It is critical that applicants follow 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 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

Since 2001, more than 2.5 million U.S. troops have been deployed for Operation New Dawn, Operations Enduring Freedom (OEF) in Afghanistan and Iraqi Freedom (OIF) in Iraq. The all-volunteer military experienced multiple redeployments to the war zone, extensive use of the reserve components of the military and National Guard, that also involved the deployment of women and parents of young children. Many of these deployed service members sustained severe injuries that in previous wars would have resulted in death. Significant and continuing improvements in outer tactical vests (body armor) and helmets saved lives. However, despite these improvements, many service members returning from these operations, and from other military operations, experienced pain, traumatic brain injuries (TBIs), symptoms of post-traumatic stress disorder (PTSD), suicidal thoughts or behaviors, substance abuse, and/or related comorbidities. Studies report nearly 45% of soldiers and 50% of veterans experience pain on a regular basis and there is significant overlap between chronic pain, PTSD, and persistent post-concussive symptoms. There is an ongoing problem with pain among military and veteran populations and an incomplete evidence base for effective pain management. Opioid medications are often prescribed for the treatment of chronic pain, but chronic use is associated with the potential for misuse, abuse and dependence and often fails to adequately control pain. As a result, there is a need for non-pharmacological approaches to complement pharmacological strategies for pain management and to reduce the needs and hazards of excessive reliance on opioids.

The NIH, DoD, and VA have been working individually and collaboratively to develop and improve pain management approaches for military personnel, veterans and their families by adopting changes in clinical protocols and implementing research initiatives. Some of these efforts include: 1) increasing availability of non-pharmacological approaches for pain management in some VA and DOD medical facilities; 2) DoD funding of studies on comparative effectiveness of integrative approaches for chronic pain and co-morbid conditions, 3) VA funding of studies examining the efficacy of yoga therapy for chronic pain, including low back pain, and for PTSD, 4) funding of the Defense and Veterans Center for Integrative Pain Management, and 5) a 2014 NIH-VA joint funding initiative resulting in the support of 13 research projects focused on the development and testing of non-pharmacological approaches to pain management.

In a separate but related effort, the 2010 Patient Protection and Affordable Care Act required the Department of Health and Human Services (HHS) to enlist the Institute of Medicine (IOM) in examining pain as a public health problem. In June, 2011, the Institute of Medicine (IOM) released a Consensus Report on "Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research". (http://iom.edu/Reports/2011/Relieving-Pain-in-America-A-Blueprint-for-Transforming-Prevention-Care-Education-Research.aspx) The report notes that chronic pain affects an estimated 116 million American adults more than the total affected by heart disease, cancer, and diabetes combined. Pain also costs the nation up to $635 billion each year in medical treatment and lost productivity. The report notes that ideally, most patients with severe persistent pain would obtain pain care from an interdisciplinary team using an integrated approach that would target multiple dimensions of the chronic pain experience - including disease management, reduction in pain severity, and improved functioning, emotional well-being and health-related quality of life.

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), other U.S. Department of Health and Human Services agencies, the DoD, and the VA. The increased adoption of health information technology tools contributes to the increased feasibility for researchers, in partnership with health care delivery organizations, to conduct studies in real world settings with large numbers of participants.

Although there is a recognized and compelling need for research to identify effective complementary non-pharmacological approaches for pain management and comorbid conditions in military and veteran populations, many challenges exist. Ethical and regulatory issues must be addressed to perform research in health care delivery settings. Health care providers focus on providing the best treatment, based on current knowledge, whereas research typically focuses on studying which treatments work best in a precisely defined population. Further, research studies have frequently used endpoints that are not part of routine patient assessments or care, and may propose interventions that are challenging to implement in many health care delivery settings. Bridging the gap between research and practice is an important step in the direction of providing increased benefits to the patients. Education and engagement of providers and patients on the value of research in health care settings is urgently needed. This NIH-DoD-VA Pain Management Collaboratory will create a broad framework to address and overcome these challenges.

The overall goal of this initiative, jointly supported by the NIH, DoD, and VA, is to develop the capacity to implement cost-effective large-scale clinical research in military and veteran health care delivery organizations focusing on non-pharmacological approaches to pain management and other comorbid conditions. Types of non-pharmacological approaches to study could include, but are not limited to, mindfulness/meditative (e.g., mindfulness based stress reduction, meditation), and movement (e.g. structured exercise, tai chi, yoga) interventions, manual (e.g. spinal manipulation, massage, acupuncture) therapies, neuromodulation (e.g., electrical stimulation), and psychological and behavioral interventions (e.g., cognitive behavioral therapy), or an integrative approach that involves more than one intervention. Of special interest are integrated models of multi-modal care that are delivered in different settings (e.g. pain care that could include collaborative care, care management, care delivered through tele-care, peer-coaches, or informal caregivers etc.)

