NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

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) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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 is a Funding Opportunity Announcement (FOA) on the Validation of Pediatric Patient Reported Outcomes in Chronic Diseases (PEPR) Consortium. The NIAMS on behalf of NIH Institutes and Centers, invites applications from single institutions, or consortia of institutions, to participate in a consortium of chronic pediatric disease research groups focused on clinical validation of child patient reported outcomes (cPROs). The goal of the PEPR consortium is to validate existing and emerging (e.g., experience of stress bank) pediatric item banks and instruments available at the NIH Patient-Reported Outcomes Measurement Information System (PROMIS ) (www.nihPROMIS.org) in (1) clinical research settings, (2) clinical care settings and/or (3) as ancillary components of clinical trials in children in either setting. The purpose of this FOA is to capitalize on recent advances in the science of PROs to measure the patient experience in clinical care and research in children with a variety of chronic diseases and conditions using PROMIS tools and approaches coupled with detailed clinical phenotyping and/or biospecimen collection in well-characterized human cohorts. The long-term goal is to develop (1) reliable, validated clinical tools for cPROs to improve the assessment of outcomes in clinical trials or other research settings, and personalize ongoing care of chronic diseases in children and (2) examine the impact of environmental stressors on children’s health including their symptoms and quality of life.

Chronic conditions in children are common, with estimates of 15 to 27 percent of children under 18 in the U.S. affected. Examples of chronic conditions in children include: asthma, juvenile arthritis, cystic fibrosis, diabetes, obesity and overweight, chronic kidney disease, inflammatory bowel disease, sickle cell disease, malnutrition, developmental disabilities including attention deficit/hyperactivity disorder and autism spectrum disorder, cerebral palsy and mental illnesses.

Many of these diseases and conditions cause patients to have pain or experience fatigue; affect their sleep; alter their ability to physically or mentally function on a daily basis; or in other ways interfere with their social relationships and overall quality-of-life. The impact, importance, and value of pediatric self-reporting (and parent-proxy reporting) in the evaluation of treatments efficacy and effectiveness support the need for a universal, common metric in order to allow clinically meaningful comparisons of treatments of disease, both within and across chronic pediatric diseases.

Patient outcomes are critical to clinical research and patient care. They are assessed in a variety of ways by treating physicians, imaging techniques, lab results and self-reporting. PRO domains are concepts intended to represent how a patient feels or functions and are important endpoints in clinical research and healthcare delivery.

PROMIS is an NIH Common Fund initiative. To date, PROMIS has developed item banks that have been evaluated, mostly cross-sectionally, in the general population. These populations use a mixture of healthy controls as well as self-reported and clinically diagnosed patients. However, these item banks have not yet been widely incorporated into longitudinal clinical research and care to allow for further testing of their validity and other measurement properties in diverse patient populations. Similarly, they have not been widely tested in a variety of clinical populations whose experience with the domain of interest may not correspond to the experience of the general population, or these internet-based clinical applications. Therefore, PROMIS sets the stage to develop a strategic approach to progressively develop, validate, and implement the PROMIS domains in diverse chronic pediatric diseases as well as in diverse racial/ethnic populations. Importantly, PROMIS holds the potential to facilitate comparative research on the efficacy, or effectiveness, of therapies and to be integrated into electronic health record (EHR) databases at the point of patient care as well as clinical research.

The PROMIS website (www.nihPROMIS.org) and Assessment Center (http://www.assessmentcenter.net/) contain extensive documentation of the current qualitative and quantitative evaluations and information about the PROMIS Consortium. The PROMIS Assessment Center is an online resource that provides a range of PRO assessment tools that may be tailored for use in clinical trial or clinical care settings including a selection consisting of item banks, short forms, profiles, scales and computerized adaptive testing (CAT). All available measures have undergone rigorous qualitative and quantitative testing following PROMIS standards (http://www.nihpromis.org/Documents/PROMISStandards_Vers2.0_Final.pdf) to support the precision and validity of the instruments in several chronic disease populations and the general U.S. population. All items or questions in PROMIS have been calibrated to a common metric to allow for scoring (https://www.assessmentcenter.net/Manuals.aspx) from multiple studies and different settings (e.g., clinical trial, clinical care, national surveys) to be combined for meta-analyses even if the investigators use different PROMIS measures (e.g., short forms and CATs). To facilitate international pediatric clinical validation, PROMIS measures are available in Spanish, and many other languages (http://www.nihpromis.org/measures/translations). For details on the original FOA, see http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-04-011.html.

The NIH PROMIS initiative has facilitated the development of nine pediatric extant domains or subdomains along with eight soon to be released. These are available as item banks, scales, short forms and profiles (along with parent-proxy reports) that evaluate physical, mental and social aspects of self-reported health in children. These item (question) banks have undergone state-of-the-science qualitative and psychometric development providing clinicians and researchers access to efficient, precise, valid and responsive measures of child (and proxy)-reported health status such as symptoms and health-related quality of life.

