Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	This Funding Opportunity Announcement (FOA) is developed as a Common Fund initiative (http://commonfund.nih.gov/) through the NIH Office of the NIH Director, Office of Strategic Coordination (http://dpcpsi.nih.gov/osc/). The FOA will be administered by the National Center for Complementary and Alternative Medicine (NCCAM), (http://nccam.nih.gov/) on behalf of the NIH Office of Strategic Coordination (Common Fund)
Funding Opportunity Title	NIH Health Care Systems Research Collaboratory - Demonstration Projects for Pragmatic Clinical Trials Focusing on Multiple Chronic Conditions (UH2/UH3)
Activity Code	UH2/UH3 Phase Innovation Awards Cooperative Agreement
Announcement Type	New
Related Notices	August 23, 2013 - See Notice NOT-RM-13-024. The purpose of this notice is to inform the research community that a technical assistance videocast will be conducted. August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications.
Funding Opportunity Announcement (FOA) Number	RFA-RM-13-012
Companion Funding Opportunity	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.310
Funding Opportunity Purpose	The purpose of this FOA is to solicit applications for UH2/UH3 cooperative agreements for Demonstration Projects for efficient, large-scale pragmatic clinical trials focused on management of patients with multiple chronic conditions. Trials must be conducted across two or more health care systems (HCS) and must be conducted as part of the NIH HCS Research Collaboratory supported through the NIH Common Fund (see https://commonfund.nih.gov/hcscollaboratory). Awards made through this FOA will initially support a one-year milestone-driven planning phase (UH2), with possible rapid transition to the implementation phase (UH3) for a pragmatic trial Demonstration Project. UH3s will be awarded after administrative review of eligible UH2s that have met the scientific milestone and feasibility requirements necessary for the UH3 implementation phase, depending on the availability of funds. The UH2/UH3 application must be submitted as a single application, and applicants should note specific instructions for each phase in this FOA. The overall goal of the NIH HCS Research Collaboratory program is to strengthen the national capacity to implement cost-effective, large-scale research studies that engage health care delivery organizations as research partners. 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. After awards are made by NIH, the CCC (https://www.nihcollaboratory.org/Pages/default.aspx) will work with successful awardees from this FOA to facilitate the planning and rapid execution of high impact Demonstration Projects that conduct research studies in partnerships with health care delivery systems, ultimately making available data, tools and resources from Collaboratory research projects to develop a broadened base of research partnerships with HCS. This FOA extends the current Collaboratory program to address the critical need for pragmatic research on the management of multiple chronic conditions.

Posted Date	August 7, 2013
Open Date (Earliest Submission Date)	November 2, 2013
Letter of Intent Due Date(s)	November 2, 2013
Application Due Date(s)	December 2, 2013, by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
AIDS Application Due Date(s)	December 2, 2013, by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
Scientific Merit Review	March-April 2014
Advisory Council Review	May 2014
Earliest Start Date	July 2014
Expiration Date	December 3, 2013
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the 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.

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

This initiative is funded through the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for transformation of research processes.

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 (https://www.nihcollaboratory.org/Pages/default.aspx) that is providing national leadership and technical expertise. The CCC will work with successful awardees from this FOA to facilitate the planning and rapid execution of high impact Demonstration Projects that conduct research studies in partnerships with health care delivery systems, ultimately making 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 research, not to support a defined health care research network. Demonstration Projects will be expected to provide innovative approaches to address and overcome important barriers to research in the setting of HCS partnerships. HCS have interest in participating in studies that may potentially impact the care they deliver, including pragmatic clinical trials (http://www.cmaj.ca/cgi/content/full/180/10/E47), longitudinal cohort studies, population-based studies and studies addressing the incorporation of new technologies into 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 for research partnerships with health care systems should have a major impact on clinical research in the US (see http://commonfund.nih.gov/hcscollaboratory/).

