Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Center for Complementary and Integrative Health (NCCIH)

National Heart, Lung, and Blood Institute (NHLBI)

National Institute on Aging (NIA)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

National Institute of Nursing Research (NINR)

National Institute on Minority Health and Health Disparities (NIMHD)

All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Division of Program Coordination, Planning and Strategic Initiatives, Office of Disease Prevention (ODP)

Office of Behavioral and Social Sciences Research (OBSSR)

Funding Opportunity Title
NIH Health Care Systems Research Collaboratory - Pragmatic and Implementation Trials of Embedded Interventions (UG3/UH3, Clinical Trials Optional)
Activity Code

UG3/UH3 Exploratory/Developmental Phased Award Cooperative Agreement

Announcement Type
New
Related Notices

None

Funding Opportunity Announcement (FOA) Number
RFA-AT-22-001
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.213, 93.361, 93.838, 93.837, 93.839, 93.840, 93.233, 93.307, 93.866, 93.846
Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) encourages UG3/UH3 phased cooperative research applications to conduct efficient, large-scale pragmatic or implementation trials to improve health and care delivery, with a particular focus on health care systems (HCS) with less historical involvement in research studies focused on improving health outcomes for US patient populations. Awards made under this FOA will initially support a one-year milestone-driven planning phase (UG3), with possible transition to a trial conduct phase (UH3). UG3 projects that have met the scientific milestone and feasibility requirements may transition to the UH3 phase. The UG3/UH3 application must be submitted as a single application, following the instructions described in this FOA.

The overall goal of this initiative is to support the "real world" assessment of health care strategies and clinical practices and procedures in health care systems (HCS) that lead to improved care for populations in a variety of healthcare contexts, with a strong focus on populations with health disparities. Results from the pragmatic studies supported by this FOA should inform policy makers, payers, doctors and patients across diverse patient care settings. This FOA requires that the intervention under study be embedded into health care delivery system, “real world” settings. Studies can propose to integrate multi-modal or multiple interventions that have demonstrated efficacy into HCS; or implement HCS changes to improve adherence to evidence-based guidelines. Trials should be conducted across three or more health care systems (HCS) that provide care to patient populations and will become part of and work with the NIH HCS Research Collaboratory. The NIH HCS Research Collaboratory Program has established a Collaboratory Coordinating Center (CCC) that is providing national leadership and technical expertise in all aspects of research with HCS. Awarded applicants will work with the HCS CCC (https://rethinkingclinicaltrials.org/) to facilitate further planning and refinement of the proposed study.

Key Dates

Posted Date
October 14, 2021
Open Date (Earliest Submission Date)
November 15, 2021
Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
December 15, 2021 December 15, 2021 Not Applicable March 2022 May 2022 July 2022
June 17, 2022 June 17, 2022 Not Applicable November 2022 January 2023 April 2023

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.

Expiration Date
June 18, 2022
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

This Funding Opportunity Announcement (FOA) encourages UG3/UH3 phased cooperative research applications to conduct efficient, large-scale embedded pragmatic or implementation trials with a high priority on improving health outcomes in Americans across the lifespan and health disparity populations who experience higher rates of certain diseases and higher mortality compared with the general population. The specific population with health disparities may be defined by race, ethnicity, geography or socioeconomic status. For the purposes of this funding opportunity, the NIH-designated U.S. health disparity populations definition includes: Blacks/ African Americans, Hispanics/ Latinos, American Indians / Alaska Natives, Asian Americans, Native Hawaiians and other Pacific Islanders, socioeconomically disadvantaged populations, underserved rural populations, and sexual and gender minorities (More information can found at the following link: https://www.nimhd.nih.gov/about/overview/). Awards made under this FOA will initially support a one-year milestone-driven planning phase (UG3), with possible transition to a trial conduct phase (UH3). UG3 projects that have met the scientific milestones and feasibility requirements may transition to the UH3 phase. The UG3/UH3 application must be submitted as a single application, following the instructions described in this FOA.

The overall goal of this initiative is to support the "real world" assessment of health care strategies and clinical practices and procedures in health care systems (HCS) with a strong emphasis on research that leads to improved care with the aim to reduce or eliminate health disparities in specific health populations. Results from the pragmatic studies supported by this FOA should inform policy makers, payers, doctors and patients across diverse patient care settings. This FOA requires that the intervention under study be embedded into multiple health care delivery systems, “real world” settings. “Real world” data includes data from a variety of resources including information from patients, healthcare workers, electronic health records, and payers. This approach broadens who is included in research studies and enhances efficient data collection. Studies can propose to integrate multi-modal or multiple interventions that have demonstrated efficacy into HCS; or implement HCS changes to improve adherence to evidence-based interventions or guidelines. Trials or studies should be conducted across three or more health care systems (HCS) that include systems that provide care to patient populations with health disparities. Trials will become part of and work with the NIH HCS Research Collaboratory. The NIH HCS Research Collaboratory Program has established a Collaboratory Coordinating Center (CCC) that is providing national leadership and technical expertise in all aspects of research with HCS . Awarded applicants will work with the HCS CCC (https://rethinkingclinicaltrials.org/about-nih-collaboratory/) to facilitate further planning and refinement of the proposed study.

The NIH Health Care Systems Research Collaboratory Program

The overall goal of the NIH Health Care Systems (HCS) Research Collaboratory program is to strengthen the national capacity to implement cost-effective large-scale research studies that engage health care delivery organizations and patients as research partners. The NIH HCS Research Collaboratory Program established a Collaboratory Coordinating Center (CCC) led by Duke University in 2012 (https://rethinkingclinicaltrials.org/about-nih-collaboratory/) that is providing national leadership and technical expertise. Since 2012, the CCC has facilitated the successful planning and conduct of 19 full-scale Pragmatic Clinical Trials launched in the NIH HCS Research Collaboratory Program. Awardees from this FOA will work with the NIH and CCC for both the planning and conduct of their pragmatic clinical trial or implementation trial. All Projects should conduct research studies in partnership with at least three health care delivery systems, some of the participating Institutes and Centers will give high priority to studies that address care in populations with health disparities (see Institute and Center priorities below). Projects will work with the NIH and the CCC to ultimately make available data, tools, resources and lessons learned from Collaboratory research projects to facilitate a broadened base of research partnerships with HCS.

The aim of the HCS Research Collaboratory program is to provide a framework of implementation methods and best practices that will enable the participation of many HCS in pragmatic and implementation research, not to support a defined health care research network. Health care systems have interest in participating in studies that may potentially impact the care they deliver, including pragmatic and implementation trials addressing the uptake of new interventions or technologies into routine care. Research conducted in partnership with health care systems is essential to strengthen the relevance of research results to ‘real world’ health practice. Successful approaches and best practices established through this initiative to create research partnerships with HCS should have a major impact on clinical research in the US. The Collaboratory is also well-suited for testing how practice guidelines can be implemented in HCS, and for assessing outcomes of implementation across a broad range of HCS serving various patient sub-groups. The Collaboratory could also leverage existing efforts, such as those of the US Preventive Services Task Force (http://www.uspreventiveservicestaskforce.org/BrowseRec/Index/browse-recommendations), for generating evidence regarding screenings, counseling services and preventive medications and services to improve the health of Americans.

The increased adoption of health information technology tools is not only changing how care is delivered but also providing opportunities for expanded participation of health care delivery organizations in research. The current COVID-19 pandemic has precipitated a marked shift from in-person patient care to virtual clinician-patient interactions, which may produce sustained alterations in US health care delivery. Evolution of care delivery during the pandemic provides an opportunity to understand the impacts of these changes on access to care, particularly for patient populations with health disparities.

