Internal Deadline: Friday, June 10th, 2022, 5pm PT
LOI: July 11, 2022
External Deadline: August 11, 2022
Award Type: Cooperative Agreement
Estimated Number of Awards: 1
Anticipated Award Amount: An estimated total of $3,100,000.
Who May Serve as PI: For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide. See Section I for more about DCC PI responsibilities.
Companion Funding Opportunity: https://orif.usc.edu/rfa-hd-23-002/
Process for Limited Submissions
PIs must submit their application as a Limited Submission through the Office of Research Application Portal: https://orif.usc.edu/oor-portal/.
Materials to submit include:
- (1) Single Page Proposal Summary (0.5” margins; single-spaced; font type: Arial, Helvetica, or Georgia typeface; font size: 11 pt). Page limit includes references and illustrations. Pages that exceed the 1-page limit will be excluded from review.
- (2) CV – (5 pages maximum)
Note: The portal requires information about the PIs and Co-PIs in addition to department and contact information, including the 10-digit USC ID#, Gender, and Ethnicity. Please have this material prepared before beginning this application.
The purpose of the Neonatal Research Network (NRN) is to improve healthcare and outcomes for newborns. This includes finding ways to improve the chances for survival without neurodevelopmental impairment for infants born premature, low-birth weight, or with other serious conditions. NICHD expects the NRN to be its primary and first-line infrastructure involved in implementing multi-site neonatal clinical trials.
As such, the NRN helps address several Congressional and public health goals:
- The Prematurity Research Expansion and Education for Mothers Who Deliver Infants Early (PREEMIE) Act (Public Law 109-450) was passed originally in 2006 and reauthorized in 2018 (Public Law 115-328) to: (1) reduce rates of preterm labor and delivery, (2) work toward an evidence-based standard of care for pregnant peopleat risk of preterm labor or other serious complications, and for infants born preterm, and (3) reduce infant mortality and disabilities caused by premature birth.
- The Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC), established under the 21st Century Cures Act (Public Law No: 114-255), recommended that the Secretary of Health and Human Services “increase the quantity, quality, and timeliness of research on safety and efficacy of therapeutic products used by pregnant women and lactating women.”
- Ongoing and potential future public health crises that impact the health of pregnant people and/or their infants, such as the COVID epidemic, Zika epidemic, and the opioid crisis.
The NRN will also help NICHD address its Strategic Plan 2020, specifically for: Theme 4, Improving Child and Adolescent Health; and Theme 5, Advancing Safe and Effective Therapeutics and Devices for Pregnant and Lactating Women, Children, and People with Disabilities.
The objective of the NRN, therefore, is to conduct definitive, rigorous, and reproducible, multi-site clinical trials and observational studies in newborns and lactating people, providing evidence to guide neonatology, pediatric pharmacology, and lactation clinical practice. This Network of research institutions will work collaboratively to implement common protocols to enroll and follow-up enough patients to achieve statistical power to answer protocol hypotheses more rapidly and definitively than individual centers acting alone.
Study designs may include, but are not limited to: investigational new drug or device, comparative effectiveness, and management trials; biomarker validation studies that are immediately preparatory to trials; and observational studies. Studies may assess both short-term (clinical) and long-term infant and child outcomes (i.e., up to school age). The Network may conduct Phase 3 pharmacologic research to address gaps in knowledge for the use of drugs and therapeutics during pregnancy and lactation – both therapeutics designed to treat lactation complications and therapeutics for other health issues that people may need to use while lactating. Phase 1 and 2 trials will generally be conducted outside of this Network but may be considered on a case-by-case basis (e.g., for trials in rare conditions). When relevant and appropriate, NICHD encourages the inclusion of genomic and proteomic studies, sub-studies, and/or collection of related biospecimens for such research. Examples of studies conducted in the Network can be found at: https://neonatal.rti.org/index.cfm?fuseaction=home.studies.
The Network will also be uniquely poised to collaborate on studies and projects with other networks and initiatives – such as the NICHD Maternal-Fetal Medicine Units (MFMU) Network, the NICHD Maternal and Pediatric Precision in Therapeutics (MPRINT) Initiative, the NIH Helping to End Addiction Long-term (HEAL) Initiative, the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative, the Foundation for the NIH, and other NIH institutes and Federal agencies, such as the Centers for Disease Control and Prevention.
