Office of Strategic Coordination (Common Fund)
This Funding Opportunity Announcement (FOA) is developed as a Common Fund initiative (https://commonfund.nih.gov/) through the Office of the NIH Director, Office of Strategic Coordination (https://dpcpsi.nih.gov). All NIH Institutes and Centers participate in Common Fund initiatives. This FOA will be administered by the National Institute of Neurological Disorders and Stroke (NINDS) on behalf of the NIH.
Reissue of RFA-RM-18-033
The purpose of this FOA is to support a Multisite Clinical Center to implement the enrollment and multimodal longitudinal assessment of a large cohort of patients that EITHER experienced an acute musculoskeletal trauma OR an acute peri-operative pain event to identify a biosignature for resilience to and/or the transition from acute to chronic pain.
August 29, 2019
October 25, 2019
New Date December 27, 2019 as per NOT-RM-20-001
All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).
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.
New Date December 28, 2019 per issuance of NOT-RM-20-001. (Original Expiration Date: November 27, 2019 )
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.
There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.
The United States faces a crisis due to the high prevalence of chronic pain and associated opioid use disorder and overdose deaths. More than 25 million adults in the U.S. report experiencing pain every day. A major challenge in pain care is the lack of evidence-based best practices to prevent chronic pain from occurring after an acute pain episode. For most people, acute pain resolves over time as the injury or trauma heals. In many people however, acute pain from injury, surgery, or disease processes persists well beyond the initial insult (sometimes throughout life) and is often intractable. Chronic pain persists beyond recovery due to changes in the peripheral and central nervous systems. However, the mechanisms driving acute pain transition to a chronic state are poorly understood.
The ability to predict which patients are more likely to be susceptible versus resilient to the development of chronic pain is a crucial step towards the development of personalized prevention strategies to transform acute pain treatment approaches and reduce or prevent chronic pain. Toward this end, the NIH Common Fund supported Acute to Chronic Pain Signatures (A2CPS) Program aims to identify biosignatures (a combination of several individual biomarkers) that predict susceptibility or resilience to the development of chronic pain after an acute pain event. Furthermore, if any of the predictive biomarkers identified through this program play a mechanistic role in the development of chronic pain, then the molecules, pathways, and/or brain circuits identified could serve as new potential therapeutic targets for reversing chronic pain or increasing patient resilience to chronic pain.
A2CPS is related to the multi-pronged HEAL (Helping to End Addiction Long-term) Initiative, an aggressive effort to speed scientific solutions to stem the national opioid public health crisis (https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative). HEAL will build on extensive, well-established NIH research to address the opioid crisis and provide safer therapies for people with pain. Funding for A2CPS will be from the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress.
Overall A2CPS Program Description: The A2CPS program will be funded as cooperative agreements through five linked FOAs. Awardees will work together as a consortium with strong communication and cooperation. The A2CPS program will support two longitudinal prospective studies (Multisite Clinical Centers (MCC) on large cohorts of patients who experience acute pain. Awards have been made in response to four A2CPS FOAs - Data Integration and Resource Center (DIRC), Omics Data Generation Centers (ODGCs), a Multisite Clinical Center (MCC): Acute Peri-Operative Pain, and a Clinical Coordination Center (CCC). Please see the A2CPS website for additional information concerning the Common Fund A2CPS Program. The goal of the A2CPS program is to identify candidate biomarkers and combine them into biosignatures predictive of the susceptibility or resilience to the development of chronic pain. The candidate biomarkers to be tested as primary outcomes in the two longitudinal prospective studies will be selected by a panel of external experts, consortium awardees, and NIH staff, who will consider the most promising biomarkers of transition or resilience to chronic pain based on current evidence. The size of each cohort is expected to be approximately 1800 patients, and the number of study biomarkers identified as primary study outcomes is expected to be approximately 40, based on a NIH power analysis calculation.
Overall, the A2CPS program will:
Timeline: The first 6 months of an award made from this RFA (estimated to be summer 2020-January 2021) will be a planning period. Patient enrollment is estimated to begin in January 2021. The awardee for this project will join the A2CPS Steering Committee once the award is made.
Awards have been made in response to four FOAs in summer 2019. During the first (planning) year of the A2CPS program, the EPCs and Steering Committee will be established, the consortium will develop the clinical protocols, standard operating procedures, staff training plans, recruitment plans, electronic health record standardization, safety standards, and regulatory processes, identify biospecimen types and amounts to be collected, and develop biospecimen collection and storage protocols. The consortium will assess and refine the statistical analysis plan (including power analysis) for each cohort. At the kick-off meeting in September 2019, an expert panel, including consortium members, the EPCs, and outside experts will recommend approximately 40 evidence-based high value candidate biomarkers for primary study outcomes.