Although the importance of engaging health care delivery organizations for expanding informative biomedical research programs is clear, many challenges exist, both cultural and practical. Many ethical and regulatory issues must be addressed to perform research in the health care delivery setting. Technical challenges to accessing and aggregating quality-controlled data from HCS in understandable ways are not trivial. Research studies frequently use endpoints that are not part of the normal evaluation of patients during a routine visit or monitor the fidelity of intervention delivery in ways that are difficult to translate to most care delivery settings, which may limit external validity. Education and engagement of providers and patients on the value of research in the care setting, and of researchers on the relevance of their work to health systems, are urgently needed for optimizing the medical care for all people in the US. The NIH HCS Research Collaboratory program created a broad framework to tackle some of these major challenges and will continue to further address these issues.

Although 20th century scientific and technological advances have improved the health and well-being of the U.S. population overall, as noted above in the NIH definition of populations with health disparities, some racial and ethnic groups, socioeconomically disadvantaged, underserved rural and sexual and gender minority populations continue to experience a disproportionate share of many acute or chronic diseases and adverse health outcomes. The COVID-19 pandemic caused by the novel coronavirus (SARS-CoV-2) pandemic, and/or other pandemics, epidemics (e.g., dengue fever, zika, chikungunya) or public health emergencies have starkly provided evidence of the reality of differences in outcomes based on health disparities. There is some concern that telehealth may be exacerbating these disparities and utilizing race as an imperfect surrogate for disparity limits the ability to address true and more complex social determinants of health that contribute to health disparities. The challenges lie in the interactions of influences at various levels (e.g., individual, interpersonal, family, community, societal), the diversity of the relevant mediators (e.g., exposures, risk and resilience factors), and the multiple interacting mechanisms involved (e.g., biological, behavioral, environmental, sociocultural, and healthcare system). Proportional representation in studies, defined as inclusion that parallels population demographics is required by law in NIH research and is a minimum threshold. Investigators should consider study population and heterogeneity as a critical element of the study design.

Pragmatic clinical effectiveness trials and implementation trials can be used to carefully assess HCS Policies, clinical practice guidelines, tools and interventions as they are used within HCS to improve existing health care delivery. Research is needed to study strategies to effectively, equitably, and efficiently implement evidence-based interventions and guidelines and further assess their effectiveness in “real world” settings, when appropriate. The scientific approach to studying and publishing on racial inequalities can be improved to ensure that race is not considered a biological variable, but instead defining the population by social, environmental and structural factors.

For the purpose of this FOA, we define "embedded pragmatic clinical trial" and "implementation research", as follows:

Embedded pragmatic clinical trials are conducted within the health care delivery setting and are “primarily designed to determine the effects of an intervention under the usual conditions in which it will be applied”, which is in contrast with explanatory trials that “are primarily designed to determine the effects of an intervention under ideal circumstances” (http://www.bmj.com/content/350/bmj.h2147). "There are “three key attributes of pragmatic clinical trials (PCTs): (1) an intent to inform decision-makers (patients, clinicians, administrators, and policy-makers), as opposed to elucidating a biological or social mechanism; (2) an intent to enroll a population relevant to the decision in practice and representative of the patients or populations and clinical settings for whom the decision is relevant; and (3) either an intent to (a) streamline procedures and data collection so that the trial can focus on adequate power for informing the clinical and policy decisions targeted by the trial or (b) measure a broad range of outcomes (https://rethinkingclinicaltrials.org/chapters/pragmatic-clinical-trial/what-is-a-pragmatic-clinical-trial-2/)."

Implementation research seeks to understand the behavior of practitioners and support staff, organizations, consumers and family members, and policymakers in context as key influences on the adoption, implementation and sustainability of evidence-based health interventions and guidelines (e.g., Community Guide to Preventive Services, U.S. Preventive Services Task Force, and clinical and professional societies' recommendations and guidelines). Implementation research studies should not assume that effective interventions can be integrated into any service setting and for consumer groups and populations without attention to local context, nor that a unidirectional flow of information (e.g., publishing a recommendation, trial, or guideline) is sufficient to achieve practice change.

The HCS Research Collaboratory program encourages sharing of resources with broad availability of policies, practices, materials, and tools to facilitate collaboration, reuse, and replication. In addition, the HCS Research Collaboratory program encourages sharing of study data from Projects in a timely manner with appropriate privacy and confidentiality protections, in accordance with the Data Sharing Policy developed by the HCS Research Collaboratory Steering Committee (https://dcricollab.dcri.duke.edu/sites/NIHKR/KR/Collaboratory.DataSharingPolicy_June232014.pdf) . Thus, the HCS Research Collaboratory program requires awardees to implement a Resources and Data Sharing Plan consistent with achieving these program goals.

Research Objectives

This FOA solicits applications for UG3/UH3 exploratory/developmental phased award cooperative agreements for large-scale embedded pragmatic trials or implementation research trials to be conducted through at least three HCS that provide care that include a diverse patient population that approximates the US population of patients with the condition being studied. For projects that aim to reduce or eliminate health disparities the proposed HCS should have adequate proportions of patient populations with health disparities to assess the proposed intervention effect on study outcomes. The design of the proposed project should maximize external validity of the study, by testing generalizability, feasibility and sustainability of findings across distinct health care settings, and diverse staff and patient populations.

The proposed pragmatic or implementation trials must meet all of the following criteria:

  • The project must test an intervention, or coordinate several interventions (which can be treatments, preventive actions, or organizational changes) that are robust, apply broadly to patient populations and are suitable for use in multiple health systems, with the broad goal of determining whether the intervention(s) improves health outcomes and adds value to the nation’s health care delivery.
  • The results of the question being tested will have a significant impact on care and care delivery within HCS.
  • The intervention(s) must be well-characterized and available such that it could be reliably delivered by clinical providers and/or HCS. If an intervention includes a drug, biologic or device, it must be a legally marketed drug, biologic or medical device in the US, and used as approved/cleared for use by the US Food and Drug Administration.
  • The intervention(s) must be reasonably simple and not require a complex structure for implementation or monitoring. System level interventions may be particularly suitable.
  • As in routine practice, the pragmatic trial must allow for interventions to be implemented with maximal flexibility and by all appropriate practitioners (not just those with high levels of training or competence).
  • The project must leverage opportunities made available by the nature of health care systems; and use of outcomes that can be captured by passive follow-up such as electronic health records, and with minimal need for adjudication. Augmentation of the electronic health record is allowable for patient reported data and outcomes, although this should be streamlined and collected only at necessary time points.
  • The project outcome measure(s) must be clinically meaningful and important to stakeholders including patients, providers, health care systems, and policy makers. Additional outcome measures such as use of health care services or medications, and other resources may be included. Outcome measures must provide useful information to medical decision makers, whether patients, care providers, health care systems or payers.
  • The study design must 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 must provide comparable rigor.
  • Proposed analytic plans for projects that propose studies, including cluster-randomized trials, must address adequacy of sample size and study power; and employ analytic strategies relevant for such pragmatic trial designs. Applicants are strongly encouraged to consult Collaboratory Biostatistical Guidance documents (https://rethinkingclinicaltrials.org/chapters/design/experimental-designs-randomization-schemes-top/experimental-designs-and-randomization-schemes-introduction/) and the NIH Research Methods Resources website on group- or cluster-randomized trials (https://researchmethodsresources.nih.gov/grt.aspx ) when developing pragmatic trial analytic plans.
  • The study must address, and potentially overcome, important barriers to research in the setting of HCS partnerships.
  • There must be a strong scientific rationale for population selection to meet all NIH requirements for gender and minority recruitment in the overall study population. There should be strong scientific justification for any variables related to patient selection and ensure there are no intentional or unintentional exclusions based on risk, age, health literacy, expected adherence, or demographics.
  • Selection of the HCSs must be based on characteristics that will ensure the study question can be answered.

Embedded Effectiveness trials must include:

  • Clinical outcomes measures to assess meaningful changes that are defined at the patient, provider, or system level.

