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The overall goal of this FOA is to support the development of a collaborative research and resource network to synergize the expertise, skills, and resources of investigators within the geriatric emergency medicine and Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD) research communities to identify and address research gaps towards optimizing recognition and emergency care of older adults with AD/ADRD. Support is provided for up to 2 years of planning/development (R61 phase) of a milestone-driven infrastructure including the initial identification of top-priority research gaps and the establishment of strategies to address them. Areas identified as needing additional evidence-based research include, but are not limited to, pre-emergency department (ED) strategies to avoid non-emergency ED visits, recognition of early cognitive impairment in the ED, strategies to optimize the ED environment and providers for patients with AD/ADRD, development of safe disposition criteria, and methods to minimize system fragmentation within and across health and social services. Contingent on the achievement of pre-established milestones as assessed by internal NIA administrative review, support may be provided for up to 3 additional years (R33 phase) for the establishment and testing of the strategies developed in the R61 phase. It is anticipated that, if successful, this funding will support the planning, establishment, initial operations of a network over the 5-year grant period, including development of collaborations, resources, research infrastructure, and a plan to attract and foster early career investigators in the emergency care of older adults with AD/ADRD.
October 23, 2019
January 3, 2020
February 3, 2020, by 5:00 PM local time of applicant organization. All applications allowed for this funding opportunity announcement are due on this date. No late applications will be accepted for this Funding Opportunity Announcement.
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.
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.
Background
Emergency departments (ED) in the U.S. currently provide care for acute medical problems, illness, and injury, as well as serve as a ‘safety net’ for those lacking a primary care provider. Yet, delivering efficacious, efficient, and reliable emergency care for persons with Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) presents multiple challenges in the current strained healthcare system based on crowded, fast-paced, often chaotic ED visits. Moreover, failure to adequately recognize a patient with underlying dementia can result in diagnostic inaccuracies and inappropriate treatment of the patient's acute medical issues. With older adults, especially those over 85 years of age, having the highest rate of ED visits of any age cohort, and AD/ADRD affecting 1 in 10 adults over 65 years of age and 50% of those over 85 years of age, the challenges of optimally recognizing and treating those with underlying AD/ADRD present a very common problem which has not been systematically addressed.
It is estimated that 47 million people in the U.S. have mild cognitive impairment. These individuals, especially those who do not yet recognize, acknowledge, or verbalize their cognitive challenges, constitute a highly vulnerable patient population in the ED. The main goals of emergency medicine providers are to assess, treat, and/or stabilize acute conditions and to determine the safest disposition for the patient, namely hospitalization, transfer to another facility, or discharge to home, all of which are primarily dependent on the patient’s (or a surrogate’s) description/history of the acute illness or injury. Thus, the inability to give an adequate or accurate description of their acute medical problem, or to have someone corroborate their medical history, places persons with dementia (PWD) at risk for misdiagnoses; unnecessary and/or risky tests, medications, and treatments; inability to give informed consent for treatment; and unsafe discharge to hospital or home. The majority of EDs lack a routine screening process to ensure patients do not have an element of cognitive impairment affecting their treatment or disposition. In one observational study, failure to recognize cognitive impairment in an ED occurred in 90% of PWD. Several brief screening tools have been tested in EDs to evaluate their sensitivity, specificity, and positive and negative likelihood ratios but were still limited in their ability to recognize PWD. Further studies and focus groups have also identified additional challenges to the universal dissemination and integration of employing a tool to recognize PWD routinely in the ED. Such challenges include the waxing and waning of symptoms; reluctance to ‘diagnose’ a complex condition with multiple repercussions to the patient; hospital liability; privacy issues; time taken to administer tests; lack of an optimal environment, training, staff availability for testing, and follow-up for those PWD who were unaware of their condition; and challenges of false positive and negative tests. These issues require further examination to determine whether a brief, efficient strategy to identify PWD can be developed and to evaluate whether the integration of such a strategy would outweigh the risk associated with not recognizing underlying dementia in patients with acute medical illness or injury, including misdiagnosis, adverse drug events from newly prescribed contradicted medications, extended ED and hospital lengths of stay in ED/hospital, unnecessary hospital admissions and readmissions, falls, exacerbations of behavioral symptoms, overwhelmed caregivers, increased episodes of delirium, and other increased morbidities and mortality.
