Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

This announcement is part of the Science of Behavior Change (SOBC) initiative supported by the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress. The overall goal of the SOBC Program is to implement a mechanisms-focused, experimental medicine approach to behavior change research and to develop the tools required to implement such an approach. An experimental medicine approach involves identifying an intervention target, developing assays (measures) to permit verification of target engagement, engaging the target through experimentation or intervention, and testing the degree to which target engagement produces the desired behavior change. For the purposes of this announcement, putative intervention targets represent mechanisms or processes that are hypothesized to be malleable and to play a causal role in producing behavior change, including adherence to medical regimens. Behavior change, as defined here, includes the initiation, cessation, modification, maintenance, and/or adherence to health behaviors (e.g. diet, exercise, abstinence from substance use, behavioral regimens, treatment regimens, etc.) that have broad health implications across a wide range of clinical endpoints.

Work supported by the initial SOBC program [http://commonfund.nih.gov/behaviorchange/index] identified three domains with promising behavior change targets, given strong evidence for their central role in health behaviors relevant to multiple clinical endpoints. Each of these broad domains contains multiple putative intervention targets with a variety of existing assays (measures). The domains are:

1. Self-regulation,
2. Stress reactivity and stress resilience, and
3. Interpersonal and social processes.

Research supported by this funding opportunity announcement (FOA) is meant to support a range of target validation and assay research and development projects focused on the stress reactivity and stress resilience domain. Companion FOAs focus on the interpersonal and social processes (RFA-RM-14-018) and self-regulation (RFA-RM-14-020) domains; and the Resource and Coordinating Center (RCC) (RFA-RM-14-017).

This UH2/UH3 FOA solicits applications to support a collaborative research infrastructure involving an interdisciplinary team of basic and clinical scientists to develop the foundation for an experimental medicine approach to behavior change. The applicant should propose activities to address the Research Objectives (below) through four main target validation steps:

1. Identify a set of putative targets within the stress reactivity and stress resilience domain that are implicated in medical regimen adherence and at least one other health behavior;
2. Leverage existing or develop new experimental or intervention approaches to engage identified targets;
3. Identify or develop appropriate assays (measures) to permit verification of target engagement;
4. Test the degree to which engaging identified targets produces a desired change in medical regimen adherence and at least one other health behavior. While testing target engagement in specific clinical samples is permitted, the targets identified and the behavior change outcomes measured should be selected based on their hypothesized relevance to at least two clinical endpoints or disease conditions.

Success in these areas will lay the foundation for a systematic improvement of behavior change trial designs, advancing a more unified science of behavior change.

Activities under the UH2/UH3 mechanism may include, but are not limited to, the following:

• Comprehensive compilation and review of targets under the broad domain of stress reactivity and stress resilience;
• Development of a functional ontology (at the behavioral, social, psychological, and/or biological level of analysis) that defines targets within the broad domain--stress reactivity and stress resilience and specifies the relationships between these targets;
• Comprehensive compilation and review of experimental manipulations and plausible intervention approaches thought to engage the specified target;
• Systematic identification or development and refinement of experimental manipulations to be used to engage the specified target;
• Pilot-testing to establish that identified or developed manipulations are likely to engage the specified target at pre-specified, clinically meaningful levels;
• Pilot-testing to establish how different assays assess target engagement, and compare to one another;
• Pilot-testing to ensure that assays are relevant to and feasible for different health behaviors, relevant to multiple clinical contexts and conditions;
• Delivering one or more intervention approaches intended to engage a putative target potentially relevant for multiple health behaviors, one of which must be medical regimen adherence.

A UH2/UH3 application need not have preliminary data or extensive background material; however, this information can be included if available. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data.

Human behavior accounts for about 40 percent of the risk associated with preventable premature deaths in the United States. Substance use and abuse, physical inactivity, poor diet, poor sleep habits, and risk-taking in a variety of contexts are among the many behaviors known to play a role in adverse health conditions. Well-documented non-adherence to medical regimens serves as an exemplar of the challenges in initiating and sustaining healthful behavior change.

Researchers are beginning to make progress in understanding some of the basic mechanisms that account for less-than-optimal initiation and maintenance of behavior change. The first phase of work under SOBC (http://commonfund.nih.gov/behaviorchange/index ) capitalized on this emerging basic science to accelerate investigation of common mechanisms of behavior change applicable across a broad range of health-related behaviors, linking approaches from the laboratory and the field. Through a series of activities, SOBC 1 identified the challenges to testing causal mechanisms in behavior change studies, including the need for validated consensus assays, support for incorporating mechanisms tests across the intervention development pipeline, and opportunities to study common mechanisms associated with health behaviors that impact a wide range of clinical endpoints.