Implementation trials must include:

  • Sufficient evidence for the proposed intervention to justify implementation or de-implementation or the need for intervention adaptation. A strategy to de-implement care is proposed for low-value interventions where there is evidence of no benefit or there is more harm than benefit for patients.
  • Main outcomes focused on implementation that are most likely at a system or individual provider level. Patient-level implementation outcomes may be possible, if focused not on health but on the use of the targeted intervention.
  • There is a conceptual model and theoretical justification of the proposed study design and variables tested with a well-defined strategy and reasonable readiness to adopt if primary outcome met.

Partnerships with health care delivery organizations will be critical in implementing this work. It is anticipated that the Projects will generally be performed with high volume electronically supported integrated HCS to establish efficiencies. The HCS partnership must facilitate access to all data sources relevant to the project, which may include inpatient, outpatient, imaging, clinical laboratory, pharmacy and community data. Applicants, who may be from academic institutions or other organizations, must demonstrate experience in successful conduct of clinical research in partnerships with HCS. In general, applicants should identify at least three HCS that provide care to patient populations as partners for the proposed Project. Investigators that propose fewer than three HCS must provide justification that there is adequate geographic, provider, and racial diversity within the proposed HCS that the trial will be generalizable to other HCSs.

These projects will be funded as phased awards with a one-year planning phase (UG3) and a two-to-four-year trial conduct phase (UH3). Activities in both phases will depend on the specific study (e.g. disease domains, type of interventions, experimental design, randomization strategy and proposed outcome measures).

During the UG3 or planning phase, activities will generally include, but are not limited to:

  • Identify project staff that will participate in the Collaboratory Work Groups (see Section I.5 Additional Information (https://rethinkingclinicaltrials.org/cores-and-working-groups/), which will develop guidelines and practices to be implemented across projects.
  • Work with the Collaboratory to implement approved guidelines and practices for electronic data extraction and quality control methods and tools, as well as for electronic data sharing. In the planning phase, this will include developing and validating all electronic data methods and tools within the HCS needed for the Project (e.g., electronic health records, electronic methods for patient identification and outcomes assessment, patient reported data, biospecimens, images, high-throughput genomic data, family history data, data abstraction and survey instruments) and complete quality control testing at all sites.
  • Assess adequacy and finalize clinically relevant outcome measures with other Collaboratory investigators. Awarded applicants will work with other Collaboratory investigators and NIH to identify common outcome measures (quality of life, pain, fatigue, physical functioning and other measures); and will work with the CCC and NIH to develop metrics for resource utilization for planning and implementing Collaboratory pragmatic trials. If an award is made, NIH and CCC staff will work with the Program Directors/Principal Investigators to facilitate coordination among projects, if appropriate.
  • Refine estimates of requirements with guidance from NIH and the CCC, for sample size, numbers of sites, site to site heterogeneity, and implementation timetable based on data derived from the partnering HCS.
  • Develop detailed plans for site implementation, including site staff, method of identification, randomization (as applicable) and participant recruitment and acquisition and administration/implementation of the intervention if applicable.
  • Address all ethical issues and issues related to human subject safety oversight for the Project, including development of informed consent documents or opt-out consent if applicable, and finalizing site of IRB review. Applicants must propose a single IRB or centralized IRB approach for trial oversight, to facilitate both appropriate and timely study conduct.
  • Address all potential regulatory elements of the proposed trial (if applicable).
  • Develop a detailed budget for conduct and completion of the Project, including preparation of a final planning phase report.
  • Finalize detailed plans for data coordination and quality control for the UH3 phase. The CCC will not provide these functions for individual Projects. Data coordinating activities for individual Projects must be separately budgeted as part of the UH3 budget.

Project Trial Conduct Phase (UH3): The objective of the two-to-four-year UH3 trial conduct phase is to conduct the Project in accordance with activities planned in the UG3 phase. Activities will depend upon the study, but in general the following goals should be achieved:

  • Each project is expected to conduct all aspects of the proposed pragmatic effectiveness or implementation trial including the identification and recruitment of proposed sample sizes of patients, practice sites, and/or clinicians; the execution of the intervention and its delivery within the HCS, and the assessment of outcomes.
  • Each project is expected to provide complete assessment of all issues related to patient, clinician and site identification, and EHR tools used in these steps.
  • Each project is expected to provide definitive information about the execution of the intervention at all sites.
  • Each project is encouraged to assess fidelity to the intervention, when possible.
  • Each project is to provide detailed and definitive testing of the validity of methods used for monitoring and outcome assessment.

Milestones and UG3/UH3 Transition

Utilization of milestones is a key characteristic of this FOA. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity. This FOA will utilize a two-phase, milestone-driven cooperative agreement (UG3/UH3) mechanism consisting of a start-up/planning phase of up to one year (UG3) and a pragmatic or implementation trial execution phase (UH3). Projects should include well-defined milestones for the planning phase (UG3) and annual milestones for the trial conduct phase (UH3). It is understood that the proposed milestones for the UH3 phase will be revised as activities in the UG3 phase progress. In the event of an award, the PD/PI and NIH staff will negotiate a final list of milestones for each year of support.

At the completion of the UG3 planning phase, the applicant will be required to submit a detailed transition request for the UH3 Project trial conduct phase. UH3 transition requests will undergo an administrative review to determine whether the Project will be awarded for the trial conduct phase (UH3). All regulatory approvals should be obtained prior to the end of the UG3 award. Training of intervention providers, comparison group providers, or other resources should be planned at the start of the UH3award to allow for the successful launch and execution of the proposed embedded pragmatic or implementation trial in the UH3 phase. Prospective applicants should note that initial funding of the UG3/UH3 Phase Innovation cooperative agreement does not guarantee support of the UH3 Project trial conduct phase. Applicants should understand that transition to the UH3 phase of the project will occur only if an administrative review process recommends that the UG3 planning milestones have been successfully met, that the UH3 phase can proceed with confidence of success, and availability of funds. It is recommended that the milestones for the UG3 phase be objectively defined to ensure clear demonstration that the proposed milestones were met at the time of the transition request. Continuation of the award is conditional upon satisfactory progress and subject to availability of funds. If, at any time, recruitment falls significantly below the projected milestones for recruitment, the NIH will consider ending support and negotiating an orderly phase-out of the award and retains, as an option, periodic external peer review of progress. NIH staff will closely monitor progress of milestones, accrual, and safety.

Research Areas of Interest

For each participating NIH IC, examples of potential research questions that could be addressed by pragmatic or implementation trials and would be responsive to this FOA are outlined below. Potential applicants are urged to contact NIH IC Scientific/Research Staff to ensure that proposed studies are responsive to this FOA.