Challenges in diagnoses, risk assessment, and treatment of emergent conditions in PWD is another aspect of care in need of evidence-based guidance. Reliable and accurate diagnoses and care are often hindered and/or complicated by multiple issues, including obtaining a valid medical history, patient/surrogate-provider communication and decision-making, a lack of prognostic and risk assessment tools that account for the degree and trajectory of the patient’s dementia, distinguishing delirium from dementia, ethical issues including obtaining truly informed consent, a lack of or unobtainable advanced directives, and intermingled behavioral and psychiatric symptoms. Identifying and evaluating strategies to mitigate or minimize these complexities would help to reduce the elevated risk of inappropriate diagnoses, care, and disposition of acute illness or injury which further elevate morbidity and mortality in PWD.
Multiple elements of the physical ED environment present further stressors to PWD, including unfamiliar setting and people, loud and unfamiliar noises, crowded and often chaotic spaces, multiple unfamiliar providers, long waits, uncomfortable stretchers and chairs, and lack of privacy, often resulting in worsening confusion and disorientation, delirium, falls, and escalation of behavioral symptoms. Additionally, as the ED serves as a transient point of care, systematic strategies to improve the resultant fragmentation of care (providers, medical records, medication reconciliation) are greatly needed to reduce medical errors and inappropriate testing and prescribing, additional morbidity/mortality, miscommunication, polypharmacy, adverse drug reactions, and ED recidivism.
As the number of older adults increases, so too will the number of PWD and their annual visits to EDs. Yet, the current system of emergency medicine is ill-prepared to optimally and efficiently care for such escalating numbers of complex older patients, especially those with AD/ADRD. Overcrowded EDs with long patient wait times are additionally challenged by PWD who present with social, behavioral, or non-emergent problems prompted by lacking or inadequate primary care, caregiver issues, and/or a lack of social support. Research supporting alternative models to address these non-medical and/or non-urgent issues to spare PWD the additional stressors and risks associated with ED visits and avoid further contributing to the problems associated with over-utilized EDs is of urgent need.
The timing for research focusing on recognizing PWD in EDs is now optimal given the recent rapid advances in geriatric emergency medicine, geriatric emergency departments, and AD/ADRD research. Approximately 3 decades ago, the Society of Academic Emergency Medicine convened a task force to evaluate and provide recommendations to improve care for older adults with acute medical illness and injury. Recommendations addressed adopting an alternative care model recognizing and accommodating the special needs of older adults, including those with AD/ADRD. This charge, mainly driven by a focused group of emergency medicine (EM) clinicians and investigators, resulted in sequential efforts addressing education of providers and staff, the creation and implementation of geriatric-based protocols, equipment/rooms/supplies, transitions of care, quality improvement, and universal policies and procedures. In 2014, Transdisciplinary ED Geriatric Care Guidelines were published, and in 2018 a Geriatric Emergency Department Accreditation System was released to set national standards for geriatric-specific care in EDs. These efforts, which were primarily focused on older adults, has fueled a community of providers and an initial infrastructure to accelerate efforts to close the multiple research gaps outlined above to optimize the recognition and care of the highly vulnerable and rapidly growing population of older adults with AD/ADRD.
The concurrent advancement of geriatric EM, development of accredited geriatric emergency departments (GEDs), and recent escalation of AD/ADRD clinical research efforts has provided optimal infrastructure components to address the needs of unrecognized PWD and their caregivers in the ED. The NIA-funded Alzheimer’s Disease Research Centers (ADRCs) and other NIA-funded centers (Shock, Roybal, Pepper, RCMAR, Demography and Economics of Aging), as well as the NIA’s Research Centers Collaborative Network (RCCN), offer additional resources and opportunities to synergize research efforts with EDs and the expanding geriatric EM community.
Purpose and Scope
The overall goal of this FOA is to support the development of a collaborative research and resource network to synergize the expertise, skills, and resources of the investigators within the geriatric EM and AD/ADRD communities to identify and address research gaps towards optimizing recognition and emergency care of older adults with AD/ADRD. This FOA utilizes a biphasic, milestone-driven mechanism (R61/R33) through which clinically focused, transdisciplinary investigators can convene to identify the top priority areas to address in the recognition and emergency care of PWD and plan and develop/validate a synergistic infrastructure of areas of expertise/skills and resources (R61, Phase 1) to test creative, effective and efficient strategies to address priority research gaps (R33, Phase 2). Milestones identified in the application must be achieved with internal administrative approval in order to proceed with Phase 2. Areas identified as needing additional evidence-based research include, but are not limited to, pre-ED strategies to avoid non-emergency ED visits, recognition of early cognitive impairment in the ED, strategies to optimize the ED environment and providers for patients with AD/ADRD, development of safe disposition criteria, and methods to minimize system fragmentation within and across health and social services. It is anticipated that, if successful, this funding will support the planning, establishment, and initial operations of a network over the 5-year grant period, including development of collaborations, resources, research infrastructure, and a plan to attract and foster early career investigators in the emergency care of older adults with AD/ADRD.
