The purpose of this Notice of Funding Opportunity (NOFO) encourages applications that will expand knowledge of the natural history of disorders that currently are, or may become, part of statewide newborn screening programs. A comprehensive understanding of the natural history of a condition is necessary to facilitate appropriate interventions for infants identified by newborn screening. Characterization of the sequence and timing of symptom development provides information crucial for developing targeted, age-appropriate treatments and for establishing a baseline against which to assess novel interventions. In addition, for some conditions, establishment of genotype-phenotype correlations may facilitate prediction of the clinical course; for others, identification of modifying genetic, epigenetic, or environmental factors may enhance understanding of clinical outcomes. Comprehensive data on the natural history of a condition will facilitate the fields ability to: 1) identify the underlying biological mechanisms; 2) understand the genetic and clinical heterogeneity and phenotypic expression of the condition; 3) improve diagnostic accuracy; 4) facilitate clinical trials by providing comprehensive natural history data; 5) prevent, manage, and treat symptoms and complications of the condition; 6) furnish physicians and families with needed support and predictive information about the condition; and 7) establish data collection systems or patient registries to collect longitudinal data (e.g., child/family outcomes following newborn screening).

PAR-25-227: Natural History of Disorders Screenable in the Newborn Period (R01 Clinical Trial Optional)

Posted Date: November 06, 2024 Open Date (Earliest Submission Date): January 05, 2025 Expiration Date: January 08, 2028

Participating Organization(s): National Institutes of Health (NIH) Components of Participating Organizations: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Funding Opportunity Title: Natural History of Disorders Screenable in the Newborn Period (R01 Clinical Trial Optional) Activity Code: R01 Research Project Grant Announcement Type: Reissue of PAR-21-115

Related Notices:

• March 31, 2025: This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission.
• April 4, 2024: Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084.
• August 31, 2022: Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198.
• August 5, 2022: Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189.

Funding Opportunity Number (FON): PAR-25-227 Companion Funding Opportunity: None Assistance Listing Number(s): 93.865

Part 1. Overview Information

Funding Opportunity Purpose

This Notice of Funding Opportunity (NOFO) encourages applications that will expand knowledge of the natural history of disorders that currently are, or may become, part of statewide newborn screening programs. A comprehensive understanding of the natural history of a condition is necessary to facilitate appropriate interventions for infants identified by newborn screening. Characterization of the sequence and timing of symptom development provides information crucial for developing targeted, age-appropriate treatments and for establishing a baseline against which to assess novel interventions. In addition, for some conditions, establishment of genotype-phenotype correlations may facilitate prediction of the clinical course; for others, identification of modifying genetic, epigenetic, or environmental factors may enhance understanding of clinical outcomes. Comprehensive data on the natural history of a condition will facilitate the field’s ability to:

1. identify the underlying biological mechanisms;
2. understand the genetic and clinical heterogeneity and phenotypic expression of the condition;
3. improve diagnostic accuracy;
4. facilitate clinical trials by providing comprehensive natural history data;
5. prevent, manage, and treat symptoms and complications of the condition;
6. furnish physicians and families with needed support and predictive information about the condition; and
7. establish data collection systems or patient registries to collect longitudinal data (e.g., child/family outcomes following newborn screening).

Funding Opportunity Goal(s)

This purpose of this Notice of Funding Opportunity (NOFO) encourages applications that will expand knowledge of the natural history of disorders that currently are, or may become, part of statewide newborn screening programs. A comprehensive understanding of the natural history of a condition is necessary to facilitate appropriate interventions for infants identified by newborn screening. Characterization of the sequence and timing of symptom development provides information crucial for developing targeted, age-appropriate treatments and for establishing a baseline against which to assess novel interventions. In addition, for some conditions, establishment of genotype-phenotype correlations may facilitate prediction of the clinical course; for others, identification of modifying genetic, epigenetic, or environmental factors may enhance understanding of clinical outcomes. Comprehensive data on the natural history of a condition will facilitate the field’s ability to:

1. identify the underlying biological mechanisms;
2. understand the genetic and clinical heterogeneity and phenotypic expression of the condition;
3. improve diagnostic accuracy;
4. facilitate clinical trials by providing comprehensive natural history data;
5. prevent, manage, and treat symptoms and complications of the condition;
6. furnish physicians and families with needed support and predictive information about the condition; and
7. establish data collection systems or patient registries to collect longitudinal data (e.g., child/family outcomes following newborn screening).

Key Dates

| Event | Date