National Heart, Lung, and Blood Institute (NHLBI)

Applications will be considered of high programmatic interest if at least two of the three or more participating health care systems are Federal Qualified Health Center (FQHC) networks or similar safety net health care systems. Applications that propose embedded pragmatic clinical or implementation trials which focus on improving heart, lung, blood, or sleep (HLBS) disorders in underserved US patient populations who have suffered a disproportionate disease burden and which have the potential to reduce health disparities would be of high priority. Examples include but are not limited to:

General

  • Assessments of parameters that drive sustainable delivery of evidenced-based treatments that lower risk for HLBS in underserved US patient populations
  • Effectiveness of approaches to reduce HLBS risk among populations with health disparities

Cardiovascular

  • Effectiveness of approaches to improve the management of all types of heart failure in underserved US patient populations
  • Effectiveness of strategies to address biological and non-biological factors/barriers (e.g., structural, social, and behavioral) that predispose young or middle age adults in underserved US patient populations to cardiovascular risk
  • Translation or implementation of the lower systolic hypertension goals into practice settings in underserved US patient populations
  • Effectiveness of approaches to prevent and manage obesity in primary care settings in underserved US patient populations
  • Assessments of referral models that promote appropriate utilization of technology (e.g., implantable cardioverter-defibrillator placement) in underserved US patient populations
  • Assessments of the utilization of personalized health records or other methods to capture patient reported outcomes for cardiovascular disease prevention and management.
  • Effectiveness of strategies to reduce the risk of stroke in patients with atrial fibrillation including screening.
  • Effectiveness of intervention in the treatment of asymptomatic severe aortic stenosis
  • Effectiveness of approaches to improve the peri-partum and post-partum management and continued monitoring of hypertension, diabetes, and obesity (risk factors that predispose to later cardiovascular morbidity) in underserved US patient populations
  • Implementation of strategies to engage older adults in routine physical activity in underserved US patient populations in order to improve cardiovascular health (as well as other organ systems and overall health)
  • Interventions to engage cardiac rehabilitation participation of patients who have indications for cardiac rehabilitation in underserved US patient populations
  • Interventions to reduce any health disparity in pharmacologic management of patients with diabetes and heart failure in underserved US patient populations
  • Effectiveness of technology to monitor and manage patients with chronic cardiovascular-predisposing conditions (e.g., diabetes and hypertension) in underserved US patient populations
  • Translation or implementation of strategies from transition and timing from acute to chronic compensated HF
  • Effectiveness of strategies to reduce cardiovascular events by SGLPT2 in cardiorenal syndrome
  • Effectiveness of exercise rehab training to improve HFpEF outcomes.
  • Effectiveness of wearables for detecting asymptomatic AFIB in moderate risk population.
  • Effectiveness of Health literacy intervention to mitigate SDOH and improve HF outcomes in Medicare population
  • Effectiveness of Interventions to address EHR identified SDOH risk and effect on HF outcomes.
  • Effectiveness of strategies for early airway stabilization in OHCA
  • Effectiveness of endovascular stabilization in OHCA cardiogenic shock
  • Effectiveness of strategies for early metabolic support in OHCA
  • Effectiveness of public neighborhood network based on iPhone regional connectivity and local citizen-based CPR
  • Effectiveness of strategies to reduce the risk of amputation in patients with PAD/critical limb ischemia including referral for arterial testing in underserved US patient populations.
  • Effectiveness of strategies for smoking cessation in young and middle age adults in underserved US patient populations.
  • Effectiveness of approaches to implement home-based supervised exercise therapy in adults with PAD in underserved US patient populations.
  • Implementation of guideline-directed medical therapy for PAD into practice settings in underserved US patient populations.
  • A pragmatic trial in diabetic medication/dietary management seems reasonable since we know that diabetes is both a huge cardiovascular risk factor due to its effects on the vasculature and a big problem in the underserved communities.

Lung or Sleep

  • Use of computer decision support systems to rapidly screen, evaluate, diagnose, and manage sleep disorders in routine care to reduce risk of cardiovascular disease.
  • Effectiveness of virtual pulmonary rehabilitation to reduce hospital readmissions in COPD patients without private insurance.
  • Use of tailored patient navigator services for high utilization asthma patients in Federally Qualified Health Centers (FQHCs).
  • Pragmatic strategies to increase adherence to pain, agitation/sedation, and delirium guidelines in mechanically ventilated patients.
  • Effectiveness of pre-operative screening and treatment of sleep-disordered breathing on surgical morbidity, mortality, and re-hospitalization
  • Effectiveness of and adherence to thresholds for oxygen administration in preterm babies

Blood Disorders

  • Effectiveness of hydration protocols to manage acute sickle cell disease events in the emergency room.
  • Effectiveness of health promotion and education for hemophilia patients to promote adopting and sustaining health behaviors that optimize physical functioning.
  • Effectiveness of blood banking policies and procedures to prevent adverse outcomes related to transfusions.
  • Effectiveness of patient education to prevent deep vein thrombosis.

Implementation

  • Assessments of health system characteristics associated with successful implementation of any protocol-based treatment strategy for HLBS.
  • Tests of sustainable implementation strategies for HLBS guidelines across various health care systems that employ implementation research primary outcome metrics (i.e. measures of acceptability, adoption, appropriateness, costs, fidelity, penetration, and sustainability).

National Institute on Aging (NIA)

Examples of research topic areas that may be relevant to this FOA for NIA include, but are not limited to:

  • Compare effectiveness of treatment strategies for comorbid conditions that occur frequently in combination with Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD).
  • Evaluation of beneficial and adverse outcomes from differing management strategies for multiple chronic conditions, testing an intervention, or coordinating several interventions.
  • Evaluation of benefits and harms of screening for cognitive impairment in community-dwelling older adults in primary care–relevant settings, and effect on decision-making, patient, family or caregiver, and/or societal outcomes.
  • Evaluation of benefits and harms of interventions for mild cognitive impairment or mild to moderate dementia in older adults in terms of decision-making, patient, family or caregiver, and/or societal outcomes.
  • Incorporation of specific palliative care services (e.g., symptom management, establishment of care goals consistent with patient and family preferences, discontinuation of potentially unnecessary treatments) into care of older adults within and/or across specific settings.
  • Development and validation of effective strategies to reconcile medication type and dose across care setting transitions (e.g., hospital to home, home to hospital including intermediate care such as between inpatient units, rehabilitation facilities and nursing homes).
  • Evaluation of interventions for managing post-operative cognitive decline in health care settings, including hospitals and rehabilitation facilities.
  • Effectiveness of incorporating an automated notification system into an electronic pharmacy ordering system that alerts providers to the potential for drug-drug interactions or adverse drug effects in individual patients meeting specific age-associated clinical parameters (e.g., creatinine clearance: body surface area).
  • Effectiveness of an automated electronic health record notification system that identifies older patients at increased risk of major bleeding based on hematologic/coagulation factors, medications, renal function, anthropomorphic and/or other variables.
  • Effectiveness of incorporating geriatric assessment (i.e., systematic assessment of functional, cognitive, medical, and other parameters) into care of older adults referred for invasive medical or surgical procedures.
  • Effectiveness of anticoagulation strategies for non-valvular atrial fibrillation in patients older than 80 years, including those with multiple chronic conditions and/or renal dysfunction.
  • Evaluation of the long-term benefits and harms of bisphosphonate medication for low bone density or osteoporosis, comparing continued use of pharmacotherapy with an alternative of discontinuation.
  • Behavioral economics-based interventions which change choice architectures to improve health care of older adults.
  • Effectiveness of simple, scalable incentive-based interventions to improve health-promoting behavior in midlife and/or older adults in one or more of the following settings: workplaces, community, nursing homes, assisted living facilities, rehabilitation facilities.
  • Technology-based interventions to improve affect regulation and emotional well-being of midlife and/or older adults with chronic health conditions, or of their caregivers.
  • Assessment of new organizational and delivery models, which include innovations and care coordination in home health care and adult day services for the frail older adults.


National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

 

Study topics for pragmatic trials of interest to NIAMS include:

  • Approaches to improve the management of chronic rheumatic, muscle, bone, joint, and/or skin diseases in adults and children, particularly through testing the use of different regimens to optimize outcomes and reduce known risks.


National Institute of Nursing Research (NINR)

NINR supports research that builds the scientific foundation for nursing practice and policy across diverse clinical and community settings to advance the prevention, detection, and management of disease and disability across the lifespan. NINR encourages research that integrates factors at multiple levels to identify their role in health, health improvement and health inequities with the goal of improving the health of individuals, families, and populations by translating science in order to maximize the impact of findings on practice and policy. In the context of this FOA, priority will be given to studies that propose projects that:

  • Study social needs care, integrating services that address health-related social risk factors and social needs within the context of clinical practice and health care delivery
  • Projects that are targeted at the medically underserved, uninsured, and underinsured populations


National Institute on Minority Health and Health Disparities (NIMHD)

NIMHD is interested in multilevel pragmatic intervention studies within the context of health care systems that serve primarily or a significant number of patients from populations with health disparities. NIH-designated U.S. health disparity populations include Blacks/African Americans, Hispanics/Latinos, American Indians/Alaska Natives, Asian Americans, Native Hawaiians and other Pacific Islanders, socioeconomically disadvantaged populations, underserved rural populations, and sexual and gender minorities.

