National Institutes of Health (NIH)
U24 Resource-Related Research Projects Cooperative Agreements
NOT-TR-22-018 - Notice of Availability of Application Information for RFA-TR-22-012 Emergency Awards: HEAL Initiative-Limited Competition: HEAL Initiative Resource Centers for the Pain Management Effectiveness Research Network (ERN) (U24 Clinical Trial Not Allowed)
RFA-AT-22-005 - HEAL Initiative: Sickle Cell Disease Pain Management Trials Utilizing the Pain Management Effectiveness Research Network Cooperative Agreement (UG3/UH3, Clinical Trial Required)
Only one application per institution is allowed, as defined in Section III. 3. Additional Information on Eligibility.
NCATS is issuing this FOA in response to the declared public health emergency issued by the Secretary, HHS. Please see Determination that a Public Health Emergency Exists Nationwide as the Result of the Opioid Crisis as renewed in Renewal of the Determination that a Public Health Emergency Exists Nationwide as the Result of the Continued Consequences of the Opioid Crisis.
The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications to continue support of Resource Center activities funded under RFA-TR-15-002 and RFA-TR-15-004; thus only applicants funded by RFA-TR-15-002 and RFA-TR-15-004 are eligible to apply for this FOA. Applications to this FOA will support Resource Centers (RCs) for clinical trials funded through the HEAL Pain Management Effectiveness Research Network (ERN) initiatives, including those funded under RFA-NS-19-021 and RFA-NS-20-028. Applicants are expected to continue provision of the existing HEAL ERN infrastructure to support comparative effectiveness clinical trials/studies with a shared common theme of improving pain management and reducing the reliance on opioid medications when appropriate. The RCs will provide clinical and data coordination, biostatistical resources, and recruitment and retention support. They will also continue working with other HEAL Data Coordination Resource Centers (DCRCs) to harmonize data elements creating valuable combined data sets that can be used for future meta-analyses or to add to our knowledge of under-studied pain conditions.
15 days prior to the application due date
| Application Due Dates | Review and Award Cycles | ||||
|---|---|---|---|---|---|
| New | Renewal / Resubmission / Revision (as allowed) | AIDS | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
| March 15, 2022 | Not Applicable | Not Applicable | Not Applicable | Not Applicable | July 2022 |
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.
Not Applicable
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.
Purpose
NCATS is issuing this FOA in response to the declared public health emergency issued by the Secretary, HHS. Please see Determination that a Public Health Emergency Exists Nationwide as the Result of the Opioid Crisis as renewed in Renewal of the Determination that a Public Health Emergency Exists Nationwide as the Result of the Continued Consequences of the Opioid Crisis.
This Funding Opportunity Announcement (FOA) invites cooperative agreement applications from current National Center for Advancing Translation Sciences (NCATS) Trial Innovation Network (TIN) recipients, funded under RFA-TR-15-002 and RFA-TR-15-004, that propose to serve as Resource Centers (RCs) for clinical trials/studies within the HEAL Pain Management Effectiveness Research Network (ERN) program. This program, initiated in 2019, is part of the NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative bolsters research across NIH to: (1) improve treatment for opioid misuse and addiction, and (2) enhance pain management. More information about the HEAL Initiative is available at: https://heal.nih.gov/.
Background
The Nation faces a crisis of opioid use disorder and overdose deaths, which often is associated with long-term administration of an opioid for the treatment of chronic non-cancer pain. More than 20% of adults in the U.S. experience chronic pain and need safe, non-addictive methods to manage their pain (2019 National Health Interview Survey data). Many groups report a relatively high prevalence of chronic pain and high-impact chronic pain including women, older adults, previously but not currently employed adults, adults living in poverty, adults with public health insurance, and rural residents. Reducing the burden of pain nationwide is a significant unmet need.
Severe pain is often associated with diseases and chronic conditions such as diabetes, cancer, endometriosis, and sickle cell disease, and it may persist as chronic pain following many surgical procedures or trauma. Chronic pain conditions such as complex regional pain syndrome, migraine, and fibromyalgia are diseases themselves, and many chronic pain conditions co-occur in individuals. Current strategies for managing chronic pain outlined in the CDC Guideline for Prescribing Opioids for Chronic Pain and AHRQ’s Noninvasive Nonpharmacological Treatment for Chronic Pain: A Systematic Review include non-pharmacologic treatments for specific chronic pain conditions, non-opioid drugs, and opioid therapy with various methods for initiating and titrating opioid dosing. However, the strength of evidence supporting these strategies is considered to be low to moderate and is primarily based on clinical studies with significant limitations, observational studies, and case reports. More studies are needed to inform evidence-based treatments for chronic pain and effective, non-addictive opioid dosing regimens.
To generate this needed evidence, the HEAL ERN was established in 2019. HEAL ERN awardees conduct clinical trials to test the comparative effectiveness of existing therapies for prevention or management of pain while reducing risk of addiction. Studies that inform providers and patients on best practices to manage acute or chronic pain in the primary care, emergency department, hospital or dental settings are priority areas of interest. The studies must evaluate methods and approaches to manage pain. Strategies tested might include safe use of medications including appropriate use of opioids, biologics, devices or delivery systems, and/or behavioral interventions or multimodal approaches. The overall goal is to provide clinicians with robust evidence to best manage patients with acute or chronic pain.
HEAL Effectiveness Research Network Organization
The HEAL ERN was established using the existing NCATS TIN infrastructure and contains four unique Resource Centers: 1) Clinical Coordinating Resource Center (CCRC), 2) Data Coordinating Resource Center (DCRC), 3) Statistical and Safety Resource Center (SSRC), and 4) Recruitment Resource Center (RRC). This combined TIN infrastructure provides clinical trial scientific guidance, clinical and data coordination, biostatistical support, unique recruitment and retention strategies and additional clinical sites for enrollment if needed. Clinical trials are conducted at the Clinical and Translation Science Award (CTSA) Program hubs and/or any other non-CTSA clinical sites selected by the investigator. Currently, TIN Resource Centers can support approximately seven independent trials, but more trials may be added in the future.