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. Equally, the potential to conduct research studies in real world settings on large numbers of participants allows questions to be addressed that researchers could not feasibly address with paper records. In the last two decades, health care delivery organizations have played valuable roles in a number of research projects and health surveillance activities funded by NIH institutes and centers (ICs) and by other U.S. Department of Health and Human Services agencies including the Agency for Healthcare Research and Quality, the Centers for Disease Control and Prevention, and the Food and Drug Administration, as well as the Veterans Health Administration. However, although most scientific work has utilized health data, until recently, many studies have not required active engagement of patients or their practitioners as research participants or researchers.

Although the importance for biomedical research and strengthened partnerships with organizations that deliver health care 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 health care systems in understandable ways are not trivial. Research studies have frequently used endpoints that are not part of the normal evaluation of patients during a routine visit and interventions that are impractical in most care delivery settings. 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 care in all people, but especially in patients with multiple chronic conditions, who pose special management challenges for clinicians and whose presence in research has not been optimal. The NIH HCS Research Collaboratory program has created a broad framework to tackle some of these major challenges.

The purpose of this FOA is to solicit applications for UH2/UH3 cooperative agreements for Demonstration Projects for efficient, large-scale pragmatic clinical trials focused on the management of multiple chronic conditions, to be conducted as part of the NIH HCS Research Collaboratory. We define pragmatic trials as trials 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.cmaj.ca/cgi/content/full/180/10/E47). The Collaboratory is well-suited to measuring both the negative and positive health impacts, as well as resource implications, of treatments delivered in real world settings.

The NIH HCS Research Collaboratory Program initiated the first set of seven UH2/UH3 Pragmatic Clinical Trial Demonstration Projects in distinct disease areas in 2012 (https://www.nihcollaboratory.org/Pages/default.aspx). Demonstration Projects for this FOA will use the same cooperative agreement mechanism, with a planning (UH2) and an implementation (UH3) phase. The CCC and NIH have worked with the awarded UH2/UH3 Collaboratory Pragmatic Clinical Trial Demonstration Projects to 1) develop, adapt, and adopt technical guidelines and best practices for the effective conduct of research studies in partnership with health care systems; 2) work collaboratively with each Demonstration Project team, including their partnering HCS, to develop and test an implementation plan for the proposed Demonstration Projects while providing technical, design, and coordination guidance; and 3) disseminate widely Collaboratory endorsed policies, practices and lessons learned in the Demonstration Projects to inform best practices for broad participation of HCS and their patients, practitioners, and staff in research studies to improve health and care delivery. The CCC also serves as the central resource for the activities of the HCS Research Collaboratory program, including providing administrative support for the Steering Committee and its Work Groups and subcommittees. This FOA will utilize resources and experiences of the Collaboratory, and will focus on projects that address managing patients with multiple chronic conditions.

During the UH2 phase the Demonstration Project team, in cooperation with the CCC and NIH, will develop detailed plans for site implementation, determine resource needs, test data extraction methods for patient identification and outcome assessment, and develop plans for all aspects of ethical and regulatory oversight and protection of human subjects (e.g., collect feasibility or pilot data). The CCC and Collaboratory Work Groups will provide pragmatic trial expertise and guidance to help finalize plans for implementation for the UH2 phase of these awards, which will generally be one year in duration. All projects will be milestone-driven, and all planning grants will need to meet all milestones to have an opportunity to move to the implementation phase (UH3), if sufficient funds are available.

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 Demonstration Projects in a timely manner with appropriate privacy and confidentiality protections. Thus the HCS Research Collaboratory program expects grantees to implement a Resources and Data Sharing Plan consistent with achieving these program goals. In addition, the HCS Research Collaboratory program encourages sharing of software and code that are developed or modified to accomplish aims of this program. This may include, but is not limited to, software, tools, or code sets for extraction or definition of data from the EHR, clinical systems, and other health care data systems; implementation of new workflows for research studies; analytic and analysis programs; and tools for incorporation of patient input (such as the NIH PROMIS tool, http://www.nihpromis.org). While software development is not the primary goal of this program, it is expected that software or sets of code may be developed under this program, thus, grantees and their sub-contractors are expected to implement a Software Sharing Plan consistent with achieving the goals of this program.

