National Institute on Aging (NIA)
This Funding Opportunity Announcement (FOA) invites applications proposing to conduct research involving pragmatic clinical trials into improving the effectiveness of treatment strategies for comorbid conditions that occur frequently in combination with Alzheimer’s disease and Alzheimer's disease-related dementias (AD/ADRD). The research will: (1) be designed to address practical comparative questions faced by AD/ADRD patients and clinicians, (2) include broad and diverse populations, and (3) be conducted in real-world settings. These trials are intended to produce results that can be directly adopted by healthcare systems for rapid translation.
This FOA will support pilot research to test the feasibility of implementing care interventions (R61 phase) that, if successful, can transition to an R33 phase for implementation of large pragmatic trials.The transition from the R61 phase to the R33 phase of the award will be administratively reviewed and determined by successful completion of the Go/No-Go Criteria that are specified for the R61 phase.
May 9, 2019
January 3, 2020
February 3, 2020, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates. No late applications will be accepted for this Funding Opportunity Announcement.
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).
Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.
Applications that do not comply with these instructions may be delayed or not accepted for review.
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.
Multimorbidity, or having two or more chronic conditions, is a complex challenge for patients, doctors, and healthcare systems. This challenge becomes even more complex when treating patients with Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD), as the clinical presentation and prolonged course of AD/ADRD influence the diagnosis and treatment of comorbid illness. Compared to patients with other long-term disorders, those with dementia may have extreme multimorbidity, averaging four additional chronic medical disorders. The most common chronic comorbid conditions for AD/ADRD patients are hypertension and diabetes, but other significant comorbidities include, but are not limited to, heart disease, heart failure, obstructive lung disease, and incontinence, as well as acute conditions like infectious diseases and hip fracture.
Dementia can be characterized as a clinically dominant multimorbidity, meaning that it is so serious that it overshadows the management of other health problems. The presence of multimorbidity in patients with dementia has been associated with accelerated functional decline and other adverse outcomes. Furthermore, certain medical comorbidities can exacerbate cognitive and mental deterioration in persons with dementia. Consensus-based diabetes treatment guidelines suggest relaxed glucose control for persons with cognitive impairment, dementia, complex illness, or poor health. Most other treatment guidelines, however, focus on a single disease and lack such detailed recommendations, likely reflecting a lack of evidence of the balance of risks and benefits in AD/ADRD patients with comorbidities, or perhaps lack of a professional consensus. Although self-management approaches may be appropriate in early stages, throughout the course of dementia family members increasingly assume the role of caregivers to provide the first line of support for treatment.
Some groups have been working toward guidelines for dementia care practice which would apply across care settings, emphasize person-centered care and quality of life, and recognize that needs may change over time. These groups also emphasize that the complex care needs are attributable to both the dementia and the multimorbidity, the potential effectiveness of non-pharmacological interventions for symptoms, and that selective discontinuation of therapies may be beneficial.
This is a continuation of past initiatives released as RFA-AG-17-059 and RFA-AG-18-028, which have led to funding of pragmatic trials on relevant topics, including diabetes management in AD/ADRD and deprescribing potentially inappropriate medications for persons with ADRD. However, there is still a considerable need for research in this area, and this FOA is using a different mechanism for two-stage pragmatic trials. Phase 1 is for trial planning and feasibility, and Phase 2 is for the conduct of the pragmatic trial in health systems.
Purpose and Scope
This FOA invites applicants to develop evidence, through pragmatic trials, of the effectiveness of treatment strategies for one or more comorbid conditions that occur frequently in combination with AD/ADRD, with a focus on improving health outcomes of importance to the patient. Pragmatic clinical trials are performed in real-world clinical settings with highly generalizable populations to generate actionable clinical evidence, in contrast to a traditional explanatory clinical trial. This evidence will inform practice guidelines for the prevention and treatment of comorbid diseases in the presence of AD/ADRD, which may include recommendations to discontinue widely used but inadvisable treatments.
Approaches should take into account the following:
Areas of research interest and opportunity include, but are not limited to, the following:
R61 Planning Phase
During an initial planning phase, researchers may wish to test the feasibility of interventions for the comorbid conditions accompanying AD/ADRD which, if successful, can be transitioned to the R33 phase for implementation of a pragmatic trial. The specific activities within a planning phase, if included, will depend on the type of intervention under study and its stage of development. Generally, activities and milestones for this R61 phase could include, but are not limited to, the following:
After completion of the planning phase, the PDs/PIs would transition to the next phase for implementation of the pragmatic trial.