The TIN Resource Centers work with Principal Investigators who have been awarded an independent HEAL grant to develop and execute a clinical trial, as described in RFA-NS-19-021 and RFA-NS-20-028. Briefly, the trial Principal Investigators determine the clinical question and the research approaches for their subsequent trials. Most trials are awarded in two phases: a planning phase during which the design and statistical analysis are finalized, the protocol is completed and reviewed by the single Institutional Review Board and any Data and Safety Monitoring Boards; and an implementation phase when the study enrolls subjects. Only studies approved by NIH leadership transition to the implementation phase.
Additionally, Principal Investigators of the clinical trials and TIN Resource Centers form the ERN Program Steering Committee, which meets once a year and at additional times if needed throughout the program. The Program Steering Committee will recommend the frequency of other in-person and teleconference meetings as needed. All award recipients agree to accept close coordination, cooperation, and participation of NIH staff in those aspects of scientific and technical management of the study as stated in the terms and conditions of their cooperative agreement awards. NIH Program staff ensure that standardized and consistent pain and other relevant outcome measures and common data elements are used appropriately in studies to ensure translation of shared data across HEAL supported clinical studies.
The NIH HEAL Initiative will require a high level of coordination and sharing among investigators. It is expected that NIH HEAL Initiative recipientswill cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings, including an annual HEAL Investigators Meeting, as well as other activities.
Research Objectives:
This FOA will organize the infrastructure of the Trial Innovation Network (TIN), dedicated to HEAL activities, into discrete Resource Centers referred to as HEAL ERN Resource Centers moving forward to optimize the coordination of individual HEAL ERN clinical trials/studies and to facilitate the dissemination of strategies and best practices for conducting pain management studies that result from the collaborative activities of the TIN and HEAL ERN.
The specific objectives of the HEAL ERN Resource Centers are to:
- Work collaboratively with each Effectiveness Research Network study team supported through the NIH HEAL ERN program to develop, test, and implement the proposed ERN studies and trials while providing customized technical, data management, design, biostatistical, safety and coordination support for meritorious pain management clinical trials/studies;
- Ensure recruitment goals are met in a timely manner and develop/implement enrollment corrective action plans in conjunction with individual investigator teams and NIH staff if needed;
- Facilitate sharing of data from HEAL ERN trials/studies to improve future meta-analyses and comparison of outcomes from HEAL trials testing pain management strategies;
- Facilitate timely publication and dissemination of individual trial results;
- Test and disseminate the best strategies to incorporate HEAL Common Data Elements into HEAL ERN studies and trials as well as facilitate data transfer/deposit into NIH-designated repositories;
- Evaluate and disseminate the best strategies for engaging, recruiting and retaining populations, including those that are under-represented, as research participants in pain management trials;
- Develop and disseminate the best methods for conducting effectiveness research studies for pain management. This could include enhancing tools for electronic consenting, remote monitoring, and other methods to engage a broader, more diverse group of participants.
Award recipients will continue to support existing HEAL ERN clinical trials and must be flexible enough to incorporate future HEAL trials/studies if needed. Separate FOAs will solicit and provide support for any future HEAL ERN clinical trials/studies.
Applicants responding to this FOA may propose to act as only one of the following HEAL ERN Resource Centers. Applicants should clearly identify which resource center they are applying for in the application.
Data Coordination Resource Center (DCRC). The DCRC will utilize robust methods and systems to enable data collection, provide sound data management, and assure data quality. They will also work with other HEAL DCCs to harmonize data elements to create valuable combined data sets that can be used for future meta-analyses or add to our knowledge of under-studied pain conditions.
Significant responsibilities include:
- Collaborating with the Principal Investigators of the individual trials/studies and the other HEAL ERN Resource Centers in the development, implementation, and monitoring of the study protocol(s), the collection and analysis of data, and publication of trial/study results.
- Providing data management, including development of appropriate data collection forms and systems, implementing masking and randomization methods.
- Developing and maintaining databases for each of the ERN trials/studies from the planning phase through the implementation phase (enrollment) phase.
- Creating and maintaining data management plans describing in detail the data collection tools and systems used, as well as the data flow between patients, study sites, the other Resource Centers and the DCRC.
- Supporting all forms of data collection, including direct entry by staff at clinical centers and direct entry of patient reported outcomes (PROs) by participants by telephone or web-based portals.
- Working with the CCRC to conduct data cleaning and quality control efforts, reviewing study participant data, and working with the recruiting sites to resolve any outstanding missing or inconsistent data items.
- Working with the other HEAL ERN Resource Centers to train study personnel as needed.
- Preparing needed reports for the Steering Committee, its subcommittees, the Principal Investigators of individual trials and other committees as needed.
- Preparing DSMB reports and other oversight committees in conjunction with the Statistical and Safety Resource Center.
- Preparing datasets for deposition into public data repositories for broad data sharing in compliance with the NIH data sharing requirements.
- Working with each of the trial/study investigators to support harmonization of data elements for each trial by incorporating the NIH HEAL CDEs into protocols.
- Acting as single IRB for at least one HEAL ERN study. The DCC will be responsible for acting as the single IRB for at least one study, including providing coordination services to help individual sites prepare needed individual applications.
Clinical Coordinating Resource Center (CCRC). The Clinical Coordinating Resource Center oversees clinical operations for the trials/studies, developing detailed project management plans, training study teams, monitoring sites, developing and implementing project-specific problem resolution and improvement plans, implementing continuous quality improvement across the trials/studies, and helping trial/study clinical investigators identify additional sites.