After satisfactory completion of the 6 month planning period, the awardee from this FOA will begin patient enrollment (January 2021). In January 2022 or at approximately 50% completion of 6 month phenotyping, a futility assessment will be performed to determine whether the rate of transition to chronic pain and patient retention is adequate to meet the assumptions of the power analysis. In the event of lower than expected transition or poor retention of patients, the A2CPS Steering Committee with the EPCs will make recommendations to NIH to either increase enrollment or terminate the study. NIH leadership will make the final determination. We expect enrollment to be complete by January 2023, and clinical assessments to be complete by July 2023. Data analysis and public archiving of the data for data mining efforts by the scientific community should be complete by August 2024.
The purpose of this FOA is to support one Multisite Clinical Center (MCC) to implement the enrollment and multimodal longitudinal assessment of a large cohort of EITHER an acute musculoskeletal trauma OR an acute peri-operative pain event patients to identify biosignatures for resilience to and/or the transition from acute to chronic pain. NIH staff may give priority to a musculoskeletal trauma grant vs. an acute peri-operative pain event grant. Applications will be reviewed for responsiveness to this FOA. A total knee arthroplasty (TKA) application will not be responsive to this FOA. No foreign applications or foreign components will be allowed. Applications deemed non-responsive to this FOA by NIH staff will be withdrawn without review. NIH staff do not anticipate that applications submitted to this FOA will be clinical trials given that there is no proposed intervention.
UM1 mechanism. Awards made under this FOA will be through the UM1 mechanism for Research Projects with Complex Structure. This mechanism is for cooperative agreements to support large-scale research activities with complicated structures that cannot be appropriately categorized into an available single component activity code. The components represent a variety of supporting functions and are not independent of one another. Substantial federal programmatic staff involvement is intended to assist investigators during performance of the research activities, as defined in the terms and conditions of the award. The UM1 is typically reserved for high-priority research areas that require a significant level of involvement from NIH staff (oversight, coordination, or facilitation).
Key activities of the MCC will be to:
Applicants should plan to address the following items:
Informational Webinar. Prospective applicants are strongly encouraged to attend an informational webinar with NIH staff on September 19, 2019 from 11:00AM – 1:00PM EDT. Applicants also may contact NIH scientific staff and see the A2CPS FAQs (https://commonfund.nih.gov/pain/faq) for further information.
Date/Time: September 19, 2019 from 11am-1pm EDT
To join the event as an attendee
2. Click "Join Now".
Meeting password: A2CPS
To join the audio conference only
Call-in toll number (US/Canada): 1-650-479-3208
Access code: 624 829 378
Applicants also may contact NIH scientific staff and see the A2CPS FAQs (https://commonfund.nih.gov/pain/faq) for further information.
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.
The Office of Strategic Coordination (Common Fund) intends to commit $3.4 million in FY20 – this will include a 6 month preparation period as well as the first year of funds for recruitment, $2.5 million in FY21, and $700K in FY22.
Projects cannot exceed three years including the FY20 planning period.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
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.
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.
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.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
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.
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:
The letter of intent should be sent to:
Linda L. Porter, Ph.D.
National Institute on Neurological Disorders and Stroke (NINDS)
with the following exceptions:
The UM1 mechanism requires that the research strategy consist of separate components describing supporting functions that are interdependent. For this specific FOA, the research strategy should consist of the following sub-sections with the indicated page limits, all sections are required:
All instructions in the SF424 (R&R) Application Guide must be followed.
Specific Aims: The overall programmatic goal of the MCC is to implement the enrollment and multimodal longitudinal assessment of a large cohort of patients recovering from EITHER an acute musculoskeletal trauma OR an acute peri-operative pain event to identify biosignatures for resilience to and/or the transition from acute to chronic pain. Describe the goals of the MCC for the performance period of this project.
Research Strategy: The overall research strategy should be sure to address the following items:
The following modifications also apply:
The following modifications also apply:
Sharing within the A2CPS
The A2CPS program aims to maximize the benefits of sharing, while protecting the intellectual property of the data generators. Prepublication sharing of data within the consortium will allow collaboration across initiatives and further the progress of the A2CPS program towards its goals and objectives. Therefore, the A2CPS program requires that data, metadata, and resources generated from A2CPS funding be made available to other A2CPS members immediately upon being considered “shareable”. When A2CPS-generated material under embargo is shared within the A2CPS program, it will be considered confidential with the understanding that the information will not be used or disclosed by A2CPS members unless explicitly agreed upon by the originator of the data under mutually acceptable terms. That is, consortium members may not publish using material generated by other consortium members without a collaboration or other agreement, or until the material in question has been made available to the public. A2CPS investigators accessing embargoed material only available to members of the A2CPS must sign a non-disclosure form agreeing to these terms.
Prior to funding, NIH Program Staff may negotiate modifications to the Sharing Plan with the applicant.
