Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

PURPOSE AND OBJECTIVE OF THE NETWORK

The purpose of the Global Network for Women’s and Children’s Health Research is to improve health outcomes for women and children in low- and lower middle-income countries (as defined by the World Bank) by researching sustainable, cost-effective health interventions, and strengthening research infrastructure and public health intervention capabilities in developing countries. The Network will increase opportunities for scientific linkages, interaction, knowledge development and transfer, and collaborative partnerships among U.S. and foreign investigators and institutions.

As such, the Global Network helps the U.S. Government meet the United Nation’s Sustainable Development Goals (SDGs) to:

• Reduce the global maternal mortality ratio to less than 70 per 100,000 live births by 2030.
• End preventable deaths of newborns and children under 5 years of age, with all countries aiming to reduce neonatal mortality to at least as low as 12 per 1,000 live births and under-5 mortality to at least as low as 25 per 1,000 live births by 2030.
• Substantially increase health financing and the recruitment, development, training and retention of the health workforce in developing countries, especially in least developed countries and small island developing States.

In addition, the Network can help the U.S. to address 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 Global Network will help the NICHD address its Strategic Plan 2020, specifically for: Theme 3, Setting the Foundation for Health 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 Global Network, therefore, is to conduct high-impact clinical trials and observational studies of sustainable, cost-effective health interventions and their implementation in women and children in low- and lower middle-income countries, while simultaneously building sustainable professional capacity and infrastructure in obstetric, neonatal, and pediatric research in those countries.

This Network of research institutions will work collaboratively to implement common protocols. Proposed interventions may focus on the development, testing, adaptation, and implementation of cost- effective, integrated biomedical, behavioral, social, and public health interventions to reduce causes of premature morbidity and mortality among women of reproductive age and young children. Study designs may include, but are not limited to, translational research, implementation science, investigational new drug or device, comparative effectiveness, and management trials,and observational studies. Studies may assess both short-term (clinical) and long-term infant and child outcomes (up to 3 years of age). 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://globalnetwork.azurewebsites.net/Research-Studies/Active-Studies. All Global Network research must be designed such that health improvements in the study population are meaningful, sustainable, culturally appropriate, and likely to produce a measurable and significantly improved health outcome.

The Network may 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 21^st 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):

1. Enhancing rigor and reproducibility
2. Promoting greater availability of multisite clinical trial infrastructure to support trials from a wider range of investigators
3. Facilitating data sharing and access to biospecimens
4. Facilitating greater involvement of diverse populations in multisite clinical trials.

All institutions participating in the Network will be expected to align with the following goals as a condition of inclusion.

1. Enhancing rigor and reproducibility

NICHD will develop new peer-reviewed protocol proposal and selection processes to increase transparency and rigor of Network study selection. With rare exceptions, all proposed trials to be conducted within the Network infrastructure will be submitted as individual NIH applications, will undergo NIH peer review, and funding decisions will be made by NICHD. During the next project period, the NICHD expects the Network will conduct approximately 4-7 trials, sometimes concurrently. The exact number of protocols supported will depend on the nature and extent of the investigations proposed and the availability of funds. The areas of study will be expanded to cover the research needs identified by Congress, the NICHD Strategic Plan, and the Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC) recommendations, as applicable, as well as public health crises affecting pregnant and lactating people and infants.

2. Promoting greater availability of multisite clinical trial infrastructure to support trials from a wider range of investigators

To facilitate this guiding principle, investigators from outside the core Network will be encouraged to propose studies to be conducted in the Network. Investigators from Network Research Units (RUs) will also propose studies via the new peer-reviewed proposal process. To be considered, these studies will need to align with the purpose and objectives of the Network and NICHD priorities and are dependent on funding availability. In addition, NICHD will develop new protocol proposal and selection processes to increase transparency and rigor of study selection. Network Policies and Procedures that govern Network structure and activities will be posted on a public facing website. A Principal Investigator (PI) from outside investigator institutions that successfully competes for a trial award will become an “adjunct PI,” and they may also oversee an adjunct research units (adjunct RU) for the purposes of the awarded trial only.

3. Facilitating data sharing and access to biospecimens

The Network, including all participating recruiting sites for each protocol, will be required to share data and any remaining biospecimens. The Network will abide by the NIH Policy for Data Management and Sharing, as amended, effective January 2023 that “shared scientific data should be made accessible as soon as possible, and no later than the time of an associated publication, or the end of the award/support period, whichever comes first.”

For Network studies and/or sub-studies that collect biospecimens, after completion and publication of the main analysis for which they are collected, any remaining biospecimens will be made available for sharing via the NICHD Data and Specimen Hub (DASH) or another NIH-approved system. These remaining specimens may be stored in the NICHD biospecimen repository, with the approval of NICHD, depending on funding availability.

Study consent forms must include appropriate language to allow broad sharing and future use of study data and biospecimens in alignment with Federal and local regulations and policies.

A major opportunity for the Network is to coordinate data across NICHD-funded perinatal research. This may incorporate new methods, including collecting patient-reported outcomes and/or electronic health record data in large, pragmatic clinical trials. Comparison of results across studies in metadata analyses will increase the value of collected data, and the contributions of participants. The use of Common Data Elements (CDEs) will be a priority of Network studies to ensure uniform collection of demographic, clinical, imaging, and biological data among studies inside and outside of the Network. If relevant CDEs have not been developed, Network PIs may collaborate with NIH staff to develop them.

4. Facilitating greater involvement of diverse populations in multisite clinical trials.

It is an NIH priority to develop diversity in the workforce (see Notice of NIH’s Interest in Diversity, NOT-OD-20-031); as such, NICHD encourages applications from Network Center and protocol PIs and Co-PIs from diverse populations. Ensuring diverse populations in multi-site clinical trials for both investigators and participants will be a high priority for Program staff.

NETWORK STRUCTURE, ROLES, AND RESPONSIBILITIES

The Global Network consists of a Data Coordinating Center (DCC) and clinical Research Units (RUs). The current Network includes 7 RUs.

It is each institution’s responsibility to:

• Meet, and continue to meet, the requirements outlined in this RFA and the Notices of Grant Award. This includes having adequate and qualified staff, facilities, and equipment available, and supervision to oversee its staff and that of any satellite sites to conduct Network protocols in a safe and effective manner.
• Abide by U.S. Federal, state, and local laws and regulations, including those of the Common Rule, the U.S. Food and Drug Administration (FDA), and the in-country regulations of the RUs, as applicable.
• Participate in a cooperative and interactive manner with the other Network PIs, NICHD staff, and with non-network study investigators and recruiting sites.
• Follow all Network policies and procedures. By accepting the Notice of Grant Award, each successful Awardee agrees to abide by the Network’s Policies and Procedures and adhere to Network study protocols.