Significant responsibilities include:
- Collaborating with the Principal Investigators of the individual trials/studies and the other HEAL ERN Resource Centers in the development, implementation, and monitoring of the study protocol(s), the collection and analysis of data, and publication of trial/study results.
- Providing overall project management for each trial/study, including working with the Principal Investigators of each trial/study and the other HEAL ERN Resource Centers to develop detailed project management plans.
- Maintaining a detailed study timeline to ensure completion of all required tasks.
- Preparing regular study update summaries, distributed to team members and NIH, to communicate major completed and upcoming meetings, action items, and milestones.
- Leading development and finalization of the individualized Manual of Procedures and Clinical Monitoring Plan (CMP) for each trial, with assistance from the other Resource Centers.
- Site Management and Clinical Monitoring: Remote and on-site monitoring of case report form (CRF) completion, data collection, and query resolution in conjunction with the DCC.
- Working with the DCC to resolve any outstanding missing or inconsistent data items.
- Meeting and communication management, including planning and facilitating key meetings and weekly to monthly operations meetings, and ad hoc meetings to review items such as monitoring reports.
- Developing trial specific websites.
- Coordinating external services, including procuring study drugs, equipment, and other supplies, and assistance with executing subcontracts/vendor services, such as for study drug distribution and subcontracting with recruiting sites.
- Assisting with additional investigator and site selection.
- Assisting investigators with communications to ensure regulatory compliance with agencies such as the Food and Drug Administration.
- Acting as the call center to collect data in real time and provide continuity between subject calls.
- Monitoring and reporting on data quality, protocol adherence, and recruitment status.
- Creating and maintaining ClinicalTrials.gov records, including reporting of results, for the Steering Committee.
- Acting as single IRB for at least one HEAL ERN study. The CCRC will be responsible for acting as the single IRB for at least one study, including providing coordination services to help individual sites prepare needed individual applications.
Statistical and Safety Resource Center (SSRC). The SSRC will provide biostatistical support over the duration of the trials/studies. They will also assist ERN trial awardees with the design and implementation of protocols, safety monitoring, reporting and adjudication procedures. They will develop DSMB charters and processes and create DSMB reports in conjunction with the DCC as needed for the oversight committees.
Significant responsibilities of the SSRC include the following:
- Collaborating with the Principal Investigators of the individual trials and the other HEAL ERN Resource Centers in the development, implementation, and monitoring of the study protocol(s), the collection and analysis of data, and publication of trial/study results.
- Reviewing and finalizing study protocols and statistical analysis plans with the study team to determine the analytical approaches for each primary, secondary, and exploratory outcome of the HEAL ERN trials/studies.
- Harmonizing statistical approaches across all HEAL ERN trials/studies, when possible, to allow for cross study analysis at the conclusion of the trials/studies.
- Generating the randomization scheme for each trial/study.
- Completing the statistical analyses for HEAL ERN trials/studies at the conclusion of each study.
- Drafting, reviewing, finalizing data safety monitoring plans and DSMB charters with the study teams and various NIH Institutes and Centers administering the trials.
- Hosting the DSMB calls, maintaining minutes and distributing recommendations to the study team.
- Working with the HEAL ERN DCC to generate any needed blinded and unblinded reports for the DSMB.
- Reporting to the DSMB, as needed, any unexpected, serious, and protocol-related adverse events or apparent trends in data possibly relevant to patient safety.
- At periodic intervals, as specified in an individual protocol, the providing the DSMB or other oversight bodies with confidential interim analyses of study data related to protocol performance, sample size re-estimations, patient safety, and emerging results related to efficacy and futility.
- Acting as single IRB for at least one HEAL ERN trial/study. The SSRC will be responsible for acting as the single IRB for at least one study, including providing coordination services to help individual sites prepare needed individual applications.
Recruitment Resource Center (RRC). The RRC will provide expertise in recruitment and retention of participants including community and stakeholder engagement and other strategies that cover the entire continuum of recruitment and retention in clinical trials/studies. They will be responsible for development and finalization of recruitment and retention plans, working with the specific study investigators, to identify barriers and facilitators to recruitment and retention and offering mitigation strategies that result in effective clinical trial/study recruitment and retention plans. In addition, the RRC will be responsible for utilizing innovative information technologies to identify potential additional clinical trial/study sites for HEAL ERN trials/studies.
Significant responsibilities of the RRC include the following:
- Collaborating with the Principal Investigators of the individual trials and the other HEAL ERN Resource Centers in the development, implementation, and monitoring of the study protocol(s), the collection and analysis of data, and publication of trial/study results.
- Developing comprehensive, study-specific recruitment and retention plans, including feasibility assessments, to ensure HEAL ERN studies efficiently enroll and retain participants.
- Developing strategies, including culturally and linguistically tailored approaches as appropriate, within each HEAL ERN study’s recruitment and retention plan focused on ensuring equitable recruitment and inclusion of racial/ethnic minority populations and NIH-designated populations that experience health disparities.
- Monitoring race/ethnicity/age/gender screening and enrollment information for all HEAL ERN trials/studies and developing strategies to help studies meet their recruitment targets, including monitoring enrollment and retention at the individual study sites and working with sites that fail to meet their enrollment targets.
- Developing recruitment and retention plans that have attention to adequate gender, race, and ethnicity inclusion to assure that a valid analysis may be conducted if appropriate.
- Developing innovative approaches to recruitment and retention for different research settings.
- Assisting with Community Engagement activities for individual trials.
- Developing centralized recruitment and retention materials in appropriate languages that are easily adaptable across study sites.
- Developing tools, software, and instruments that have the potential for broad dissemination to help investigators recruit and retain participants for HEAL studies.
- Using electronic cohort identification and characterization methods to identify sites for individual studies as needed.
The exact boundaries of the activities of the HEAL ERN Resource Centers, the individual HEAL ERN clinical trial/study teams and NIH may vary across time and will depend in large part on the settings, designs and approaches of the individual trials/studies within the Network.