The NIH-DoD-VA Pain Management Collaboratory Program, will:

• establish a Coordinating Center to provide leadership and technical expertise in all aspects of research supporting the design and execution of high impact demonstration projects on non-pharmacological approaches for pain management and other comorbid conditions;
• support the design and execution of a set of high-impact Demonstration Projects that will conduct pragmatic clinical trials on non-pharmacological approaches to pain management and comorbidities with patients in health care delivery systems that provide care to military personnel, veterans and their families;
• make data, tools, best practices, and resources from these and other projects available to facilitate a research partnership with health care delivery systems that provide care to military personnel, veterans and their families.

The purpose of this FOA is to solicit UG3/UH3 phased cooperative agreement research applications to conduct efficient, large-scale pragmatic clinical trials Demonstration Projects within the NIH-DoD-VA Pain Management Collaboratory on non-pharmacological approaches to pain management and other co-morbid conditions in U.S. military personnel, veterans and their families. 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, in contrast with explanatory trials which are primarily designed to determine the effects of an intervention under ideal circumstances (http://www.cmaj.ca/cgi/content/full/180/10/E47). The NIH-DoD-VA Pain Management Collaboratory is well-suited to measuring both the negative and positive health impacts, as well as resource implications, for treatments delivered in real world settings.

Demonstration Projects will be expected to provide innovative approaches to address and overcome important barriers to conduct pragmatic clinical trials on non-pharmacological approaches to pain management and comorbid conditions. Military and veteran health care systems (HCS) and other HCS that provide services to military personnel, veterans and their families are eligible to participate in this program (e.g., research conducted in partnership with eligible VA and DoD health care providers is essential for obtaining meaningful and relevant research results in real world health care delivery systems serving this population). Ultimately, it is expected that successful approaches and best practices established through this initiative will have a major impact on clinical research and, importantly, care for military and veteran populations.

Demonstration Projects on non- pharmacological approaches for pain management and comorbid conditions in settings serving military personnel, veterans and their families will be selected based on the (1) importance of the scientific questions and (2) potential to address impediments to research with health care delivery organizations. Demonstration Projects will utilize a phased award UG3/UH3 mechanism, with a planning (UG3) and an implementation (UH3) phase. All projects will be milestone-driven, and moving to the implementation phase (UH3) will be dependent upon the successful progress made during the planning phase (UG3).

The NIH-DoD-VA Pain Management Collaboratory program encourages sharing of study data resources including policies, practices, materials, and tools to facilitate collaboration, reuse, and replication. Thus the NIH-DoD-VA Pain Management Collaboratory program expects awardees to implement a Resources and Data Sharing Plan consistent with achieving these program goals. In addition, the NIH-DoD-VA Pain Management 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, thus, awardees and their sub-contractors are expected to implement a Software Sharing Plan consistent with achieving the goals of this program. Also of special interest are sharable manuals or clinical tools that can be used in different clinical systems. Adequate descriptions of interventions with replicability are important in this context.

A separate Coordinating Center solicited under RFA-AT-17-002 will be responsible for providing support to UG3 projects. Coordinating functions with the Center for the second (UH3) phase will be developed and negotiated separately following successful completion of the UG3 phase. All pragmatic trial Demonstration Projects funded through this FOA will work in cooperation with the Pain Management Collaboratory Coordinating Center to 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.

This FOA solicits applications for UG3/UH3 Demonstration Projects under a cooperative agreement for large-scale pragmatic trials to be implemented through health care systems serving military personnel, veterans and their families. All Demonstration Projects should address a question important to the health of U.S. military personnel, veterans and their families that is focused on non-pharmacological approaches to pain management or comorbid conditions. The Demonstration Project may provide a definitive test of the underlying question or provide the ground work needed for a larger or longer study to address the research hypothesis.

The pragmatic trials should meet the following criteria specified, which are also described in http://www.cmaj.ca/content/180/10/E47.full. The pragmatic trial should test an intervention, or compare interventions (e.g., treatments, preventive actions, policies or organizational changes) that are robust, apply broadly to patient populations and are suitable for use in health systems serving military personnel, veterans and their families, with the broad goal of determining whether the intervention improves health and adds value to the utilization of health care resources.

The question should be of major public health importance focusing on non-pharmacological approaches to pain management and comorbid conditions in military personnel, veterans and their families and one that will engage partnership with health care delivery systems providing services to this population. Types of non-pharmacological approaches to study could include, but are not limited to, mindfulness/meditative (e.g., mindfulness based stress reduction, meditation), and movement (e.g. structured exercise, tai chi, yoga) interventions, manual (e.g. spinal manipulation, massage, acupuncture) therapies, neuromodulation (e.g., electrical stimulation), and psychological and behavioral interventions (e.g., cognitive behavioral therapy), or an integrative approach that involves more than one intervention. Of special interest are integrated models of multi-modal care that are delivered in different settings (e.g. pain care that could include collaborative care, care management, care delivered through tele-care, peer-coaches, or informal caregivers etc.)