The Network operational structure includes the following groups:

• Steering Committee
• Data and Safety Monitoring Board
• External Scientific Committee
• Community Engagement Board

Steering Committee (SC)

The Steering Committee consists of:

• The U.S. Principal Investigator (USPI) and the International PI (iPI) from each Research Unit (one vote each)
• DCC PI (one vote)
• NICHD Project Scientist (one vote)
• Adjunct Principal Investigator for any non-Network trial (one vote for that specific trial only)

The Steering Committee has the primary responsibility for implementing the objectives of the Network, including identifying areas of potential research, developing and implementing Network protocols, and analyzing and publishing study results. The SC meets face-to-face (weather and public health issues permitting) 1 time per year and has monthly teleconferences. All SC members or their designees and Network coordinators are expected to attend these meetings. In general, SC meetings last for 2 days each, and are scheduled 12-18 months in advance.

The Steering Committee may create subcommittees to manage specific Network functions. These include, but are not limited to:

• Protocol Development Subcommittee
• Publications Subcommittee
• Concurrent Research Subcommittee
• Protocol subcommittees and/or working groups for each study being implemented and/or under development.

Data and Safety Monitoring Board (DSMB)

A Data and Safety Monitoring Board (DSMB) will be established in accordance with the NICHD DSMB Policy for Clinical Trials to monitor all Network clinical trials, as well as observational studies or sub-studies that involve more than minimal risk to participants. Full members of the DSMB cannot be from any of the Network RUs or the DCC; the DCC PI is an ex officio member, providing the statistical reports needed for DSMB review and logistical support for DSMB meetings. The DSMB is responsible for safeguarding the interests of study participants and protecting study participants from unacceptable risk. The DSMB provides recommendations to the NICHD Director and Network investigators on research design, data quality, and analysis issues, as well as conducting interim monitoring of trials for safety, efficacy, feasibility, and ethical conduct.

External Scientific Committee

An External Scientific Committee, a group of outside experts who provide feedback, feasibility assessments, and prioritization of protocols to the Network investigators and to the NICHD, as needed, will be established. They may also review applications from external sites that apply to join Network studies as “single-trial sites.” This committee will be formed as a collaborative effort with NICHD staff who will ultimately approve its membership.

Community Engagement Board

The Network will be expected to interact with a Community Engagement Board. This will be a group of lay community members from the various countries that the iPIs represent who have interest and/or experience in maternal and child medical conditions. The objective is to assure that Network research is relevant and sensitive to the needs and concerns of the communities served. Examples of services that may be provided by this Board include, but are not limited to, providing input on research outcomes of most interest to patients and families, sharing feedback on consent forms and processes, and suggesting ways to disseminate research finds into local practice. This Board will be formed as a collaborative effort with NICHD staff who will ultimately approve its membership.

Investigational Review Boards (IRBs)

The Global Network will be conducting studies in foreign countries and will need to abide by the human subject protection regulations of those countries. The Research Units’ foreign teams will need to comply with all local human subject protection regulations, including any requirements to obtain and maintain IRB approvals from their local institutions. The Research Units’ U.S. teams and the DCC will likewise need to comply with Federal, state, and local requirements for human subject protection for participating in these international studies.

Research Units (RUs)

Research Units are dyads of collaborating multidisciplinary teams of U.S. scientists linked to investigators in low and lower middle-income countries as full and equal partners.

The RUs are expected to participate collaboratively on the Steering Committee to achieve the Network’s objectives. The specific objective of the RUs is to develop and implement Network protocols, even those approved, but not proposed by non-Network investigators, including recruiting study participants, implementing study interventions, conducting required follow-up examinations, and working together to publish study results. RUs may engage in training opportunities.

Global Network RUs will be based primarily at the institution of the iPI; it is not the intention of this FOA to support multi-disciplinary teams of investigators in the United States. The Global Network emphasizes a multidisciplinary, team-based approach. Disciplines may include pediatrics, family medicine, obstetrics, infectious diseases, epidemiology, statistics, environmental science, pharmacology, and the behavioral and social sciences.

As such, RUs 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 RU. The productivity of the satellite sites will be considered part of the RU’s contribution to the Network.
• Collaborating in data analyses and publication of results.

A typical RU in the Network is generally a U.S. academic medical center partnered with a similar academic clinical center in a low or lower middle-income country.

RUs 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, or have an ongoing local study that conflicts with a Network study that is identified in its application. RUs agree to prioritize Network studies over other studies, including other NIH-funded studies, for subject recruitment.

Each RU will have the following Network staff:

• U.S. Principal Investigator (USPI)
• International Principal Investigator (iPI)
• U.S. Research Coordinator
• International Research Coordinator
• International Data Management/Information Technology Coordinator
• International Data Entry Clerk

Additional details about the Research Units can be found in RFA-HD-23-008 – Global Network: Research Units.

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 the RUs 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, RUs, 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 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).

The DCC will have the following categories of personnel:

• Principal Investigator
• Co-PI/Alternate PI
• Statisticians
• 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 RU PIs, adjunct PIs, and the NICHD Project Scientist, as a member of the Network Steering Committee.

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).
• Obtaining and maintaining required IRB approvals for the DCC and ensuring that the RUs obtain and maintain required IRB approvals for network protocols. 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 RUs and any relevant non-Network PIsin a timely manner of any suspensions, changes, and other activities affecting study integrity and recruitment.
• 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 RUs.
• 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 RU 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 RUs 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.

Co-Principal Investigator

The DCC must also designate a Co-Principal Investigator (Co-PI) or Alternate PI to act as the DCC 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.

Statisticians

DCC statisticians provide biostatistical expertise for Network protocol design, study monitoring, and results analyses. Under the supervision of the DCC PI, the statisticians are responsible for:

• Assisting investigators, including non-Network PIs who are interested in utilizing the Network infrastructure, in designing study protocols, including determining sample size and developing statistical analysis plans.
• Conducting planned interim analyses for the DSMB on protocol performance, patient safety, and emerging results.
• Analyzing study results and assist investigators in the preparation of presentations and manuscripts for publication of primary and secondary analyses.