Promoting explicit testing of mechanisms in behavior change research is long overdue. In general, behavior change interventions have not been based on explicit tests of target engagement using well-validated assays. Instead, behavior change interventions tend to combine multiple components meant to engage a variety of targets, whether specified or not. Moreover, few intervention studies are designed to test whether the intervention actually engaged the (multiple) target(s) it was meant to engage, and whether engagement of the target(s) produced the desired behavior change. As a result, even successful intervention studies do not always inform behavior change research beyond the context in which they are tested. For a variety of reasons, multi-component interventions are rarely adopted in their entirety in other settings or for other conditions; instead, interventions are unpacked, and components are adopted based on setting-specific factors. This approach is slow and costly, requiring new and expensive clinical trials to test even the most incremental changes in intervention strategy. The work of SOBC 1 set the stage for a mechanisms-focused, experimental medicine approach as an alternative to the inefficient multi-component intervention, black box approach. This experimental medicine approach seeks to develop interventions that engage targets hypothesized to be putative mechanisms of change, and includes explicit tests of both target engagement and behavior change.

Research supported by this FOA is meant to support a range of target validation and assay research and development activities within the stress reactivity and stress resilience domain. For the purposes of this announcement, processes capable of altering stress reactivity and stress resilience are appropriate targets. Target(s) will be engaged using experimental manipulations or interventions. Assay validation will involve examining whether assays are capable of capturing target engagement, as described elsewhere in this announcement.

Stress is defined as the real or perceived imbalance between environmental demands and an individual’s capacity to adapt to these requirements. Stressors, or stress exposures, are potential or actual threats or challenges to an individual. The taxonomy for stressors includes, for example, major traumatic events; acute, novel, or unpredictable situations; repeated or chronic challenges; and daily hassles. Individual responses to stressors vary in nature, quality, and temporal characteristics. The initial and acute response to a stressor includes stress reactivity and recovery of those systems, with different time courses for distinct components (e.g., neural, physiological, cognitive affective, and behavioral) of the response. Stress resilience refers to the dynamic multidimensional process encompassing positive adaptation within the context of the stressor or adversity.

A range of behavioral and psychological processes fall within the broad domain of stress reactivity and stress resilience, including perseverative cognition; cognitive flexibility; anticipatory or prolonged activation; perceptions of threat and safety; negative and positive affect/emotions and cognitions; controllability; elasticity in affective and physiological response systems; and, emotional regulatory strategies. Likewise, numerous neurobiological processes and circuits are implicated within the central and peripheral nervous systems. These processes are examples of appropriate targets for research projects supported by this announcement.

Stress reactivity and stress resilience are believed to be causal mechanisms or crucial intermediate phenotypes in the promotion of health and/or development of disease. Individual differences in patterns of stress reactivity and stress resilience affect multiple health behaviors including medical regimen adherence, substance use, risky sexual behaviors, exercise and food choice, and are associated with multiple adverse physical, mental, behavioral and social outcomes. Given the wide range of processes implicated in stress reactivity and stress resilience, it has proven difficult to measure targets in this domain consistently in the laboratory, clinical trials, or large scale observational studies. The lack of precise consensus measures of distinct targets within the stress reactivity and stress resilience domain has impeded explication of causal links to medical regimen adherence, health behaviors, clinical endpoints, and ultimately health and well-being. Work needs to be done to determine the most appropriate assessments for behavior change science. The overarching goal of such work would be to determine the extent to which various measures of stress reactivity and stress resilience are tapping distinct or overlapping mechanisms involved in behavior change, and whether measures are performing similarly across populations, context, laboratories, and age groups.

Each UH2/UH3 application in response to this FOA is required to propose aims focused on the stress reactivity and stress resilience domain to identifyputative targets that are implicated in medical regimen adherence and at least one other health behavior, that:

• Have clear potential to be measured in multiple ways (by multiple assays), and preferably at multiple levels (e.g., psychological, behavioral and biological) for the purposes of cross-validation, and increased scientific understanding; and,
• Are hypothesized or demonstrated to be malleable, either by leveraging existing or developing novel experimental or intervention-based strategies for target engagement.

This announcement aims to support the development, verification, and validation of precise, valid, and reliable assays of targets in the domain of stress reactivity and stress resilience. Within this context, it is prudent to consider the dynamic and adaptive nature of stress reactivity and stress resilience and examine magnitude, intensity, duration, and frequency of the stress response, recovery, and restoration. Identification of valid assays of malleable targets involved in stress reactivity and stress resilience within or between different levels of analysis should accelerate progress toward the development of efficacious behavior change interventions. The overarching goal is to develop new or refine existing approaches to engage stress reactivity and stress resilience targets in ways that are meaningfully related to health behavior change and ultimately, to clinically significant change in disease endpoints or health outcomes.