Multiple chronic conditions afflict a growing proportion of the US population (http://www.hhs.gov/ash/initiatives/mcc/mcc_framework.pdf). Recent estimates suggest that approximately one in 15 children and three out of four adults over the age of 65 years are affected by two or more chronic medical conditions (http://www.rwjf.org/en/research-publications/find-rwjf-research/2010/02/chronic-care.html). The prevalence of chronic conditions increases with age, and it is apparent that as patients develop more chronic conditions, they are more likely to use healthcare services and suffer outcomes such as unnecessary hospitalizations, adverse drug reactions, declining functional status and mortality (http://www.hhs.gov/ash/initiatives/mcc/mcc_framework.pdf). In view of its significant impact on the US population, in 2010 the Department of Health and Human Services released Multiple Chronic Conditions: A Strategic Framework and outlined strategies for addressing health needs of affected patients (http://www.hhs.gov/ash/initiatives/mcc/mcc_framework.pdf). Data analyses from national surveys and systems have identified prevalent combinations of chronic conditions among persons who are hospitalized or visit ambulatory care settings (http://www.cdc.gov/pcd/issues/2013/13_0104.htm). Methods for readily identifying chronic disease clusters and developing coordinated care management strategies are among the goals outlined in the Framework. Disparities in access to health care can also negatively impact health outcomes for patients with multiple chronic conditions. Although modern clinical research methods have identified many interventions that successfully treat or manage chronic conditions, much more evidence regarding how interventions, self-management support and care can be coordinated for patients that suffer from many such chronic conditions is needed.

This FOA solicits applications for UH2/UH3 Phased Innovation cooperative agreements for Demonstration Projects for large-scale pragmatic trials to be implemented through HCS. All Demonstration Projects must address a question important for the management of multiple chronic health conditions. Chronic conditions are defined as health conditions that last a year or more and require ongoing medical attention and/or limit activities of daily living (http://www.hhs.gov/ash/initiatives/mcc/mcc_framework.pdf). For this FOA, common chronic health conditions include diseases, chronic symptoms (e.g. chronic pain) as well as chronic functional impairment (e.g. disability). In view of the incidence of three or more such chronic conditions affecting adults in the general population, Demonstration Projects focusing on the management of three or more chronic conditions in adults are particularly encouraged (see Section I.3, Research Areas). Applications that focus on two chronic conditions in adults must provide a specific justification for the study that describes critical gaps in knowledge regarding the management of the proposed conditions. For applications focusing on pediatric patients, Demonstration Projects must propose studying two or more chronic health conditions. In some cases the proposed Demonstration Project may provide a definitive test of the underlying research question. In other cases, it may provide the groundwork for a larger or longer study needed for definitive data to address the research question.

The proposed pragmatic trials must meet the following criteria:

• The pragmatic trial 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 of patients with multiple chronic conditions, and adds value to the utilization of the nation’s health care resources.
• The question must be of major public health importance that focuses on prevention, diagnosis, treatment or management of patients with multiple chronic medical conditions and one that engages partnership with multiple 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 or device, it must be a legally-marketed drug or medical device in the US.
• The intervention(s) must be reasonably simple and not require a complex structure for implementation or monitoring. System level interventions may be particularly suitable.
• The trial must leverage opportunities made available by the nature of integrated health care systems; for example, the use of primary endpoint events that can be captured by passive follow-up such as by EHR, and with minimal need for adjudication.
• The trial 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 should provide comparable rigor. The design should also 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 trial must enroll patients based on broad eligibility criteria to maximize diversity, and minimize intentional or unintentional exclusions based on risk, age, health literacy, demographics, or expected adherence.
• 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 trial outcome measure(s) must be clinically meaningful and important to stakeholders including patients and policy makers and should include measures that capture the effects of the interventions on patients coexisting conditions and global measures of function and quality of life. Additional outcome measures such as use of health care services 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 must address, and potentially overcome, important barriers to research in the setting of HCS partnerships.

Partnerships with health care delivery organizations will be critical in implementing this work. It is anticipated that the Demonstration 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. The applicant must identify at least two HCS as partners for the proposed Demonstration Project, and document the commitment of the organization to the project.