Applicants should strive to incorporate diversity in their team development plan. Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust. Please refer to Notice of NIH's Interest in Diversity NOT-OD-20-031 for more details.
Applications that propose the following will be considered non-responsive and will not be reviewed:
- More than one type of Resource Center
- NIH-defined clinical trials
See Section VIII. Other Information for award authorities and regulations.
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
Not Allowed: Only accepting applications that do not propose clinical trials.
Need help determining whether you are doing a clinical trial?
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
The NIH HEAL Initiative intends to commit up to $10,000,000 in FY 2022 to fund four unique Resource Center awards.
Application budgets are limited as follows:
Data Coordination Resource Center (DCRC):
Year 1: Not to exceed $2,000,000 direct costs; Total Direct Costs for 5 years not to exceed $8,000,000.
Clinical Coordinating Resource Center (CCRC):
Year 1: Not to exceed $2,000,000 direct costs; Total Direct Costs for 5 years not to exceed $6,500,000.
Statistical and Safety Resource Center (SSRC):
Year 1: Not to exceed $1,500,000 direct costs; Total Direct Costs for 5 years not to exceed $4,500,000.
Recruitment Resource Center (RRC):
Year 1: Not to exceed $750,000 direct costs; Total Direct Costs for 5 years not to exceed $2,500,000.
The total project period may not exceed five years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.
1. Eligible Applicants
Eligibility to apply to this FOA is limited to current NCATS TIN recipients supported under RFA-TR-15-002 and RFA-TR-15-004. This limited competition will allow for continued support and completion of ongoing HEAL ERN clinical trials as well as incorporation of any future HEAL ERN clinical trials/studies if needed.
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. SAM registrations prior to fall 2021 were updated to include a UEI. For applications due on or after January 25, 2022, the UEI must be provided on the application forms (e.g., FORMS-G); the same UEI must be used for all registrations, as well as on the grant application.
- Dun and Bradstreet Universal Numbering System (DUNS) Organization registrations prior to April 2022 require applicants to obtain a DUNS prior to registering in SAM. By April 2022, the federal government will stop using the DUNS number as an entity identifier and will transition to the Unique Entity Identifier (UEI) issued by SAM. Prior to April 2022, after obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
- In the case of Emergency awards, if the applicant is unable to comply with the requirement to complete and maintain SAM registration at the time of application submission, contact the agency immediately.
- eRA Commons - Once the unique organization identifier (DUNS prior to April 2022; UEI after April 2022) 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 underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
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
Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.
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).
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:
Carol Lambert, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0814
Email: [email protected]
Page Limitations
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
Instructions for Application Submission
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.
SF424(R&R) Cover
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Project/Performance Site Locations
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Other Project Information
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Senior/Key Person Profile
All instructions in the SF424 (R&R) Application Guide must be followed.
R&R Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
Years 1 5:
- The budget must include allocations to continue support for the trial currently funded through RFA-NS-20-028 and two additional HEAL ERN trials/studies estimated to begin the first planning phase in year 1. Note there is an expectation that annual budgets will decrease as enrolling studies are completed and that final budgets will depend on the number of new trials beginning the planning phase in year 1.
- A request for travel should be included for key personnel to attend the following meetings on an annual basis: 1) one face-to-face HEAL ERN Investigators meeting at rotating geographic locations, 2) one face-to-face NIH HEAL Investigator meeting to be held in the Bethesda, Maryland or Washington, DC general geographic area, and 3) one trial/study-specific steering committee meeting with the individual studies supported by the HEAL ERN Resource Centers at rotating geographic locations.
Years 2 5:
- The budget must also include designated expenses in years 2 5 to provide HEAL ERN Resource Center services for currently funded HEAL ERN clinical trials with active participant enrollment supported through RFA-NS-19-021.
Funding requested through this FOA should not duplicate committed costs currently approved for the TIN. All applicants must justify all costs relevant to the scope of work and provide a statement confirming that the budget requested does not duplicate currently approved TIN commitments.
R&R Subaward Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Cover Page Supplement
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Research Plan
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
The Research Strategy should indicate the type of HEAL ERN Resource Center the applicant is proposing to provide. Applicants should describe prior experience in the design, conduct, data analysis, and management of major collaborative clinical research projects, preferably in pain management, and provide evidence of successful performance supporting multi-site studies within the past three to five years.
All applicants, regardless of the type of HEAL ERN Resource Center application, should provide the following:
- An overall plan to collaborate with the Principal Investigators of the individual trials/studies and the other HEAL ERN Resource Centers in the development, implementation, and monitoring of the study protocol(s), the collection and analysis of data, and publication of trial/study results.
- Plans to support the planning phase of new multi-center HEAL ERN trials/studies and operationally integrate them into ongoing HEAL ERN Resource Center activities. This should include the process of engaging all necessary investigators and NIH staff, assisting with protocol development and helping the investigator team meet the milestones of the planning phase.
- Plans to respond to issues/protocol changes that emerge during trials and initiate timely necessary changes.
- Plans to support currently funded and enrolling HEAL ERN trials to ensure the trials are completed in a timely manner and study teams meet their milestones.
- Plans for staffing the HEAL ERN Resource Center with the needed flexibility to be able to respond to the changing needs of the HEAL ERN Program. It is expected that staff effort will decrease over time as currently enrolling studies are completed.
- A detailed timeline for the planned activities.
Applicants proposing to act as the Data Coordination Resource Center (DCRC) should describe:
- A data management system, including how study-specific systems for each protocol with appropriate security controls are created.
- Process for creating and maintaining data management plans describing in detail the data collection tools and systems used, as well as the data flow between patients, study sites, the other HEAL ERN Resource Centers and the DCRC.
- How different types are collected and integrated by the data management system to yield the final study data.
- Process for developing data collection forms.
