Sleep Disorders Research Advisory Board (SDRAB) Meeting – August 3, 2023

The Sleep Disorders Research Advisory Board (SDRAB) convened virtually on Thursday, August 3, 2023. SDRAB is a Federal Advisory Committee established by the NIH Revitalization Act of 1993. The meeting opened at 1PM ET and closed at 4PM ET. Dr. Esra Tasali presided over the meeting as Chair.

Meeting Summary

BOARD MEMBERS PRESENT

Dr. Esra Tasali, Chair
Dr. Josiane Broussard
Dr. Jeffery Durmer
Dr. Erik Herzog
Ms. Ebony Lay
Dr. Shaun M. Purcell
Dr. Alberto Ramos
Dr. Tom Scammell
Ms. Alexandra Wharton

BOARD MEMBERS ABSENT

Dr. Dayna A. Johnson

EX OFFICIO MEMBERS PRESENT

Dr. Marishka Brown, NHLBI, Executive Secretary
Dr. Yejun (Janet) He
Dr. Shahla Jilani
Dr. Karen C. Lee
Dr. Miroslaw Mackiewicz

EX OFFICIO MEMBERS ABSENT

Dr. Donald Shell 

FEDERAL EMPLOYEES: 41 Federal employees were in attendance via Zoom

MEMBERS OF THE PUBLIC: The total number of public attendees (including researchers, clinicians, patients, and other stakeholders) watching online reported by Zoom was 106.

CALL TO ORDER 
Dr. Marishka Brown

• The executive secretary called the meeting to order at 1:00 PM ET as announced in the federal register [FR Doc. 2023-12375], published on June 9, 2023. The meeting was fully open to the public in accordance with the provisions set forth in sections 552b(c)(4) and 552b(c)(6), Title 5, U.S. Code and Section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. Appendix 2). Board members were reminded that they are required to absent themselves if their presence constitutes or appears to constitute conflict of interest. 
• Dr. Brown then introduced Dr. Esra Tasali as the new Chair of SDRAB.
• The Chair welcomed everyone and asked SDRAB members to introduce themselves.

Director’s Report From The National Center On Sleep Disorders Research (NCSDR), Dr. Marishka Brown

• Dr. Brown reminded participants about the purpose and role of SDRAB and shared the SDRAB webpage where meeting dates and minutes, as well as the board roster can be found. She also noted the appointment of and welcomed the newest board member Dayna Johnson, Ph.D., MPH, Assistant Professor, Department of Epidemiology, Emory University.
• The Director gave an overview of sleep and circadian research funding NIH-wide, noting many NIH institutes, centers, and offices (ICOs) support sleep and circadian research.  Overall, funding has consistently increased over the past several years.
• Per the Congressional charter, NCSDR also coordinates sleep and circadian research across the NIH and other federal agencies. The Center spearheads the NIH-wide Sleep Research Coordinating Committee (SRCC) working together on the implementation of the NIH Sleep Research Plan. Dr. Brown highlighted the SRCC’s efforts in implementing Goal 2 of the Plan, which emphasizes personalized approaches to improved treatments and reduced risk, by sharing the following:
  • Two notices of funding opportunity (NOFOs), representing a collaboration between NCSDR and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Special Diabetes Program, were recently published to study the role of sleep deficiency in persons with type 1 diabetes, RFA-HL-24-008 and RFA-HL-24-009 
  • Supporting several clinical trials in the INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) project to look at sleep in persons living with Down Syndrome. 
• The Director shared there would be a workshop in September 2023 on the Circadian Clock at the Interface of Lung Health and Disease hosted by NCSDR and the NHLBI Division of Lung Disease (DLD), and several workshops planned for FY2024 including:
  • Big Data Approaches for Novel Mechanistic Insights on Disorders of Sleep and Circadian Rhythms (Spring 2024)
  • Sleep-Disordered Breathing Heterogeneity and Personalized Approaches to Diagnosis, Treatment and Implementation (Spring/Summer 2024)
  • Sleep in Cardiovascular Resilience: Mechanisms, Implications, and Applications (Spring/Summer 2024)
• The director highlighted the designated NOFOs and that NHLBI will accept PA-20-185 applications for clinical trials that are mechanistic in nature, not trials looking at efficacy or effectiveness which are funded under other mechanisms such R61/R33, UG3/UH3, and U24. She strongly encouraged the community to contact a Program Official to discuss an application before it is submitted.
• Dr. Brown ended by announcing Dr. Michael Chiang, Director of the National Eye Institute (NEI), will be presenting at the next SDRAB meeting on December 7, 2023.