During the UH2 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://www.nihcollaboratory.org/cores/Pages/default.aspx), which will develop guidelines and practices to be implemented across Collaboratory 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 Demonstration Project (e.g. EHR, 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. Applicants must indicate 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.
• Assess adequacy and finalize clinically relevant outcome measures with other Collaboratory investigators. It is anticipated that successful applicants will work with other Collaboratory investigators and NIH to identify common outcome measures (such as measures of quality of life, physical function, pain or fatigue). If an award is made, NIH and CCC staff will work with the Program Directors/Principal Investigators to facilitate this aspect across Demonstration Projects.
• 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.
• Identify additional implementation sites, if needed, in consultation with the NIH and the CCC. All studies must use at least two HCS for implementation, which must be identified in the application.
• 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 Demonstration Project, including development of informed consent documents or opt-out consent if applicable, and finalizing site of IRB review. Applicants must propose a consolidated or centralized IRB approach for trial oversight, to facilitate both appropriate and timely study implementation.
• Address all potential regulatory elements of the proposed trial (if applicable).
• Develop a detailed budget for conduct and completion of the Demonstration Project, including preparation of a final study report.
• Finalize detailed plans for data coordination and quality control for the UH3 phase. It is not anticipated that the CCC will provide these functions for individual Demonstration Projects. Data coordinating activities for individual Demonstration Projects must be separately budgeted as part of the UH3 budget.

The objective of the two to four year UH3 implementation phase is to actually conduct the Demonstration Project within the NIH HCS Research Collaboratory, in accordance with activities planned in the UH2 phase. Implementation activities will depend upon the study, but in general the following goals should be achieved:

• Each Demonstration Project is expected to implement all aspects of the proposed pragmatic trial including the identification and recruitment of proposed sample sizes of patients, practice sites, and clinicians, the execution of the intervention and its implementation, 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 to provide detailed and definitive testing of the validity of methods used for monitoring and outcome assessment.

Applications must propose projects that address prevention, treatment and/or care management for patients with multiple chronic health conditions, and must include the rationale for proposed conditions, targeted patient populations and clinical settings. The rationale must include quantitative information from the project HCS partners, and provide information on the proposed conditions within the HCS and importance/implications of addressing the research question.

Examples of potential research questions that could be addressed by Demonstration Projects include, but are not limited to:

• Studies to test the effect of system level innovations to adapt or improve integration of established guidelines or interventions, for which there is evidence, to treat patients multiple chronic conditions and to optimize self- management and outcomes in patients with three or more chronic conditions. Such projects may include assessing ways to coordinate care for symptom management, discontinuing or not initiating specific therapy, monitoring patient adherence and optimizing patient or family outcomes based on goal attainment. Projects that address maximizing the flexibility of integrated approaches to address multiple disease or symptom clusters are encouraged.
• Pragmatic trials that test external validity, generalizability and context sensitivity of interventions for chronic conditions with established efficacy from trials of well-defined patient populations. Such trials could assess whether these interventions can be more broadly applied to the general patient population with three or more chronic conditions.
• Studies to test the impact of new approaches to managing multiple chronic conditions in priority populations, under- or un-insured patient groups, the dual Medicaid/Medicare recipient populations, or pediatric populations with multiple chronic conditions transitioning to adult care.
• Studies to compare beneficial and adverse outcomes from differing management strategies for specific combinations or conditions posing management or HCS challenges, such as (but not limited to):
  • multiple diabetes complications (i.e. retinopathy, kidney disease, vascular disease, gastroparesis) in association with a malignancy and depression
  • diabetes mellitus, in association with chronic obstructive pulmonary disease and hypertension
  • chronic infectious disease (i.e. hepatitis C or human immunodeficiency virus infection) in association with substance use disorder and a mental disorder (i.e. depression, schizophrenia or anxiety)
  • chronic low back pain, sleep apnea and a mental disorder
  • congestive heart failure with osteoarthritis and conditions that contraindicate use of beta blockers and/or angiotensin converting enzyme inhibitors
  • cognitive impairment, in association with movement disorders, chronic pulmonary disease, GI tract dysfunction and/or cardiac disorders

The application must propose a well-defined set of milestones for the planning phase (UH2) and annual milestones for the implementation phase (UH3). It is understood that the proposed milestones for the UH3 phase will be revised as activities during the UH2 planning phase. In the event of an award, the Program Director/Principal Investigator and NIH staff will negotiate a list of milestones for each year of support.