Research Coordinators and/or Project Assistants

DCC coordinators and research project assistants work closely with the DCC PI to implement Network protocols and to provide support for overall Network operations. Under the supervision of the DCC PI, Research Coordinators are 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.
• Communicating Network activities and issues to RUs/recruiting sites in a timely fashion and coordinating Steering Committee, DSMB, subcommittee, and working group meetings and communication.
• Providing project management support for protocol development, helping to develop protocol manuals and forms, querying recruiting sites about information needed for protocol development and/or implementation, liaising with DCC programmers, and planning/conducting protocol training sessions.
• Supporting Network protocol implementation, including monitoring protocol adherence, liaising with RU coordinators to resolve concerns, procuring and distributing study equipment and supplies, and monitoring recruiting site staff certification requirements.
• Managing IRB approvals and continuing renewals. With the DCC PI, setting up arrangements for a Network sIRB. Monitoring and assisting recruiting sites with setting up reliance agreements. Collecting and submitting required documentation to the IRB to obtain and maintain continuous approval throughout study implementation.
• Managing the DCC’s Network reporting requirements, including gathering documentation for FDA applications and reports, and creating and maintaining ClinicalTrial.gov records for all Network studies.
• Maintaining a central file of protocols, manuals, data forms, regulatory documents, Network correspondence, and performance reports in accordance with Good Clinical Practice (GCP).
• Attending Steering Committee meetings, the monthly Coordinator conference calls, and the meetings of any subcommittees of which they are a member.
• Setting up and participating in site visit monitoring and data audit quality assurance activities.
• Working with DCC staff to create, maintain, and update the Network’s private and public websites.

Programming staff

DCC programming staff is primarily responsible for developing, maintaining, and updating the Network data management system(s). They work with the study PIs and DCC coordinators to develop protocol randomization methods (e.g., phone call-in systems), program the data management system(s), manage data transmission, and provide support to the recruiting sites to resolve any data entry and transmission issues. DCC programming staff works with the DCC PI and coordinators to monitor data quality and to assist with data cleaning prior to statistical analysis.

Logistics and support staff

DCC support staff is responsible for providing logistical support for the Network – scheduling meetings and teleconferences, securing meeting and lodging facilities and equipment, recording and distributing meeting minutes, etc.

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NICHD provides funding to each RU and the DCC through Clinical Research Cooperative Agreements. NICHD uses this assistance mechanism when it anticipates its scientific and/or programmatic staff will need to have substantial involvement with the awardee(s) during performance of clinical research. The NICHD Program Staff will assist Network PIs in identifying research topics of high priority and in designing and implementing protocols in the areas targeted for research.

The NICHD’s Office of Clinical Research (OCR) staff, Program Official, and Grants Management will be responsible for overall grant stewardship. The Program Official, or his/her/their designee, will serve as the NICHD representative on Network’s DSMB in the manner delineated in the NICHD Data and Safety Monitoring Policy. A NICHD Project Scientist will be involved substantially with the awardees, serving as NICHD’s voting representative on the Steering Committee, and working with investigators to design and implement protocols and analyze results. A Clinical Trials Specialist or Program Analyst may work with the Program Official and Project Scientist to help coordinate Network management. The NICHD OCR will work with the NICHD Program Staff to develop efficiencies, support Network stewardship, and provide policy guidance. OCR staff may attend SC and subcommittee/working group meetings as observers.

Independent of the governance above, the NICHD Director retains responsibility for all NICHD funded research. The NICHD Director receives the DSMB’s recommendations on whether Network studies should be continued or terminated and can make an independent decision on how to proceed. The NICHD Director can override the decisions of the Steering Committee when it is in the strategic interest of the NIH/NICHD, human subject protection, and/or dependent on funding availability.

NETWORK PROTOCOL SELECTION PROCESS

Funds to implement individual protocols in the Network will be awarded via applications under separate funding opportunity announcements and/or administrative supplements in certain cases at NICHD's discretion. For any issued FOAs, protocol proposals may be submitted from investigators inside or outside the Network and/or from small businesses or industry (with appropriate agreements in place between all parties). Network investigators are strongly encouraged to submit protocols.

As part of this process, Network investigators will be expected to collaborate with investigative teams from outside institutions – both in a pre-application process to assess feasibility and design protocols for submission to NICHD/NIH peer review, as well as in the post-award phase to develop final protocols, manuals, and forms to conduct the awarded protocols in the Network. RUs will be expected to collaborate with investigator teams from outside institutions (adjunct RUs) who have successfully competed for NIH-funded clinical trial awards to be conducted in the Network.

Funding for protocol implementation costs (protocol and study-specific costs) will be distributed to the RUs and non-Network recruiting sites, generally on a per-patient basis, according to protocol budgets and submission of protocol data.

Additional external single-trial sites may be added to Network protocols as recruiting sites, when needed, for instance, for studies of rare diseases or conditions. To the extent practicable, single-trial sites will undergo a competitive peer-reviewed process (i.e., solicited by a Request for Proposals via the DCC). Such sites may be added as subcontractors/sub-grantees to the DCC.

INITIAL NETWORK ACTIVITIES POST AWARD

Year One activities may include refining Network policies and procedures, establishing committees and committee membership, and developing protocols for submission to the anticipated Protocol FOA or other funding opportunity announcements. New procedures for collaborating with non-Network investigators may need to be developed. Any changes to the policies and procedures must comply with current NIH policies and guidance and may require NICHD approval.

Ongoing studies in the Network

The following ongoing Network studies are still recruiting new participants, as of the issuance of this RFA. Successful RUs from the companion FOA may be asked to join these studies, as well as any new studies initiated between the issuance of this RFA and new awards being made, if they are still recruiting at the time of grant awards (NOTE: protocol costs for these studies should not be included in this budget – they will be awarded to the DCC award separately, as needed):

• Maternal Newborn Health Registry. A prospective, population-based study of pregnancies and their outcomes in low and or lower middle-income countries. All pregnant women in participating clusters are registered and their outcomes tracked for 6 weeks post-delivery. The primary purpose is to quantify and understand the trends in pregnancy services and outcomes over time, providing population-based statistics on stillbirths, neonatal, and maternal mortality as the basis of health care policy. The data from the registry also provide the mortality and morbidity outcomes for Global Network trials and help investigators plan future studies for the Network.
• Azithromycin-Prevention in Labor Use Study (A-PLUS). A randomized, placebo-controlled, parallel multicenter clinic trial to assess whether a single, prophylactic intrapartum oral dose of 2g azithromycin given to women in labor will reduce (1) maternal death or sepsis and (2) intrapartum/neonatal death or sepsis.