Primary outcomes of interest could include assessing pain, pain reduction, and pain interference; ability to function in daily life; quality of life; and medication usage/discontinuation (e.g., opioid medications). Secondary outcomes focusing on assessing comorbid conditions or conditions co-occurring with high frequency in this population are also of interest under the FOA. There is also interest in obtaining objective sensor based measures that provide data on people’s daily activities, to gain a better understanding of the relationship between ratings of pain with functional changes. Pilot testing of the objective measures may be accomplished as part of the UG3 planning phase.

The chosen intervention(s) should be able to be reliably delivered by clinical providers and/or health care systems serving military personnel, veterans and their families.

The intervention should be reasonably simple with standards that do not require a complex structure for implementation or monitoring. System level interventions may be particularly suitable for study. The trial should exploit integrated health care systems available to military personnel, veterans and their families and the use of primary endpoint events that can be captured easily during routine care (e.g., use of data from electronic health records requiring minimal adjudication).

The trial design should incorporate rigorous controls, prospectively identified, preferably by randomization. Novel randomization approaches, such as cluster or timing of implementation (e.g., stepped wedge design) may be proposed. 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 to the overall study design. The design chosen should strive to maximize external validity, by testing generalizability of the intervention(s) across distinct health care settings, with diverse staff and patient populations.

The trial should enroll patients based on broad eligibility criteria to maximize diversity, with minimum exclusions on risk, age, health literacy, comorbidities, or expected adherence. It is important to include women, and the comparison of men and women, into these new pragmatic clinical trials for active military service members, Veterans, and their families. Where possible include subgroups based on gender and ethnicities in analytic plans.

As in routine practice, the pragmatic trial should allow for interventions to be implemented with maximal flexibility and by all appropriate practitioners (not just those with exceptional levels of training or competence whenever possible). The study should address, and describe how to overcome, barriers to research in the HCS setting serving military personnel, veterans and their families. Partnerships with health care delivery organizations servicing this population will be critical in implementing this work.

It is anticipated that the Demonstration Projects will generally be performed within large health care systems that utilize electronic health records to leverage data collection that occurs in health care delivery rather than requiring independent research data collection. The HCSs partnership must be able to facilitate access to all data sources relevant to the project, which may include inpatient, outpatient, clinical laboratory and pharmacy data. Applicants, who may be from academic institutions or other organizations, must have demonstrated success in conducting clinical research in partnerships with HCSs serving military or veterans. Interdisciplinary teams should include necessary expertise to conduct the trial such as military researchers on military-focused applications and VA researchers on veteran-focused applications. Demonstration Project applicants will need to include and involve appropriate personnel, from health care systems servicing these populations, and be able to document the commitment of the health care organization to the project.

These projects will be funded as phased awards with a two-year planning phase (UG3) and the 2-4 year implementation phase (UH3). The UH3 budget will undergo reassessment during the UG3 planning phase. Activities in both phases will depend on the specific study (e.g. type of intervention, randomization strategy and proposed outcome measures).

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

• Identify project staff who will participate in Work Groups of the NIH-DoD-VA Pain Management Collaboratory (see Additional Information below), which will develop policies and practices to be implemented across Collaboratory projects
• Work with the NIH-DoD-VA Pain Management Collaboratory to comply with approved policies and practices for electronic data access extraction and sharing, and develop quality control methods and tools. This could include developing and validating all electronic data methods and tools within the HCSs needed for the Demonstration Project (e.g. EHRs, electronic methods for patient identification and outcomes assessment, biospecimens, images, genomic data, family history, data abstraction and survey instruments) and complete quality control testing at all sites.
• Assess adequacy and finalize clinically relevant outcome measures.
• Identify additional implementation sites, if needed, in consultation with the NIH, DoD, and VA, and the Pain Management Collaboratory Coordinating Center.
• Review of analytic plans and power calculations with biostatistics/design workgroup to optimize design.
• Develop detailed plans for site implementation, including determining need and role of site staff, method of identification, participant recruitment and acquisition, randomization (as applicable) and administration/implementation of the intervention, if applicable.
• Address all ethical, human subject safety and oversight issues for the Demonstration Project, including development of informed consent documents or opt-out consent, if applicable, and finalizing site of IRB review including use of a centralized IRB for trial oversight, if possible, and other requirements needed for implementing a study in a veteran or military facility.
• Address all potential regulatory elements of the proposed trial (if applicable).
• Develop a detailed budget for conducting and completing the Demonstration Project, including preparation of a final study report.
• Develop detailed plans for data coordination and quality control.