At the completion of the UH2 planning phase, the applicant will be required to submit a detailed transition request for the UH3 Demonstration Project implementation phase. UH3 transition requests will undergo an administrative review to determine whether the milestones have been met. It is anticipated that not all funded UH2 projects will transition to the UH3 phase.

Prospective applicants should note that funding of UH2/UH3 Phased Innovation cooperative agreement does not guarantee support of the UH3 Demonstration Project implementation phase. Transition to the UH3 phase of the project will occur only if an administrative review process recommends that the UH2 planning activities have been successful, the Demonstration Project can proceed with confidence of success, and if funds are available.

• 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.An HCS Research Collaboratory 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 Research Collaboratory, and assist in dissemination of policies and processes that enable research in partnership with healthcare systems, their patients, and practitioners. The Steering Committee is composed of one representative from each of the Demonstration 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. All members are expected to actively participate in all Steering Committee activities. The combined vote of NIH membership may never exceed 40 percent.
• NIH oversight of the HCS Research Collaboratory activities will include establishing an External Advisory Panel (EAP) to review the progress of all components of this program, and to make recommendations to the NIH. The EAP will provide recommendations to the NIH Common Fund for the continuation or termination of the program, including options for sustainability, if continuation is recommended.

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.
Application Types Allowed	New The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	NIH Common Fund intends to commit $2.5 million in FY 2014 to fund up to 3 UH2 (planning phase) Demonstration Project awards and $14 million in FY 2015-18 for up to 2 subsequent UH3 (implementation phase) Demonstration Projects, contingent upon receiving scientifically meritorious applications. Additional awards may be supported if additional funds are available.
Award Budget	The application budget for the one-year UH2 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 entire UH2/UH3 application is five years.

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

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)

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)
• 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

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

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

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• 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) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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 and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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

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

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

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

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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:

Dale Birkle Dreer, PH.D.
Telephone: 301-451-6570
Fax: 301-480-2419
Email: birkled@mail.nih.gov

All page limitations described in the SF424 Application Guide and must be followed, with the following exceptions or additional requirements:

• For this specific FOA, the Research Strategy section is limited to 30 pages, divided between the UH2 and UH3 phases of the project.

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

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.

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

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

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

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

NIH Health Care Systems Research Collaboratory Coordinating Center investigators must not be named as personnel on applications submitted in response to this FOA.

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

Budgets for bothUH2 and UH3 phases must be included in the application; the UH3 budget will undergo reassessment during the UH2 planning phase.

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

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

NIH HCS Research Collaboratory Pragmatic Trial Demonstration Projects will be funded as phased awards with a one-year planning phase (UH2) and a two to four year implementation phase (UH3). For the application, the UH2/UH3 must be submitted as a single application and should be clearly organized into two phases: UH2 (Planning Phase) and UH3 (Implementation Phase). To clearly distinguish between the two phases, applicants should specify separate UH2 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).

Description of the Demonstration Project must provide background on the underlying health question(s), and the evidence supporting the potential of the proposed intervention(s) to improve health and well-being (see Section I.3, Research Areas).

In preparing applications, applicants should note the following:

