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

Opportunity Information: Apply for PAR 25 227

The National Institutes of Health (NIH) is soliciting R01 grant applications under PAR-25-227 to strengthen what is known about the natural history of disorders that are already included in statewide newborn screening programs, as well as conditions that could reasonably be added in the future. The central idea is that newborn screening can identify infants very early, often before symptoms are obvious, but families and clinicians still need clear, evidence-based expectations about what happens next: when symptoms tend to start, how quickly they progress, how variable the condition is across patients, and which early findings actually predict later outcomes. This funding opportunity is designed to support studies that fill those gaps so that screening results translate into timely, appropriate care rather than uncertainty.

A major focus of the NOFO is careful characterization of the sequence and timing of symptom development. By mapping out when specific clinical signs typically emerge and how they change over time, researchers can help clinicians make better decisions about monitoring schedules, referral timing, and when to initiate interventions. This kind of natural history work also creates a baseline that can be used to evaluate new treatments and management strategies, since it becomes possible to compare outcomes against a well-described expected course of disease rather than relying on fragmented case reports or short-term observations. The announcement explicitly notes that clinical trials are optional, meaning applicants can propose purely observational natural history studies, studies that build the foundation for trials, or projects that incorporate interventional components when appropriate.

The opportunity also highlights the value of connecting biological variation to clinical outcomes. Projects that establish genotype-phenotype correlations can help explain why the same screened disorder may look mild in one child and severe in another, and can improve the ability to predict a likely clinical course after a positive screen. Likewise, identifying genetic modifiers, epigenetic influences, and environmental contributors is encouraged because these factors can clarify why outcomes differ, point toward underlying biological mechanisms, and potentially reveal new therapeutic targets or supportive strategies.

In practical terms, NIH is looking for work that produces comprehensive, longitudinal data that the field can use. The NOFO describes several outcomes this knowledge should enable: (1) clearer insight into underlying biological mechanisms; (2) a better understanding of genetic and clinical heterogeneity and how phenotypes are expressed; (3) improved diagnostic accuracy; (4) stronger support for clinical trials through high-quality natural history benchmarks; (5) better prevention, management, and treatment of symptoms and complications; (6) more useful predictive and supportive information for physicians and families; and (7) development or strengthening of data systems such as longitudinal registries that track child and family outcomes after newborn screening. In other words, the intent is not just to publish descriptions of disease progression, but to produce organized evidence that directly improves care pathways and research readiness.

Eligibility is broad and includes many types of organizations that might contribute to newborn screening-related research, from academic medical centers to public health partners and community-based groups. Eligible applicants listed include state, county, and local governments; special districts; independent school districts; public and private institutions of higher education; federally recognized Native American tribal governments; tribal organizations; public housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations (other than small businesses); and small businesses, as well as other entities. The NOFO also explicitly calls out additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based and community-based organizations, regional organizations, U.S. territories or possessions, eligible federal agencies, tribal governments that are not federally recognized, and foreign (non-U.S.) organizations.

Key administrative details from the source include that this is a discretionary grant opportunity using the NIH R01 mechanism, categorized under Health, Income Security and Social Services (CFDA 93.865). The posted original closing date is 2028-01-07, and the opportunity was created on 2024-11-06. The award ceiling and expected number of awards are not specified in the provided listing, which typically means applicants should rely on the full NOFO and NIH institute guidance for budget expectations and funding outlook.

• The National Institutes of Health in the health, income security and social services sector is offering a public funding opportunity titled "Natural History of Disorders Screenable in the Newborn Period (R01 Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.865.
• This funding opportunity was created on 2024-11-06.
• Applicants must submit their applications by 2028-01-07.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for PAR 25 227

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