Leadership Lens: Bruce Tromberg, Ph.D.
Director, National Institute of Biomedical Imaging and Bioengineering (NIBIB)

• Dr. Tromberg began his presentation by giving an overview of the creation and purpose of NIBIB, the mission of which is engineering the future of health. The institute was created in 2000 by an act of Congress and unlike other NIH ICs that focus on mechanistic science, NIBIB focuses on bioengineering research in imaging, engineering, computer science, and informatics. 
• Since the establishment of the NIBIB, there has been an exponential growth in accredited biomedical engineering (BME) related academic programs and a cultural shift towards prioritizing human health in engineering. The emergence of BME has also helped drive gender diversity in the field of engineering.
• There are 5 major areas of focus for NIBIB across bioengineering and bioimaging:
  • Engineered biology
  • Sensors and points of care
  • Medical imaging technologies
  • Therapeutic devices
  • Modeling, computation & machine intelligence
• NIBIB allows applicants to propose projects the with no disease focus; however, grants must address one of the following priorities: 
  • Understanding, preventing, and detecting disease
  • Personalizing diagnosis and treatment
  • Extending health span
  • Driving innovation, entrepreneurship, and partnerships
  • Expanding diversity and training in the BME/technology community
• The NIBIB has partnerships across all of NIH: in FY2022, approximately 14% of NIH expenditures went towards bioengineering projects. 
• Dr. Tromberg described a recent example of these partnerships: RADx Tech (rapid acceleration of diagnostic technologies). 
  • He indicated a desire to work with NCSDRto explore possibilities for how this model might be applied to sleep disorders and pointed to the RADx Maternal Health Challenge as an exemplary mechanism.
• NIBIB also has an intramural research program and recently launched the Biomedical Engineering and Technology Acceleration (BETA) Center, a new NIH-wide center for technology-driven interdisciplinary research, training, and clinical translation. The overall goal of the Center is to accelerate the development, validation, and dissemination of high-impact biomedical technologies. In addition, BETA nurtures collaborations with the BME/Tech community and leads the expansion of diversity, equity, and inclusion within the NIH intramural research program.
• Dr. Tromberg shared data on studies in biophotonics (biomedical optics) that his lab is conducting. They are working to develop non-invasive technologies that effectively render the body transparent.
• Data from translational sleep studies characterizing cerebral hemodynamic oscillations using pocket near infrared spectroscopy (NIRS) and polysomnography (PSG) in individuals with and without obstructive sleep apnea (OSA) to determine if optical measurements of cerebral hemodynamics can enhance understanding of apnea physiology were shared
• Translational studies are also being done in sickle cell disease (SCD), where there is a convergence with sleep disorders that can put brain oxygenation in jeopardy. 
• In summary, Dr. Tromberg described a new era of BME in which consumer devices are beginning to resemble medical devices and sleep medicine is currently at the intersection of the two. This has the potential to yield new in situ insights from relatively inexpensive wearable devices that can provide validated, quantitative data on a continuous timescale as opposed to experimental snapshots at particular time intervals. Creates new opportunities in personalized health - technologies that can expand to home/POC settings, reduce barriers/costs, and enhance our ability to prevent disease and improved outcomes.
• A robust Q&A from SDRAB and the public followed the presentation.