Demonstration Project Implementation Phase (UH3): The objective of the 2-4 year UH3 implementation phase is to actually conduct the Demonstration Project within the NIH-DoD-VA Pain Management Collaboratory, in accordance with activities planned in the UG3 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 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.
• Each project is to provide all data coordination for the implementation of the trial.

Effective prevention and treatment of mental illness have the potential to reduce morbidity and mortality associated with intentional injury (i.e., suicide attempts and deaths, see: www.suicide-research-agenda.org). Lack of attention to the assessment of these outcomes has limited our understanding regarding the degree to which effective mental health interventions might offer prophylaxis. Accordingly, where feasible and appropriate, this FOA encourages the consideration of the NIMH recommendation that effectiveness research include assessment of suicidal behavior in order to advance understanding of how effective prevention and treatment of mental disorders might impact suicide relevant outcomes.

Applicants should propose a pragmatic trial to address one or more critical research questions important for improved pain management for U.S. military personnel, veterans, and their families. The following list provides examples of some of the potential research questions that might be addressed by such pragmatic trials:

• Studies to test the effect of system level innovations to improve implementation of established guidelines for non-pharmacological approaches to pain management and comorbid conditions;
• Studies focusing on testing the timing, optimum components and overall benefit of an individualized integrated package of non-pharmacologic modalities such as exercise, mind-body therapies and other complementary health approaches;
• Evaluation of team-based versus provider-driven models of health care delivery particularly in settings in which military personnel or Veterans normally receive care; evaluation of other factors critical to optimize pain care in primary care settings;
• Evaluation of sex and gender differences important for optimizing treatment;
• Assessment of the effectiveness of integrative pain management strategies to reduce the transition from acute to chronic pain, for example in the peri-operative period;
• Assessment of the impact of provision of quantifiable patient-provided outcome systems on pain and function;
• Assessment of integrative pain management approaches and strategies to be implemented in outpatient transitions of care from DoD to VA;
• Comparative effectiveness studies of different combinations of non-opioid pain management treatments for chronic pain: for example, studies might explore the use of electrical stimulation as an add-on to conventional pharmacological approaches;
• Studies evaluating the impact of concurrent management of alcohol use and dependence on pain outcomes or of improved pain management on alcohol use;
• Studies evaluating the optimum integrative approaches to pain management in individuals with spinal cord injury, brain injury, or amputation, especially in the context of rehabilitation;
• Studies evaluating integrative approaches to chronic pain in individuals using prosthetic devices; studies to reduce overuse injury related to mobility device or prosthetic use;
• Studies evaluating the impact of behavioral approaches (e.g., CBT, motivational interviewing, meditation, aerobic exercise, balance exercises such as Tai chi, diet) to conditions that are common co-morbidities with pain such as TBI, PTSD, sleep disturbance, anxiety, and migraine;
• Studies to assess whether non-pharmacological sleep treatments (e.g. CBT or mindfulness-CBT) may improve both sleep and pain outcomes or studies to address whether treatment of sleep apnea results in improvements in chronic pain;
• Studies to identify non-pharmacologic-based best practices that can reduce pain during physical transfer of patients;
• Studies to test the value of technology-based tools for either self-monitoring or communication with providers; for example, studies could examine the value of a smart-phone application as an extension of a behavioral intervention for pain, or test the value of technology-based collaborative interactions in a primary care environment;
• Studies to assess the value of assessment of an individual s susceptibility to chronic pain (potentially through the EHR) from prior (non-military service related) episodes of acute or sub-chronic pain;
• Studies to determine the value of training of family members for example, to facilitate coping skills to reduce psychological distress in the pre- and peri-operative period.

Projects should include well-defined milestones for the planning phase (UG3) and annual milestones for the implementation 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, NIH, DoD, and VA staff and the Coordinating Center 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 Demonstration Project implementation phase. UH3 transition requests will undergo an administrative review to determine whether the Demonstration Project will be awarded the implementation phase (UH3). Prospective applicants should note that initial funding of the UG3/UH3 Phase Innovation cooperative agreement does not guarantee support of the UH3 Demonstration Project implementation 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.

Governance: The awards funded under this FOA and the companion FOAs will be cooperative agreements (see Section VI.2 Cooperative Agreement Terms and Conditions of Award). Close interaction with the NIH, DoD, and VA staff and with the Coordinating Center awardee under the Companion FOA will be required to accomplish the goals of this program.

Work Groups will be established by the Coordinating Center as the core collaborative activity of this program. The Work Groups will 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 are expected to be established in the following areas, at a minimum: Stakeholder Engagement, Ethical/Regulatory, Design/Biostatistics, Phenotype/Outcomes, Electronic Health Records, and Data Sharing. Work Groups will comprise individuals from the Demonstration Projects, the Coordinating Center, and staff from the NIH, DoD, and VA. Project personnel must be identified that would participate in Collaboratory Work Groups.