Investigators
Investigators should have sufficient expertise, commitment of effort, organizational structure, and operational effectiveness to successfully implement a plan for this undertaking. Reflecting the multidisciplinary and multi-level providers who deliver emergency care, it is expected that investigators from a variety of professional backgrounds and research expertise across multiple institutions will form an interdisciplinary consortium, including those with specific research and clinical expertise in geriatric EM and AD/ADRD research. Examples of the kinds of investigators who could be included in this network include, but are not limited to, emergency medicine (and geriatric EM) specialists, geriatricians, neurologists, first responders, neuroradiologists, geriatric psychiatrists, social workers, geriatric nurses, geriatric trauma specialists, pharmacists, primary care providers, palliative care providers, behavioral scientists, behavioral and social researchers, biostatisticians, informaticians, ethicists, and clinical trialists. Where appropriate, researchers associated with a geriatric ED and/or an ADRC are encouraged. A multiple Program Director/Principal Investigator model of leadership is encouraged for this type of research/resource building project.
Organization
Applicants are expected to propose a network of investigators and resources that span multiple institutions and, ideally, capitalize on geriatric EDs and ADRCs. A successful network will have an organizational structure that effectively addresses the proposed aims and integrates its personnel, resources, and infrastructure across institutions. Examples of the organizational components that could contribute to a successful network include a leadership or steering body to coordinate planning, evaluation, resource allocation, and administrative oversight; a data coordination body that oversees standardization of data, houses informatics resources, and coordinates exchange of data and other research resources; a mentorship body that facilitates involvement of junior and/or mid-career investigators into the research activities of the network; a pilot grant body that solicits, selects, and supports pilot projects; and a dissemination body that coordinates timely and effective information sharing with relevant stakeholders. Applicants may also consider establishment of an external advisory committee. These are merely examples and are not intended to prescribe a specific organizational structure. Investigators may propose components and functions that best suit the aims of the network.
Specific Example Activities
Specific activities of this initiative may include, but are not limited to, the following:
Applicants are strongly encouraged to visit the pre-application information page, which provides information for prospective applicants and additional technical assistance for investigators developing applications in response to this FOA.
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. Only those application types listed here are allowed for this FOA.
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The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
NIA intends to commit $1,500,000 in FY 2020 to fund one R61/R33 award.
For the R61 planning phase, the combined budget for direct costs may not exceed $1,000,000 a year.
For the R33 phase, the combined budget for direct costs may not exceed $1,000,000 a year.
The maximum project period is 5 years. The R61 phase may be 1-2 years, and the R33 phase may be 3-4 years.
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
For-Profit Organizations
Governments
Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
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:
Ramesh Vemuri, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-9666
Email: ramesh.vemuri@nih.gov
The PD(s)/PI(s), collaborators, and other researchers should be well suited to the project, and early stage investigators should have appropriate experience and training. Established investigators should demonstrate an ongoing record of accomplishments that have advanced their field(s) or relevant expertise. If the project is collaborative or multi-PD/PI, the investigators should have complementary and integrated expertise and their leadership approach, governance and organizational structure should be appropriate for the project.
The PD(s)/PI(s), collaborators, and other personnel should be well suited for their roles in the proposed Emergency Care of PWD Network. Specifically, they should have appropriate training and experience in their respective areas of expertise and demonstrate an ongoing record of accomplishments in managing aging research, geriatric-related clinical medicine, geriatric EM, and/or AD/ADRD-specific research. The leadership of the proposed Network and its cores should have complementary and integrated expertise and skills and demonstrate significant experience with coordinating collaborative clinical research. If a multi-PD/PI leadership is proposed for the Network (or cores), the investigators' leadership approach, governance, plans for conflict resolution, and organizational structure should be appropriate for the Network/core. If subawards/pilot projects are proposed, investigators overseeing this aspect should possess experience with the selection and management of subawards.
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 a specific strategy, environmental adaptation, measurement tool, or biological measure may be included.
Approach
Describe the overall aims of the Emergency Care of PWD Research and Resource Network, the specific goals of each of its components, and how each component will interact with the other(s) and the overall leadership such that the whole is greater than the sum of the parts.