R33 Implementation Phase
During the Implementation Phase, PDs/PIs will implement and evaluate the intervention in a pragmatic clinical trial in a clinical or other appropriate setting. When transitioning to the R33 phase, investigators must provide a compelling case that all of the necessary early research activities have been successfully completed such that there is compelling justification for proceeding to a pragmatic trial. General R33 activities may include
replicating pragmatic trial findings in another site. Applicants may choose, but are not required, to identify additional implementation sites for replication purposes prior to beginning the R33 phase.
Studies supported by the R33 phase require adequate power. PDs/PIs are required to provide power calculations for the R33 phase.
Applications must address all ethical issues and issues related to human subject safety oversight for the pragmatic trials (see: NIA Implementation of Policies for Human Intervention Studies, NIH Clinical Trials), including developing informed consent documents or opt-out consents (if applicable) and finalizing the site of IRB review in the "Human Subjects Protection Plan." Further, applicants should propose a consolidated or centralized IRB approach for trial oversight to facilitate the appropriate and timely implementation of the study.
Applicants should keep in mind the following guidance regarding experimental approaches:
Milestones and R61/R33 Transition
The project must be supported by a well-defined set of milestones (see suggested milestones above) for the R61 planning phase and annual milestones for the R33 implementation phase. Specifically, the transition from the R61 to the R33 phase of the award will be administratively reviewed and determined by successful completion of the Go/No-Go Criteria defined for the R61 phase.
At the completion of the R61 planning phase, the investigators will be required to submit a detailed transition request for the R33 implementation phase. R33 transition requests will undergo an administrative review to determine whether the milestones have been met. Unless the R61 meets Go/No-Go Criteria, the R61 may not transition to the R33 phase (i.e., it is anticipated that not all funded R61 projects will transition to the R33 phase).
Prospective applicants should note that funding of a R61 planning phase grant application does not guarantee support of the R33 implementation phase. Transition to the R33 implementation phase of the project will occur only if an administrative review process determines that the R61 planning activities have been successful and the implementation phase of the project can proceed with confidence of success, and if funds are available.
Applicants are strongly encouraged to consult with NIA staff when developing plans for an application (see Agency Contacts, Section VII). This early contact will provide an opportunity to identify whether the proposed project is consistent with NIA program priorities.
Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
NIA intends to commit $2,000,000 in direct costs in FY 2020 to fund 2-4 awards.
For the R61 planning phase, the combined budget for direct costs for up to two years may not exceed $500,000.
For the R33 phase, budgets are expected to go over $500,000.
The project period is limited to 5 years, which includes up to 2 years of the R61 phase followed by up to 4 years of the R33 phase.
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:
Marcel E. Salive, MD, MPH
National Institute on Aging (NIA)
All instructions in the SF424 (R&R) Application Guide must be followed.
Specific Aims: Separate Specific Aims should be presented for both the R61 and R33 phases, within the designated page limit.
Research Strategy: The Research Strategy should contain separate sections that describe both the R61 and R33 phases. Separate research design and methods could be presented, as needed, for the R61 and R33 phases. It is not necessary to repeat information or details in the R33 section that are described in the R61 section.
Preliminary data are not required for an R61/R33 application. However, any preliminary data that will support or justify the proposed hypothesis, rationale, or development plan may be included.
PDs/PIs should propose to follow best practices for the conduct of their randomized trial, and, in particular, clearly state how randomization will be performed. For example, if randomization is performed at the healthcare facility level, the applicant should describe how many effective observations there will be after accounting for intra-cluster correlation. If the randomization is at a lower level than the healthcare facility, the PD/PIs should address potential threats to validity that could occur due to contamination across treatment groups. PDs/PIs should clearly present power calculations that reflect a range of effect sizes of clinical significance.
Trial design should incorporate rigorous controls, prospectively identified, preferably by randomization. The design may incorporate novel randomization approaches, such as by cluster or timing of implementation. If another method is used to generate the comparison group, perhaps by staged assignment or staged implementation of the intervention, it should provide comparable rigor. The design should also maximize external validity of the study by testing generalizability, feasibility, and sustainability of findings across distinct healthcare settings and diverse staff, caregiver, and patient populations. Applicants are strongly encouraged to consult the Pragmatic Trial Living Textbook maintained by the NIH Collaboratory.