UH2/UH3 Phased Innovation Awards Cooperative Agreement Mechanism:

Each UH2/UH3 application should be designed to bring together a diverse team of researchers taking a mechanistic approach to the study of stress reactivity and stress resilience across a variety of disciplines, such as psychology, psychometrics, cognitive and affective neuroscience, social neuroscience, behavior and molecular genetics, computational modeling, psychoneuroimmunology, human development, psychiatry, medicine, economics, and sociology. Teams should also include individuals with expertise in behavior change interventions to address stress reactivity and stress resilience within prevention, public health, biomedical and/or clinical contexts. Teams are encouraged to include members with advanced computational, statistical, and mathematical expertise. This team will be charged to conduct experimental and early-phase interventional research and assay development activities for the purpose of developing reliable, validated assays of processes underlying stress reactivity and stress resilience (e.g. behavioral, self-report, neurophysiological, genetic measures) that can serve as putative behavior change targets (or as behavioral phenotypes to assist in tailoring behavior change interventions). All team PDs/PIs and Senior Key Personnel will participate in annual SOBC Steering Committee meetings in order to coordinate efforts.

The flexibility of this cooperative agreement will permit the use of multiple strategies to achieve these goals, such as: workshops, experimental studies, development of behavioral and neurobiological assays, development of self-report instruments, consultations with measurement specialists across multiple disciplines, secondary or meta-analysis of existing data, coordination with measurement development approaches across the NIH, and close interaction with researchers in behavior change interventions to insure that the processes tapped and measures derived hold potential for inclusion in behavior change intervention studies. The output of these UH2/UH3 awards, to be facilitated by a Resource and Coordinating Center (RCC) funded under RFA-RM-14-017, will be a toolkit of validated and documented assays (measures) of specific targets in the domain of stress reactivity and stress resilience, and experimental manipulations/interventions that engage those targets. These assays and tools will be made freely available to the field for incorporation in clinical studies.

The objectives of the UH2 phase are to complete Steps 1-3 of the target validation activities described above. Selection of targets should be based on theory and available evidence regarding the fundamental processes involved in stress reactivity and stress resilience (see definition below) and the role of stress reactivity and stress resilience in behavior change. To be responsive to this FOA, at least one target must be selected based on its potential utility in studies of medical regimen adherence. For the UH2 phase, teams should propose activities designed to demonstrate that a set of identified targets can be engaged and show pre-defined levels of change (i.e., show malleability) and that reliable and valid assays exist to measure target engagement, through a variety of validation approaches, for example: experiments to determine assay parameters and performance under varying conditions, experiments to demonstrate that the methods developed provide meaningful data under specified conditions, and experiments to establish inter-assay validity and inter-laboratory reliability. NOTE: In the UH2 phase, the purpose is not to pilot-test an intervention to be used in a subsequent trial. The potential utility of employing an intervention is to engage the target and assess the degree to which the assays capture target engagement. Progression to the UH3 phase will be determined by administrative review and will depend on the successful demonstration that reliable and valid assays exist to measure target engagement.

The objective of the UH3 phase is to complete Step 4 of the target validation activities described above. For the UH3 phase, teams should propose activities designed to evaluate the validity of putative targets by integrating these assays into controlled experimental or early stage interventional studies. The goal of activities in this phase is to produce short term health behavior change in two or more health behaviors, one of which must be medical regimen adherence, in a controlled environment via target engagement.

Progression to the UH3 phase will be determined by administrative review (see "Criteria for the UH2/UH3 transition" below). The applicant should present a clear plan, including concrete milestones, for producing data that will be used to address the objectives laid out above.

Criteria for the UH2/UH3 transition

Applicants must plan for both a UH2 and a UH3 phase. Each application should include milestones specific to the proposed project that will be reached at the end of the UH2 phase. Quantifiable metrics to measure achievement of milestones should be fully explained in the application. Additional milestones may be negotiated after funding decisions have been made.