The successful DCC awardee may be expected to work with the existing DCC to transition some or all of these ongoing studies to the new DCC's management.

See Section VIII. Other Information for award authorities and regulations.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Section II. Award Information

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Government

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed. 

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• System for Award Management (SAM)– Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See Notice of NIH’s Interest in Diversity, NOT-OD-20-031. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Multiple awards under this FOA may not be made to the same institution. Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Nahida Chakhtoura, M.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6872
Email: nahida.chakhtoura@nih.gov

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Other Attachments

Attachment 1. Special Strengths

Provide a summary of the DCC’s special strengths as a pdf attachment using the filename “Attachment 1. Special Strengths”. Applicants are encouraged to describe special or unique strengths that may be relevant to research in the Global Network. This can include, but is not limited to, biospecimen storage and processing, state-of-the art scientific capabilities that may be available for Network research, additional clinical research expertise (e.g., genomic, proteomic, pharmacokinetic, or pharmacodynamic statistical analysis) that could be drawn upon on an as-needed basis, as well as any research resources they have established at their institution. Innovative statistical, trial design, and data management methodologies are encouraged to minimize needed sample size while maximizing statistical power, and to maintain or improve data collection and integrity. Therefore, it is also advantageous if the DCC has statistical expertise or experience in using flexible adaptive statistical methodology to contribute to these objectives. If the DCC’s institution has a NIH Clinical and Translational Science Award (CTSA) grant, describe how that grant will support Network activities (study coordination and recruitment assistance, protocol development support, training and mentoring, etc.).

Special administrative strengths or experience related to clinical trial research (e.g., single institutional review boards, data and safety monitoring boards, advisory boards for clinical research, clinical research committees) may also be highlighted, including level and support of clinical trials.

Attachment 2. Clinical Research Experience

Provide a table summarizing the applicant's research productivity as a data coordinating center, including previous or ongoing international clinical trials, especially those with focus on women’s and children’s health from 2016 to present as an attachment, using the filename “Attachment 2. Clinical Research Experience.pdf”. Contributions in key areas of research development and design, data collection and analysis, monitoring of trial progress, and track record of publications should be provided. Applicants must provide evidence of successful performance as a data coordinating center in the past 3 to 5 years.

Applicants should also describe any relevant international collaborative research activity undertaken between the U.S. applicant institution and a low or middle-income partner institution. Evidence of successful domestic and/or international research network or multicenter research activity also should be provided. Contributions and collaborations in areas such as protocol design, study recruitment, data analysis and interpretation, and publication should be highlighted.

The table format must include:

• Column A: Study Title
• Column B: Brief Description
• Column C: Funding Source(s)
• Column D: Site Planned Average Monthly Enrollment
• Column E: Site Actual Average Monthly Enrollment

Also please provide a list of publications (and total number of publications) for studies completed in pregnant and lactating people and their infants over the same time period.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

DCC applicants must demonstrate leadership in the design and conduct of clinical trials, preferably in the maternal and child health fields relevant to this FOA, as well as a track record in successfully coordinating and implementing multi-center clinical trials and in low and/or middle-income countries. Applicants must demonstrate clinical research expertise in: biostatistics; computer programming of websites and clinical trial data management systems, including those that meet FDA IND requirements; and work with study investigators to design protocols, manuals and data collection forms, manage capitation funds, and monitor data integrity and study safety. Applicants are strongly encouraged to name an experienced research team that will support the project management and implementation of Network trials.

Please include descriptions and biosketches for each of the individuals filling the roles below. Describe the qualifications and experience of each person, specifically documenting their respective abilities to organize, manage, and/or coordinate a DCC in the Network and to implement clinical trials.

The PI and Alternate/Co-PI will be considered Key Personnel on any resulting awards.

Principal Investigator(s)

Applicants must identify a PI; multi-PI applications are allowed, but each awarded Center will only get one vote on the Steering Committee. The PI for the Data Coordinating Center must be a PhD candidate or recipient in a relevant field, such as statistics, biostatistics, or epidemiology. The PI must have senior leadership experience with international multicenter randomized clinical trials, biostatistics, data management, data transmission, data analysis, and project management and have familiarity with the supportive role of a data coordinating center. The PI must demonstrate a track record of successful multi-site clinical trial implementation, preferably in obstetrics and/or neonatology.

The active participation of the PD/PI is expected during all phases of a clinical research study and at Steering Committee meetings and conference calls. Due to the demands and nature of the Network, the identified PI should not have extensive departmental duties (e.g., as Department Chair); rather, he/she/they should be able to devote the required time to the development, implementation, and management of the DCC.

Alternate/Co-Principal Investigator

Applicants must also identify an alternate or Co-PI candidate to assure continuity of operations in the event the PI is unavailable. The person designated as the Alternate/Co-PI should meet the same qualification criteria as the PI. The Alternate PI may be one of the named PI(s) on a multiple PI application.

Research Coordinator(s)

Applicants must identify at least one full- or multiple nearly full-time Research Coordinator. The Research Coordinator should have strong project management experience, including experience coordinating multi-site clinical trials and FDA trials, preferably in obstetrics and/or neonatology.

Additional Specialists

The application should propose a committed multidisciplinary team to conduct Network clinical trials and studies, including

• Statisticians
• Programmers and analytical staff
• Research assistants
• Data processing staff
• Logistics and support staff

Please include biosketches of biostatisticians and programmers who will work on the DCC’s team to implement protocols. Note: while most Network studies use frequentist methodologies, some studies may require Bayesian or other types of analyses, including complex genomic and other -omic statistical analyses.