- Process for preparing reports, such as those for the Data and Safety Monitoring Board (DSMB) and individual study teams.
- How randomization and masking methods will be implemented.
- Plans for managing outstanding missing or inconsistent data items and how these problems are resolved.
- Training provided to individual study teams to use the data system.
- Details of how the DCRC works with each of the trial Principal Investigators to incorporate NIH HEAL CDEs into protocols.
- Plan to act as single IRB for at least one HEAL ERN study.
- Plan to work with other HEAL DCRCs to harmonize data elements.
- Plan to prepare study data files for submission into NIH designated data repositories in compliance with the NIH HEAL data sharing requirements.
Applicants proposing to act as the Clinical Coordinating Resource Center (CCRC) should describe:
- Process for developing and maintaining detailed project management plans for each trial/study.
- Process for developing a detailed communication plan between the Principal Investigators of individual HEAL ERN trials, site PIs and HEAL ERN Resource Centers that includes but is not limited to maintaining documentation of IRB initial approvals and amendment approvals.
- How the CCRC will provide regular study update summaries to team members and NIH to communicate action items and milestones.
- Methods for development and finalization of the individualized Manual of Procedures (MOP).
- Process for developing Clinical Monitoring Plans (CMP) for each trial.
- Methods for remote and on-site monitoring of data quality, protocol adherence and resolution of queries.
- System for monitoring and reporting study recruitment.
- Meeting and communication management, including planning and facilitating key meetings and weekly to monthly operations meetings, and ad hoc meetings to review items such as monitoring reports.
- Managing communications between the PIs of the individual trials and the other HEAL ERN Resource Centers and the overall HEAL ERN network.
- Trial specific websites development and maintenance plans.
- Ability to help coordinate external services if needed with the trial/study teams, including assistance with development of subcontracts with recruiting sites.
- Process for assisting with additional investigator and site selection.
- Process for assisting investigators with communications to ensure regulatory compliance with agencies such as the Food and Drug Administration.
- Call center capabilities to collect data in real time and provide continuity between subject calls.
- Process for creating and maintaining ClinicalTrials.gov records.
- Plan to act as single IRB for at least one ERN study.
Applicants proposing to act as the Statistical and Safety Resource Center (SSRC) should describe:
- Process for reviewing and finalizing study protocols and statistical analysis plans with the study teams for each HEAL ERN trial.
- Method for generating the randomization scheme for each trial.
- Plans to complete the statistical analyses for HEAL ERN trials/studies at the conclusion of each study.
- Process of drafting, reviewing, finalizing data safety monitoring plans and DSMB charters with the study teams and various NIH Institutes and Centers administering the trials.
- Process for hosting the DSMB calls, maintaining minutes and distributing recommendations to the study team.
- Process for working with the HEAL ERN DCRC to generate any needed blinded and unblinded reports for the DSMB.
- Process of reporting to the DSMB, as needed, any unexpected, serious, and protocol-related adverse events or apparent trends in data possibly relevant to patient safety.
- Plan to act as single IRB for at least one ERN study.
Applicants proposing to act as the Recruitment Resource Center (RRC) should describe:
- Methods for developing comprehensive, study-specific recruitment and retention plans.
- Strategies focused on ensuring equitable recruitment, retention and inclusion of racial/ethnic and minority populations and NIH-designated populations that experience health disparities in HEAL ERN trials/studies, and how the RRC will work with study teams to meet their enrollment targets.
- Capacity to culturally and/or linguistically tailor recruitment and retention materials appropriate for NIH-designated populations that experience health disparities to advance equity in HEAL/ERN trials/studies.
- Approaches to enhance recruitment and retention for different research settings.
- Any activities for engaging communities involved in individual trials/studies.
- Approaches to developing centralized recruitment and retention materials that are easily adaptable across study sites.
- Process for using electronic cohort identification and characterization methods to identify sites for individual studies as needed.
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:
Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:
HEAL Data Sharing
NIH intends to maximize the impact of HEAL Initiative-supported projects through broad and rapid data sharing.Consistent with the HEAL Initiative Public Access and Data Sharing Policy (https://heal.nih.gov/about/public-access-data), all applications, regardless of the amount of direct costs requested for any one year, are required to include a Data Management and Sharing Plan outlining how scientific data and any accompanying metadata will be managed and shared. The plan should describe data types, file formats, submission timelines, and standards used in collecting or processing the data. It is expected that data generated by HEAL Initiative-funded projects will be submitted to study-appropriate domain-specific or generalist repositories in consultation with the HEAL Data Stewardship Group to ensure the data is accessible via the HEAL Initiative Data Ecosystem.
To maximize discoverability and value of HEAL datasets and studies, and facilitate data integration and collaboration, applications submitted in response to this FOA are strongly encouraged to incorporate standards and resources where applicable:
- Applicants are encouraged to ensure that data collected by the study conform to Findable, Accessible, Interoperable, and Reusable (FAIR) principles.
- Applicants are specifically encouraged to incorporate into their planning, an alignment with the guidelines, principles and recommendations developed by the HEAL Data Ecosystem, including but not limited to preparing data to store in selected specified repositories, applying minimal metadata standards, use of core HEAL Clinical Data Elements (CDEs, https://heal.nih.gov/data/common-data-elements), and other necessary requirements to prepare data to connect to the HEAL Data Ecosystem.
- All new HEAL clinical pain studies are required to submit their case-report forms/questionnaires to the HEAL Clinical Data Elements (CDE) Program. The program will create the CDE files containing standardized variable names, responses, coding, and other information. The program will also format the case-report forms in a standardized way that is compliant with accessibility standards under Section 508 of the Rehabilitation Act of 1973 (29 U.S.C 794 (d)), which require[s] Federal agencies to make their electronic and information technology accessible to people with disabilities. HEAL Initiative clinical studies that are using copyrighted questionaries are required to obtain licenses for use prior to initiating data collection. Licenses must be shared with the HEAL CDE team and the program officer prior to use of copyrighted materials. For additional information, visit the HEAL CDE Program.