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.
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.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement .
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications 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 Common Fund through the NIH Intramural Program. NIH intramural scientists will participate in this program as PD/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.
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.
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. 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 DUNS number it provides 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.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
In addition, for applications involving clinical trials:
A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.
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?
Will the proposed study transform our ability to predict the resilience to and/or transition from acute to chronic pain? Will the proposed study provide a foundation for further exploration of predictive biomarkers in other acute pain states or biomarkers indicative of chronic pain conditions? Will the study inform the design of future human studies for discovery of biomarkers? Will the study advance the science of clinical pain research?
In addition, for applications involving clinical trials
Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?
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?
Are key personnel well suited to their roles in the MCC? Have they demonstrated experience and accomplishments in managing clinical research? Has at least one member of the investigative team led a large complex clinical project? Does the team have expertise in the assessment of the patients in areas such as patient reported outcomes, sensory testing, CNS imaging, and biospecimen collection and storage? Does the team have expertise in the extraction of meaningful data and harmonization of electronic health records?
In addition, for applications involving clinical trials
With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?
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?
In addition, for applications involving clinical trials
Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?
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?
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 included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project?
In addition, for applications involving clinical trials
For all CT FOAs, add the following questions, after the standard questions for the Approach review criterion.
Does the application adequately address the following, if applicable
Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?
Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?
Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?
Data Management and Statistical Analysis
Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?
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?
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?
Will the environment of the clinical sites enable the enrollment of the required number of patients? Do the clinical sites have the facilities and resources to perform the surgical procedure or treat the musculoskeletal trauma proposed and provide appropriate pain care? Will the facilities and staffing at the clinical sites enable assessment of the patients in areas such as patient reported outcomes, sensory testing, CNS imaging, and biospecimen collection and storage? Is the infrastructure to collaborate and communicate across the multiple sites within the MCC adequate and appropriate? Are resources available within the scientific environment to support electronic information handling? Will the Center benefit from unique features of the institutional environment, infrastructure, or personnel?
In addition, for applications involving clinical trials
If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?
Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?
If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?
If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?
Specific to applications involving clinical trials
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate? Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?
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.
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) Data Sharing Plan; (2) Sharing Model Organisms; and (3) 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.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by CSR, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
Information regarding the disposition of applications is available 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 grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.
ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm
Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols. Data and Safety
Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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.
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 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.
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. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/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. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for the A2CPS program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees 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 awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below. Awardee 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:
The NIH A2CPS Working Group consists of NIH programmatic staff from multiple Institutes and Centers of the NIH as well as the Office of the Director.
The NIH Project Scientist(s) will have substantial scientific and programmatic involvement during the conduct of this activity through technical assistance, advice, and coordination. However, the role of NIH staff will be to facilitate and not to direct the activities. The Project Scientist(s) will participate as members of the A2CPS Program Steering Committee and, the Project Scientists together will have a single vote. The Project Scientist(s) will have the following substantial involvement:
Additionally, 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 assigned Program Official may also serve as an NIH Working Group Project Scientist(s) to assist the awardee. Prior to funding an application, the Program Official will contact the applicant to discuss the proposed milestones and 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 milestones which will be specified in the Notice of Award. The NIH Program Official, in consultation with the Project Scientist and NIH A2CPS Working Group, will determine if the awardee has met the milestones required for each year of funding.
NIH reserves the right to withhold funding or curtail an award in the event of:
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 disseminate the A2CPS program. The awardees and the Project Scientist(s) will meet in person with the A2CPS Program Steering Committee twice a year throughout the duration of the A2CPS programs, 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 A2CPS Program Steering Committee will serve as the main scientific body of the program. The A2CPS Program Steering Committee will be responsible for coordinating the activities being conducted by the program and is the committee through which the NIH A2CPS Working Group formally interacts with the A2CPS investigators. The A2CPS Program Steering Committee membership will include PD(s)/PI(s) of each A2CPS award, other staff as needed (ex-officio) and the NIH Project Scientist(s). The A2CPS Program Steering Committee may add additional members, and other government staff may attend the A2CPS Program Steering Committee meetings as desired. Each project will have one vote and the NIH Program Scientist(s) together will have one vote.
The A2CPS Program Steering Committee may establish subcommittees as needed to address particular issues, which will include representatives from the program and the NIH and possibly other experts. The A2CPS Program Steering Committee will have the overall responsibility of assessing and prioritizing the progress of the various subcommittees.
The A2CPS awardee agrees to work collaboratively to:
External Program Consultants (EPCs):
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 A2CPS 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 awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.
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Linda L. Porter, Ph.D.
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Alexei Kondratyev, Ph. D.
Center for Scientific Review (CSR)
National Institute on Neurological Disorders and Stroke (NINDS)
Telephone: 301- 496-7432
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