R&R Budget

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Base Budget

Each applicant should submit Base Budget estimates for all years. The budget at the time of application will be limited to annual maximums of:

• Principal Investigator: 7.2-9 person-months (60-75%) effort
• Alternate/CoPI/senior statistician: 1.8 person-months (15%) effort
• Research coordinator(s): 24 person-months effort
• Statisticians
• Programmers and analytical staff
• Research assistants
• Data processing staff
• Logistics and support staff
• Supplies and equipment (itemized and justified)
• Travel: If not already based in the Washington, DC metro area, include trips for the PI (or designee), Research Coordinator(s), and relevant staff to attend in-person Steering Committee meetings (in their entirety) up to 2 times per year. These meetings will likely be held at NIH facilities, but the DCC will be in charge of working with conference room staff (at NIH or other non-NIH venues) to reserve and set up the room(s), get audiovisual and conference call/webinar functioning, etc. The DCC may also coordinate food catering (although the RUs will be responsible for reimbursing for this out of their travel expenses). In addition, the DCC must provide logistical arrangements for support of Steering Committee meetings (2 per year) and conference calls, DSMB meetings (2 per year) and conference calls, External Scientific Committee meetings (1 per year) and conference calls, as well as other selected consultants as needed by the NICHD.
• Other costs: This might include data management system costs, cloud server expenses, and other allowable items not already covered under the Applicant’s indirect cost rate. Budgets for the first project year should include funds for new computer equipment (as required), training, and software needed to establish a computer-based distributed data entry system at all recruiting sites.

The PD/PI and a Co-PI may split the combined minimum of 9.0 to 10.8 person months (75 to 90 percent) effort required for the Data Coordinating Center activities. If a different split than listed above is proposed, please describe in the management plan how the roles and responsibilities will be split between the two. The PD/PI is still expected to play an active role in DCC management and network activities.

Total funding for the DCC includes both the base award (via this RFA) and funds for approved study-related expenses via other protocol awards to the DCC and/or via subcontract from adjunct RU(s) and is dependent on the availability of funding. This application's budget should only include the Base Budget covering the items above.

In general, the NIH does not have a policy on salary escalation submitted in an application. We advise applicants to request in the application the actual costs needed for the budget period and to request cost escalations only if the escalation is consistent with institutional policy. See https://grants.nih.gov/grants/policy/salcap_summary.htm and https://grants.nih.gov/grants/policy/fy2012_salary_cap_faqs.htm.

Protocol Costs

For successful trial proposals that are submitted under future FOA(s), the DCC and/or adjunct RU will be awarded “Capitation” funds to cover study expenses. The DCC and/or adjunct RU will then be responsible for issuing payments as available for approved and funded protocol expenses to the RUs, DCC, and/or non-Network recruiting sites. The protocol budgets funded from other FOAs will cover study-related costs, generally funded at fixed rates on a per-subject enrolled or per-site basis. As appropriate, Capitation funds can be utilized to support Network operations and protocols, for instance, supporting additional personnel time for study screening, recruitment, and implementation or covering other allowable costs that are Network-related. Capitation funds are generally distributed based on milestone achievements (e.g., recruiting and/or randomizing a subject and/or transmitting specific study data to the DCC).

Participating sites will be required to accept protocol budgets for approved and funded Network studies. For this reason, PIs and Coordinators are required to assist in the development and review of protocol budgets prior to approval and funding. Awards may be restricted at sites unable to successfully participate in Network protocols, including timely start-up of studies, adequate participant enrollment, and other milestones.

Applicants should not include specific study expenses, such as capitation, IRB setup and management, etc., in this budget; they will be included in separate protocol budgets requested at a future date. The DCC should include personnel time to cover setting up and managing master agreements with the RUs, adjunct RUs, and single-trial sites.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy: Applicants must provide a description of the DCC’s capabilities in multi-center collaborative research. This should demonstrate detailed knowledge of the conduct of international multi-center clinical trials and observational studies in women and children.

NOTE: For this FOA, applicants are not required to include a research plan or protocol.

The DCC will participate in all clinical trials and observational studies conducted by the Global Network. The merit of the applications will be assessed for the applicant's ability to carry out such studies.

Collaborating with Network and Non-Network Investigators
Describe the applicant’s experience and plans to collaborate with investigators to design multi-site study protocols (e.g., primary and secondary outcomes and measures, sample size calculations), procedures (centralized randomization and/or stratification processes available 24 hours/day, 7 days/week, blinding procedures, follow-up schedules, etc.), statistical analysis plans, and budgets. The DCC will be required to work with Network and non-Network investigators to submit applications for protocol funding to NICHD or other NIH institutes for protocol funding.

Data Integrity and Safety Monitoring
Describe the applicant’s experience in data quality assurance (edits, audits, and data cleaning) and monitoring for clinical trials for safety, protocol adherence, and recruitment. Include experience with conducting, coordinating site monitoring visits and data audits. Describe the applicant’s experience conducting interim analyses for study safety and efficacy and reporting these, and unexpected, serious, and protocol-related adverse events to DSMBs and the FDA.

Staffing and Management
Provide an overview of DCC staff, including their biostatistical expertise with obstetric, lactation, and neonatology clinical research, their computer programming expertise in developing and/or customizing online, secure, data management systems, and their project management experience in facilitating clinical trial protocol development and implementation.

Describe the applicant’s management plan for its statistician resources and working with multiple stakeholders (NIH staff, the Steering Committee, and study investigators) to prioritize competing statistical analysis needs (i.e., for protocol development, conference presentations and manuscripts statistical analyses, etc.). The DCC should have flexibility in staffing to meet the changing needs and variation in work effort in the Network over time. Provide a description of the organization and supervisory structure of the DCC team and experience in implementing multiple studies simultaneously with high-quality data collection and safety monitoring.

Experience in Conducting Clinical Trials
Without duplicating information requested in Other Project Information (Clinical Research Experience), describe how the applicant has handled up to three trials/studies, especially those of a cooperative or multi-site design, that struggled with recruitment and/or retention of subjects and up to three that succeeded, with a particular focus on key challenges, successes, and lessons learned. Include contributions in key areas of study development and design; patient recruitment, retention, and follow-up; study monitoring, data collection and statistical analysis; and study closeout, including data sharing and reporting final results to ClinicalTrials.gov. Describe the applicant’s experience in designing and conducting multi-site clinical trials and studies, particularly in low- and lower middle-income countries, and acting as the sponsor or co-sponsor of FDA IND or IDE applications, collaborating with study PIs, NIH, and/or other study sponsors to provide data and documentation for FDA reporting.

Study Implementation
Describe the applicant’s process for preparing and disseminating study materials – final protocol, manual of operations, data collection forms, data management system, and other study materials – and training recruiting site staff in study procedures and data management system use.

Describe the applicant’s experience and approach in procuring and distributing coded medications (e.g., investigational drugs, matching placebos) for international multicenter clinical trials, assisting site pharmacies and/or packaging/distribution companies with medication masking procedures, training pharmacy staff in randomization and other study procedures, and managing central reading and specimen analyses under subcontracts. The applicant will be expected to provide training for all RU personnel as needed on data management and analysis, quality control, and quality assurance.

