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PA-20-195 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

Issued by

Office of The Director, National Institutes of Health (OD)

National Eye Institute (NEI)

National Heart, Lung, and Blood Institute (NHLBI)

National Institute on Aging (NIA)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute on Deafness and Other Communication Disorders (NIDCD)

National Institute of Dental and Craniofacial Research (NIDCR)

National Center for Complementary and Integrative Health (NCCIH)

National Cancer Institute (NCI)

RFA-OD-21-007 - INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Exploratory/Developmental Research Grant Award (R21 Clinical Trial Not Allowed)

Purpose

The last decade has seen an explosion of new technologies aimed at assessing and improving health. Examples include wearable devices, communication aids, robotics and e-textiles, just to name a few. During this period, there have also been enormous advances in technologies that were not created for health-related purposes, but that have potential applicability to health assessments and interventions, including mobile device applications ( apps ) and social media platforms.

However, most of these technologies were originally developed for use in adults with typical cognitive and motor function. As a result, there is currently a relative paucity of valid and reliable technological tools for children and adults with intellectual and developmental disabilities (IDD) with a focus on Down syndrome (DS).

This Notice therefore invites applications specifically aimed at developing or building upon existing technological tools to improve diagnosis, assessments, interventions, management, and outcomes for infants, children, adolescents and adults with DS.

The INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project was developed in response to Fiscal Year 2018, 2019, and 2020 Omnibus Appropriations Reports, which encouraged the NIH to expand its current efforts on DS and common co-occurring conditions also seen in the general population while increasing the pipeline of DS investigators. Information about projects that were funded from 2018 through 2020, as well as the INCLUDE Project Research Plan, is available on the INCLUDE Project website.

The purpose of this Notice of Special Interest (NOSI) is to support exploratory and developmental research project grant (R21) applications focused on digital technologies and/or mHealth that meet programmatic objectives for the INCLUDE Project. Sharing of resources and effective communication of outputs of appropriate interest to broader communities are a high priority of the INCLUDE Project. Applicants responding to this NOSI are strongly encouraged to describe plans for rapid sharing of data and results as well as innovative data analytics approaches (see Goal 3,NIH Strategic Plan For Data Science).

Applications in response to this NOSI should be aligned with the INCLUDE Project Research Plan, which consists of three components, two of which apply to this Notice:

• Component 2: Cohort Study to connect existing resources and expand to inclusion of individuals with DS
• Component 3: Inclusive clinical trials research for co-occurring conditions in individuals with DS

Projects that propose to recruit subjects with DS are encouraged to promote enrollment of research subjects in the DS patient registry supported by NIH,DS-Connect . For other data and biospecimens from human genetic or non-genetic studies, awardees are encouraged to use biorepositories designated by INCLUDE staff that meet requirements for broad sharing. An NIH resource describing Common Data Elements may be helpful during the planning phases of a project when considering ways to optimize data collection in order to facilitate broad data sharing. For those applications that generate clinical data, it is expected that the data sharing plan will include the INCLUDE Data Coordinating Center (DCC).

Background

The INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project was developed in response to Fiscal Year 2018, 2019, and 2020 Omnibus Appropriations Reports, which encouraged the NIH to expand its current efforts on DS and common co-occurring conditions also seen in the general population while increasing the pipeline of DS investigators. Information about projects that were funded from 2018-2020, as well as the INCLUDE Project Research Plan, is available on the INCLUDE Project website.

Individuals with DS face significant and changing health challenges but have often been excluded from participation in research that could improve their health outcomes and quality of life. This population is understudied even though DS is the most common genetic cause of intellectual and developmental disabilities (IDD) and, in the past 25 years, the average lifespan has doubled from 30 to 60 years. In addition to intellectual disability, DS is associated with an increased prevalence of autism and epilepsy. About 75% of individuals with DS experience cognitive decline in a syndrome that resembles Alzheimer’s disease, but with onset a decade or two earlier than typical Alzheimer’s disease. Individuals with DS also have high rates of hearing loss, eye abnormalities, congenital heart defects, sleep apnea, pulmonary hypertension, gastrointestinal malformations, thyroid disease, leukemia, and other autoimmune or immune dysregulation disorders including celiac disease. However, people with DS infrequently develop solid tumors such as breast or prostate cancer. Despite multiple risk factors for coronary artery disease and high rates of obesity, sleep apnea, and type 1 diabetes, people with DS rarely develop atherosclerosis or have myocardial infarctions. Understanding this unique combination of risk and resiliencies will inform medical advances for individuals with DS and for individuals who do not have DS but who share these co-occurring conditions.