Advancing Technology in Sleep Healthcare: Jeffrey Durmer, M.D., Ph.D.
Chief Medical Applications Officer, SleepImage, Denver, CO

• Dr. Durmer began his presentation with a review of polysomnography (PSG) and recent advances made in the component arenas, such as:
  • Evolution of EEG-based sleep technologies - typically utilize these channels to measure state of sleep as well as interruptions in cortical activity during sleep. 
    • Recently machine learning (ML) algorithms (specifically fast Fourier transform) have been used to achieve a deeper understanding of EEG to establish brain age, which has led to the development of a brain age index (BAI) defined as the difference between brain age and chronological age. 
    • The BAI concept has been advanced to develop sleep cognitive indices (SCI) that predict neurocognitive abilities this could potentially be useful as an investigative procedure for evaluating medications, therapies, and changes in neurocognitive ability over time
    • Another EEG-based algorithm that has been developed is cyclic alternating patterns (CAP), a marker that has been used in children and adults; increased CAP is a signal of unstable sleep, poor sleep quality, and autonomic arousal; the CAP rate could potentially be used to personalize medical care and changes in CAP could become a therapeutic outcome. 
  •  Evolution of chin EMG-based sleep technologies – mandibular movement (MM) analysis and respiratory effort (RE)-based sleep technology were also described. (RE)-based sleep technology device has FDA clearance as a HSAT and is currently on the market.
  • Evolution of PPG-based sleep technology
    • There is a significant change in PPG signal across the night through REM and NREM stages of sleep; PulseOx has been the primary use of this signal but there are now other applications.
    • Many consumer based technologies use PPG and actigraphy together.
    • Multiple devices show excellent agreement with PPG in heart rate detection, heart rate variability, and sleep vs. wake detection, but poor agreement with PPG for multi-stage sleep detection.
  • Evolution of Leg EMG-based sleep technology
    • Analytics can measure intermovement intervals to characterize periodic leg movements of sleep PLMS subtypes (restless leg syndrome [RLS], REM sleep behavior disorder, narcolepsy, OSA) using a Periodicity Index (PI)
    • Concept updated with the addition of Random Matrix Theory to refine the establishment PLMS subtypes in OSA and RLS and PI associated with actigraphy can detect normal vs. abnormal PLM in different populations
    • Now there are device-independent algorithms that can be utilized; contactless, visual, automated 3-D analysis tools can detect PLMS and OSA in populations that don’t tolerate contact well (e.g. children, individuals with neurodevelopmental or sensory integration disorders) 
• Finally, Dr. Durmer shared that we are starting to see the development of combination devices, the integration of hardware/software tools. There is an oral device with analytics of PPG, MM, AF, PulseOx, actigraphy, and EEG that has the ability to treat OSA within the same device, via airway stimulation/jaw movement. There’s also the potential to manage multiple sleep treatments for disorders other than OSA.
• He highlighted that the future of sleep technology development is moving from genotype to endotype and phenotype for more personalized treatments. 
• In response to Dr. Durmer’s presentation, the SDRAB noted: 
  • Before we can expand the use of these technologies there is much to understand mechanistically about how diverse a condition sleep apnea is.
  • Access to home devices could be challenging for some populations and consideration should be given to dissemination in low-income communities who tend to be more at risk for OSA.

Update on the National Sleep Research Resource (NSRR): Shaun Purcell, Ph.D.
Division of Sleep and Circadian Disorders, Brigham Health, Boston, MA
Senior Associate, Broad Institute, Stanley Center for Psychiatric Research, Cambridge, MA