Describe the applicant’s plans for organizing and conducting both on-site and off-site monitoring for international clinical multicenter research studies and for attending to data errors, needed edits, and protocol deviations.

Clinical Trial Management and Communications
Describe the applicant’s experience and approach to clinical research management, financial management, and communications, including managing study capitation funds, setting up master agreements with sites to enable transfer of earned capitation funds and study data between the DCC and each RU, adjunct RU, and/or single-trial site and transferring these funds as it is earned. Describe the approach for working with NICHD Program staff to generate regular budget monitoring reports to manage available funds and estimate future annual study costs.

Provide details on the approach to developing and maintaining a Network website, drafting and disseminating study materials and technical memos, providing technical support to RU staff, coordinating Steering Committee, subcommittee, and DSMB meetings/videoconferences, and polling PIs and/or sites for key votes or study-related background information.

Data Management System(s)
Describe capabilities and experience in developing and/or customizing online, secure, data management systems that incorporate: real-time data entry, skip logic functionality, real-time edit checks (e.g., out-of-range values), and auditing capability; data import compatible with standard data formats; online data discrepancy and problem resolution; regular or real-time report generation; adverse event reporting and adjudication; randomization functionality; and email alert systems. Describe security and backup features to protect study participant data and Network resources.

Culture of Clinical Research
Describe the applicant’s environment and approach to team science and creating a culture that encourages clinical research. Successful DCCs involve their entire teams in Network research, including coordinators, programmers, and assistants, providing input into protocol design, implementation, monitoring, data analysis, publication of results, and study closeout. These teams may also be involved in proposing secondary analyses of studies and/or proposing new studies or secondary studies. This promotes team science and helps mentor and train more junior staff and new investigators.

Letters of Support

Data Coordinating Center Institution

Because this program requires a team effort to be successful, departmental and institutional commitments to participate in Global Network research should be clearly documented. Please provide letters of support from appropriate individuals at the DCC detailing:

• Institutional support in areas of grants management, personnel provision and management, space allocation, procurement, and equipment, as well as general support of the research. Evidence of past support can be cited.
• Clearly expressed intent to:
  • Participate in a cooperative manner with the Network Research Units, adjunct RUs, and NICHD staff, as needed, in all aspects of research as outlined in this FOA;
  • Prioritize Network research, including committing to safeguard staff time for the satisfactory conduct of the studies. Awards may be restricted at sites unable to successfully participate in Network protocols, including timely start-up of studies, and achievement of other milestones;
  • Participate in all Network trials
  • Cooperate with the policy for capitation of research costs as outlined in this FOA and the Network policy manual ;
  • Comply with the Network Data Sharing Plans as outlined in this FOA and in the Network policy manual; and
  • Keep confidential and do not disclose any confidential or proprietary information when working with Network and non-Network investigators and/or industry partners, other than to employees, agents, subcontractors, consultants, vendors, or affiliates who have a need to know that information, and/or to make use of it, only for the purpose of discussing, evaluating, and assisting in the development of potential studies for conduct in the Network, and subsequently to conduct approved and funded studies in the Network.

Institutions with Clinical and Translational Science Awards (CTSA)

Applications from institutions that have a NIH Clinical and Translational Science Award (CTSA) should provide a letter of agreement from the CTSA PI that identifies the level and type of support that will be provided for this grant, should it be awarded.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

The following modifications also apply:

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Sharing Plan.

NICHD Plans for Sharing Human and Non-Human Data and/or Biospecimens

NICHD expects that data, biospecimens, and results of NICHD-funded research will be shared with the wider scientific community to the extent feasible and in a timely manner, per NIH Policy, as amended.

NIH Data Management and Sharing Policy expects the timely release and sharing of data to be no later than the time of an associated publication, or the end of the award/support period, whichever comes first. Per the Policy, all applications, regardless of the amount of direct costs requested for any one year, are required to include a Data Management and Sharing Plan (“the Plan”) outlining how scientific data and any accompanying metadata will be managed and shared, regardless of whether the data are used to support scholarly publication. For this cooperative agreement clinical research Network, protocols submitted via future protocol funding opportunity announcements or other NIH FOAs will include a detailed Plan that will be approved by NIH. Each Plan should describe data types, file formats, submission timelines, standards used in collecting or processing the data and other elements described in Supplemental Information to the NIH Policy for Data Management and Sharing: Elements of an NIH Data Management and Sharing Plan (NOT-OD-21-014). The Plan will be subject to assessment and approval by NIH Program Staff prior to funding. The approved Plan may be incorporated into the Terms & Conditions of each protocol award, and awardees are required to comply with the approved Plan and any approved updates to the Plan. The Plan should be included with the final protocol for IRB approval as well.

For sharing human and non-human data, unless stipulated otherwise in each protocol’s approved Plan, the Network’s DCC is responsible for preparing and submitting protocol datasets to the NICHD Data and Specimen Hub (DASH) and/or other NIH-approved repositories on behalf of the Network. For protocols that generate large-scale human genetic data, recruiting sites will have to provide a Provisional or Institutional Certification specifying whether the individual-level data can be shared through an NIH-approved repository, such as dbGaP, in line with the NIH Genomic Data Sharing Policy. This will be done on a protocol-by-protocol basis. If any ongoing Network protocols require this, it will be requested before the Awardee can start recruiting into the study.

For sharing biospecimens, the Network’s DCC is responsible for maintaining an inventory of biospecimens managed across the Network and, upon NICHD approval, coordinating submission of any remaining biospecimens to an NIH-approved repository on behalf of the Network.

Each Research Unit, adjunct RU, and/or recruiting site is responsible for ensuring that each study’s informed consent forms contain language allowing broad sharing and future use of study data and biospecimens in alignment with federal and local regulations and policies. Consent forms must notify participants that their data and, when relevant, imaging data and biospecimens (potentially for both maternal and child) may be shared with other Network investigators, the study sponsor(s), applicable federal agencies, and, when relevant, industry partners. In addition, de-identified data, imaging data, and remaining biospecimens from each study may be shared with researchers outside of the Network, including depositing them in NIH-approved public repositories. Research Unit, adjunct RU, and/or recruiting site may also be required to obtain approval(s) from appropriate regulatory authorities (e.g., IRB) for sharing that data, particularly for studies conducted under a waiver of consent.