Scope

Applications responsive to this Notice will address tools and/or technologies and target populations of interest. Proposals must address one or more target populations of interest: infants, children, adolescents, and adults with DS.

Applications proposing tools and/or technologies may include, but are not limited to, home monitors, point-of-care diagnostic technologies, mobile devices, mobile device apps (including social media apps), and wearable sensors and monitors. They may also include tools that help share information between caregivers, or between families and clinicians, including tools that interface with electronic health record (EHR) platforms.

Technological areas of interest include, but are not limited to:

• Tools and technologies for assessing health and functional status among target populations. These may include:
  • tools and technologies that identify physical, mental health, or behavioral comorbidities among individuals with DS, such as seizures, sensory impairments, sleep impairments, or metabolic disorders
  • tools and technologies that aid in monitoring and promoting optimal quality of life, including physical well-being, mental health, social interactions, or nutritional status among individuals with DS
  • tools and technologies that support activities of daily living (ADLs) and independence
• Programs to create or integrate approved electronic consent/assent platforms or apps to advance remote participation in existing and/or new trials and clinical studies in DS
• Tools and technologies that identify robust and reliable clinical outcome measures or biomarkers or validate existing measures for use in treatment trials and assessments for those with DS
• Tools and technologies to deliver interventions to target populations. These may include:
  • tools and technologies that aim to improve compliance with interventions such as medications
  • tools and technologies that allow interventions to be delivered remotely
  • tools and technologies that aid caregivers in caring for individuals with DS
• Tests of the efficacy of technologies (i.e., digital, wearable technology) to promote healthy behaviors in individuals with DS across the lifespan
• Study the feasibility and validation of at-home diagnostic tools including actigraphy, home sleep apnea testing, and wearable technologies
• Development of apps and computer-based therapies that can be used in telehealth, home- based, and school-based treatment programs to improve intelligibility. These should be designed to accommodate different levels of cognitive or linguistic ability
• Self-support technologies and apps that can increase independence and reduce dependency on others in various areas of daily living

Specific examples of tools and technologies that could be applied to individuals with DS include but are not limited to the following:

• Validation of eye tracking technology to identify and monitor social gaze preferences in children with DS at risk for autism
• Development and/or validation of tools to detect cognitive decline or changes in behavior
• Wearable monitors, oximeters, actimetry sensors and other less disruptive technologies to assess obstructive sleep apnea (OSA) and other sleep disorders
• Using machine learning and /or artificial intelligence (ML/AI) to detect digital biomarkers of cognitive decline
• Devices that monitor physiologic parameters that may be valuable on their own or as proxy measures of other outcomes of interest; examples include heart rate monitors, multi-channel EEGs, instruments that measure metabolite levels, or devices that measure heart rate, blood pressure and skin conductance as proxy measures of anxiety
• Mobile device applications ( apps ) to aid communication in individuals with DS who also have language impairments, regression, or dementia
• Social media platforms or apps that can help individuals with DS connect to caregivers, health or medical services, or support communities
• E-textiles and clothing applications to improve the mobility and functioning of individuals with DS who also have motor impairments