The term “multi-level” refers to the multi-dimensional framework of determinants relevant to understand and address minority health and health disparities. This concept is further described under the NIMHD Research Framework (https://www.nimhd.nih.gov/about/overview/research-framework/).

We also encourage investigators to use metrics of social determinants of health based on the PhenX toolkit.

In addition to the research objectives described above, NIMHD is primarily interested in the following topics:

  • Multi-level interventions (including health care coordination) focused on reducing unnecessary or preventable emergency care utilization,
  • Multi-level interventions focused on reducing delayed health care system response to needed emergency care especially in remote or low-income settings and for patients for whom English is not their primary language.
  • Interventions testing the incorporation of technology to enhance communication between the patient and the health care system, and promote patient agency and decision making (especially patient reported outcomes related to pharmacological or surgical treatments) and/or medical adherence
  • Interventions focused on older adult wellness aimed at reducing polypharmacy and serious or incapacitating medication side effects, and accounting for sociocultural determinants of health
  • Studies focused on enhancing timely access to services conspicuously delayed for many patients from populations with health disparities, including but not limited to post-surgical, and post-cardiac and post-stroke rehabilitation and care; physical/occupational medicine therapy after injury, surgery, or as part of routine care; primary and continuity of care after recovery from cancer; and primary and continuity of care after recovery from mental health disorders’ or drug use relapse
  • Multi-level interventions on facilitating access and referral to timely palliative and/or end of life care for patients from populations with health disparities, especially those living in remote areas and for whom English is not their primary language. Interventions that integrate cultural perspectives, caregivers or family members or the patient’s social network, and social determinants of health are of interest.

National Center for Complementary and Integrative Health (NCCIH)

NCCIH is interested in pragmatic or implementation trials that evaluate the effectiveness of complementary interventions or how to implement these interventions into health care delivery. The complementary interventions proposed should have strong evidence of efficacy to warrant their inclusion in health care delivery. Applications will be considered of high programmatic priority if they propose projects that study a mind and body or integrated approach for one of the following high priority topic areas: management of chronic pain syndromes; promotion of whole person health, health restoration, emotional well-being, or resilience; prevention or treatment of symptoms including sleep disorders or disturbances, depression, anxiety, post-traumatic stress (disorder), and obesity; improving minority health and eliminating disparities in priority health conditions; the role of social and structural determinants of health; enhancement of adherence to medications or prescribed behavioral approaches (e.g., physical activity and healthy eating); reduction of inappropriate use of medications or substances (e.g., substance use disorder or medications that are contraindicated in specific patient populations). Applications are not responsive to this FOA if they propose trials of regulated products (dietary supplements, devices or biologics) for indications that have not been approved or cleared by the US Food and Drug Administration.

Office of Disease Prevention (ODP)

The ODP is the lead office at the NIH responsible for assessing, facilitating, and stimulating research in disease prevention. In partnership with the 27 NIH Institutes and Centers, the ODP strives to increase the scope, quality, dissemination, and impact of NIH-supported prevention research. The ODP is interested in providing co-funding support for research that has strong implications for disease prevention and health equity and that include innovative and appropriate design, measurement, and analysis methods. The ODP has a particular interest in projects that develop and/or test intervention to prevent the leading risk factors and causes of death (https://vizhub.healthdata.org/gbd-compare; https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm. Accessed June 3, 2021). For additional information about ODP’s research priorities and interests, please refer to the ODP Strategic Plan for Fiscal Years 2019–2023.

The ODP does not award grants; therefore, applications must be relevant to the objectives of at least one of the participating NIH Institutes and Centers (IC) listed in this announcement. Please contact the relevant IC Scientific/Research Contact(s) listed for questions regarding IC research priorities and funding.

It is expected that the pragmatic and implementation trials supported under this FOA will recruit women in sufficient numbers to better understand the influence of sex as a variable.

Types of Clinical Trials Not Responsive to this FOA

The following types of clinical trials are not responsive to this FOA and applications proposing such activities will be deemed non-responsive and will not be reviewed:

  • Phase I (first-in-human) trials whether single or multi-site
  • Single site trials
  • Studies to understand the mechanism of the intervention
  • Studies to assess initial feasibility of an intervention
  • Drug or device safety trial
  • Studies that propose to conduct studies in animals or in vitro studies

Additional Information

Governance: The awards funded under this FOA will be cooperative agreements (see Section VI.2 Cooperative Agreement Terms and Conditions of Award). Close interaction with the NIH and with the CCC will be required to accomplish the goals of this program.

HCS Research Collaboratory Work Groups have been established by the CCC and the NIH as the core collaborative activity of this program. The Work Groups provide a forum for discussion of challenges and solutions across projects. Harmonized and standardized policies and processes will be vetted in these groups. Work Groups have been established in the following areas: Electronic Health Records, Regulatory /Ethics, Biostatistics & Study Design, Health Care Systems Interactions, and Patient Reported Outcomes (https://rethinkingclinicaltrials.org/cores-and-working-groups/). Additional Work Groups may be identified as the HCS Research Collaboratory expands with new projects as part of this initiative. Work Groups will comprise individuals from each of the Projects, the Coordinating Center, and staff from the NIH. PD/PIs must identify study staff or investigators that will participate in Collaboratory Work Groups.

A Steering Committee has been established by the CCC to address issues that span all projects, provide input into the policies and processes of the HCS Collaboratory, and assist in dissemination of policies and processes that enable research in HCS, involving their patients and practitioners. At a minimum, the Steering Committee will have one representative from each of the Projects, one representative from each Work Group, one representative from the Coordinating Center, and NIH Program Officers and Project Scientists for the CCC and Projects. All members are expected to actively participate in all Steering Committee activities. The combined vote of NIH membership may never exceed 40 percent. NIH may convene an external panel of experts to provide advice on the overall program progress.

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

Section II. Award Information

Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed
New
Resubmission

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.

Clinical Trial?

Optional: Accepting applications that either propose or do not propose clinical trial(s).

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The following NIH components intend to commit the following amounts in FY 2022:

NCCIH, up to $1,000,000 direct costs, 1-2 UG3 planning awards

NIA, up to $1,000,000 direct costs, 1-2 UG3 planning awards

NHLBI, up to $500,000 direct costs, 1 UG3 planning awards

NIAMS, up to $500,000 direct cost, 1 UG3 planning award

NIMHD, up to $500,000 direct cost, 1 UG3 planning award

NINR, up to $500,000 direct cost, 1 UG3 planning award

Award Budget

The application budget for the one-year UG3 phase is limited to $500,000 in direct costs.  Costs for each year of the UH3 phase are limited to $1 million in direct costs.

Award Project Period

The maximum period of funding for the UG3 phase is one year and the maximum period of funding of the UH3 phase is four years, for a total of five years for the entire UG3/UH3 award. 

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

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

Other

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

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

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

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

Required Registrations

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.

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

Key Personnel of the NIH HCS Research Collaboratory Coordinating Center must not be named as key personnel on applications submitted in response to this FOA.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

Letter of Intent

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

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

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

The letter of intent should be sent to:

Martina Schmidt, PhD
Chief, Office of Scientific Review
National Center for Complementary and Integrative Health
Telephone: 301-594-3456
Email: SchmidMa@mail.nih.gov

Page Limitations

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

For this specific FOA, the Research Strategy section is limited to 30 pages, divided between the UG3 and UH3 phases of the project.