For this FOA, applicants must indicate in their institution’s Letter of Support their agreement to comply with the Network Data and Specimen Sharing Plans, including abiding by the negotiated Data Management and Sharing Plans for studies conducted in the Network, and cooperate with Network procedures needed to finalize and share study data per these Plans.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential fieldof the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NICHD, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this FOA, the awarded DCC will participate in clinical trials and observational studies conducted by the Global Network for Women’s and Children’s Health Research. The review of this application will emphasize the overall research environment, capabilities, and experience of the Applicant and its personnel. In addition to the review criteria below, the merit of the application will include how well the Applicant can carry out such studies, with particular emphasis on the statistical analysis, database programming, and clinical research project management capabilities, as well as collaboration with other RUs in the Network.

NOTE: For this FOA, applicants are not required or expected to include a research plan or protocol.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the proposed Center address the needs of the research Network that it will coordinate? Is the scope of activities proposed for the Center appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research Network?

Specific to this FOA:

To meet the Global Network’s purpose and objectives, how adequately does the application demonstrate:

• Experience and/or plans to collaborate with investigators, including non-Network investigators, to design multi-site study protocols, procedures, statistical analysis plans, and budgets?
• Quality assurance and reporting procedures for monitoring data integrity and safety?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigator(s)

Are the PD(s)/PI(s) and other personnel well suited to their roles in the Center? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing multi-site clinical trials and studies research? Do the investigators demonstrate significant experience with coordinating collaborative clinical research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, and organizational structure appropriate for the Center? Does the applicant have experience overseeing selection and management of subawards, if needed?

Specific to this FOA:

To meet the Global Network’s purpose and objectives, how well does the applicant’s PI and team meet the needs of a DCC in terms of:

• A strong organizational and supervisory structure to manage a DCC’s statistician resources, working with multiple stakeholders (NIH staff, the Steering Committee, and study investigators) to prioritize competing statistical analysis needs?
• Biostatistical experience, particularly with obstetric, lactation, and/or neonatology clinical research, to design, implement, and analyze Network studies?
• Computer programming experience in developing and/or customizing online, secure, data management systems?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Innovation

Does the application propose novel organizational concepts, management strategies, or instrumentation in coordinating the research network the Center will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts, management strategies or instrumentation proposed?

Specific to this FOA:

To help further the Global Network’s purpose and objectives, does the applicant include evidence of:

• Innovative statistical, trial design, and data management methodologies to minimize needed sample size while maximizing statistical power, and to maintain or improve data collection and integrity?

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research Network the Center will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the Network, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the Network is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the network? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA:

To further the Global Network’s purpose and objectives, how adequately does the applicant meet the following requirements:

• A track record in conducting recent clinical trials and studies, including study design, patient recruitment, retention and follow-up monitoring, database management system programming (including for FDA trials), data quality monitoring, and publications in maternal and child health? Experience in designing and conducting international multi-site clinical trials and studies?
• A clear process for preparing, obtaining, and disseminating study materials and supplies and training Research Unit staff, including pharmacy staff when required, in study procedures and data management system use?
• A financial management plan for managing and disseminating capitation funds?
• Clinical research project management and communication capabilities to meet the needs of the Network?
• Procedures ready to meet the Network and NIH Data Sharing requirements?

As noted above, applicants are not required or expected to include a research plan or protocol for this FOA.

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Environment

Will the institutional environment in which the Center will operate contribute to the probability of success in facilitating the research network it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Center proposed? Will the Center benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

Specific to this FOA:

To further the Global Network’s purpose and objectives, how adequately does the applicant meet the following requirements:

• Strong capabilities to provide, program, and maintain online, secure, data entry and management system(s) for the Network, including back-up systems and, when needed, systems capable of meeting FDA requirements?
• A culture of clinical research that promotes team science and encourages staff participation in research?
• A willingness to work and cooperate with the Global Network Research Units, adjunct research units, and the NICHD staff in a manner summarized in this FOA?
• Institutional assurances and commitments to support the Network, in such areas as fiscal administration, personnel management, space allocation, procurement, planning, and budgeting?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Study Timeline

Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3)  Genomic Data Sharing Plan (GDS).

Authentication of Key Biological and/or Chemical Resources:

For [programs/projects/networks/consortia/resources] involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NICHD, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Child Health and Human Development Council (NACHHD). The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federalwide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identity, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.
• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75 and 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be a cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Staffing
  • Obtaining prior written approval of the NICHD Grants Management Specialist, in consultation with the Program Official for any change in any of the key personnel identified in the Notice of Grant Award.
  • For multi-PI awards, designating a PI to be its voting representative on the Network Steering Committee.
• Protocol Development and Implementation
  • Providing input and subject matter expertise for study development, data analysis and interpretation, preparation of publications, and collaboration with other investigators. This may require working with outside non-Network investigators to develop protocols and/or grant applications for potential studies to be conducted in the Network. When working with Network and non-Network investigators and/or industry partners, recipients will keep confidential and not disclose any confidential or proprietary information other than to employees, agents, subcontractors, consultants, vendors, or affiliates who have a need to know that information, and/or make use of it, only for the purpose of discussing, evaluating, and assisting in the development of potential studies for conduct in the Network, and subsequently to conduct approved and funded studies in the Network.
  • Participating in all Network studies at all recipient recruiting sites and prioritizing Network studies over other studies, including other NIH-funded studies for subject recruitment, unless it is known before start-up that the institution does not have the relevant eligible population or has an ongoing local study that conflicts with a Network study that was identified in its application.
  • Monitoring study recruitment, participant follow-up, and study funding. The recipient will provide monthly and/or real-time reporting of enrollment and/or follow-up for each study. Working with NICHD Staff to monitor and project study capitation fund expenditures and project future study costs on no less than an annual basis to ensure good stewardship of Federal funding.
  • Maintaining quality control measures to ensure protocol adherence and collection and transmission of accurate data within required timeframes to the Network data coordinating center and/or other coordinating centers identified in protocol awards.
• Protocol Results Reporting and Data and Specimen Sharing
  • Publishing and publicly disseminating study results, in accordance with Network and NIH policies, including publishing results on ClinicalTrials.gov and submitting study publications to the PubMed Central within the required timeframes.
  • Complying with Network data and specimen sharing plans, including ensuring the appropriate language is included in study informed consent forms.
  • Acknowledging NIH funding support in all relevant publications and presentations of work performed under this agreement.
• Recipients(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access consistent with current DHHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

NICHD’s Office of Clinical Research staff, a Program Official, and a Grants Manager will be responsible for overall grant stewardship. A NICHD Project Scientist will provide scientific input to the Network. A Clinical Trials Specialist or Program Analyst will work with the Program Official and Project Scientist to help coordinate Network management.

