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: The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
Anticipated Award Amount: NIH intends to fund Clinical Center awards, corresponding up to a total of $5,200,000, for fiscal year 2023. A maximum of $220,000 per year in direct costs may be requested for up to 7 years.
Who May Serve as PI: Standard NIH requirements.
Companion Opportunity: https://orif.usc.edu/rfa-hd-23-017/
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.
Clinical Centers (CCs)
The CCs are expected to participate collaboratively on the Steering Committee to achieve the Network’s objectives. The CC’s specific objective is to develop and implement Network protocols even those approved, but proposed by non-Network investigators, including recruiting study participants, implementing study interventions, conducting required follow-up examinations, and working together to publish study results. CC’s may also be able to engage in training opportunities.
As such, CCs are responsible for:
- Identifying areas for potential Network research.
- Collaborating with study investigators – both within and outside the Network – in developing Network protocols and budgets for NIH grant submission and/or funding approval.
- Participating in the development and implementation of Network protocols, whether the PI is from within the Network or a non-Network PI.
- Implementing funded Network studies, including meeting recruitment goals based on information provided at the time of application, with minimal protocol violations/deviations, and completing any protocol follow-up activities.
- Collecting and transmitting study data to the Data Coordinating Center in an accurate and timely manner.
- Overseeing and monitoring the participation of any satellite sites within the CC. The productivity of the satellite sites will be considered part of the CC’s contribution to the Network.
- Collaborating in data analyses and publication of results.
A typical CC in the Network is generally a regional academic medical center or tertiary care facility, capable of providing research support and supervision for any satellite sites. CCs may choose to partner with additional geographically or organizationally linked satellite sites, particularly to access participant populations not traditionally cared for at the CC. Single, large volume, delivery centers are preferred over multi-site arrangements with smaller centers. CCs are expected to have a minimum of 3,000 deliveries per year, at least 30 percent of which must be high-risk pregnancies.
CCs are expected to participate in all approved Network studies, (including those proposed by non-Network PIs), unless they do not have the relevant eligible population (e.g., opioid-addicted patients), or have an ongoing local study that conflicts with a Network study that is identified in its application. Centers agree to prioritize Network studies over other studies, including other NIH-funded studies, for subject recruitment.
Each CCs will be required to set up appropriate master agreements (memoranda of understanding, subcontracts, data use agreements, etc.) with the DCC and/or adjunct CCs to enable transfer of earned capitation funds and study data for all Network protocols between the CC and those entities. CCs are responsible for setting up similar agreements and/or mechanisms with each of their satellite sites, as needed.
Each CC will have the following Network staff:
- Principal Investigator (PI)
- Co-PI/Alternate PI
- Research Coordinator
- Data entry personnel
CC Principal Investigator
The PI participates, with the other CC PIs, the DCC PI, and the NICHD Project Scientist as a member of the Network Steering Committee, with each CCgetting one vote. If a CC proposes multiple PIs, it will need to designate which PI will be the attending and voting member on the Steering Committee.
The 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).
- 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/renewals to the DCC, and notifying NICHD and the DCC in a timely manner of any suspensions, changes, and other activities affecting study integrity and recruitment.
- Reporting serious adverse events and/or protocol deviations to the DCC, medical monitor, and/or NICHD Project Scientist within required timeframes.
- Ensuring collection and transmission of accurate data to the DCC in a timely manner.
- Participating in Network quality assurance efforts, including cooperating during site visits and responding promptly to DCC inquiries.
- Hiring and supervising qualified study personnel, verifying staff qualifications and required training certifications, and reporting these to the DCC, as needed for protocol implementation. Notifying NICHD and the DCC of any staff changes in a timely manner.
- Securing the cooperation of his/her/their institution and colleagues in Network research efforts. Communicating with CC and satellite site staff on ongoing and upcoming protocols and opportunities to build buy-in, identify potential feasibility issues, and manage issues related to protocol equipoise.
- Communicating Network activities and issues to CC research staff, and any satellite sites, in a timely fashion, including issues affecting day-to-day operations of Network protocols.
- Attending, or designating another CC staff member to attend, all Steering Committee meetings and teleconferences and the subcommittee meetings of which they are a member.
- 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.
Each institution must also designate a Co-Principal Investigator (Co-PI) or Alternate PI to act as the CC PI whenever he/she/they is not available. As acting, the Co-PI should have full authority and ability to act in the PI’s stead, including attending required Network meetings and/or teleconferences, voting on Steering Committee and subcommittee issues, and having full access to Network records. Ideally, the Co-PI is a partner to the PI and is designated to take on some of the PI’s responsibilities, in whole or in part.
Each CC will also appoint one research coordinator to oversee the conduct of Network clinical trials. Under the direction of the PI, the Research Coordinator is responsible for ensuring the successful conduct and coordination of Network protocols.
The Research Coordinator is responsible for:
- Assisting in the day-to-day operations of implementing Network protocols, including adhering to protocols, collecting data, supervising data transmission, monitoring data quality, training staff, procuring study equipment and supplies, and liaising with follow-up clinic staff to ensure appropriate study participant follow-up.
- Maintaining routine data quality assurance methods for staff under his/her/their supervision and assisting the PI with quality assurance at the CC and all of its satellite sites.
- Supervising data entry activities, including instructing and certifying data entry personnel in software and hardware usage.
- Maintaining a central file of protocols, manuals, data forms, regulatory documents, network correspondence, and performance reports in accordance with Good Clinical Practice (GCP).
- Collaborating with the PIs (including non-Network PIs) and DCC in developing protocols, manuals of operation, and data collection forms. Assisting in answering Network queries for information, such as those needed to inform protocol development and improve protocol implementation.
- Attending at least two Steering Committee meetings per year, the monthly Coordinator conference call, and the meetings of any subcommittees of which they are a member.
The Research Coordinator supervisory duties should require no more than half time; the remainder of efforts should be devoted to Network subject recruitment and day-to-day site needs and administrative issues, including IRB submissions and renewals, SC attendance, site visits, training sessions, protocol development, participation in conference calls, etc., as well as CC data collection as required.
Data entry personnel
Data entry personnel are responsible for entering data and preparing and uploading documentation into Network data management system(s) in a timely manner.
Personnel conducting data abstracts from the medical records should have relevant medical expertise and training in the Network protocols, manuals, and forms and in the hospital medical records (electronic and hard copy). Appropriate supervision and oversight are required to ensure high data quality.
Visit our Institutionally Limited Submission webpage for more updates and other announcements.