The NIH notices referenced below provide additional NIH guidance that should be considered in developing a strong data management and sharing plan. The list is instructive but not comprehensive.
- Elements of an NIH Data Management and Sharing Plan (NOT-OD-21-014)
- NIH has provided guidance around selecting a repository for data generated by NIH-supported research and has developed desirable characteristics for all data repositories (NOT-OD-21-016).
- NIH encourages the use of data standards including the PhenX Toolkit (www.phenxtoolkit.org) (for example, see NOT-DA-12-008, NOT-MH-15-009)
- NIH encourages researchers to explore the use of the HL7 FHIR (Fast Healthcare Interoperability Resources) standard to capture, integrate, and exchange clinical data for research purposes and to enhance capabilities to share research data (NOT-OD-19-122). The FHIR standard may be particularly useful in facilitating the flow of data with EHR-based datasets, tools, and applications.
- NIH encourages clinical research programs and researchers to adopt and use the standardized set of data classes, data elements, and associated vocabulary standards specified in the United States Core Data for Interoperability (USCDI) standards, as they are applicable (NOT-OD-20-146). Use of the USCDI can complement the FHIR standard and enable researchers to leverage structured EHR data for research and enable discovery.
Recipients conducting research that includes collection of genomic data should incorporate requirements under the NIH Genomic Data Sharing Policy (NOT-OD-14-124, NOT-OD-15-086).
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
- No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.
PHS Human Subjects and Clinical Trials Information
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.
PHS Assignment Request Form
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.
4. Submission Dates and Times
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.
6. Funding Restrictions
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.
7. Other Submission Requirements and Information
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 (DUNS number or UEI as required) provided on the application is the same number 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 components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
In order to expedite review, applicants are requested to notify the NCATS Referral Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.
Applications Involving the NIH Intramural Research Program
The requests by NIH intramural scientists will be limited to the incremental costs required for participation.As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.
If selected, appropriate funding will be provided by the NIH Intramural Program. NIH intramural scientists will participate in this program as PDs/PIs in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.
Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above.
Post Submission Materials
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.
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.
Review Process
Applications will be evaluated for scientific and technical merit by an appropriate merit review panel convened by NIH staff, in accordance with the review criteria specified in the FOA.
For this particular announcement, note the following:
These awards will support the completion of ongoing HEAL ERN clinical trials as well as support of new HEAL ERN clinical trials/studies. Thus, review criteria will focus on capabilities of each Resource Center to provide the needed chosen Resource Center expertise for the completion of ongoing HEAL trials and the planning, implementation, and completion of new HEAL ERN clinical trials/studies. Reviewers will also consider the ability of the proposed HEAL ERN Resource Centers to work collaboratively with each other as well as with ERN clinical trial study teams to accomplish these objectives.
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).
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.
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Specific to this FOA: For all proposed Resource Centers:
- Will the proposed Resource Center increase the likelihood of successful and timely completion of the HEAL Effectiveness Research Network clinical trials/studies?
- To what extent will the proposed Resource Center optimize collaboration with/coordination of individual HEAL ERN clinical trials/studies?
- To what extent have applicants articulated plans for collaboration, coordination, and synergy among the proposed Resource Centers?
- Will the proposed infrastructure, resources, services and other activities address important needs or critical barriers for researchers conducting individual HEAL ERN clinical trials/studies, including completion of ongoing HEAL trials and planning, implementation, completion of new HEAL trials/studies?
For the Data Coordination Resource Center (DCRC) only:
- To what extend has the proposed DCRC described robust methods and systems to enable data collection, provide sound data management, harmonize data elements and assure data quality throughout the conduct of individual HEAL ERN clinical trials/ studies to ensure successful trial/study completion?
For the Clinical Coordinating Resource Center (CCRC) only:
- To what extent has the proposed CCRC described a high-quality process to provide oversight of clinical operations, develop detailed project management plans, train study teams, site monitoring, develop and implement project specific problem resolution/improvement plans, implement continuous quality improvement across all HEAL ERN trials/studies, and assist investigators with identification of additional sites to ensure successful trial/study completion?
For the Statistical and Safety Resource Center (SSRC) only:
- To what extent has the proposed SSRC provided a plan to provide high-quality biostatistical and safety support over the duration of the HEAL ERN trials/studies to ensure sound analysis plans and effective data and safety oversight?
For the Recruitment Resource Center (RRC) only:
- To what extent will the proposed RRC provide expertise and support for recruitment and retention of trial/study participants to ensure successful trial/study completion? Does this include assisting investigators with community and stakeholder engagement, strategies for equitable recruitment and inclusion of racial/ethnic minority populations and NIH-designated populations that experience health disparities, as well as other strategies that cover the continuum of recruitment and retention in clinical trials/studies?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
Specific to this FOA: Do key personnel have appropriate expertise and experience in the conduct of multi-center trials or analysis of clinical data to achieve the scientific objectives of the HEAL Effectiveness Research Network?
Have applicants articulated prior experience in the design, conduct, data analysis, and management of major collaborative clinical research projects? Do they have the experience and expertise needed for the Resource Center specified in their application?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Specific to this FOA: Does the application provide evidence to suggest that the proposed Resource Center could institute novel and innovative procedures that would increase efficiency and/or quality of clinical trials designed to improve management of acute or chronic pain?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or 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? Does the proposed DCRC include a plan to comply with the HEAL Initiative Public Access and Data Sharing Policy?
Specific to this FOA: For All Proposed Resource Centers:
- To what extent have applicants included plans to create a harmonized infrastructure to support the trials/studies of the HEAL Effectiveness Research Network?
- Is there evidence demonstrating the capacity to establish and maintain a secure and efficient infrastructure with capacity to support multiple trials/studies simultaneously?