Criteria to determine whether an award will transition from the UH2 phase to the UH3 phase include:

1. Completion of awardee-specified milestones for a plan to employ the experimental medicine approach of behavior change. For example, these might include

• Identification of a set of putative behavior change targets in the domain of stress reactivity and stress resilience, and demonstration that these targets are: (1) promising as drivers of adherence to medical regimens and at least one other health behavior; (2) likely to be measureable in multiple ways and at multiple levels (psychological, behavioral, social, biological); (3) relevant to at least two clinical endpoints or disease conditions; and (4) likely to be malleable.
• Demonstration that the identified targets in the domain of stress reactivity and stress resilience are malleable, and that the chosen assays reliably measure target engagement, by using existing, new or adapted experimental manipulations/interventions to engage the target.
• Development of aims for the UH3 Phase including plans for: (1) testing the degree to which engaging identified targets produces a desired change in medical regimen adherence and at least one other health behavior hypothesized to be related to at least two clinical endpoints or disease conditions; (2) refining manipulation/intervention approaches aiming for optimal target engagement; and (3) refining assays that optimize measurement of target engagement.
• In accordance with procedures agreed upon by the Steering Committee, validated assays, experimental manipulation protocols, and all relevant data will have been shared with the Resource and Coordinating Committee (RCC) as appropriate.

2. Availability of funds;

3. NIH program priorities; and

4. NIH leadership approval.

The UH3 awards will be made after administrative review of UH2s by NIH staff and an external scientific panel established for the SOBC Program. Awarding the UH3 will depend on the successful achievement of study objectives, including awardee-specified milestones, the feasibility of study continuation, and the availability of funds. UH2 projects that do not meet the objectives by the end of the third project year will not receive continued project support.

Characteristics of Responsive Applications

1. Activities supported through this award may include information exchange, measurement development, pilot and validation studies, experimental studies, development of novel intervention strategies to engage a putative target, identification or modification of existing targeted intervention strategies, and analyses of existing data sets.

2. This FOA supports early stage behavior change intervention activities related to developing and testing specific experimental manipulations or controlled interventions that engage a specified behavioral or social target. This FOA will not support the development of diffuse or multi-component interventions, or large-scale randomized behavioral trials (e.g., Phase III or IV, or Stage 2-4).

3. At least one element of the application must include a focus on medical regimen adherence.

4. This FOA will not support assay development in animal models, though a team may include expertise in animal models relevant to behavior change where relevant.

Responses to FAQs regarding this FOA will be posted at http://commonfund.nih.gov/behaviorchange/faq/

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, including the NIH Intramural Program
• 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)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are 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.

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).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:

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

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

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, 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:

Paige Green McDonald, PhD, MPH
National Cancer Institute (NCI).
Telephone: 240-276-6899
Fax: 240-276-7907
Email: mcdonalp@mail.nih.gov

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

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.

Other Attachments: An attachment called "Team Science Justification and Organization" should be uploaded in Other Attachments. Although no specific page limitation applies to this section of the application, please be succinct. Applicants may not use this section to circumvent the page limits of the Research Strategy. The following points should be addressed in this attachment and are an important part of the UH2/UH3 application:

A clear plan of operation should be provided for the administrative structure and proposed interactions among the investigators. Also a clear description of the collaborative team aspect of the work proposed including the requirements and roles to be played by each member of the team. It is anticipated that members of the team may not already be interacting on this, or other, projects. Lines of communication and exchange of data should be clearly established. A rationale must be provided explaining how integration and collaboration among participants will be fostered. The role(s) for each member of the team and how this will provide the requisite synergies for the research activities in the UH2/UH3 should be clearly articulated.

Applications lacking this attachment will be deemed incomplete.

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

The UH2/UH3 research teams should include both basic and clinical scientists. Teams should include expertise in research on stress reactivity and stress resilience, as defined in this FOA, across multiple levels of analysis (e.g., neurobiological, psychological, behavioral, social). Teams should also include expertise in behavior change research relevant to one or more health behaviors, including research issues related to medical regimen adherence. These scientists will collaborate with NIH staff and with the other UH2/UH3 teams working on different intervention targets to develop comprehensive ontologies for the target domain, and permit further cross-validation of assays. Substantial expertise in measurement development and tests of target engagement at multiple levels of analysis is required as well as appropriate expertise in clinical and behavior change fields. Teams can include scientists from a variety of disciplines, which may include, but are not limited to, psychology, psychometrics, cognitive and affective neuroscience, social neuroscience, behavior and molecular genetics, computational modeling, psychoneuroimmunology, human development, psychiatry, medicine, economics, and sociology. Teams need not be from the same research program, institution, discipline, or field. It is expected that most teams will be comprised of investigators from several different laboratories and institutions, to fulfill the requirements of this announcement. Teams have the flexibility within this mechanism to engage a broader range of researchers in the UH2 and UH3 phase, to extend the scope of activities to other laboratories and institutions, as appropriate.

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

The application must include funds for the UH2/UH3 PDs/PI(s) and key personnel to travel and attend the following in-person meetings:

• One 1.5-day kick-off meeting to be held within 2 months of award in the Washington, DC area;
• Annual 1.5-day SOBC Steering Committee meetings in the Washington, DC area; and
• Annual 1-day Stress Reactivity and Stress Resilience Subcommittee meetings. This subcommittee will be comprised of all the projects awarded from this FOA in a location to be determined by the Resource and Coordinating Center funded under RFA-RM-14-017.