• Applicants must not propose work that duplicates efforts already funded or underway. When possible, applicants should adopt or adapt resources of 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, Health Care Innovation Awards, DEcIDE, eMERGE, other networks, CERTs, SHARP, Vaccine Safety Datalink, the Sentinel Initiative.
• Applications must include a strong letter of support from each of the HCS partners that describes their commitment to the proposed research and outlines how the project fits with organizational priorities; the capability of the proposed EHR and data systems; and the commitment of their IT staff and resources to the project. The letters must also 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.
• Scientific Collaboration: Applications must budget to travel several key persons (at a minimum the project PD(s)/PI(s), program manager/coordinator, lead informaticist, lead biostatistician and 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. Based on project needs, interdisciplinary team members (persons with backgrounds in environmental health sciences, health policy, economics, and social and behavioral sciences, and, if applicable, PDs/PIs of main research projects and site PDs/PIs/coordinators), must also travel to NIH HCS Research Collaboratory program meetings. Minimum effort of personnel: The PD/PI must devote a minimum level of effort of 20% annually (2.4 calendar months) to the project. If a project includes multiple PD s/PI s, the total annual PD/PI effort must be at least 20%. There 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 informaticists, clinical investigators and staff with expertise in the administrative aspects of clinical trials oversight.
• 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 Provider-Systems Interactions, Stakeholder Engagement, Phenotype & Data Standards, and Patient Reported Outcomes (https://www.nihcollaboratory.org/cores/Pages/default.aspx). 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 Demonstration Projects, the CCC, and the NIH. Applicants should describe how project personnel would participate in the Collaboratory Work Groups and budget for their participation.

In preparing the application, investigators should consider the fact that applications will be assigned a single impact score for both UH2 and UH3 phases. Thus, clarity and completeness of the application with regard to specific goals and the feasibility of milestones are critical.

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 for both the UH2 and UH2 phase, and clearly label them as UH2 specific aims and UH3 specific aims. Each specific aims section is limited to one page. The specific aims for the UH2 phase must be uploaded as the Specific Aims attachment. The specific aims for the UH3 phase must be the first page of that section of the Research Strategy.

Research Strategy: Within the Research Strategy, applicants should first describe the UH2 Phase and then the UH3 Phase. The Research Strategy section should have a clear demarcation of the UH2 and UH3 portions of the application. It is not necessary to repeat background information or details of methods in the UH3 portion that were provided in the UH2 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 Collaboratory program. Clearly describe the rationale for the proposed multiple chronic conditions.

Both the UH2 and the UH3 portions of the Research Strategy must have a separate section of proposed milestones, which should be well described, quantifiable, and scientifically justified to allow an assessment of progress. For UH2 milestones, applicants should delineate what they aim 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 UH2 Phase, and a discussion of the implications of successful completion of these milestones for the proposed UH3 Phase. Annual milestones for the Demonstration Project implementation (UH3) phase should also be included, although it is understood that timelines and milestones for implementation in the UH3 phase that are proposed in the application will evolve as activities in the UH2 phase progress, if an Award is made.

The Research Strategy section is limited to 30 pages.

Letters of Support: Applications must include letters of support from the HCS partners that relate 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. At least two HCS partners must be proposed for the Demonstration Project. The letters must provide a description of how the project would directly impact delivery of healthcare within their organization. The letters must also relate a willingness to adopt and implement the proposed Resources and Data Sharing Plan and Software Sharing Plan.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modifications:

Resources and Data Sharing Plan: 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 Demonstration Projects in a timely manner with appropriate privacy and confidentiality protections to facilitate further research, reuse of data, and replication. Thus the HCS Research Collaboratory program expects grantees to implement a Resources and Data Sharing Plan consistent with achieving these program goals.

A Resources and Data Sharing Plan is expected to be included in the application. The initial review group will comment on the appropriateness and adequacy of the proposed Resources and Data Sharing Plan. These comments will be factored into the determination of the overall score. Program staff and advisors will also consider the adequacy of the proposed plan as one criterion for award. The proposed Resources and Data Sharing Plan, after negotiation with the applicant when necessary, will be made a condition of award. Evaluation of the annual non-competing progress reports will include assessment of the responsiveness to the Resources and Data Sharing Plan included in the Notice of Award.

Software Sharing Plan: The HCS Research Collaboratory program encourages sharing of software and code that are developed or modified to accomplish aims of this program. This may include, but is not limited to, software, tools, or code sets for extraction or definition of data from EHRs, clinical systems, and other health care data systems; implementation of new workflows for research studies; analytic and analysis programs; and tools for incorporation of patient input. While software development is not the primary goal of this program, it is expected that software or sets of code may be developed under this program by the Coordinating Center or the Demonstration Projects, thus, grantees and their sub-contractors are expected to implement a Software Sharing Plan consistent with achieving the goals of this program.

