch:

  • Dr. Heidi Kong: the microbiome (recently, the microbiome in children with atopic dermatitis)
  • Dr. Isaac Brownell: sensory Merkel cells and Merkel cell carcinoma as well the biology of Merkel cells
  • Dr. Chris Nagao: cellular immunology of skin 
  • Drs. Ed Cowen and Dominique Pichard: graft versus host disease and the effects of JAK inhibitors.

Dr. O’Shea then provided highlights of progress and advances made by the NIAMS IRP:

Systemic Autoimmunity Branch / Lupus Clinical Trials Unit:

  • For SLE, a phase 1 trial of omalizumab has been completed and the analysis is being performed. Similarly, a phase 1 trial of tofacitinib has been completed and that analysis is being performed.  
  • IRP staff are in the planning stages for a Phase 2 trial of tofacitinib in lupus nephritis.
  • A trial on PPAR-gamma agonists has met 50% of its recruitment goal.
  • Imaging studies on the vascular complications of lupus are in progress at the NIH Clinical Center; gene expression studies are also ongoing.
  •  For pediatric lupus, IRP staff are conducting whole-genome sequencing of a multinational cohort of pediatric lupus patients and relatives in the United States, Canada, Mexico, and South America. Sequencing has been completed; analysis is ongoing.

Vasculitis Translational Research Program

  • A total of 331 patients with vasculitis were evaluated at the NIH Clinical Center in 2017. Also in 2017, IRP staff published papers on novel mechanisms of drug-induced vasculitis in JCI Insight and Arthritis and Rheumatism. In 2018, IRP staff published a paper on advanced molecular imaging in large-vessel vasculitis in Arthritis & Rheumatology.
  • IRP researchers are studying relapsing polychondritis. This is a new disease of interest being studied by IRP staff, with 51 patients evaluated at the NIH in 2017. A comprehensive clinical phenotyping and specimen repository has been established. An international working group has been formed and tasked with creating classification criteria as its initial activity.

Translational and Genomics Unit

  • IL-1 receptor antagonist has been identified as a risk locus in systemic juvenile arthritis. One particular type of variant (sJIA-associated variants) has been shown to predict non-response to anakinra treatment.

Laboratory of Muscle Stem Cells and Gene Regulation

  • A paper was published earlier this year in Molecular Cell examining Spt6 and its role in interacting with superenhancer loci in muscle stem cells and showing its criticality in the expression of these genes and promoting the stemness of muscle genes.

Muscle Disease Unit

  • IRP researchers discovered that children can have anti-HMG coA reductase myopathy. The class II HLA allele DRB1*07:01 is a strong risk factor in children. Younger patients have more severe disease and show slower recovery. A child who came to the NIH Clinical Center diagnosed with a muscular dystrophy was found to have anti-HMGCR antibodies and showed rapid improvement with IVIG treatment. Results were published in AC&R, Rheumatology, and Muscle and Nerve.

RNA Biology Group

  • IRP researchers found that DND1 binds specific sequences in mRNA and degrades the bound mRNA. The loss of DND1 results in disruption of RNA clearance pathway, infertility, inflammation, and cancer. Results of this work were published in a 2017 issue of Nature.
  • Micro RNA-mediated posttranscriptional silencing has been found to be critical for stem cells.
  •  A new autoinflammatory disease resulting from mutations of the gene TRNT1 called sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD) has been identified and being studied in collaboration with investigators at the NHGRI. SIFD has been found to be responsive to TNF inhibitors.

Laboratory of Molecular Immunogenetics

  • A 2017 paper published in Molecular Cell shows that Myc regulates B cell chromatin remodeling.
  • IPR researchers are trying to relate this finding to transcription and create/modulate these loops. The molecule cohesin has been identified as being important in the formation of these loops.

IRP staff have been recognized for some their accomplishments. Dr. Mariana Kaplan (Senior Investigator and Chief of the Systemic Autoimmunity Branch and Acting Director of the Lupus Clinical Trials Unit) was inducted into the Association of American Physicians. Dr. Robert Walker (Chief of the Career Development and Outreach Branch) was recognized by Meharry Medical College with the Harold D. West Distinguished Biomedical Science Award. Dr. O’Shea received the American Association of Immunologists’ 2018 Steinman Award for Human Immunology Research.

Moving forward, the NIAMS IRP plans to recruit a new Assistant Clinical Investigator. There are plans to develop a joint NIAMS, NIDDK, NHLBI, and NINDS cryo-EM facility. An initiative led by Dr. Siegel known as the Genome Ascertainment Cohort is ongoing. This joint effort with collaborators at the NHGRI, NIMHD, and elsewhere at the NIH has enrolled 1,500 NHGRI Clinseq participants, including 500 African American participants, as well as 8,000 participants from the Inova Longitudinal Genomics Cohort, individuals on NIH study protocols, and new recruits focused on Hispanic ethnicity. This 2-year IRP pilot project will be made available to the extramural community. Participants have been consented for re-contact for the purpose of secondary studies.

Discussion

Dr. Koretzky, a former BSC Chair, commented that the IRP is a very different intramural research program compared to those from other NIH ICs, in a positive way. The leadership it provides within the NIH is extremely valuable, and there are significant and beneficial intra-program interactions between clinicians and basic investigators as well as interactions between other IRPs. He congratulated Dr. O’Shea and the IRP for all of its accomplishments.

Dr. Bechtold asked about IRP plans in the area of bone and biomechanics. Dr. O’Shea commented that the NIAMS IRP has struggled in the area of orthopedics with regard to finding a good balance between examining genes and seeing patients (i.e., basic vs. clinical science). The NIAMS IRP has a contract in place with an orthopedic surgeon (Dr. Timothy Bhattacharyya, Head of Orthopedics Research, NIAMS), who has recruited a cohort of melorheostosis patients for study. Dr. Katz noted that the NIAMS has made a number of efforts to build up the orthopedics program within the NIAMS IRP.

IX.   REORGANIZATION OF THE NIAMS EXTRAMURAL PROGRAM

This portion of the meeting occurred during closed session.

XII.   STAR AWARDS DISCUSSION

This portion of the meeting occurred during closed session.

XIII.   SPECIAL ACTIONS

This portion of the meeting occurred during closed session.

XIV.   CONSIDERATION OF APPLICATIONS

In closed session, the Council reviewed 770 primary and 251 secondary applications. The total cost requested in year -01 for all applications was $390,877,646. 

XVI.   ADJOURNMENT

The 94th National Arthritis and Musculoskeletal and Skin Diseases Advisory Council Meeting was adjourned at 3:00 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.

Melinda Nelson
Executive Secretary, National Arthritis and
Musculoskeletal and Skin Diseases Advisory Council

Acting Director, Division of Extramural Research
Activities, National Institute of Arthritis and
Musculoskeletal and Skin Diseases

Stephen I. Katz, M.D., Ph.D.
Chairman, National Arthritis
and Musculoskeletal and Skin
Diseases Advisory Council

Director, National Institute of
Arthritis and Musculoskeletal and
Skin Diseases