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:

Research Strategy:

The Research Strategy should be organized into sections on Significance, Innovation, and Approach.

The Significance section should include a discussion of how this project relates to the overall SOBC goal to advance an experimental medicine approach to behavior change. Provide justification for the selection of specific targets that are implicated in medical regimen adherence and at least one other health behavior, within the stress reactivity and stress resilience domain. The selection of targets should be based on theory and available evidence regarding the fundamental processes involved in stress reactivity and stress resilience, and the role of stress reactivity and stress resilience in behavior change. Describe the potential of these targets to be measured in multiple ways (by multiple assays), and preferably at multiple levels (e.g., psychological, behavioral and biological), for the purposes of cross-validation and increased scientific understanding. Articulate evidence for the malleability of these targets. Describe existing experimental or intervention-based strategies for target engagement or steps needed for development of novel strategies.

The Innovation section should address how work conducted under this project will lay the foundation for a systematic improvement of behavior change trial designs, advancing a more unified science of behavior change. Discuss how the proposed approach will generate evidence supporting the utility of these assays for future implementation in behavior change trials.

The Approach section should describe the set of activities proposed to support target validation in the domain of stress reactivity and stress resilience. These may include, but are not limited to: procedures for information exchange, measurement development, conduct of pilot and validation studies, experimental studies, development of novel intervention strategies to engage a putative target, identification or modification of existing targeted intervention strategies, and analyses of existing data sets.

Address how the project will implement the four main target validation steps described in the specific aims: (1) Identify or describe procedures for identifying a set of putative targets within the stress reactivity and stress resilience domain that are implicated in behavior change, including adherence to medical regimens; (2) Describe how the project will leverage existing or develop new experimental or intervention approaches to engage identified targets; (3) Describe how the project will develop or adapt appropriate assays to permit verification of target engagement; (4) Describe how the project will test the degree to which engaging identified targets produces a desired change in two or more health behaviors, one of which must be medical regimen adherence, that are hypothesized to be related to at least two clinical endpoints or disease conditions.

Applicants should describe plans for both a UH2 and a UH3 phase. The UH2 section must include a description of the milestones that will be reached at the end of the UH2 phase. The applicant should present a clear plan, including concrete milestones, for producing data that will be used to address the objectives of this FOA.

For the UH2 Phase, applicants should describe plans for completion of target validation Steps 1-3.

• 1. Identification of a set of putative targets within the self-regulation domain that are implicated in medical regimen adherence and at least one other health behavior;
• 2. Leveraging of existing or develop new experimental or intervention approaches to engage identified targets;
• 3. Identification or development of appropriate assays (measures) to permit verification of target engagement;

For the UH3 Phase, applicants should describe a plan for completion of target validation Step 4

• Equipped with identified targets, assays, and manipulations/interventions that engaged the target(s), approaches to testing the degree to which engaging a specified target produces a pre-specified short-term desired change in two or more health behaviors, one of which must be medical regimen adherence, that are hypothesized to be related to at least two clinical endpoints or disease conditions.
• Approaches for refining at least two manipulation/intervention approaches, aiming for optimal target engagement.
• Approaches for refining assays that optimize measurement of target engagement.

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

• All applications submitted for the January 25, 2015 due date or after are expected to comply with the NIH Genomic Data Sharing Policy as detailed in NOT-OD-14-111, as applicable.

The SOBC Program encourages sharing of resources with broad availability of policies, practices, materials, and tools to facilitate collaboration, reuse, and replication, both in other SOBC-supported projects and by other behavior change researchers. In addition, consistent with achieving the goals of the program, the SOBC Program expects the sharing of study data from both the RCC funded under RFA-RM-14-017 and the UH2/UH3 Target Validation Projects in a timely manner, and with appropriate privacy and confidentiality protections to facilitate further research, reuse of data, and replication. Thus, the SOBC Program expects awardees to implement a Resource and Data Sharing Plan consistent with these program goals.

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

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

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

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

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

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.

The requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the NIH Intramural Program. NIH intramural scientists will participate in this program as PD/PIs in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above. The intramural project should be added as a separate component to the parent application.

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

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

For this particular announcement, note the following:

This UH2/UH3 phased target validation mechanism supports investigation of novel scientific ideas or new interventions, tools, or technologies that have the potential for significant impact on biomedical or behavioral and social sciences research. A UH2/UH3 application need not have preliminary data or extensive background material; however, this information can be included if available. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Accordingly, the review will emphasize the conceptual framework, the proposed target validation activities, the level of innovation, and the potential to significantly advance our knowledge or understanding. Reviewers will assign a single impact score for the entire application, which includes both the UH2 and UH3 phases.