A Software Sharing Plan, with appropriate timelines, is expected to be included in the application. There is no particular software dissemination license required for this program. However, NIH does have goals for software sharing and reviewers will be instructed to evaluate the sharing plan relative to the following goals:

• The software should be freely available to biomedical researchers, health care delivery systems, research institutions, and government health care systems and researchers.
• The terms should also permit the dissemination and commercialization of enhanced or customized versions of the software, or incorporation of the software or components of it into other software packages.
• The terms of software availability should include the ability of individuals outside the applicant institution and its collaborating organizations to modify the source code and to share modifications with other colleagues.

The review group will comment on the appropriateness and adequacy of the proposed Software Sharing Plan to meet the goals of the NIH in this program and factor their review into the determination of the overall score. Program staff and advisors will also consider the adequacy of the proposed plan as one of the criteria for award. The proposed Software Sharing Plan, after negotiation with the applicant when necessary, will be made a condition of the award. Evaluation of the annual non-competing progress reports will include assessment of the responsiveness to the Software Sharing Plan included in Notice of Award.

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.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

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 by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NCCAM Review Office by email at birkled@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

This FOA includes Additional Review Criteria on Milestones and Resource and Data Sharing and Software Sharing which require comment by reviewers and which are to be considered when determining the overall impact score.

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

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Will addressing the research question realistically serve the goals of the overall Collaboratory program and strengthen the capacity, capability and cost-effectiveness of conducting large multi-site studies within health care delivery organizations? Is the proposed project a pragmatic trial addressing a major public health issue for patients with multiple chronic conditions? Does the application include a compelling rationale (with sufficient quantitative information from the partnering HCS) for the proposed multiple chronic conditions to be studied? If only two multiple conditions in adults are proposed, does the application provide sufficient justification regarding current gaps in managing the conditions? Will the completion of the proposed pragmatic trial change the concepts, methods and technologies used in large scale community-based clinical research? Will the UH2 planning activities and subsequent Demonstration Project implementation in the UH3 phase achieve significant advances in the ability to perform large-scale pragmatic clinical trials? Does it inform how HCS can work together effectively and efficiently?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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? Do the PD(s)/PI(s) and key personnel have the necessary expertise in design and implementation of large-scale clinical studies within multiple HCS, (including using the EHR for recruitment and outcomes assessment)? Do the PD(s)/PI(s) have extensive experience in performing proposed Planning Phase activities, and do they have a track record of successful recruitment and retention in prior studies, investigative collaborations or partnerships with (within) health delivery organizations in conducting clinical studies within a HCS?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Does the application challenge and seek to enhance or improvet current conventional approaches to the prevention, treatment and/or care management of multiple chronic conditions by utilizing novel approaches or methodologies for a pragmatic trial? Is the comparison condition(s) proposed informative given the state of the science in this area? Is a refinement, improvement or new strategy of approaches proposed? Does the application include mechanisms for leveraging novel collaboration and study oversight strategies?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? Are the projections for recruitment, ongoing engagement, attrition and effect size estimations based on data in the proposed HCS or similar settings? Are the approaches, measures, design and outcomes proposed pragmatic? And generalizable? Will the results provide relevant information and adequate data for other potential adopting HCS settings to determine applicability? Will proposed planning activities (including plans for identifying a sufficiently large target patient population), and proposed milestones, allow for implementing the Demonstration Project?

Environment

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? Does the application provide sufficient quantitative information and rationale for the HCS selected for the Demonstration Project? Have the HCS partners successfully conducted clinical studies, such that there are sufficient infrastructure and expertise (e.g. clinical investigators, informaticists) to implement the proposed pragmatic trial within all proposed HCS? Does the application include documentation from the HCS partner organizations that outline strong commitment to the project planning and implementation?

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.

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 UH2 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?

Resources and Data Sharing Plan

The reviewers will comment on the appropriateness and adequacy of the proposed Resources and Data Sharing Plan to meet the goals of the HCS Research Collaboratory program and factor their evaluation into the determination of the overall impact score.