Instructions for Application Submission

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

Biosketches should reflect the PD(s)/PI(s) and key personnel's expertise in design and conduct of large-scale clinical or implementation trials within multiple HCS including using electronic health records for recruitment and outcomes assessment. The experience of the investigative team with successful recruitment and retention of participants should be described.

R&R Budget

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

Budgets for both phases (UG3/UH3) must be included; the UH3 budget will undergo reassessment during the UG3 planning phase.

Application budgets must include a minimum effort for the PD/PI of 2.4 person months to the project. If a project includes multiple PDs/PIs, the total annual PD/PI effort must be at least 2.4 person months.

Application must be an appropriate mix of time allocated for senior and junior scientists to ensure the successful conduct of the study. Budgeted effort of other personnel must be appropriate to the needs of the project.

The budget must include personnel at all partnering HCS with expertise relevant to the project, which might include electronic health record IT specialists, clinical investigators and staff with expertise in the administrative aspects of clinical trials oversight.

Applications should budget for study personnel to participate in each of the Work Groups.

Applications must budget to travel several key persons (at a minimum the project PD(s)/PI(s), program manager/coordinator, lead biostatistician and/or research methodologist) to attend two separate, one and a half day meetings of the HCS Research Collaboratory program steering committee in the first year and an annual meeting in subsequent years in the Bethesda MD area. Travel for additional meeting (s) in the Planning Phase may be required. 

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

To clearly distinguish between the two phases, applicants should specify separate UG3 and UH3 information in each subsection (Specific Aims and Research Strategy) of the PHS 398 Research Plan as appropriate. Activities in both phases will depend on the specific study (e.g. disease domains, type of interventions, experimental design, randomization strategy and proposed outcome measures).

In preparing the application, investigators should consider the fact that applications will be assigned a single impact score for both UG3 and UH3 phases.

Specific Aims: Applicants should address the scientific questions to be answered, what specifically will be done during the proposed funding periods and the impact of addressing the research question on public health. Specific aims should be scientifically appropriate for the distinct phases of the project. Include separate aims, within the designated page limit, for both the UG3 and UG3 phase, and clearly label them as UG3 specific aims and UH3 specific aims.

Research Strategy: Within the Research Strategy, applicants should first describe the UG3 Phase and then the UH3 Phase. The Research Strategy section should have a clear demarcation of the UG3 and UH3 phases of the application. It is not necessary to repeat background information or details of methods in the UH3 portion that were provided in the UG3 portion. The UH3 Phase must be described in sufficient detail to permit reviewers to assess significance and innovation of the proposed work and the strength of the experimental design. Address how the research question serves the goals of the overall Collaboratory program and addresses a major public health issue. Applications should describe details for the proposed pragmatic trial including projections for recruitment, attrition and effect size estimations.  Investigators are encouraged to describe how the approaches, measures, design and outcomes proposed are pragmatic.

The application should describe the health care system partners and the investigative team's experience conducting pragmatic trials within health care systems. In general, all studies must use at least three HCS for trial conduct, unless a specific rationale for limiting this aspect of the project is provided, which must be identified in the application. The application must provide a rationale for the HCS selected for the Project and provide a description of the infrastructure and expertise to implement the proposed pragmatic trial within all proposed HCS.

Both the UG3 and the UH3 phases of the Research Strategy must have a section of proposed milestones, which should be well described, quantifiable, and scientifically justified to allow an assessment of progress. For UG3 milestones, applicants should delineate what they propose to achieve in order to proceed to the UH3 phase. The milestones should also include a timeline, a discussion of the suitability of the milestones for assessing success in the UG3 Phase, and a discussion of the implications of successful completion of these milestones for the proposed UH3 Phase. Annual milestones for the Project trial conduct phase (UH3) should also be included in the application, although it is understood that timelines and milestones for conduct of the trial in the UH3 phase that are proposed in the application will evolve as activities in the UG3 phase progress, if an Award is made.

Collaboratory Work Groups are open to participation by individuals from all funded Projects, the CCC, and the NIH. Applicants should describe how project personnel would participate in the Collaboratory Work Groups (Electronic Health Records, Regulatory /Ethics, Biostatistics & Study Design, Health Provider-Systems Interactions, Stakeholder Engagement, Phenotype & Data Standards, and Patient Reported Outcomes). https://www.nihcollaboratory.org/cores/Pages/default.aspx.

Applicants must describe their willingness to comply with policies, guidelines and practices developed by the Work Groups, and to work with the CCC in providing relevant information and materials.

Applicants must not propose work that duplicates efforts already funded or underway. Although novel theoretical approaches and methodologies may be needed,  when possible applicants should leverage, adopt or adapt resources from ongoing NIH-supported efforts in informatics as well as other national efforts including but not limited to the many federal investments in the HMO Research Network, the CTSAs, REDCap, PROMIS, NIH Toolbox, PhenX Toolkit including the SDOH Collection, Health Care Innovation Awards, DEcIDE, eMERGE, other networks, CERTs, SHARP, Vaccine Safety Datalink, the Sentinel Initiative.

Applicants should address how they will adhere to the NIH Policy on Good Clinical Practice Training. This policy establishes the expectation that all NIH-funded investigators and staff who are involved in the conduct, oversight, or management of clinical trials should be trained in Good Clinical Practice (GCP), consistent with principles of the International Conference on Harmonisation (ICH) E6 (R2). 

The principles of GCP help assure the safety, integrity, and quality of clinical trials. This Policy applies to NIH-funded investigators and clinical trial site staff who are responsible for the conduct, management and oversight of NIH-funded clinical trials (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-148.html

Letters of Support: Applications must include a strong letter of support from each of the HCS partners that relates their commitment to the proposed research and outlines how the project fits with organizational priorities, the quality of the proposed EHR and data systems and the commitment of their IT staff to the project. The letter must provide a description of how the project would directly impact delivery of healthcare within their organization and indicate level of intention to sustain the intervention(s) based upon results. The application is expected to include letters from the officials responsible for intellectual property issues at the applicant institutions (including sub-contractor institutions) stating that the institution supports and agrees to abide by the Resources and Data Sharing Plan and the Software Sharing Plan put forth in the application. These letters should be clear expressions of commitment consistent with achieving the goals of the program.

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

The following modifications also apply:

  • Applicants must provide a description of the resources that will be made broadly available including policies, practices, materials, and tools to facilitate collaboration, reuse, and replication of the project. Describe any plans to disseminate toolkits or other resources developed for the pragmatic or implementation trial. Applications must provide descriptions of how privacy and confidentiality will be maintained.  The plan must include a description of how data will be shared to allow for transparency and reproducibility of study findings (e.g. access to data, data enclave, or data repository).

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

  • No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Section 2 - Study Population Characteristics

2.4 Inclusion of Women and Minorities

Describe strategies for outreach to minorities and women.

2.5 Recruitment and Retention Plan

Describe the following: 1) the planned recruitment methods, including use of contact lists (participants and/or sites), databases or other pre-screening resources, advertisements, outreach, media / social media and referral networks or groups; 2) if there are known participant or study-related barriers to accrual or participation (based on literature or prior experience), please list these barriers and describe plans to address them to optimize success; 3) contingency plans for participant accrual if enrollment significantly lags behind accrual benchmarks; 4) participant retention and adherence strategies; and 5) possible competition from other trials for study participants.

Applicants must provide strong evidence of the availability of appropriate institutional resources, and suitable patient populations, providers, clinics, or facilities (depending on unit of randomization. Documentation of availability of eligible participants, clinic sites, or unites of randomization, presented in tabular format must be provided. The application must include relevant information that addresses the feasibility of recruiting participants who are eligible for the pragmatic or implementation trial. Specifically, applicants must provide evidence that each recruiting center in the trial has access to a sufficient number of participants who meet the eligibility criteria as defined in the submitted protocol. For multisite applications, information must be provided for each participating site.

