Request for Information (RFI): Invitation to Comment on Updates to NIH Research Plans on Down Syndrome

Notice Number: NOT-HD-20-013

Key Dates
Release Date: April 13, 2020
Response Date: July 10, 2020

Related Announcements

NOT-HD-21-014 - Request for Information (RFI): Invitation to Comment on the Draft NIH INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Down Syndrome Research

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

National Eye Institute (NEI)

National Heart, Lung, and Blood Institute (NHLBI)

National Human Genome Research Institute (NHGRI)

National Institute on Aging (NIA)

National Institute of Allergy and Infectious Diseases (NIAID)

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

National Institute on Deafness and Other Communication Disorders (NIDCD)

National Institute of Dental and Craniofacial Research (NIDCR)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

National Institute of Environmental Health Sciences (NIEHS)

National Institute of General Medical Sciences (NIGMS)

National Institute of Mental Health (NIMH)

National Institute of Neurological Disorders and Stroke (NINDS)

National Institute of Nursing Research (NINR)

National Institute on Minority Health and Health Disparities (NIMHD)

National Center for Complementary and Integrative Health (NCCIH)

National Center for Advancing Translational Sciences (NCATS)

Division of Program Coordination, Planning and Strategic Initiatives, Office of Research Infrastructure Programs (ORIP)

National Cancer Institute (NCI)

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



Given rapidly evolving science in this area, the National Institutes of Health (NIH) recognizes the need for updating its two current Down syndrome-related research plans and invites comment from the Down syndrome community to update and unify these plans. Down Syndrome Directions: The NIH Research Plan on Down Syndrome was published in 2014. More recently, in 2018, the INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project released a Research Plan to address three major domains of research - basic science, cohort building, and clinical research. The NIH now proposes to combine these two plans into one NIH INCLUDE Down Syndrome Research Plan to capture the breadth of research supported by NIH on Down syndrome. As part of this process, NIH welcomes comments from the public concerning the effectiveness of the previous plans, advances made since 2014, remaining research gaps, and suggestions concerning new future research objectives.


The mission of the NIH is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability. Research on lifelong disorders, such as Down syndrome, has been a fundamental part of the NIH’s mission for over 60 years. Medical improvements and societal changes have extended the life expectancy of people with this condition, and the average lifespan of a Caucasian with Down syndrome has doubled from approximately 30 to 60 years over the past 30 years; however, comparable data do not exist for racial and ethnic minorities with Down syndrome, whose average lifespan is considerably lower. While intellectual disability is the primary consequence of having a third copy of chromosome 21 (trisomy 21), people with Down syndrome are also at higher risk than the general population for Alzheimer’s disease and dementia, leukemia, autism, cataracts, celiac disease, congenital heart disease, sleep apnea, diabetes, and other health conditions. At the same time, people with Down syndrome are protected from other health conditions such as solid tumors and myocardial infarction. The INCLUDE project was designed to fill some of these knowledge gaps.

The first NIH Research Plan on Down Syndrome was published in October 2007. It was developed by the Trans-NIH Down Syndrome Working Group, composed of program scientists from Institutes and Centers across NIH, who had been charged with coordinating ongoing research related to Down syndrome and to bolster new research efforts based on identification of the areas of greatest scientific opportunity, especially as they related to the development of future treatments. By organizing the research objectives into groupings by subject area and timeframe, the 2007 plan served to inform the Down syndrome community of NIH’s goals for moving ahead in this area and fostered collaborations between NIH and other agencies and groups. The 2014 plan, Down Syndrome Directions, was revised to take into account extensive input from the Down syndrome community, particularly as represented by the Down Syndrome Consortium ( ), a public-private partnership that includes researchers, constituency organizations and professional societies, and individuals with Down syndrome and their families. The plan included research goals in five major areas: Pathophysiology of Down Syndrome and Disease Progression; Down Syndrome-Related Conditions: Diagnosis, Screening, and Functional Measures; Treatment and Management; Down Syndrome and Aging; and Research Infrastructure. For details of the research plan, see:

