Research Bases for HIV/Cervical Cancer Prevention 'CASCADE' Clinical Trials Network (UG1 Clinical Trial Required) | RFA CA 21 046

Opportunity Information: Apply for RFA CA 21 046

The National Institutes of Health (NIH) funding opportunity RFA-CA-21-046 supports the creation of a multicenter clinical trials network focused on improving secondary cervical cancer prevention for women living with HIV. The network is called the HIV/Cervical Cancer Prevention "CASCADE" Clinical Trials Network, and its central purpose is to address real-world breakdowns in the cervical cancer prevention pathway, from screening through follow-up care and treatment of cervical precancer. The emphasis is on pragmatic clinical trials, meaning studies designed to test interventions under typical, intended-use conditions in clinics and health systems rather than under tightly controlled laboratory-style environments. The overall goal is to generate practical evidence that can directly improve how screening and treatment programs are implemented and, in turn, reduce cervical cancer risk in this high-priority population.

A key theme of the opportunity is the "cascade" concept: many women may be screened but never receive results, or may receive abnormal results but face delays or barriers to confirmatory evaluation, referral, or treatment. CASCADE aims to evaluate innovative, implementation-focused approaches to prevent these drop-offs and failures. The trials supported through the network are expected to concentrate on the full continuum of care for secondary prevention, including increasing screening uptake, improving timely and appropriate management of positive screening results, reducing loss to follow-up, expanding access to precancer treatment services, and optimizing the treatments themselves. Importantly, the trials are meant to test clinically proven interventions (things that already work clinically) and evaluate how best to deliver them effectively, efficiently, and equitably in the settings where women living with HIV actually receive care.

The evidence produced by these studies is intended to have direct downstream impact on guidelines and policy. NIH is looking for results that can refine clinical practice guidance and inform public health decision-making, especially around how cervical cancer screening and precancer treatment programs should be structured for women living with HIV. In other words, the opportunity is not just about showing that an intervention can work, but about generating actionable findings that can improve real-world prevention programs at scale, including clearer best practices for implementation across diverse health systems and resource settings.

The award mechanism is a UG1 cooperative agreement, which signals substantial scientific and programmatic involvement by NIH compared with a standard research grant. Under this structure, awardees are expected to operate as part of a coordinated network, collaborating on multi-institutional trial development and execution. The opportunity specifically funds two to three "Research Bases" that will serve as the scientific backbone of the network. Each Research Base is envisioned as a self-organized consortium of investigators with complementary expertise, brought together to provide leadership in trial concept development, protocol design, and analysis planning across multiple institutions and sites. This includes strong statistical leadership, since pragmatic multi-site trials typically require robust design, power calculations, and analytic approaches that account for clustered data, variable clinical workflows, and implementation heterogeneity.

Beyond scientific leadership, the Research Bases are responsible for ensuring compliance with regulatory requirements and human subjects protections across the network. This includes coordinating or supporting Institutional Review Board (IRB) processes, data and safety monitoring expectations, participant protection standards, and other policy requirements that are especially important in clinical trials involving potentially vulnerable populations. The network structure also includes an explicit workforce development component: the Research Bases are expected to help create training and mentorship opportunities for emerging investigators, building future capacity in HIV-associated cervical cancer prevention research and implementation science.

Eligibility is broad and includes many types of U.S. governmental and non-governmental entities, as well as certain non-U.S. organizations. Eligible applicants listed in the source information include state, county, city or township, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; tribal organizations that are not federally recognized; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations other than small businesses; small businesses; and other organizations. The announcement also highlights additional eligible applicant categories such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), faith-based or community-based organizations, U.S. territories or possessions, regional organizations, eligible federal agencies, and non-domestic (non-U.S.) entities.

From the funding details provided, this is a discretionary NIH opportunity using the cooperative agreement funding instrument, with activity categories spanning education and health and CFDA numbers 93.393, 93.395, and 93.399. The original closing date was 2021-12-28, and the listed award ceiling is $400,000. Taken together, the opportunity is designed to build a small number of strong coordinating research hubs that can drive rigorous, real-world clinical trials to strengthen every step of the cervical cancer screening and treatment cascade for women living with HIV, producing evidence that can be translated into improved practice and policy.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Research Bases for HIV/Cervical Cancer Prevention 'CASCADE' Clinical Trials Network (UG1 Clinical Trial Required)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.393, 93.395, 93.399.
• This funding opportunity was created on 2021-10-26.
• Applicants must submit their applications by 2021-12-28. (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.

Apply for RFA CA 21 046

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