Applicants should provide a description of how the study designs, methods, and assessments are complementary, such that outcomes from the planning phase will enhance the interpretation of outcomes at the implementation stage.
Since the intent of this announcement is to leverage findings from planning phase to implementation phase and increase the potential for translation research, the PDs/PIs are encouraged to collaborate with healthcare providers to maximize the possibility of translation.
Applicants should provide evidence of how the planned collaboration will work among team members with potentially very different backgrounds.
Milestones and R61/R33 Transition
The application must include milestones applicants expect to achieve by the end of the R61 phase. Milestones should be specific, quantifiable, and scientifically justified; they should not be simply a restatement of the specific aims for the R61 phase. It is recommended that PDs/PIs include a section labeled "Milestones" describing milestones to be achieved during the R61 phase to qualify for the transition to the R33 as part of the Research Strategy within the approach section.
Applicants can establish Go/No-Go Criteria as they deem fit for their application, but must include the following: (1) establish partnership with healthcare provider (e.g., health system or practice), and document commitment of the organization to the project; (2) obtain access to needed administrative data and modify and implement pilot intervention(s); and (3) pilot test intervention(s) and produce preliminary data for R33 administrative review showing feasibility of the intervention(s).
It is understood that the proposed milestones for the R33 phase may be revised based on activities during the R61 planning phase. In the event of an award, the PD/PI and NIH staff will negotiate a list of milestones for each year of support.
The following modifications also apply:
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 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.
In order to expedite review, applicants are requested to notify the NIA Referral Office by email email@example.com when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
For this particular announcement, note the following:
The R61/R33 phased innovation grant supports investigation of novel scientific ideas or new interventions, model systems, tools, or technologies that have the potential for significant impact on biomedical, behavioral, or social sciences research. An R61/R33 grant application need not have preliminary data, extensive background material, or preliminary information; however, they may be included if available. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Reviewers will assign a single impact score for the entire application, which includes both the R61 and R33 phases.
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?
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, 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?
How well did the PDs/PIs characterize the pragmatic trial intervention (or combination of several interventions)? Does the intervention apply broadly to the AD/ADRD patient population or their caregivers? Is the intervention suitable for use in real-world settings? Can the interventions be adopted?
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?
With regard to the proposed leadership for the project, do the PDs/PIs 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 provide evidence of how the planned collaboration will work among team members with potentially very different backgrounds?
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?
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?
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 application adequately address the following, if applicable:
Is the study design justified and appropriate to address primary and secondary outcome variables/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previous 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?
Is there a unifying and testable hypothesis that transcends both R61 and R33 phases? Does the application provide clear milestones for the R61 phase and related scientific goals for the R33 phase? Are those milestones conducive to accomplishing the study aims? Are the goals of the R33 phase based, in part, on findings collected during the R61 phase?
How well did the PDs/PIs operationalize definitions and objective measures of the intervention? What is the quality of the evidence (note that we are not requesting preliminary data) that the mechanism of action can be manipulated reliably and validly in the care delivery setting to carry out the pilot R61 phase? Will the R61 phase produce preliminary data for R33 administrative review showing feasibility (i.e. will the PD/PI show he/she can make changes in the care delivery settings and conduct an intervention)?
How appropriate is the power analysis for the R33 phase? (Note that power calculations are not required for the R61 phase.) How appropriate are the sample size, analytic plan, and overall design for the planned pragmatic trial? How well did the applicant assess, justify the adequacy of, and finalize clinically relevant outcome measures?
How strong are the partnerships with health systems and/or care providers, and did the PDs/PIs document commitment of the organization to the project? Will the PDs/PIs be able to access administrative data (e.g. Medicare or Medicaid claims or electronic health records) and implement pilot interventions in health care delivery settings (e.g. is there a letter of support if the PD/PI proposed to access electronic health records in a health system and intervention delivery)?
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?
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 there are multiple 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?
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?
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.
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 of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/
Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the 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.
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.
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.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Marcel E. Salive, MD, MPH
National Institute on Aging (NIA)
Ramesh Vemuri, Ph.D.
National Institute on Aging (NIA)
Lesa McQueen, M.Sc.
National Institute on Aging (NIA)
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