2.7 Study Timeline
Include a table or graph of the overall study timeline. This is expected to be a visual representation (such as a Gantt chart) of core milestones and key project management activities. A narrative is not expected in this section.

The study timeline should include core milestones that need to be met throughout the lifecycle of the clinical trial (to include both the UG3 and UH3 phases) to ensure its success, and the subtasks that will be used to reach the milestones. In the timeline, the study duration is expected to be displayed in months. The timeline should include, but is not limited to, the following:

(a) When the study opens to enrollment
(b) When core milestones (see below) are met
(c) What subtasks are needed to reach the core milestones
(d) When final transfer of the data will occur
(e) When analysis of the study data will occur
(f) When the primary study manuscript will be submitted for publication

Section 3 - Protection and Monitoring Plans

3.3 Data and Safety Monitoring Plan

In addition to the NIH application requirements for data and safety monitoring for clinical trials, applicants should refer to NIH’s policy on data and safety monitoring (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html).

Section 4 - Protocol Synopsis

4.1.a. Detailed Description
Describe the protocol to be followed in each arm of the trial. Include a brief description of how the trial will standardize the intervention and whether there are any plans to intervene to improve adherence to the intervention at the sites. Specify concomitant interventions, if applicable. Describe the proposed experimental design, including a discussion of the clinical trial design and the rationale for the particular design chosen (pragmatic, explanatory, cluster-randomized, adaptive, etc.).

4.7 Dissemination Plan
Describe how the investigators will facilitate and support timely publication and dissemination of results and developed tools as appropriate and consistent with achieving the goals of the program. .

Section 5 - Other Clinical Trial-related Attachments

5.1 Other Clinical Trial-related Attachments

The following attachments must be included as a part of the cooperative agreement application. Attachments permit expansion of certain elements that cannot be appropriately described in the Research Strategy. All attachments listed below must be provided or the application will not be peer reviewed.

1. Clinical Trial Experience

Applicants must provide a detailed table listing the characteristics of trials that demonstrate Key Personnel experience in trial coordination in the last 5 years. The table must be provided as an attachment called "Clinical Trial Experience.pdf", appended with 1, 2, 3, etc. as needed, and must not exceed 3 pages.

The table columns should include:

  • Clinical trial title

  • Applicant's role in the trial

  • A brief description of the trial design

  • Planned enrollment

  • Actual enrollment

  • Number of sites

  • Whether the trial(s) was/were completed on schedule or not

  • Publication reference(s)

2. Milestone Plan

A Milestone Plan must be provided as an attachment called "Milestone Plan.pdf" and must not exceed five pages.

The milestones should be well described, quantifiable, and scientifically justified to allow an assessment of progress. For UG3 milestones, applicants should delineate what they propose to achieve in order to proceed to the UH3 phase. The milestones should also include a timeline, a discussion of the suitability of the milestones for assessing success in the UG3 Phase, and a discussion of the implications of successful completion of these milestones for the proposed UH3 Phase. Annual milestones for the Project trial conduct phase (UH3) should also be included in the application, although it is understood that timelines and milestones for conduct of the trial in the UH3 phase that are proposed in the application will evolve as activities in the UG3 phase progress, if an Award is made.

All applicants must use the following definition of a milestone in their application: a scheduled event in the project timeline that signifies the completion of a major project stage or activity. Milestones must be relevant, achievable, and measurable. Milestones should address overall recruitment and retention goals. The Terms and Conditions under this FOA will include a milestone plan that is mutually agreed upon by the investigators and NIH.

Delayed Onset Study

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

PHS Assignment Request Form

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential 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 NCCIH Referral Office by email at schmidma@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Post Submission Materials

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

All post-submission materials must be received by the Scientific Review Officer (SRO) no later than 30 calendar days prior to the peer review meeting. In addition to the NIH policy allowed post-submission materials in NOT-OD-19-083, the follow post-submission materials are allowed:

  • Updated Clinical Trial Experience Table (e.g. due to updated enrollment numbers, publication of trial results, or newly started clinical trials)
  • Updated Milestone Plan (e.g. due to the hiring, replacement, or loss of an investigator; change to health care systems participating in the trial; or change in electronic health record or IT infrastructure)

Section V. Application Review Information

1. Criteria

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

For this particular announcement, note the following: This FOA includes Additional Review Criteria on Milestones, which require comment by reviewers and which are to be considered when determining the overall impact score.

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.

Overall Impact

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

Scored Review Criteria

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

 

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?
 

Specific to this FOA:

Will this project develop effective methods at the health care system level to address a clinical issue of significance? For studies that integrate an intervention into health care delivery, how strong is the evidence of efficacy or effectiveness for the intervention? For studies that propose to improve adherence to established guidelines, how strong is the evidence for the guidelines that are being used? Is the proposed pragmatic trial or implementation trial addressing a major public health issue? Does the application provide a compelling rationale regarding howpotential outcomes will provide clinically meaningful information to stakeholders? Is there a strong likelihood that the UG3 planning activities and subsequent trial conduct in the UH3 phase achieve significant advances in the ability to perform large-scale pragmatic clinical trials or implementation research?

 

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?

In addition, for applications involving clinical trials

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

Specific to this FOA:

Do interdisciplinary teams include ?

 

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

In addition, for applications involving clinical trials

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

Specific to this FOA:

Does the application in a HCS environment? Does the application include mechanisms for leveraging novel collaboration and study oversight strategies?

 

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?

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

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

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

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

Specific to this FOA:

Will proposed planning activities (including plans for identifying a sufficiently large target patient population), allow for implementing the Project? Are the projections for recruitment, ongoing engagement, attrition and effect size estimations based on data in the proposed HCS or similar settings? Is the degree of pragmatic aspects of the approaches, measures, design and outcomes well justified for the design elements of the proposed study? Will the results provide relevant information and adequate data for others potentially adopting the intervention into HCS settings to determine applicability? Will rigorous controls be included in the design? Will broad but adequate eligibility criteria be used, as proposed? Can interventions be easily implemented? Has the application sufficiently described the approaches proposed to overcome barriers to research in the HCS setting? Are the goals of the UG3 phase reasonable and if accomplished will they provide the basis for the proposed UH3 phase?

Does the resource sharing plan sufficiently describe what tools, polices, materials, or other trial resources will be made broadly available as well as how they will be disseminated? Does the data sharing plan describe how data will be shared and how privacy and confidentiality will be maintained?

 

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?

In addition, for applications involving clinical trials

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

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

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

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

Specific to this FOA:

Does the application provide sufficient rationale for the HCS (s) selected for the Project? Is commitment from the HCS to the project evident? Has/have the HCS (s) successfully conducted clinical studies, such that there are sufficient infrastructure and expertise (e.g. clinical investigators, informaticists) to implement the proposed pragmatic or implementation trial within all proposed HCSs?

Additional Review Criteria

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

 

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.

 

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

 

Not Applicable.

 

Not Applicable.

 

Milestones

Are the steps and milestones clearly defined? Are the milestones feasible, well developed and quantifiable with regard to specific goals and accomplishments? Are adequate criteria provided for the UG3 phase that will be utilized in determining milestone completion before proceeding to the next phase of the project? Are the UH3 milestones appropriate for the next phase of the project?

Additional Review Considerations

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

 

Reviewers will assess 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 assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

 

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

 

 

Not Applicable.

 

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).