Priorities by Institute and Center

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

• Use of digital technologies and mHealth technology for networking support systems that integrate family-focused primary healthcare and preventive services (e.g., infant and childhood nutrition, immunizations)
• Use of digital technologies and mHealth technologies to enhance screening for co-morbidities associated with DS such as sleep apnea, obesity, and/or thyroid dysfunction and to develop community-based treatment paradigms for the co-occurring conditions associated with DS
• Use of digital technologies and mHealth technology to enhance prevention and treatment of injury and illness in children with DS
• Use of technology to respond to the needs of children with DS exposed to and affected by traumatic events such as a pandemic (such as COVID-19) or natural disaster
• Use of digital technologies and mHealth to support physical rehabilitation, health management, and community participation for people living with DS, in settings with limited resources and clinical support. This may include remote support of therapeutic exercise, assistive devices, periodic feedback on key clinical outcome measures, monitoring of progress, and interactive communication between therapists and the caregiver of the person with DS or the self-advocate
• Innovative and new digital technologies and mHealth solutions for improving transition of adolescents to adult healthcare providers by improving health literacy, enabling self-management and encouraging adherence to existing treatments among adolescents

The National Institute on Deafness and Other Communication Disorders (NIDCD)

• Use of digital technologies and mHealth for novel augmentative and alternative communication for individuals with DS who have a communication disorder
• Use of digital technologies and mHealth that promote improved access to and/or affordability of hearing healthcare for persons with DS who also have hearing impairment
• Use of digital technologies and mHealth solutions to evaluate efficacy of wearable monitoring devices, imaging procedures, tissue engineering and bioreactors for individuals with DS and communication disorders
• Use of digital technologies and mHealth for diagnosis, prognosis, or treatment monitoring for developmental and acquired voice, speech, and language impairments in people with DS across the lifespan

National Institute of Dental and Craniofacial Research (NIDCR)

• Develop safe and effective biosensors, monitoring devices and systems for reliable, reproducible, and highly sensitive automated detection and diagnosis of dental, oral, and craniofacial disease specifically for children and adults with Down syndrome.
• Optimize existing biosensing devices and diagnostic imaging approaches that integrate specific functional and usability requirements for individuals with Down syndrome.
• Develop advanced data-driven tools that integrate with electronic health records (EHR) systems to enable aggregation, harmonization, analysis, and retrieval of complex clinical data from individuals with Down syndrome to infer hidden relations that support decision-making across basic and clinical research in the dental, oral, and craniofacial domains.
• Develop or refine mobile tools for unobtrusive sensing and/or objective assessment of tooth brushing or other oral-health relevant behaviors, to facilitate the provision of dental or oral care delivery via telepractice, to prevent or treat dental fear or anxiety, to facilitate coordination between caregivers and care partners to maintain oral health and hygiene, or to otherwise improve or support the dental and oral health of individuals with Down Syndrome.

The National Institute on Aging (NIA)

• Use of mobile devices for early detection of cognitive decline in adults with DS across the life span
• Applying digital devices for monitoring location of adults with DS across the life span
• Promoting social engagement and emotional connections with digital devices for people with DS across the life span
• Use of mobile technology to support and monitor the well-being of DS caregivers

The National Heart, Lung, and Blood Institute (NHLBI)

• Less invasive, better tolerated wearable devices to monitor respiratory rate and oxygen saturations in children and adults with DS and obstructive sleep apnea
• Digital devices that measure ambulatory trans-cutaneous CO₂ when awake and asleep
• Digital devices to quantify diaphragmatic movements during sleep
• Digital sound sensors specific for snoring and/or upper airway sounds
• Wearables that monitor oxygen saturation, heart rate, rhythm, or other parameters for children and adults with congenital heart disease
• Implementation science to identify promising practices for dissemination and implemention in routine clinical care

Resource Sharing Plan:

NIH intends to maximize the impact of INCLUDE-supported projects through broad and rapid data sharing.?Consistent with the new NIH Policy for Data Management and Sharing (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-21-013.html), all applications, regardless of the amount of direct costs requested for any one year, are required to include a Data Management and Sharing Plan outlining how scientific data and any accompanying metadata will be managed and shared, regardless of whether the data are used to support scholarly publication. The plan should describe data types, file formats, submission timelines, and standards used in collecting or processing the data. It is expected that all de-identified human data generated by INCLUDE-funded projects will be submitted to NIH-designated repositories in coordination with the INCLUDE Data Coordinating Center (DCC). All applications generating human genomic data should include, as an attachment, an Institutional Certification (https://osp.od.nih.gov/scientific-sharing/institutional-certifications/) which indicates the data use limitations and/or modifiers stating how individual level sequence data can be shared with and used by secondary users, under the guidance of the NIH Genomic Data Sharing Policy?http://grants.nih.gov/grants/guide/notice-files/NOT-OD-14-124.html. For more information regarding INCLUDE data sharing, visit https://www.nih.gov/include-project/frequently-asked-questions.