A Steering Committee will be established by the Pain Management Collaboratory Coordinating Center to address issues that span all projects, provide input into the policies and processes of the NIH-DoD-VA Pain Management Collaboratory, and assist in dissemination of policies and processes that enable research in healthcare systems, involving their patients, and practitioners. At a minimum, the Steering Committee will have one representative from each of the Demonstration Projects, one representative from each Work Group, one representative from the Coordinating Center, Program Officers and Project Scientists from the NIH, DoD, and VA, and representatives from various NIH ICs, DoD, and the VA. All members are expected to actively participate in all Steering Committee activities. The combined vote of NIH, DoD, and VA membership may never exceed 40 percent.

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

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 eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

• 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. 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.

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.

In order to be eligible for VA funding, all VA eligibility criteria must be met by applicants. Please refer to Handbook 1200.15(2) for full details: http://www.va.gov/vhapublications/publications.cfm?pub=2.

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.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. 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 NOT-OD-11-101).

Buttons to access the online ASSIST system or to download application forms 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.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions 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:

Martina Schmidt, Ph.D
National Center for Complementary and Integrative Health (NCCIH)
6707 Democracy Blvd.
Suite 401, MSC 5475
Bethesda, MD 20892-5475 (For FedEx, etc., use 20817)
Telephone: 301-594-3456
Email: [email protected]

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

For this specific FOA, the Research Strategy section is limited to 30 pages.

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.

Facilities and Other Resources: The application should provide sufficient rationale for the HCS(s) selected for the Demonstration Project. Applicants should provide a description of successfully conducted clinical studies within the partnering HCS, and describe the infrastructure and expertise (e.g. clinical investigators, informaticists) to implement the proposed pragmatic trial within all proposed HCSs.

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

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

Budgets for both phases (UG2/UH3) should be included; the UH3 budget will undergo reassessment during the UG3 planning phase.

Minimum effort of personnel: The PD/PI must devote a minimum level of effort of 20% annually (2.4 -person months) to the project. 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 participating NIH-DoD-VA HCS with expertise relevant to the project, which might include a health informatics expert, clinical investigators and staff with expertise in the administrative aspects of clinical trials oversight.

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

Applications must budget for project PD(s)/PI(s) travel to attend two, one-and-a-half-day NIH-DoD-VA Pain Management Collaboratory program meetings in the first year, and an annual meeting in subsequent years in the greater Washington D.C. area.

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:

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. Within in the designated page limit, include separate aims for both the UG3 and UH3 phase, and clearly label them as UG3 specific aims and UH3 specific aims.

Research Strategy: Description of the Demonstration Project should provide background on the underlying health question, and the evidence supporting the potential of the tested intervention to improve health and well-being.

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.

Applications should describe the significance of the proposed pragmatic trial to improve non-pharmacological approaches to pain management and comorbidities in U.S. military personnel, veterans and their families. In addition, the application should describe how the completion of the proposed pragmatic trial will change the concepts, methods and technologies used in large scale community-based clinical research. Beyond the success of the specific pragmatic trial proposed in the application, investigators should describe how conducting the pragmatic trial as part of the Pain Management Collaboratory will strengthen the capacity, capability and cost-effectiveness of conducting large multi-site studies using primary clinical data and samples generated within health care delivery organizations. Innovative strategies to impact current conventional approaches to trials utilizing novel approaches or methodologies for a pragmatic trial that will allow it to be successfully implemented in a DoD/VA environment should be described.

Applications should describe the expertise of the interdisciplinary teams as a whole including military researchers on military-focused applications and VA researchers on veteran-focused applications; and design and implementation of large-scale pragmatic trials within a HCS network serving military personnel, veterans, and their families (including using electronic health records for recruitment and outcomes assessment). Do not repeat information described on individual biosketches.

The application must include a thorough description of the proposed pragmatic trial including: appropriate rigorous controls; broad but adequate eligibility criteria; interventions that can be easily implemented. Investigators should describe the approaches that will be proposed to overcome barriers to conducting research in the HCS setting.

Milestones for each phase should be provided in a separate subheading at the end of the specific UG3 portion and the UH3 portion of the Research Strategy. Both the UG3 and the UH3 phases of the Research Strategy must have a section of proposed milestones, which should be well described, feasible, quantifiable, and scientifically justified to allow an assessment of progress. For UG3 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 UG3 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 UG3 phase progress, if an Award is made.

Applicants must indicate their willingness to comply with policies and practices developed by the Work Groups, and to work with the Coordinating Center in providing relevant information and material.