- Is there a clear plan for starting and integrating new trials/studies while maintaining and completing others? Does the approach suggest that the investigators will have sufficient interactions with the other components of the HEAL ERN such as the other HEAL ERN Resource Centers and the individual trial Principal Investigators and their teams and the NIH?
- To what extent are plans to respond to issues/protocol changes that emerge during trials/studies and implementation of necessary changes to ensure successful trial/study completion described?
- To what extent are plans for staffing the HEAL Resource Center with the needed flexibility to respond to the changing needs of the HEAL ERN Program described?
For the Data Coordination Resource Center (DCRC) only:
- To what extent have applicants described a process to develop and maintain data management that includes data collection tools and systems used as well as data flow between participants, study sites, HEAL ERN clinical trial/study teams, and other Resource Centers? Are appropriate security controls described?
- Are there sufficient plans for collection of different data types and integration by the data management system to yield final study data?
- To what extent are plans included describing how the proposed DCRC will work with HEAL ERN trial/study to include NIH HEAL CDEs into protocols?
- Are processes for the development of data collection forms and report preparation (DSMD, individual study teams, etc); implementation of randomization and masking; managing outstanding missing/inconsistent data; and support for final data file submission into NIH designated data repositories described?
For the Clinical Coordinating Resource Center (CCRC) only:
- To what extent are there sufficient processes for developing and maintaining detailed project management plans for each individual HEAL ERN trial/study?
- Has the process for developing effective communication plans between individual HEAL ERN trial/study Principal Investigators, site PIs, and other HEAL Resource Centers as well as NIH (including IRB/amendment activities/milestone, action item updates, etc) been described adequately?
- Are the processes/methods for the following described adequately and is there evidence that the processes/methods will lead to robust trial data? 1) development and finalization of Manual of Procedures (MOP) and Clinical Monitoring Plans (CMP) 2) remote/on-site monitoring of data quality, protocol adherence and resolution of queries; 3) monitoring and reporting study?
- Does the proposed CCRC have the ability to effectively: assist the individual trial investigators with the coordination of external services (e.g. subcontracts with recruiting sites); assist with additional investigator/site selection; and assist investigators with regulatory compliance related communications?
For the Statistical and Safety Resource Center (SSRC) only:
- Does the proposed SSRC adequately describe the processes for: reviewing/finalizing study protocols and statistical analysis plans; generating randomization schemes for each trial/study; and completing statistical analysis for trials/studies at their conclusion?
- Are the processes for drafting, reviewing, finalizing data safety monitoring plans and DSMB charters; hosting DSMB meetings; generating blinded and unblinded reports; and reporting adverse events or data trends relevant to patient safety to the DSMB adequately described and provide confidence that the trials will have high-quality safety oversight?
For the Recruitment Resource Center (RRC) only:
- Does the proposed RRC describe adequately methods for development of comprehensive, study specific recruitment and retention plans that will help investigators reach their recruitment goals?
- Does the application address adequately strategies to ensure equitable recruitment, retention and inclusion of racial/ethnic and minority populations and NIH-designated populations that experience health disparities in HEAL ERN trials/studies and describe how the RRC will work with study teams to meet their enrollment targets?
- Does the proposed RRC have the capacity to culturally and/or linguistically tailor recruitment and retention materials appropriate for NIH-designated populations that experience health disparities to advance equity in HEAL/ERN trials/studies?
- Are approaches for development of centralized recruitment/retention materials that are adaptable across study sites and use of electronic cohort identification/characterization to identify study sites described adequately?
- Are resources to assist investigators with community and stakeholder engagement activities to enhance recruitment/retention for different research settings described adequately?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
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.
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.
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.
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.
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.
Not Applicable.
Not Applicable.
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.
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
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).
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) ) Genomic Data Sharing Plan (GDS).
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
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 review group using the stated review criteria.
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 assessment score.
Appeals of initial merit 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. The following will be considered in making funding decisions:
- Scientific and technical merit of the proposed project.
- Availability of funds.
- Relevance of the proposed project to HEAL Initiative program priorities.
3. Anticipated Announcement and Award Dates
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
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.6. 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.
Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that 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.
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 identify, 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, 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for the HEAL Pain Management Effectiveness Research Network (ERN) Resource Centers will be the 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 award 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. Recipient will retain custody of and have primary rights to the data and software developed under this award, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
The PD(s)/PI(s) will have the primary responsibility for:
- Determining research approaches, designing protocols with the individual trial/study PD/PIs and the HEAL ERN Resource Centers, formulating implementation plans, and conducting research. The recipient agrees to accept close coordination, cooperation, and participation of NIH staff in those aspects of scientific and technical management of the study as stated in these terms and conditions.
- Implementation of the protocol, whether as a single entity or a consortium of entities, and following the procedures required by the protocol regarding study conduct and monitoring, participant management, safety management, data collection, and quality control.
- Participating in group activities, including the Program Steering Committee, the Clinical Trial Steering Committee, and subcommittees as needed.
- The Program Steering Committee will meet once a year, either in-person or virtually, and additional times by teleconference as needed. The Clinical Trial Steering Committees will meet regularly throughout the during of the study. The Program Steering Committee will recommend the frequency of other teleconference meetings as needed.
- Providing reports and data in a timely fashion as agreed upon by the HEAL ERN Program Steering Committee.
- Preparing abstracts, presentations, and publications and collaborating Consortium-wide in making the public and professionals aware of the program.
- Assessing and disseminating data and methods developed for or derived from the HEAL ERN program within and outside the Consortium.
- Adhering to policies regarding data sharing and publication established by the NIH and the HEAL ERN Program Steering Committee.
- Abiding by common definitions, protocols, and procedures, as determined in collaboration with the Program Steering Committee.