This UH2/UH3 initiative is intended to develop the foundations for a focus on stress reactivity and stress resilience in an experimental medicine approach to behavior change through the four main target validation steps described in Section I of this announcement. Reviewers will evaluate the potential of the proposed target validation activities to advance implementation of a mechanisms-focused, experimental medicine approach to behavior change research.

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? 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?

Is there a clear discussion of how this project relates to the overall SOBC goal to advance an experimental medicine approach to behavior change? Are the application-specific stress reactivity and stress resilience targets likely to have a significant impact on behavior change science, including research on adherence to medical regimens?

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?

Does the UH2/UH3 research team include both basic and clinical scientists? Does the team include expertise in research on stress reactivity and stress resilience, as defined in this FOA, across multiple levels of analysis (e.g., neurobiological, psychological, behavioral, social)? Does the team include expertise in behavior change research relevant to one or more health behaviors, including research issues related to medical regimen adherence? Is there evidence of sufficient expertise in measurement development and tests of target engagement at multiple levels of analysis? Is there evidence of sufficient expertise in disciplines relevant to the proposed study (e.g., psychology, psychometrics, cognitive and affective neuroscience, social neuroscience, behavior and molecular genetics, computational modeling, psychoneuroimmunology, human development, psychiatry, medicine, economics, sociology)?

Is there a clear plan of operation for the administrative structure and proposed interactions among the investigators? Is there a clear description of the collaborative team aspect of the work proposed including the requirements and roles to be played by each member of the team? While investigators on a UH2/UH3 project may be located at different institutions, and may not already be interacting on this, or other, projects, is there clear evidence of ability to collaborate to achieve project goals? Are lines of communication and exchange of data clearly established? Is there a rationale explaining how integration and collaboration among participants will be fostered? Is the role(s) for each member of the team clearly articulated?

Is there clear evidence of the ability of the team to collaborate with the SOBC Resource and Coordinating Center (RCC) to share refined assays, experimental/intervention protocols, and other tools developed with support from the SOBC Research Network (defined below)?

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 address how work conducted under this project will lay the foundation for a systematic improvement of behavior change trial designs, advancing a more unified science of behavior change? Does the proposed approach have potential to generate evidence supporting the utility of new assays and target engagement strategies for future implementation in behavior change trials?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

Does the application clearly describe a set of activities that will support target validation in the domain of stress reactivity and stress resilience? These may include, but are not limited to: procedures for information exchange, measurement development, conduct of pilot and validation studies, experimental studies, development of novel intervention strategies to engage a putative target, identification or modification of existing targeted intervention strategies, and analyses of existing data sets.

Reviewers will evaluate the plans for implementation of the following target validation steps: Specifically, (1) (2) Are there appropriate plans for leveraging existing or developing new experimental or intervention approaches to engage identified targets? (3) Are plans for developing or adapting appropriate assays to permit verification of target engagement clearly described and justified? (4) Are plans for testing the degree to which engaging identified targets produces a desired change in two or more health behaviors, one of which must be medical regimen adherence, clearly described and justified?

Specific to the UH2 phase: Does the UH2 phase propose appropriate plans for selection of targets based on theory and available evidence regarding the fundamental processes involved in stress reactivity and stress resilience (see definition in Section I) and the role of stress reactivity and stress resilience in behavior change? Are appropriate validation approaches included, for example: experiments to determine assay parameters and performance under varying conditions, experiments to demonstrate that the methods developed provide meaningful data under specified conditions, and experiments to establish inter-assay validity and inter-laboratory reliability.

Specific to the UH3 phase: Does the UH3 phase propose appropriate plans for target validation activities, such as the following:

(1) Testing the degree to which engaging a specified target produces a pre-specified short-term desired change in two or more health behaviors, one of which must be medical regimen adherence, that are hypothesized to be related to at least two clinical endpoints or disease conditions

(2) Refinement of at least two manipulation/intervention approaches, aiming for optimal target engagement;

(3) Refinement of assays that optimize measurement of target engagement?

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 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?

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.

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.

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

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.

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

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

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

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

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

As part of the scientific peer review, all applications:

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

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate National Advisory Council or Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Overall program balance.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

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

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

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

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

Any application awarded in response to this FOA will be subject to 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.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

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

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

SOBC Research Network: The total collection of projects, committees, and staff that encompass the four companion FOAs: RFA-RM-14-017, RFA-RM-14-018, RFA-RM-14-019, and RFA-RM-14-020.

SOBC Resource and Coordinating Center (RCC): The awardee of RFA-RM-14-017 that will be responsible for coordinating activities across the network and other tasks as detailed below.