To increase the yield of the programs and improve comparisons between studies, as well as facilitate data sharing, multiple Institutes encourage the use of common data elements (CDEs). A plan to incorporate CDEs, where appropriate, should be included in the Approach. Examples of recommended CDEs include: NINDS: http://www.commondataelements.ninds.nih.gov/Stroke.aspx; VA, NIDA & NIMH: https://www.phenxtoolkit.org/

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. 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 expected to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

NIH, DoD, and VA considers the sharing of unique research resources developed through NIH, DoD, and VA-sponsored research an important means to enhance the value of, and advance research. If the final data/resources are not amenable to sharing, this should be explained in the proposed Sharing Plans.

The NIH-DoD-VA Pain Management Collaboratory program encourages sharing of resources with broad availability of policies, practices, materials, and tools to facilitate collaboration, reuse, and replication. In addition, the NIH-DoD-VA Pain Management 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 NIH-DoD-VA Pain Management 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.

Software Sharing Plan

The NIH-DoD-VA Pain Management 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 in the application. There is no particular software dissemination license required for this program. However, NIH, DoD, and VA 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.

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 PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

Awards considered for VA funding will be subject to VA ORD rules and regulations governing the support of scientific research and development projects. For specific information see VHA Handbook 1204.01 available at www.hsrd.research.va.gov/funding/budget-limitations.pdf.

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. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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 [email protected] 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 the policy.

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.

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 this FOA includes additional review considerations on and Resource and Data Sharing and Software Sharing, which will be considered by reviewers but will not be scored individually or influence the overall impact score. This FOA supports demonstration projects that are feasible and impactful in nature and will significantly move the overall program forward.

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.

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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 NIH-DoD-VA Pain Management Collaboratory program? How will it strengthen the capacity, capability and cost-effectiveness of conducting large multi-site studies using primary clinical data and samples generated within health care delivery organizations? Is the proposed pragmatic trial addressing a major public health issue focused on non-pharmacological approaches to pain management and comorbidities in U.S. military personnel, veterans and their families? How will the completion of the proposed pragmatic trial change the concepts, methods and technologies used in large scale community-based clinical research? Is there a strong likelihood that the UG3 planning activities and subsequent Demonstration Project implementation in the UH3 phase achieve significant advances in the ability to perform large-scale pragmatic clinical trials?

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 interdisciplinary teams include necessary expertise to conduct the trial? For example, are there military researchers included on military-focused applications and are there VA researchers included on veteran-focused applications? Do the PD(s)/PI(s) and key personnel have the necessary expertise in design and implementation of large-scale clinical studies within a HCS network serving military personnel, veterans, and their families? For example, do they have expertise in using electronic health records for recruitment and outcomes assessment?

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 impact current conventional approaches to trials by utilizing novel approaches or methodologies for a pragmatic trial that will allow it to be successfully implemented in a DoD/VA environment? Is a refinement, improvement or new strategy of approaches proposed? 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 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 children, justified in terms of the scientific goals and research strategy proposed?

Will proposed planning activities (including plans for identifying a sufficiently large target patient population), allow for implementing the Demonstration Project?

Will rigorous controls be included in the design? Will broad but adequate eligibility criteria be used, as proposed? Can interventions be easily implemented? How will the approaches proposed 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?

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 rationale for the HCS (s) selected for the Demonstration Project? 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 trial within all proposed HCSs?

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 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?

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.

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 children 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.

Not Applicable

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Not Applicable

Not Applicable

Not Applicable

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.

Not Applicable

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; (3) Genomic Data Sharing Plan (GDS) and (4) Software Sharing Plan.

How strong are the letters from the officials responsible for intellectual property issues at the applicant institutions (including sub-contractor institutions) regarding stating that the institutional supports and agrees to abide by compliance with the Resources and Data Sharing Plan and the Software Sharing Plan?

Is sharing of manuals and clinical tools across different institutions feasible and appropriate?

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.

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by 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.

Following receipt of applications agency representatives (NCCIH, other NIH ICs, DoD OASD(HA), and VA) will make decisions regarding mission relevance of applications. Following the initial peer review, decisions will be made regarding assignment of applications to agencies (NCCIH, other NIH ICs, DoD OASD(HA), and VA ORD) for funding. Applications recommended for funding will receive a second level of review by the appropriate NIH National Advisory Council or Board, DoD OASD Joint Program Committee-8, and/or VA ORD. 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.
• Policies consistent with goals for resources and data sharing and sharing of software.
• Willingness of PD(s)PI(s) to collaborate with the NIH, DoD, and VA and with other investigative groups participating in the program.
• Complementarity to and synergy with other funded projects.
• Program staff and advisors will also consider the adequacy of the proposed Resources and Data Sharing Plan as one criterion for award.
• Program staff and advisors will consider the adequacy of the proposed Software Sharing Plan as one of the criteria for award.