 

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

2. Review and Selection Process

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

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

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

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:
  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

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

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

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

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

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

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

2. Administrative and National Policy Requirements

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

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

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

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

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

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

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

  • Overseeing the overall budget, activities and performance of the Project. The institution must obtain appropriate prior approval for any change in PI effort.
  • Accepting the participatory and cooperative nature of the collaborative research process and complying with policies and practices developed by the NIH HCS Research Collaboratory governing structure.
  • Sharing data, resources and software according to the approved sharing policies for the NIH HCS Research Collaboratory program.
  • Participating in all meetings of the HCS Research Collaboratory Steering Committee. Identifying study team members with relevant expertise to participate in program-wide Work Groups and sub-committees (as appropriate).
  • Cooperating with the NIH HCS Research Collaboratory Steering Committee, Collaboratory Coordinating Center, research partners, and NIH staff in the design and conduct of protocols, analysis of data, and reporting of results of research.
  • Agreeing to accept close coordination, cooperation and management of the project with NIH, including those outlined below under "NIH Responsibilities."
  • Submitting materials to the NIH Program Director, Coordinating Center, and/or Steering Committee as requested. This will include regular reports of accomplishments and roadblocks, conference and meeting summaries, and other reports as requested.
  • Materials submitted will meet all subject and formatting requirements.
  • Recipients will submit a detailed transition request for the UH3 Project trial conduct phase, outlining UG3 progress, how negotiated UG3 Milestones have been met, as well as detailed plans, budget and annual milestones for the UH3 trial conduct phase. Note that, funding of the UG3 project planning phase cooperative agreement does not guarantee support of the UH3 Project trial conduct phase.
  • Any of the above function may be performed by the applicant organization or by subcontract to the applicant organization.
  • Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

  • The NIH Project Scientist will work with the PD(s)/PI(s) and the Steering Committee to ensure the objectives of the program are being met. The primary responsibility for the program resides with the recipient, although specific tasks and activities will be shared among the awardee and the NIH Project Scientist.
  • NIH staff will interact with the PD(s)/PI(s) on a regular basis to monitor progress. Monitoring may include: regular communication with the PD(s)/PI(S) and his/her staff, periodic site visits for discussion with the recipients’ research team, observation of field data collection and management techniques, fiscal reviews, and other relevant stewardship activities.
  • The NIH reserves the right to terminate or curtail the award (or an individual component of the award) in the event of inadequate progress or data reporting.
  • Additional NIH staff may participate in all Work Groups, implementation teams and committees, including the Steering Committee, as appropriate. NIH may designate staff from other federal agencies to participate, if advantageous to facilitate the activities of the program.
  • NIH staff will act as a resource and facilitator for activities of the with non-NIH HCS researchers and other NIH, DHHS, or other federally-sponsored research networks that may be relevant to this effort.
  • NIH staff will provide input, expert advice, and suggestions in the design, development, and coordination of the infrastructure development and implementation efforts.
  • NIH staff will report periodically on progress of the program to the NIH Common Fund Executive Committee and interested IC Directors.
  • NIH staff will conduct an administrative review of the UH3 transition request to determine whether the Project will transition to UH3 funding and be implemented. Criteria for transition to the UH3 phase used in the NIH administrative review include: successful achievement of the UG3 milestones, potential for successfully meeting the UH3 trial conduct phase plans and milestones, demonstrated ability of the team to work within the consortium arrangement, and the availability of funds.
  • Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

  • Ensuring that NIH HCS sites and investigators as well as NIH and other research partners fully comply with federal regulatory requirements. This includes, but is not limited to those relating to human subjects’ protections, informed consent, and reporting of adverse events.
  • Jointly developing appropriate confidentiality procedures for data collection, processing, storage and analysis to ensure the confidentiality of data on individual health care provider organization patients, health care providers and other institutions involved in any Collaboratory research projects.
  • Participating in the HCS Research Collaboratory Steering Committee to address issues that span all projects, provide input into the policies and processes of the HCS Research Collaboratory, and assist in dissemination of policies and processes that enable research in partnership with health care systems, their patients, and practitioners. At a minimum, the Steering Committee will be composed of one representative from each of the Projects, one representative from each Work Group, one representative from the CCC, the NIH Program Coordinator, and representatives from various NIH ICs and the Common Fund. The combined vote of NIH membership may never exceed 1/3 of the total committee membership.
  • Participating in the HCS Research Collaboratory Work Groups that have been established as the core collaborative activity of this program. The Work Groups provide a forum for discussion of challenges and solutions across projects; harmonized and standardized policies and processes will be vetted in these groups. Work Groups have been established in the following areas: Electronic Health Records, Regulatory /Ethics, Biostatistics & Study Design, Health Provider-Systems Interactions, Stakeholder Engagement, Phenotype & Data Standards, and Patient Reported Outcomes (http://www.rethinkingclinicaltrials.org/cores-and-working-groups/). Additional Work Groups may be identified as the HCS Research Collaboratory expands with new projects. Work Groups are open to participation by individuals from all funded Projects, the CCC, and the NIH.
  • Recipients will work with other Collaboratory investigators and NIH to identify common clinical outcome measures (such as measures of quality of life, physical function, pain or fatigue). NIH and CCC staff will work with the Principal Investigators to facilitate this aspect of Projects.
  • Establishing and adherence by each Project Team (Project grantee, CCC grantee, and NIH staff) to a written plan of engagement, with timelines, to ensure timely delivery of the tested implementation plan.
  • Working together with the CCC through all phases of the projects, including the trial conduct and close out, to assure all resources, materials, protocols, data, best practices, program policies, and lessons learned, as well as software or sets of code, are disseminated broadly through the CCC, to inform researchers and health care systems engaged in research in health care settings.

Dispute Resolution:

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

3. Reporting

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

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

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

In accordance with the regulatory requirements provided at 45 CFR 75.113 and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 and 2 CFR Part 200 – Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

Application Submission Contacts

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

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

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

Scientific/Research Contact(s)

Wendy Weber, ND, PhD, MPH
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-402-1272
Email: weberwj@mail.nih.gov

Marcel Salive, MD, MPH
National Institute on Aging (NIA)
Telephone: 301-496-6761
Email: marcel.salive@nih.gov

Jeri L. Miller, Ph.D.
National Institute of Nursing Research (NINR)
Telephone: 301-594-6152
Email: jmiller@mail.nih.gov

  Elizabeth L Neilson, PhD, MPH, MSN
Office of Disease Prevention (ODP)
Telephone: 301-827-5578
Email: Elizabeth.Neilson@nih.gov
  Lawrence J Fine
National Heart, Lung, And Blood Institute (NHLBI)
Phone: 301-435-0305
E-mail: Lawrence.Fine@NIH.gov
 

Marcel Salive, M.D.
National Institute on Aging (NIA)
Phone: 301-496-6761
Email: marcel.salive@nih.gov
 

Charles H Washabaugh, PhD
National Institute Of Arthritis And Musculoskeletal And Skin Diseases (NIAMS)
Phone: 301-496-9568
E-mail: washabac@mail.nih.gov
 

Larissa Aviles-Santa, MD, MPH
National Institute on Minority Health and Health Disparities (NIMHD)
Phone: 301-827-6924
E-mail: avilessantal@mail.nih.gov
 

Peer Review Contact(s)

Martina Schmidt, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3456
Email: schmidma@mail.nih.gov

Financial/Grants Management Contact(s)

Shelley Carow
National Center for Complementary and Integrative Health
Telephone: 301-594-3788
Email: CarowS@MAIL.NIH.GOV

Lesa McQueen
National Institute on Aging (NIA)
Phone: 301-496-1472
Email: mcqueenl@mail.nih.gov
 

Erik Edgerton
National Institute Of Arthritis And Musculoskeletal And Skin Diseases (NIAMS)
Phone: 301-594-7760
E-mail: erik.edgerton@nih.gov

Priscilla Grant, JD
National Institute on Minority Health and Health Disparities (NIMHD)
Phone: 301-594-8412
E-mail: pg38h@nih.gov
 

Section VIII. Other Information

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

Authority and Regulations

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

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