External Scientific Panel (ESP): A panel of four to six senior scientists with relevant expertise who are not PDs/PIs of a project involved in the SOBC Research Network that will provide recommendations to the SOBC Working Group about continued support of the components of the SOBC Research Network

SOBC Research Network Steering Committee: The main governing board of the SOBC Research Network comprised of PDs/PIs and NIH Project Scientists from each UH2/UH3 award and the U24 RCC award as well as additional investigators and NIH staff as appropriate. The Steering Committee will have subcommittees including one for each of the three target behavioral domains, and other subcommittees as deemed appropriate.

SOBC Working Group: The trans-NIH committee of NIH staff members that lead the NIH SOBC Common Fund Program. See http://commonfund.nih.gov/behaviorchange/members for more information.

Target Validation Project: One of the UH2/UH3 awards working on one of the three behavioral domains, namely, Self-regulation, Stress Reactivity and Resilience, or Interpersonal and Social Processes.

The Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) will have the primary responsibility for defining the details for the UH2/UH3 project within the guidelines of this FOA and for performing the scientific activities. The PD/PI will agree to accept close coordination, cooperation, and participation of NIH Science of Behavior Change (SOBC) program staff in those aspects of scientific, and technical management of the project as described under "NIH Program Staff Responsibilities." For institutions/organizations proposing multiple PD/PIs, all PD/PIs will share the rights and responsibilities of a cooperative agreement awarded to an individual PD/PI, as described by the NIH Multiple Program Director/Principal Investigator Policy (http://www.grants.nih.gov/grants/multi_pi/).

The PD/PI(s) of an SOBC Research Network UH2/UH3 project will:

• Participate as a voting member of the Steering Committee and join relevant subcommittees;
• Determine experimental approaches, design protocols, set intermediate project objectives, and conduct experiments;
• Ensure that the data produced meets the quality standards and costs agreed upon at the time of award, or any improved quality standards and costs negotiated during the award period;
• Adhere to the NIH policies regarding intellectual property, data release and other policies that might be established during the course of this activity;
• Participate in activities to ensure adherence to Good Clinical Practices in human subjects research, as determined by relevant IRB(s), and NIH.
• Cooperate and coordinate activities as requested by the SOBC Resource and Coordinating Center (RCC);
• Provide assays, manipulation protocols, and other supporting data and documentation to the RCC for public release;
• Submit quarterly progress reports during the first year phase, in a format as agreed upon by the Steering Committee and the ESP. Projects that are selected for continued support through the UH3 mechanism will submit progress reports on a regular basis, at least biannually. Whether in the UH2 or UH3 phase, projects involving human subjects will submit regular reports on safety and quality management, as part of adhering to GCP;
• Participate with the other Steering Committee members in determining the group process of setting research priorities, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted;
• Work cooperatively with the assigned SOBC Research Network Project Scientist to schedule and plan for site visits annually or as appropriate;
• Accept and implement any other common guidelines and procedures developed for the SOBC Research Network and approved by the Steering Committee and the ESP;
• Accept and participate in the cooperative nature of the SOBC Research Network;
• Respond promptly and cooperatively to requests for information or input from the SOBC RCC, Steering Committee, SOBC Working Group, or ESP;
• Participate in conference calls (at least quarterly) with Project Scientists and/or other members of the SOBC Research Network including the SOBC RCC, as scheduled and agreed upon by the Steering Committee;
• Attend a 1.5-day kick-off meeting within 2 months of award in the Washington, DC metro area, and budget and arrange for other key collaborators to attend the meeting as well;
• Attend annual 1.5-day SOBC Steering Committee meetings in the Washington, DC metro area;
• Attend annual 1-day Stress Reactivity and Stress Resilience Subcommittee meetings. This subcommittee will be comprised of all the projects awarded from this FOA in a location to be determined by the RCC funded under RFA-RM-14-017.

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 HHS, PHS, and NIH policies.

NIH Project Scientists will have substantial scientific and programmatic involvement that is above and beyond the normal stewardship role in awards through technical assistance, advice and coordination, as described below. However, the role of NIH SOBC Research Network Project Scientists will be to facilitate, not direct, the activities. It is anticipated that decisions in all activities will be reached by consensus of the Steering Committee and the Project Scientists will be given the opportunity to offer input to this process.

Each NIH SOBC Research Network Project Scientist shall participate as a member of the Steering Committee where the Project Scientists may vote, but their combined votes will count as a maximum of one-third of the total number of votes.