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 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 . Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council for Complementary and Integrative Health. 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.
• Willingness of PD(s)/PI(s) to collaborate with the NIH, DoD, and VA.
• There are additional requirements that will need to be adhered to prior to award of applications selected for funding by the Department of Defense (DoD), Office of the Assistant Secretary of Defense for Health Affairs (OASD(HA) (http://www.usamraa.army.mil/pages/pdf/General_Guidelines_for_Awards_Funded_by_the_DoD.pdf) (See Section VI.1)
• Awards considered for VA funding will be subject to VA ORD rules and regulations the support of scientific research and development projects. For specific information see VHA Handbook 1204.01 available at www.hsrd.research.va.gov/funding/budget-limitations.pdf.
• For VA awardees, ORD (or the appropriate service) will provide notification of approval to the principal investigator's VA Medical Center.

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.

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 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.

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

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

VA Specific Information

Awards considered for VA funding will be subject to VA ORD rules and regulations governing the support of scientific research and development projects. For specific information see VHA Handbook 1204.01 available at www.hsrd.research.va.gov/funding/budget-limitations.pdf

If the application is under consideration for VA funding, the VA will request "just-in-time" information from the applicant. For details, applicants may refer to the VAHSRD website http://www.hsrd.research.va.gov/funding/ .

For VA awardees, the HSRD will provide notification of approval to the principal investigator's VA Medical Center.

There are additional requirements that will need to be adhered to prior to award for those applications chosen to be funded by the Department of Defense (DoD), Office of the Assistant Secretary of Defense for Health Affairs (OASD/HA); please see website (http://www.usamraa.army.mil/pages/pdf/General_Guidelines_for_Awards_Funded_by_the_DoD.pdf) for "General Guidelines for Awards Funded by the Department of Defense.

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.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

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 Part 75, 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 agency (NIH, DoD, or VA, depending upon the funder) programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH, DoD, or VA (depending upon the funder) 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, DoD, or VA, 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) is (are) expected to participate in all meetings of the NIH-DoD-VA Pain Management Collaboratory Steering Committee as a voting member. In addition, the PD(s)/PI(s) will identify study team members with relevant expertise that will participate in program-wide Work Groups and sub-committees.
• The PD(s)/PI(s) is (are) expected to cooperate with the NIH-DoD-VA Pain Management Collaboratory Steering Committee, research partners, and NIH/VA/DoD staff in the design and conduct of protocols, analysis of data, and reporting of results of research undertaken by the Pain Management Collaboratory Coordinating Center on behalf of the program.
• The PD(s)/PI(s) will agree to accept the participatory and cooperative nature of the collaborative research process, and will comply with policies and practices developed by the NIH-DoD-VA Pain Management Collaboratory Work Groups, and to work with the Coordinating Center in providing relevant information and materials.
• The PD(s)/PI(s) is expected to participate in all meetings of the NIH-DoD-VA Pain Management Collaboratory with appropriate staff. The PD(s)/PI(s) compile(s) for the Steering Committee and NIH, DoD, and VA Program Directors regular reports of accomplishments and roadblocks, as well as conference and meeting summaries, CC performance reports, and other reports as needed and requested.
• Awardees will support additional subcommittees, task forces, and advisory panels as needed.
• Any of the above functions may be performed by the applicant organization or by subcontract to the applicant organization.
• Sharing data, resources and software according to the approved sharing policies for the NIH-DoD-VA Pain Management Collaboratory program.
• Agreeing to accept close coordination, cooperation and management of the project with NIH, DoD, and VA, including those outlined under "NIH, DoD, and VA Responsibilities"
• Submitting periodic progress reports, including materials for the In Progress Review (IPR) in a standard format, as agreed upon by the Steering Committee, and the NIH, DoD, and VA.
• 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, DoD, and VA policies and achieving the goals of this program.
• 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, DoD, and VA (depending upon the funder) staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• The NIH, DoD, and VA Program Official and Project Scientists 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, DoD, and VA Project Scientists.
• Additional NIH, DoD, and VA staff may participate in all Work Groups, implementation teams and committees, including the Steering Committee, as appropriate. Participation by staff from other federal agencies may also be appropriate and advantageous to facilitate the activities of the program.
• The NIH, DoD, and VA 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.
• NIH, DoD, and VA staff will act as a resource and facilitator for activities of the awardee with non-HCS researchers and other NIH, DoD, VA, DHHS, or other federally-sponsored research networks that may be relevant to this effort.
• NIH, DoD, and VA staff will provide input, expert advice, and suggestions in the design, development, and coordination of the infrastructure development and implementation efforts, and the domain development and research projects.
• NIH, DoD, and VA 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 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 matters.
• An agency program official or IC program director will be responsible for the normal programmatic stewardship of the award and will be named in the award notice. Additionally, an agency project scientist will be responsible for the scientific stewardship of the cooperative agreement award and will be named in the award notice.