NICHD Office of Clinical Research

NICHD’s Office of Clinical Research will work with NICHD Program Staff to develop efficiencies, support Network stewardship, and provide policy guidance. Staff from the NICHD Office of Clinical Research (OCR) may attend SC and subcommittee/working group meetings as observers.

NICHD Program Official

In addition to general grant stewardship, a NICHD Program Official will:

• Monitor progress of study milestones to ensure that the objectives are being met and that all regulatory, fiscal, and administrative matters are handled according to NIH guidelines. Continuation of funding will be dependent upon the awardee’s ability to show adequate progress towards milestone accomplishment.
• Conduct site visits, as needed, to review/on-board new sites and monitor study implementation at existing sites. In conjunction with the Grants Manager, the Program Official may withhold support of a recipient if technical performance requirements such as protocol compliance, enrollment targets, or randomization and/or follow-up of subjects are not met.
• Serve as the NICHD representative, or designate a NICHD representative, on the Network’s Data and Safety Monitoring Board (DSMB) in the manner delineated in the NICHD Data and Safety Monitoring Policy.
• Monitor Network base budget and study funding and developing annual budget projections for outyears with assistance from the NICHD Program Analyst/Clinical Trials Specialist.

NICHD Project Scientist

A NICHD Project Scientist will have substantial programmatic involvement that is above and beyond the typical stewardship role in other awards. As described below, the Project Scientist will:

• Serve as the NICHD’s voting representative on the Steering Committee and all Network subcommittees.
• Provide scientific/programmatic support and input for study design, implementation, results analysis, publication, study closeout, and development of solutions to major problems, such as insufficient participant enrollment. He/she/they will work with investigators, both within and outside of the Network, to design protocols, manage study implementation, and analyze and publish results.
• Assist in the development and review of study budgets, including the identification of capitation costs and special institutional needs.
• Have access to study data and may periodically review the data and administrative progress reports. For these purposes, any individual-level data should be de-identified, and data from ongoing trials should be blinded until it is time to analyze study results. Program staff may use information obtained from the data for the preparation of internal reports on the activities of the study.
• Oversee the adequacy of adverse event management and reporting.
• Monitor study progress, of each participating facility and of the Network as a whole, through recipient's annual reports, Network study reports, site visits, screening logs, etc. This review may include, but is not limited to, compliance with the study protocol, meeting enrollment and participant follow-up targets, adherence to uniform data collection procedures, and the timeliness and quality of data reporting.

Director of the NICHD

NICHD reserves the right to terminate or curtail a study (or an individual award) under a range of scenarios including but not limited to: (a) failure to implement the study protocol; (b) a substantial shortfall in subject recruitment, follow-up, data reporting and dissemination, quality control, or other major breach of the protocol; (c) substantive changes in the agreed-upon protocol with which NIH does not concur; (d) reaching a major study objective substantially ahead of schedule with persuasive statistical evidence; (e) human subject safety or ethical issues that may dictate a premature termination; or (f) a change in the state of science that changes equipoise or has other significant impact on the relevance of the question under study. Studies in which recruitment and/or participant follow-up milestones are not met, or for which regulatory approval has not been met within one year, and are unlikely to improve sufficiently to bring the study to completion within an acceptable budget or timeframe, may be closed for lack of progress. If NIH or the awardee concludes that the study is no longer feasible, the Network shall submit a close-out plan to NIH within 2 months.

Independent of the governance above, the NICHD Director retains responsibility for all NICHD-funded research. The NICHD Director receives the DSMB’s recommendations on whether Network studies should be continued or terminated and can make an independent decision on how to proceed. The NICHD Director may advise the Steering Committee on the strategic interest of the NIH/NICHD.

Areas of Joint Responsibility include:

• All parties will agree to accept the coordinating role of the group and the participatory and cooperative nature of the group process. As part of this, all parties will form a joint Steering Committee to govern the Network, consisting of:
  • The U.S. PI and International PI from each recipient Research Unit (one vote per center)
  • One PI from the recipient Data Coordinating Center (voting member)
  • NICHD Project Scientist (voting member)
  • Adjunct PI for any non-Network trial (one vote for that specific trial only)

• The Steering Committee has primary responsibility for implementing the objectives of the Network, including:
  • Identifying areas of potential research
  • Working with investigators within and outside of the Network to develop protocols. As part of this process, the Steering Committee, PIs (both Network and non-Network), and their involved staff must keep protocol development materials (drafts, unpublished data, and other intellectual property) from investigators and potential industry partners confidential.
  • After NIH peer review and funding approval of studies to be conducted in the Network, overseeing the organization and execution of the studies
  • Analyzing and publishing study results
  • Depositing results in ClinicalTrials.gov
  • Complying with NIH requirements for data and specimen sharing and software development, subject to Government rights of access consistent with current HHS, PHS, and NIH policies, including for data and specimen sharing.
• As part of its governance responsibilities, the Steering Committee will develop a Network Policies and Procedures Manual that delineates the structure and function of the Network, its standard operating procedures, and general rules (e.g., publication authorship). The NICHD Program Staff will help ensure that these policies follow NIH and other Federal guidelines and appropriately address the strategic interests and stewardship responsibilities of the NIH. The Steering Committee will vote on the overall Network Policies and Procedures Manual and any amendments; the NICHD Program Official will have approval authority for this Manual.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

Multiple PD/PI Dispute Resolution
If a conflict develops between PD(s)/PI(s) in a multiple PD/PI application, the following procedures will apply:

The Departmental administrators representing the PD(s)/PI(s) shall meet and attempt in good faith to settle any dispute, claim or controversy arising out of or relating to the interpretation, performance or breach of this disagreement. However, if the Departmental administrators fail to reach resolution in 30 days, then the NIH may invoke dispute resolution procedures as described in the above paragraph.

3. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Nahida Chakhtoura, MD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6872
Email: nahida.chakhtoura@nih.gov

Sherry Dupere, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-496-1485
Email: duperes@mail.nih.gov

Kelly Fritz
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-827-5429
Email: kelly.fritz@nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 2 CFR Part 200, 42 CFR Part 52, and 45 CFR Part 75.