The Project Scientists will:

• Participate as a voting member of the Steering Committee and join relevant subcommittees;
• Participate with the other Steering Committee members in facilitating (not directing) the group process of setting research priorities, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted;
• Serve as a liaison between the PDs/PIs and the ESP, the SOBC Working Group, the Common Fund Program, and individual Institutes and Centers;
• Attend annual face-to-face Steering Committee meetings as a voting member and assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action;
• Periodically report progress to the SOBC Working Group;
• Lend relevant expertise and overall knowledge of NIH-sponsored research to facilitate the selection of scientists not affiliated with the awardee institutions to serve on the ESP;
• Serve on subcommittees of the Steering Committee as appropriate;
• Provide advice in the management and conduct of SOBC-funded activities;
• Participate in data analyses, interpretation, and where warranted, co-authorship of the publication of results of studies conducted through the SOBC Research Network;
• Assist awardees in the development, if needed, of policies for dealing with situations that require coordinated action;
• Retain the option to recommend, with recommendations from the ESP, the withholding or reduction of support from any cooperative agreement that substantially: 1) fails to achieve its goals according to the awardee-specified milestones agreed to at the time of award; 2) fails to maintain state-of-the-art capabilities; or 3) fails to comply with the Terms and Conditions of the award.

Additionally, a Program Official from the administering IC will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The Project Scientist is not required to be from the administering Institute, Center, or Office. A single individual may not serve the roles of both Program Official and Project Scientist.

A Steering Committee will serve as the main governing board of the SOBC Research Network. The Steering Committee membership will include NIH Project Scientists and the PD/PI(s) of each awarded cooperative agreement. The PD(s)/PI(s) of each UH2/UH3 project will have one vote on the Steering Committee. For projects functioning under a multiple PD/PI structure, the multiple PDs/PIs will be expected to cast one collective vote. The Project Scientists may vote, but their combined votes will count as a maximum of one-third of the total number of votes. The contact PD/PI of the Resource and Coordinating Center (RCC) will serve as chair of the Steering Committee, for the first project year. Thereafter, members may serve as chair on a rotating basis, as agreed by the Steering Committee. Additional members may be added by action of the Steering Committee. Other NIH staff may attend the Steering Committee meetings if their expertise is required for specific discussions.

The Steering Committee will:

• Discuss progress in meeting the goals and objectives of the UH2/UH3 projects;
• Develop recommendations for uniform procedures and policies necessary to meet the goals of the SOBC Research Network.
• Adoption of procedures and policies developed by the Steering Committee will require concurrence by the ESP;
• Serve as a venue for coordination on the improvement of assay development and target validation scientific methods, for example by disseminating best practices and collectively evaluating new procedures, resources, and technologies;
• Designate subcommittees as appropriate;
• Each full member will have one vote. PD/PI members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

External Scientific Panel:

The External Scientific Panel (ESP) will be responsible for reviewing and evaluating the progress of the SOBC Research Network projects toward meeting their individual and collective goals and objectives. The ESP will provide recommendations to the SOBC Working Group about continued support of the components of the SOBC Research Network. The ESP is composed of four to six senior scientists with relevant expertise who are not PD(s)/PI(s) of a project involved in the SOBC Research Network. The membership of the ESP may be enlarged permanently, or on an ad hoc basis, as needed.

The ESP will meet face-to-face at least once a year, to overlap with the annual Steering Committee meeting. During part of this meeting, there will be a joint meeting with the Steering Committee to allow the ESP to interact directly with the awardees. Annually, the ESP will make recommendations regarding progress of the SOBC Research Network and present advice to the SOBC Working Group about changes, if any, which may be necessary in the SOBC Research Network.

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 arbitration. An Arbitration Panel will be convened, composed of 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 arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 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.

Awardees may also be required to submit periodic (biannually) progress reports in a standard format, as agreed upon by the Steering Committee and the ESP. As needed, the NIH may request information essential to an assessment of the effectiveness of the SOBC Research Network. Accordingly, recipients are hereby notified that awardees may be asked to provide information for program evaluation purposes, both locally and at the national level.

Additional reporting will be required for studies involving human subjects. In addition to progress reports, awardees will be expected to submit regular reports on adherence to Good Clinical Practices, including reviews of informed consent procedures, data quality, and participant safety. The content, format, and frequency of these reports will be established before human subjects recruitment begins.

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

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Paige Green McDonald, Ph.D., M.P.H.
National Cancer Institute (NCI)
Telephone: 240-276-6899
Email: mcdonalp@mail.nih.gov

Minda Lynch, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-435-1322
Email: mlynch1@mail.nih.gov

Dana Plude, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-402-2309
Email: pluded@mail.nih.gov

Jeff Balll
National Institute on Aging (NIA)
Telephone: 301-402-7732
Email: ballj@nia.nih.gov

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

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