Areas of Joint Responsibility include:

• The PD(s)/PI(s) provide, in concert with the NIH, DoD, and VA staff, support necessary to ensure that HCS sites and investigators, and NIH, DoD, VA and other research partners fully comply with federal regulatory requirements, including but not limited to those relating to human subjects protections, informed consent, and reporting of adverse events.
• Awardees and NIH, DoD and VA will jointly develop 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 NIH-DoD-VA Pain Management Collaboratory research projects.
• The PD(s)/PI(s) agrees to the governance through a Steering Committee. An NIH-DoD-VA Pain Management Collaboratory Steering Committee will be established to address issues that span all projects, provide input into the policies and processes of the NIH-DoD-VA Pain Management Collaboratory, and assist in dissemination of policies and processes that enable research in partnership with health care systems, their patients, and practitioners that provide care for military personnel, veterans and their families. 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 Coordinating Center; the NIH, DoD, and VA Program Officials and Project Scientists for each of the awards in the program; and representatives from various NIH ICs, the DoD, and VA. All members are expected to actively participate in all Steering Committee activities. The combined vote of NIH, DoD, and VA membership may never exceed 40 percent.
• NIH-DoD-VA Pain Management Collaboratory Work Groups will be established as the core collaborative activity of this program. The Work Groups will 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 are expected to be established in the following areas, at a minimum: Stakeholder Engagement, Ethical/Regulatory, Study Design/Biostatistics, Phenotype/Outcomes, Electronic Health Records, and Data Sharing. Work Groups will be chaired by Coordinating Center staff and open to participation by individuals from all funded Demonstration Projects, the Coordinating Center, and the NIH, DoD, and VA.
• Establishment and adherence by each Demonstration Project Team (Demonstration Project grantee, Coordinating Center grantee, and NIH, DoD, and VA staff) to a written plan of engagement, with timelines, to ensure timely delivery of the tested implementation plan.
• Demonstration Project grantees will work with the Coordinating Center and NIH, DoD, and VA through all phase of their projects, including the implementation and close out phase, to assure all resources, materials, protocols, data, best practices, and lessons learned, as well as software or sets of code, are disseminated broadly through the Coordinating Center with all NIH-DoD-VA Pain Management Collaboratory program resources.
• All awardees and NIH, DoD, and VA will cooperate to ensure the timely and broad dissemination of all NIH-DoD-VA Pain Management Collaboratory program endorsed policies and practices and lessons learned in the program, 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 Research Performance Progress Report (RPPR) annually 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.

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, 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)

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

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Eve E. Reider, Ph.D.
National Center for Complementary & Integrative Health (NCCIH)
Telephone: 301-443-8374
Email: [email protected]

Ranjana Banerjea, MBA, Ph.D.
Department of Veterans Affairs Office of Research & Development
Telephone: 202-595-4708
Email: [email protected]

Smita Bhonsale, Ph.D.
Pain Management USAMRMC Clinical and Rehabilitative Medicine Research Program
Telephone: 301-619-8930
Email: [email protected]

Ronald Hoover, Ph.D.
U.S. Army Medical Research & Materiel Command-Military Operational Medicine Research Program (USAMRMC-MOMRP)
Telephone: 301-619-6602
Email: [email protected]

Will M. Aklin, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-1428
Email: [email protected]

Michael L. Oshinsky, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301 496 9964
Email: [email protected]

Mark Egli, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-594-6382
Email: [email protected]

Alison Cernich, Ph.D., ABPP-Cn
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-496-0295
Email: [email protected]

Lisa Begg, Dr.P.H., R.N.
Office of Research on Women’s Health (ORWH)
Telephone: 301-496-3975
Email: [email protected]

Martha Matocha, PhD
National Institute of Nursing Research (NINR)
Telephone: 301-594-2775
Email: [email protected]

Martina Schmidt, Ph.D.
National Center for Complementary & Integrative Health (NCCIH)
Telephone: 301-594-3456
Email: [email protected]

Shelley Carow
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3788
Email: [email protected]

Tijuanna E. DeCoster, Ph.D., MPA
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: [email protected]

Pamela G. Fleming
National Institute on Drug Abuse (NIDA)
Telephone: 301-253-8729
[email protected]

Judy S. Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: [email protected]

Bryan Clark, M.B.A.
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Telephone: 301-435-6975
Email: [email protected]

Judy Sint
National Institute of Nursing Research (NINR)
Telephone: 301-402-6959
Email: [email protected]

Faith A. Booker, MPH
Office of Research & Development, Department of Veterans Affairs
Telephone: 202-443-5714
Email: [email protected]

Dave Ruane
United States Army Medical Research Acquisition Activity (USAMRAA)
Telephone:301-619-1156
Email: [email protected]

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 Part 75.