Limited Competition: Clinical Trials in Organ Transplantation in Children (CTOT-C): Mechanistic Ancillary Studies (U01) | RFA AI 16 078

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The National Institutes of Health (NIH) funding opportunity titled "Limited Competition: Clinical Trials in Organ Transplantation in Children (CTOT-C): Mechanistic Ancillary Studies (U01)" (Funding Opportunity Number RFA-AI-16-078) is a discretionary grant program that uses a cooperative agreement mechanism (U01). It is designed to fund focused, hypothesis-driven mechanistic research that takes advantage of existing clinical data and biospecimens from pediatric solid organ transplant recipients. Rather than supporting new large-scale clinical trials, the emphasis is on ancillary mechanistic studies that can be completed efficiently by leveraging samples and datasets that have already been collected under rigorous clinical trial conditions.

A key feature of this FOA is that it is a limited competition intended for investigators already connected to the CTOT-C program. Specifically, it solicits applications from currently funded CTOT-C Program Directors/Principal Investigators, members of the CTOT-C Mechanistic Subcommittee, core laboratory leaders, and clinical site leaders. The practical intent is to ensure the funded projects are closely integrated with the CTOT-C consortium and are able to use its established infrastructure, standardized procedures, and well-characterized patient cohorts to produce timely and credible mechanistic insights.

The scientific purpose of the opportunity is to deepen understanding of immune mechanisms that contribute to poor outcomes after pediatric transplantation, particularly graft dysfunction, graft loss, and immune-mediated morbidity and mortality. In pediatric transplant patients, immune responses can drive acute or chronic injury to the transplanted organ, complicate long-term immunosuppression, and contribute to infections, malignancies, or other serious immune-related complications. By focusing on immune mechanisms, the FOA aims to support studies that clarify why some children experience stable long-term graft function while others progress to rejection, chronic dysfunction, or other adverse outcomes.

The FOA is structured around using samples and clinical data drawn from two main sources: (a) ongoing or completed CTOT-C clinical studies, and (b) other clinical trials where the samples and data were collected with a demonstrably similar level of investigational rigor. This wording matters because it sets an expectation for high-quality, well-annotated specimens and dependable clinical phenotyping. In other words, the research must be grounded in datasets and biospecimen collections that were gathered under controlled conditions with strong documentation, quality control, and protocols that make mechanistic findings interpretable and reproducible.

Another central goal is to increase the value of CTOT-C as a resource. The CTOT-C consortium has assembled a unique cohort of well-characterized pediatric transplant recipients, along with linked clinical outcomes and stored biospecimens. This FOA encourages researchers to mine that resource to answer targeted mechanistic questions that can complement and extend the parent CTOT-C studies. The expectation is that these ancillary investigations will generate insights that might not have been possible within the scope, timeline, or primary endpoints of the original clinical studies.

Beyond near-term mechanistic discoveries, the FOA highlights longer-range translational payoffs. Successful projects are expected to contribute to the identification of novel and robust surrogate endpoints for future interventional trials, as well as potential therapeutic targets and biomarkers that can improve diagnosis, treatment selection, and monitoring. In practice, this could mean developing or validating immune signatures that predict rejection before clinical deterioration, biomarkers that distinguish different causes of graft injury, or immune monitoring approaches that help tailor immunosuppression to reduce toxicity while maintaining graft protection. The emphasis on surrogate endpoints is especially important in pediatrics, where event rates may be low, follow-up needs to be long, and invasive procedures can be challenging; credible biomarkers can make future trials faster, safer, and more informative.

From an administrative standpoint, the cooperative agreement (U01) mechanism signals that NIH expects substantial programmatic involvement during the life of the award. Compared with a standard research project grant, cooperative agreements typically involve closer collaboration with NIH staff on aspects such as project milestones, data sharing, coordination with consortium activities, and alignment with the broader CTOT-C research agenda. This approach fits the consortium-based nature of CTOT-C, where harmonization and shared infrastructure are major strengths.

In terms of eligibility, the FOA lists a wide range of eligible applicant organizations, including various levels of government (state, county, city/township, special districts), independent school districts, public and private institutions of higher education, federally recognized tribal governments, tribal organizations, public housing authorities/Indian housing authorities, nonprofits (including 501(c)(3) and non-501(c)(3)), for-profit organizations (other than small businesses), and small businesses, among others. It also explicitly notes additional eligible applicant types such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, and non-U.S. entities (foreign organizations). While that broad eligibility language is included, the practical limitation remains that the competition is targeted to those already participating in CTOT-C in specified leadership roles, reinforcing that these awards are intended to build directly on CTOT-C resources and governance.

The opportunity falls under NIH CFDA numbers 93.855 and 93.856, which correspond to NIH funding areas within infectious and immune-mediated disease research. The FOA was created on 2016-11-28 and listed an original closing date of 2017-03-15, indicating it was a time-limited call aligned to the needs and readiness of the CTOT-C program at that point. The award ceiling is listed as $400,000, which signals a project scale appropriate for discrete mechanistic aims using existing samples and datasets rather than large prospective enrollment or major infrastructure buildouts. The number of expected awards is not clearly specified in the provided source, but the limited competition design implies a targeted set of awards selected to complement CTOT-C priorities and available resources.

Overall, this FOA is best understood as a mechanism to rapidly generate high-impact mechanistic knowledge in pediatric transplantation by capitalizing on CTOT-C's rigorously collected biospecimens and clinical data, and by using consortium coordination to move from clinical observations to immune mechanisms. The intended outcome is not only better biological understanding of graft injury and immune complications in children, but also practical tools for the field: biomarkers, monitoring strategies, and surrogate endpoints that can sharpen future trials and improve patient management.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Limited Competition: Clinical Trials in Organ Transplantation in Children (CTOT-C): Mechanistic Ancillary Studies (U01)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.855, 93.856.
• This funding opportunity was created on 2016-11-28.
• Applicants must submit their applications by 2017-03-15. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $400,000.00 in funding.
• 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.

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