Internal Deadline: June 10, 2022, 5pm PT
LOI: 30 days prior to the application due date.
External Deadline: August 11, 2022
Award Type: Cooperative Agreement
Estimated Number of Awards: 1
Anticipated Award Amount: $3,950,000
Who May Serve as PI: Standard NIH requirements.
Companion Opportunity: https://orif.usc.edu/rfa-hd-23-016/
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 Maternal-Fetal Medicine Units (MFMU) Network is to improve obstetric care, pregnancy health, and outcomes for pregnant and lactating people and their babies. This includes finding ways to: reduce maternal mortality, complications, and morbidities related to pregnancy, labor, and post-partum recovery; reduce prematurity, low-birth weight, infant mortality, and morbidities; and expand the evidence base about the safety and efficacy of therapeutic products used during pregnancy and lactation. NICHD expects the MFMU Network to be its primary and first-line infrastructure involved in implementing multi-site obstetric clinical trials.
As such, the MFMU Network 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 people at 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 Opioids crisis.
The MFMU Network will also help NICHD address its Strategic Plan 2020, specifically for: Theme 3, Setting the Foundation for Healthy Pregnancies and Lifelong Wellness; 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 MFMU Network, therefore, is to conduct definitive, rigorous, and reproducible, multi-site clinical trials and observational studies in pregnant and lactating people, providing evidence to guide obstetrics, obstetric 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 maternal and infant/child outcomes. 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 pregnancy and lactation complications and therapeutics for other health issues that people may need to use during pregnancy and post-partum. 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://mfmunetwork.bsc.gwu.edu/PublicBSC/MFMU/MFMUPublic/research-projects.
The Network will also be uniquely poised to collaborate on studies and projects with other networks and initiatives – such as the NICHD Neonatal Research 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 summary of the 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.
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 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 CCsn and the NICHD/NIH.
- 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/or 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.).
DCC Principal Investigator
The DCC PI participates, with the CC PIs, adjunct PIs, and the NICHD Project Scientist, as a member of the Network Steering Committee, with each Center getting one vote.
The DCC PI’s responsibilities include:
- Ensuring that the research is conducted in accordance with all applicable federal regulations and guidelines, such as from the NIH, FDA, and Office for Human Research Protections (OHRP).
- Setting up, working with, and/or subcontracting with IRBs for Network protocols. Obtaining and maintaining required IRB approvals and reliance agreements. Ensuring that the necessary financial arrangements and federal assurances are in place before participation, and during study implementation. This includes submitting required documentation for IRB approvals/continuing renewals and notifying NICHD, the CCs and any relevant non-Network PIs in a timely manner of any suspensions, changes, and other activities affecting study integrity and recruitment.
- Setting up and maintaining appropriate master agreements (memoranda of understanding, subcontracts, data use agreements, etc.) with the CCs, relevant non-Network PIs, and/or single-trial sites to enable transfer of earned capitation funds and study data for all Network protocols between the DCC and each site.
- Providing support to the DSMB. Working with DCC staff to prepare meeting agendas, provide meeting logistics, facilitate meetings, develop reports for interim/final results analyses and other DSMB requests, submit any DSMB recommendations to NICHD for approval, and draft and distribute related Technical Memos to the CCs.
- Monitoring and reporting serious adverse events and/or protocol deviations to the medical monitor and/or NICHD Project Scientist within required timeframes and submitting them to the DSMB, FDA, and/or OHRP as required in a timely manner.
- Participating in Network quality assurance efforts, including cooperating during site visits and responding promptly to NIH inquiries, reviewing data collection and integrity, building data checks into the data management system, conducting data audits, and participating in CC site visits.
- Conducting statistical analysis and/or supervising the analyses of DCC statisticians.
- Managing Network reporting and data sharing compliance, including submitted study results to ClinicalTrials.gov, managing and/or assisting with Network FDA reporting requirements, and submitting data and specimens to the NICHD Data and Specimen Sharing Hub (or other approved repositories) in a timely manner.
- Hiring and supervising qualified study personnel and verifying DCC staff qualifications and required training certifications, as needed for protocol implementation. Managing staff resources to address changing Network work effort requirements. Notifying NICHD of any staff changes in a timely manner and notifying CCs of these changes to maintain Network communications.
- Securing the cooperation of his/her/their institution and colleagues in Network research efforts.
- Communicating Network activities and issues to DCC research staff in a timely fashion, including issues likely to affect the day-to-day operations of ongoing or upcoming Network protocols.
- Attending, or designating another DCC staff member to attend, all Steering Committee meetings and video/teleconferences and the meetings of any subcommittees of which they are a member. Supervising logistical support for Network meetings and site visits.
- For sites that are also members of the NICHD Neonatal Research Network (NRN), communicating with the NRN PI, reviewing ongoing and planned research of the two Networks to alert staff to potential conflicts, collaborating on areas of common interest, and offering advice within the primary areas of expertise.
Visit our Institutionally Limited Submission webpage for more updates and other announcements.