Highlight specific strategies to convene transdisciplinary leaders and investigators to identify and select top-priority areas of research in the recognition and emergency care of PWD. Identify metrics that will be used to assess progress toward specific goals. Provide timelines and an organizational chart. Describe how the proposed research/resource network leverages and synergizes resources supported by the National Alzheimer's Project Act and current geriatric ED resources.
Describe the organizational structure of the research and resource network. Describe plans for day-to-day operations, such as:
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 PD(s)/PI(s) include a section labeled "Milestones" as part of the research strategy within the approach section describing milestones to be achieved during the R61 phase to qualify for the transition to the R33.
Applicants can establish go/no-go criteria as they deem fit for their application, but must include the following:
Prior to the end of the R61 phase, awardees will submit a package that requests transition to the R33 phase. This package will include a progress report that describes accomplishments toward each of the R61 milestones and plans for studies during the R33 phase. This package will be reviewed by NIA program staff and, if approved, the grant will be transitioned to an R33 award without the need to submit a new grant application. Decisions on transitioning to the R33 phase will be based on the peer review recommendations of the original application, successful completion of the described milestones, NIA program priorities, and availability of funds.
The following modifications also apply:
All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan consistent with NIH policy, which stipulates release and sharing of data no later than the acceptance for publication of the main findings of the study.
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.
Important reminders:
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.
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, level of innovation, and 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.
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?
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 the PD(s)/PI(s) and other personnel well suited to their roles in the Emergency Care of PWD Network? Do they have appropriate experience and training and have they demonstrated experience and an ongoing record of accomplishments in managing aging research, geriatric-related clinical medicine, geriatric EM, and/or AD/ADRD-specific research? Do the investigators demonstrate significant experience with coordinating collaborative clinical research? If the Network (or core) leadership is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the network/core? Does the applicant have experience overseeing selection and management of subawards, if needed?
In addition, for applications involving clinical trials
With regard to the proposed leadership for the project, do the PD(s)/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?
Does the application propose novel organizational concepts or management strategies in coordinating the research consortium the network will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts or management strategies proposed? Are strategies considered to divert non-emergency medical or psychiatric issues in PWD to an alternative setting? Are specific skills and physical environmental issues which have been shown to reduce adverse effects in PWD incorporated and/or new skill/environmental adaptations integrated into the proposed strategies?
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?
Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research consortium the network will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the network, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented?
If the network is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the network? Are an appropriate plan for work flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects? Will the resources be allocated adequately across the network to accomplish the goals and activities of the consortium? Are the proposed infrastructure developments feasible, well-coordinated, and likely to contribute to the overall aims of the research/resource network? Are proposed scientific meetings and/or pilot projects well-reasoned and is the process for soliciting, developing, and selecting topics and/or projects suitable and unbiased? Are the plans for meetings and/or pilot projects suitable for enhancing the careers of beginning and/or mid-career investigators?
In addition, for applications involving clinical trials
Does the application adequately address the following, if applicable:
Study Design
Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group, level of cognitive impairment), 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 institutional environment in which the Network or core will operate contribute to the probability of success in facilitating the consortium it serves? Are the institutional support, equipment, and other physical resources available to the investigators adequate for the Network or core proposed? Will the Network or core benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling? Does the proposed Network build upon existing resources, including NIA-funded Centers, Alzheimer's Disease Research Centers, and geriatric EM expertise? Are specific skills and physical environmental issues which have been shown to reduce adverse effects in PWD incorporated and/or new skill/environmental adaptations integrated into the proposed strategies?
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?
Study Timeline
Specific to applications involving clinical trials
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?
Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Not Applicable
Not Applicable
Not Applicable
Not Applicable
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; and (2) 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 NIA, 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 the application as well as 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 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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Contact Center Telephone: 800-518-4726
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Susan Zieman, M.D., Ph.D.
Division of Geriatrics and Clinical Gerontology
National Institute on Aging (NIA)
Telephone: 301-496-6761
Email: susan.zieman@nih.gov
Nina Silverberg, Ph.D.
Director, Alzheimer's Disease Centers Program
Division of Neuroscience
National Institute on Aging (NIA)
Telephone: 301-496-9350
Email: SilverbergN@mail.nih.gov
Ramesh Vemuri, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-9666
Email: ramesh.vemuri@nih.gov
Mahasin Ingram
National Institute on Aging (NIA)
Telephone: 301-402-7736
Email: mahasin.ingram@nih.gov