Considerations

To maximize comparisons across datasets or studies, and facilitate data integration and collaboration, applications submitted in response to this NOSI are strongly encouraged to incorporate the following standards and resources (where applicable):

• Projects that propose to recruit subjects with DS are encouraged to promote enrollment of research subjects in the DS patient registry supported by NIH,DS-Connect .
• Applicants are encouraged to ensure that data collected by the study conform to Findable, Accessible, Interoperable, and Reusable (FAIR) principles.
• NIH encourages researchers to explore the use of the HL7 FHIR (Fast Healthcare Interoperability Resources) standard to capture, integrate, and exchange clinical data for research purposes and to enhance capabilities to share research data (NOT-OD-19-122). The FHIR standard may be particularly useful in facilitating the flow of data with EHR-based datasets, tools, and applications.
• NIH encourages clinical research programs and researchers to adopt and use the standardized set of data classes, data elements, and associated vocabulary standards specified in the United States Core Data for Interoperability (USCDI) standards (NOT-OD-20-146), as they are applicable. Use of the USCDI can complement the FHIR standard and enable researchers to leverage structured EHR data for research and enable discovery.
• NIH encourages the use of data standards including common data elements, such as those available through the PhenX Toolkit (www.phenxtoolkit.org) and the NIH CDE repository (cde.nlm.nih.gov), terminologies and ontologies such as Mondo Disease Ontology (mondo.monarchinitiative.org), Human Phenotype Ontology (hpo.jax.org), and common data models such as the Observational Medical Outcomes Partnership (OMOP; ohdsi.org).
• For studies that propose clinical trials, please consider submitting an application to RFA-OD-20-003 (Clinical Trials Development for Co-Occurring Conditions in Individuals with Down syndrome: Phased Awards for INCLUDE (R61/R33 Clinical Trial Required)).
• Recruitment Plan to Enhance Diversity. The applicant must provide a Recruitment Plan (when applicable) to Enhance Diversity. The application should include outreach strategies and activities designed to recruit potential participants who are from diverse backgrounds, including participants from underrepresented racial and ethnic groups (see https://www.nimhd.nih.gov/about/overview/). Describe the specific efforts to be undertaken by the participating investigators to coordinate with efforts to recruit individuals from underrepresented groups. Please name the file "Recruitment Plan.pdf".

Additional Review Considerations

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Recruitment Plan to Enhance Diversity

Peer reviewers will separately evaluate the recruitment plan (when applicable) to enhance diversity after the overall score has been determined. Reviewers will examine the strategies to be used to recruit a diverse pool of potential candidates that includes individuals from underrepresented groups. The overall plan will be rated as ACCEPTABLE only if the recruitment strategies for all of the relevant groups identified in the Notice of NIH's Interest in Diversity are viewed by the review panel as acceptable, otherwise the plan will be rated as UNACCEPTABLE. The consensus of the review committee will be included in an administrative note in the summary statement.

PA-20-195 NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

Application and Submission Information

This notice applies to standard submission dates.

Submit applications for this initiative using the following funding opportunity announcement (FOA) or any reissue of this announcement through the expiration date of this notice.

• PA-20-195 NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include "NOT-OD-21-092" (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.

Inquiries

Scientific/Research Contact(s)

Sujata Bardhan, Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-0471
Email: [email protected]

Kelly King, Ph.D.
National Institute on Deafness and Other Communication Disorders (NIDCD)
Telephone: 301-402-3458
Email: [email protected]

Erika D. Tarver, M.S.M
National Institute on Aging (NIA)
Telephone: 301-827-2617
Email: [email protected]

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Maggie Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email: [email protected]