- Submitting periodic progress reports in a standard format, as agreed upon by the Program Steering Committee and Clinical Trial Steering Committees.
- Attending and participating in HEAL ERN Program and Clinical Trial Steering Committee meetings and accepting and implementing decisions by these groups, as appropriate.
- The PD(s)/PI(s) will manage the involvement of industry or any other third party in the study. Except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by the NIH.
NIH staff will have substantial scientific and programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The NIH Project Scientist(s) will have substantial scientific and programmatic involvement during the conduct of this activity through technical assistance, advice, and coordination. The Project Scientist(s) will have the following substantial involvement:
- Participating through the HEAL ERN Program Steering Committee as voting members in addressing issues that arise with HEAL ERN planning, operation, assessment, and data analysis. The Project Scientist(s) will assist and facilitate the group process and not direct it.
- Serving as a liaison, helping to coordinate activities, including acting as a liaison to other NIH Institutes/Centers, and as an information resource for the recipients. The Project Scientist(s) will also help coordinate the efforts of the HEAL ERN Program with other groups conducting similar efforts.
- Attending all HEAL ERN Program Steering Committee meetings, assisting in developing standard operating procedures, and consistent policies for dealing with situations that require coordinated action. The Project Scientist(s) will be responsible for working with the recipients as needed to manage the logistic aspects of the HEAL ERN program.
- Reporting periodically on HEAL ERN progress to the NIH Leadership.
- Serving on subcommittees of the HEAL ERN Program Steering Committee as appropriate.
- Assisting award recipients in the development, if needed, of policies for dealing with situations that require coordinated action.
- Providing advice in the management and technical performance of the award.
- Assisting in promoting the availability of the data and related resources developed in the course of this program to the scientific community at large.
In addition, an agency Program Official or IC Program Director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The NIH Program Official will be responsible for the following:
- Enforcement of general statutory, regulatory, or policy requirements.
- Approval of recipient plans prior to award and review of performance after completion.
- Evaluation of progress by reviews of technical or fiscal reports, site visits, or external consultants, to determine that performance is consistent with the terms and conditions of the award.
- Technical assistance requested by recipients, or unanticipated procedures to correct programmatic or financial deficiencies in recipients' performance.
- Scientific/technical discussions with recipients, or actions to facilitate or expedite interactions between recipients, e.g., organizing and holding meetings of investigators.
Prior to funding an application, the Program Official will contact the applicant to discuss any changes suggested by NIH staff or the NIH review panel. The Program Official and Project Scientist will negotiate with the applicant and agree on a final set of approved changes that will be specified in the Notice of Award. Any additional future changes must be approved in writing by the Program Official.
In addition, the assigned Program Official may also serve as an NIH Project Collaborator. The Project Collaborator will have the combined responsibilities of a Project Scientist and of a Program Official as described above with the exception that the Project Collaborator will be a non-voting member of the Steering Committee.
NIH reserves the right to withhold funding or curtail an award in the event of:
- Substantive changes in the project, or failure to make sufficient progress toward the work scope with which NIH concurred, or
- Ethical or conflict of interest issues.
Areas of Joint Responsibility include:
- Close interaction among the participating investigators will be required, as well as significant involvement from the NIH, to manage, assess, and implement the HEAL ERN program. The recipients and the Project Scientist(s) will meet annually through the HEAL ERN Program Steering Committee during the planning and enrolling years, through the Clinical Trials Steering Committees regularly over subsequent years, and on conference calls as needed to share information on methodologies, analytical tools, and preliminary results. PDs/PIs, key co-investigators and pre- and post-doctoral trainees, especially those who are members of under-represented minority groups or those from different but related disciplines, are eligible to attend these meetings.
The HEAL ERN Program Steering Committee will be responsible for coordinating the activities conducted by the program and is the committee through which the individual NIH HEAL ERN Clinical Trials Steering committees will formally interact. The HEAL ERN Program Steering Committee membership will include PD(s)/PI(s) of each HEAL ERN award, other staff as needed, the NIH Project Scientist(s), and the dedicated pain and clinical trial experts from the ERN CCRC, DCRC, SSRC, and RRC. The HEAL ERN Program Steering Committee may add additional members, and other government staff may attend the HEAL ERN Program Steering Committee meetings as desired.
The HEAL ERN award recipient agrees to work collaboratively to:
- Provide for secure, accurate, and timely data submission.
- Participate in presenting and publishing new processes and substantive findings.
- Assess and disseminate HEAL ERN data and resources
- Interact with other relevant NIH activities, as needed, to promote synergy and consistency among similar projects.
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. The three members will be: a designee of the HEAL ERN Program 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 recipient. This special dispute resolution procedure does not alter the recipient'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.
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.
Funds awarded using appropriations provided by the Extending Government Funding and Delivering Emergency Assistance Act-September 20, 2021 will be issued in unique subaccounts in the HHS Payment Management System, and will require separate financial reporting from any other funds awarded.
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 the threshold. 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 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.
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: [email protected] (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: [email protected]
Yolanda F. Vallejo, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-451-1751
Email: [email protected]
Pete Murray, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-496-4054
Email: [email protected]
Leslie K Derr, PhD
National Institute Of Arthritis And Musculoskeletal And Skin Diseases (NIAMS)
Phone: (301) 594-8174
E-mail: [email protected]
Devon Oskvig, Ph.D.
National Institute on Aging (NIA)
Phone: 301-827-5899
Email: [email protected]
Carol Lambert, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0814
Email: [email protected]
Matthew Zeback
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-451-8309
Email: [email protected]
Shelley Headley
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-594-3788
Email: [email protected]
Erik Edgerton
National Institute Of Arthritis And Musculoskeletal And Skin Diseases (NIAMS)
Phone: 301-594-7760
E-mail: [email protected]
National Institute on Aging (NIA)
Phone: 301-827-4020
Email: [email protected]
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 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.
and Human Services (HHS)