Software Sharing Plan

Reviewers will evaluate the Software Sharing Plan relative to the following goals:

• The software should be freely available to biomedical researchers, health care delivery systems, research institutions, and government health care systems and researchers.
• The terms should also permit the dissemination and commercialization of enhanced or customized versions of the software, or incorporation of the software or components of it into other software packages.
• The terms of software availability should include the ability of individuals outside the applicant institution and its collaborating organizations to modify the source code and to share modifications with other colleagues.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six 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 six 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.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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).

Resource Sharing Plans

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) Genome Wide Association Studies (GWAS) .

Budget and Period of Support

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Center for Complementary and Alternative Medicine, 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:

• 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.
• Will receive a written critique.

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

Applications will be assigned 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.

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.

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

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 grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

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 awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

• Overseeing the overall budget, activities and performance of the Demonstration Project. The PD(s)/PI(s) must devote a minimum level of effort of 20% annually (2.4 calendar months) to the project. If a project includes multiple PIs, the total annual PI effort must be at least 20%. 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, Steering Committee, and/or External Advisory Panel (EAP) 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.
• Awardees will submit a detailed transition request for the UH3 Demonstration Project implementation phase, outlining UH2 progress, how negotiated UH2 Milestones have been met, as well as detailed plans, budget and annual milestones for the UH3 implementation phase. Note that, funding of the UH2 Demonstration Project planning phase cooperative agreement does not guarantee support of the UH3 Demonstration Project implementation phase.
• Any of the above function may be performed by the applicant organization or by subcontract to the applicant organization.
• Awardees 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 have 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 awardee, 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 awardees 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 awardee 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 will establish an EAP to review the progress of all components of this program, and to make recommendations to the NIH. The EAP will provide recommendations to the NIH Common Fund for the continuation or termination of the program, including options for sustainability, if continuation is recommended.
• NIH staff will conduct an administrative review of the UH3 transition request to determine whether the Demonstration 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 UH2 milestones, potential for successfully meeting the UH3 implementation 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 Demonstration 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 40 percent.
• 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 (https://www.nihcollaboratory.org/cores/Pages/default.aspx). 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 Demonstration Projects, the CCC, and the NIH.
• Awardees 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 Demonstration Projects.
• Establishing and adherence by each Demonstration Project Team (Demonstration 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 implementation 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 awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
TTY: 301-451-5936
Email: GrantsInfo@nih.gov

Catherine M. Meyers, M.D.
National Center for Complementary and Alternative Medicine (NCCAM)
Telephone: 301-443-8206
Email: meyersc@mail.nih.gov

Barbara Wells, Ph.D.
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-435-0417
Email: wellsb@nhlbi.nih.gov

Stephen Taplin MD, MPH
National Cancer Institute
Division of Cancer Control and Population Sciences
Branch Chief,
Process of Care Research Branch
Behavioral Research Program
9609 Medical Center Dr.
Rockville, MD 20850
240 276-6947
Email: taplins@mail.nih.gov

David Chambers, D. Phil.
National Institute of Mental Health (NIMH)
Telephone: 301-443-3747
Email: dchambers@mail.nih.gov

Peter Savage, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8858
Email: savagep@niddk.nih.gov

Sarah Duffy, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-6504
Email: duffys@nida.nih.gov

Clayton Huntley, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-451-2570
Email: chuntley@niaid.nih.gov

Linda L. Porter, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9964
Email: porterl@ninds.nih.gov

Danuta Krotoski, Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-496-5576
Email: krotoskd@mail.nih.gov

Sue Marden, Ph.D., R.N.
National Institute of Nursing Research (NINR)
Telephone: 301-496-9623
Email: mardens@mail.nih.gov

Dale Birkle Dreer, Ph.D.
National Center for Complementary and Alternative Medicine (NCCAM)
Telephone: 301-451-6570
Email: birkled@mail.nih.gov.

George Tucker, MBA
National Center for Complementary and Alternative Medicine (NCCAM)
Telephone: 301-594-9102
Email: tuckerg@mail.nih.gov

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.