A Congressional directive in the fiscal year (FY) 2018 Omnibus Appropriations legislation called for a new trans-NIH research initiative on critical health and quality-of-life needs for individuals with Down syndrome. NIH launched the INCLUDE project in June 2018 in support of this initiative. Its primary focus is to investigate conditions that affect individuals with Down syndrome and the general population, such as Alzheimer’s disease/dementia, leukemia, autism, cataracts, celiac disease, congenital heart disease, and diabetes. In FY 2018, NIH dedicated almost $23 million under this new project through administrative supplements to both Down syndrome-focused and non-Down syndrome-focused grants. In FY 2019, NIH provided about $35 million in new funding under Funding Opportunity Announcements ( The INCLUDE project, supported by multiple NIH Institutes and Centers, aims to include people with Down syndrome in all aspects of research, from support for dedicated basic science studies through opportunities to participate in existing and future clinical trials. Importantly, the INCLUDE project does not represent the entire sum of NIH investments related to Down syndrome. In FY 2019, for example, the total was $86 million. Congress provided $60 million for INCLUDE for FY 2020.

The INCLUDE project’s goals are summarized in the following 3 components:

  • Conduct targeted, high-risk, high-reward basic science studies on chromosome 21
  • Assemble a large study population of individuals with Down syndrome
  • Include individuals with Down syndrome in existing and future clinical trials

For further details, see:

Information Requested

The NIH is interested in soliciting comments and suggestions from a range of stakeholders, including the scientific community, people with Down syndrome and their families, constituency organizations, and professional societies, regarding the topics to be included in the revised, combined NIH INCLUDE Down Syndrome Research Plan. This Notice will remain open until July 10, 2020.

The NIH is interested in responses to the following topics:

  • Whether any of the objectives from the 2014 NIH Research Plan on Down Syndrome have been achieved, in full or in part.
  • Achievements to date (in full or in part) under the INCLUDE project, and whether any of the goals of its 2018 Research Plan have been met.
  • Seminal publications that have resulted from research on Down syndrome supported by NIH since 2014, including the INCLUDE project.
  • Revised research objectives aimed at expediting research on Down syndrome, including unmet needs in basic, translational, or clinical research, and identifying whether each is a short- or longer-term priority.
  • Remaining research gaps not addressed by either the 2014 NIH Research Plan on Down Syndrome, or the 2018 INCLUDE Research Plan, especially those that can be started or completed within a five- to seven-year timeframe.
  • Strategies for disseminating evidence-based information from NIH-supported research more widely to health care professionals and families who may be caring for people with Down syndrome.
  • Strategies for facilitating collaborations, such as public-private partnerships, to expand the scope and number of research objectives that can be addressed.
  • Whether the following overall structure for the revised, combined NIH INCLUDE Down Syndrome Research Plan captures major goals for NIH research efforts:
  • Conducting basic science studies on chromosome 21 and areas highly relevant to Down syndrome
  • Conducting translational research, including connecting existing resources and establishing a cohort of individuals with Down syndrome for study
  • Including individuals with Down syndrome in existing and future clinical trials, including individuals from underrepresented racial or ethnic minority groups, a range of functional abilities, or underserved areas, and including research on co-occurring conditions
  • Research Infrastructure (including models for study; DS-Connect : The Down Syndrome Registry

How to Submit a Response

Responses will be accepted until July 10, 2020. All responses must be submitted via email to Please include the notice number, NOT-OD-20-013, in the subject line and include your complete contact information with your response. All submission will be considered in revising the Research Plan. Confidential, personal, or private identifiable information should not be included as part of responses to this RFI. An anonymized summary of the responses will be posted on the INCLUDE website:


Please direct all inquiries to:

Lisa Kaeser, JD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)