GUIDING PRINCIPLES OF NICHD-SUPPORTED MULTI-SITE CLINICAL RESEARCH
In 2019 the Director of the NICHD, Dr. Diana Bianchi, outlined four guiding principles shaping the 21st century landscape of NICHD-supported multi-site clinical research (see NOT-HD-19-034 Infrastructure for NICHD Multisite Clinical Trials; NOT-HD-19-041 Request for Information on the NICHD Vision for Multisite Clinical Trials Infrastructure; a recorded webinar by Dr. Bianchi outlining NICHD’s vision for multi-site clinical research infrastructure; a concept clearance to the National Advisory Child Health and Human Development Council; and the 2020 NICHD Strategic Plan):
- Enhancing rigor and reproducibility
- Promoting greater availability of multisite clinical trial infrastructure to support trials from a wider range of investigators
- Facilitating data sharing and access to biospecimens
- Facilitating greater involvement of diverse populations in multisite clinical trials.
More information on each guiding principle is available in the Link to Award above.
Data Coordinating Center (DCC)
The DCC is expected to participate collaboratively on the Steering Committee to achieve the Network’s objectives. As such, the DCC’s specific objective is to develop, implement, and analyze results for Network protocols, especially providing biostatistical expertise, computer programming, and project management to design protocols, develop statistical analysis plans, develop data management systems, manage Network study funds, monitor data integrity and study safety, and work with study investigators to analyze, and publish study results. The DCC is responsible for:
- Collaborating with study investigators – both within and outside the Network – in developing Network protocols and budgets for NIH grant submission and/or funding approval.
- Supporting Network protocol design, training, implementation, and study monitoring. The DCC works with study investigators to design protocols, including developing statistical analysis plans, power analyses, and study budgets. As part of this, the DCC and the study team will review available NIH Common Data Elements (CDEs) and include them in Network studies, as appropriate, to ensure data harmonization with uniform collection of demographic, clinical, imaging, and biological data to the extent feasible. If relevant CDEs have not been developed, the DCC and study investigators may collaborate with NIH staff to develop them. In addition, the DCC may coordinate external services, including procuring study drugs, equipment, and other supplies, implementing masking and randomization methods, and executing subcontracts, such as for additional recruiting sites, vendor services for diagnostic tests, specimen analyses, etc., and consultancy agreements with outside experts.
- Coordinating closely with and/or managing the Network sIRB(s) to obtain and maintain IRB approvals and continuing renewals for all studies and ensure all recruiting sites have appropriate reliance agreements in place.
- Providing data management, including developing protocol manuals and forms, programming data management systems, and preparing reports for the DSMB, the FDA, the SC, Network subcommittees, CCs, and NICHD.
- Conducting statistical analyses of study data for interim monitoring, final results, and secondary data analyses, and collaborating with study investigators to publish results of Network trials and studies in a timely and accurate manner.
- Sponsoring (or sharing sponsorship obligations with NICHD and/or other institutions) for FDA Investigational New Drug (IND) and Investigational Device Exemption (IDE) applications on behalf of the Network, as needed, such as submitting and/or providing support for FDA-required reports.
- Managing study (“capitation”) funds, disbursing payments to CCs and non-Network recruiting sites based on enrolled patients and other study-specific milestone triggers specified in the study protocols and budgets. Working with NICHD Program Staff to develop a detailed financial reporting system, reporting at least quarterly and/or as needed on capitation budget expenditures and projections through the anticipated protocol end dates.
- Managing Network-wide reporting and data and specimen sharing requirements, including, but not limited to: submitting annual data to the NIH Human Subject System; creating and updating ClinicalTrials.gov records for all Network studies, including reporting study results within required timelines; fulfilling Network Data Sharing requirements by preparing and submitting study data and documentation to NIH-approved data repositories; and submitting, or managing the submission of, remaining biospecimens to a NIH-approved specimen repository.
- Providing the logistical support necessary to run an efficient and productive network, including video/teleconference support, meeting facilitation, and taking meeting minutes. The DCC also creates and maintains a Network website that includes both public-facing pages about the Network and its studies, and private/investigator-only pages to facilitate Network communication (i.e., to distribute study documents to the Network).
As with the CCs, the DCC will be required to set up appropriate master agreements (memoranda of understanding, subcontracts, data use agreements, etc.) with each CC, adjunct CC, and single-trial sites to enable transfer of earned capitation funds and study data for all Network protocols between the DCC and each site.
The DCC will have the following categories of personnel:
- Principal Investigator
- Co-PI/Alternate PI
- Research Coordinators and/or Project Assistants
- Programming staff
- Logistics and support staff
The DCC should have some degree of flexibility in staffing to be able to respond to changing work effort needs (i.e., changing number and complexity of protocols in various stages of development and implementation, submission deadlines for major conferences, etc.).
Visit our Institutionally Limited Submission webpage for more updates and other announcements.