• Dr. Purcell shared the mission of NSRR, an NHLBI funded resource for sharing sleep data, that offers free web access to large collections of de-identified physiological signals and clinical data elements collected in well characterized research cohorts and clinical trials.
• He underscored the importance of archiving, aggregating, and reusing data. Benefits of being able to leverage previously collected data include achieving larger samples, powering analyses of rare outcomes, providing a platform for new methods development, datasets can be repurposed to address new scientific questions, ultimate way to achieve rigor and reproducibility in research by transparency.
• From the end user’s perspective, there are some challenges: combining different datasets can be logistically/technically difficult, subtle biases can be amplified in large datasets, and the original studies likely were not specifically designed to answer your current research question.
• The NSRR approach to alleviating some of these difficulties is to provide context to the datasets collected, adding value to original data by harmonizing and documenting the datasets, providing tools for working with large numbers of studies (for example, to allow for sensitivity studies to address bias), and offering technical support. 
• The data are one component of the NSRR’s ecosystem, the other aspects are the tools to work with those data, standardized ways to distribute and share those data, sharing, and outreach efforts to the broader community, to promote the resource and to solicit new ideas and data to sustain the resource.
• Regarding the tools:
  • Interested in open data and open tools to make results reproducible
  • Developed Luna, an open source tool for sleep signal analysis 
  • Built NAP – NSRR automated pipeline, another open source tool, harmonizes/flags issues with incoming PSG data 
  • Goal - a tighter coupling between code and data, progressing towards “referenced-based” approach to analysis that uses prior data/models to inform/augment analysis of newly collected data (as has evolved in human genetics over the last decades)
    • Leveraging representative reference panels in whom the same set of metrics have been derived
    • If reference data contain other features that track well with PSG data, those features can be statistically imputed/predicted
• Regarding sharing:
  • Data are only as valuable as their metadata; make data accessible and interpretable
  • Standardized hierarchically organized data dictionaries and folder structures
  • Collate/share key device metadata (e.g. make/model, software versions, filters, etc.)
  • Previously shared data by traditional download to user’s local environment for analysis; exciting new initiative underway to integrate NSRR with NHLBI’s BioData Catalyst to facilitate cloud-based analysis; represents future direction of informatics and biomedical research
  • Adding new ways for users to access NSRR data – Moonbeam model allows users to directly pull NSRR data into the browser for interactive viewing (Moonlight) and analysis (Luna)
• Regarding outreach:
  • Sleep research community includes users, potential data depositors, professional bodies
  • For dissemination - initiated a series of webinars, active in social media, regular blogs on NSRR webpage, quarterly newsletter
  • To solicit new data - developed streamlined process, working with contributors to facilitate data deposition into the NSRR
  • In light of the new NIH data management sharing (DMS) policy, NSRR provides guidance to researchers on building a DMS plan and a repository for their research data
• Dr. Purcell closed by summarizing the gaps and future directions of NSRR.
• A robust Q&A from SDRAB and the public followed the presentation.

NIH Data Management and Sharing (DMS) Policy and NHLBI Supplement: Shilpy Dixit, Ph.D., Program Director, Prevention and Sleep Health, NCSDR

• Dr. Dixit reviewed the new NIH DMS policy to promote the sharing of scientific data that became effective January 25, 2023, highlighting the scope, requirements, and timelines in the policy. 
• She also reviewed the 6 elements of a successful DSM plan: data types; related tools, software, and/or code; standards; data preservation, access, and associated timelines; access, distribution, or reuse considerations; and oversight of data management sharing. 
• Dr. Dixit noted the supplemental information found in NOT-OD-21-061 regarding selecting a data repository was particularly relevant to Dr. Purcell’s presentation and she referred the community to the DSM policy FAQ page.
• She then briefly reviews the NHLBI Supplement to the NIH policy which became effective May 5, 2023, noting the Supplement is harmonized with the new NIH DMS policy and replaces the previous NHLBI Policy for Data Sharing from Clinical and Epidemiological Studies that became effective in 2006. Dr. Dixit also highlighted the Data Sharing Policy Comparison Table as a resource to help understand the new NIH DMS policy and the NHLBI supplement theret0, focusing on the policy provisions for ancillary studies and repository specifications.
• Following Dr. Dixit’s presentation, the SDRAB reminded the community that the NSRR meets the requirements of both the NIH DMS policy and the NHLBI Supplement for a data repository.

SDRAB Member Discussion

• The Board discussed how some of the technologies presented can be successfully used in pediatric populations and whether we should be screening for sleep disorders in newborns. 
  • PPG and non-contact technologies are good alternatives to PSG and are currently being used in some neonatal intensive care units (NICUs), but not broadly and the analyses and not well understood. There is strong scientific basis for their use but limited clinical adoption at this time. 
  • New technologies have been used to assess sleep quality in children and have revealed conditions other than apnea that contribute to poor sleep quality, which would have been missed on PSG
  • One of the gaps to be considered more is how to leverage these technologies in clinical decision making. Also need more research to develop normative data.
• The SDRAB also discussed how NCSDR might work with NIBIB to facilitate the development of at home or POC diagnostics for sleep biomarkers, similar to what was done for COVID-19. There could be an opportunity to use data from NSRR.
• Lastly, Dr. Brown encouraged the community to sign up for the SleepRFA listserv which regularly posts announcements about sleep funding opportunities and events.

NEXT MEETING

The next meeting of SDRAB will occur fully virtually on December 7th, 2023 from 10:00 AM to 4:00 PM ET.