PROMIS pediatric self-report item banks were developed for children ages 8-17 and parent-proxy forms items were developed for children ages 5 7. Currently available and soon-to-be-released PROMIS pediatric and parent-proxy banks (https://www.assessmentcenter.net/documents/InstrumentLibrary.pdf) can measure domains such as listed below.

Presently available:

• emotional distress - anger
• emotional distress - anxiety
• emotional distress - depression
• physical functioning
  • mobility
  • upper extremity
• pain interference
• fatigue
• peer relationships
• asthma symptoms

Pediatric instruments under development:

• experience of stress (psychological stress experience)
• family belongingness
• pain behavior
• pain intensity
• pain quality
• physical activity
• subjective well being
• lobal health

In particular, the PROMIS Pediatric Psychological Stress Experiences (e.g., experience of stress) item bank assesses the thoughts or feelings about self and the world in the context of environmental or internal challenges. Items represent three facets of psychological stress reactions: feeling overwhelmed, perceived lack of control of capacity to manage one s life, and cognitive-perceptual disruption. The pediatric Psychological Stress Experiences item bank uses a 7-day recall period and consists of 19 items.

Capturing the patient experience in clinical care and research is especially important in children. These standardized, dynamic pediatric tools were developed to enable meaningful comparisons of patients/participants across chronic diseases not only in childhood, but also as children transition into adulthood. These tools can be included in clinical, observational or comparative effectiveness research as primary, secondary or exploratory endpoints. In addition, these tools are intended for population surveillance as well as health care delivery. Importantly, since PROMIS is based on item-response theory (IRT), this novel, common platform means that direct comparisons can be made in these diverse clinical and research settings.

Research Objectives
The main goal of this FOA is to conduct robust clinical (in contrast to psychometric) validation studies in diverse chronic pediatric diseases to evaluate whether PROMIS measures are sensitive to change over time or in response to treatments, and can measure clinically important differences. Equally important for the clinical care setting is establishing how to interpret PROMIS scores in terms of disease activity, the decision whether to change therapy and whether certain symptoms or outcomes need particular attention. Pain, impairment of physical functioning, anger, anxiety, stress, fatigue from disease or its treatment, and how diseases or their therapies influence the social aspects of childhood, such as subjective well-being or peer relationships are all important domains impacted by many chronic diseases of childhood. An important element of the proposed research will be to capture how environmental stressors, as opposed to substances in the environment, impact clinical outcomes and care.

Environmental stressors reflecting diverse ecosocial and biopsychosocial factors may affect health and disease outcomes in children. Examples include: Poverty, homelessness and housing security, food insecurity, violence, foster care, natural disasters, disabilities, incarcerated parent(s) and/or sibling(s), social capital, social economic position, access to flexible financial resources, religiosity, spirituality, and access to safe play areas within and outside the home.

This initiative seeks clinical projects that are focused on the validation of extant, emerging and potentially new PROs in well-defined human cohorts using modern measurement instruments and approaches to generate robust clinical tools for the clinical evaluation and care of children with chronic diseases and conditions.

Areas of interest include, but are not limited to:

• Studies that focus on utilizing and optimizing the use of pediatric PRO instruments applicable in a variety of chronic diseases in the research or patient care settings.
• Validation of currently available and soon to be released PROMIS Pediatric banks/instruments in large, well characterized cohorts.
• Test and validate PROMIS domains and instruments assessing disease activity and response to therapy in clinical populations and settings.
• Comparisons of patient burden and precision of PROMIS domains and tools compared to current disease-specific instruments.
• Evaluation of PROMIS short forms, profiles and/or CAT responsiveness to change with pharmacologic or non-pharmacologic interventions, establishing minimally important differences (MID) in clinical research or care settings.
• Studies that contribute evidence (e.g., cognitive interviews) to improve the content or construct validity of existing pediatric PROMIS domains in clinical research and care settings.
• Studies that ultimately contribute robust clinical evidence necessary to qualify PROMIS pediatric banks for use in industry trials.
• Development of new domains that extend the measurement science of PROs (e.g., environmental stressors/exposures) that fit the PROMIS domain framework and can be initially developed adhering to PROMIS standards.
• Studies testing the items and item banks in different racial, ethnic and underrepresented groups with chronic diseases to demonstrate their clinical validity. Such testing could also include conducting cognitive interviews and patient-centered focus groups to ensure PROMIS domains accurately capture the patient experience in those groups.
• Studies that aim to optimize mode of administration of PROMIS measures to age appropriate or special populations.
• Studies that develop instruments that assess cPROs in early childhood (birth to 5 years) that complement existing PROMIS pediatric banks.
• Projects that develop cPRO instruments that measure psycho-social exposures that impact health.
• Studies that include pediatric patients with multiple chronic diseases.

Investigators are encouraged to integrate comprehensive laboratory and bioinformatics technologies in order to facilitate the validation of pediatric PROs as a key component of personalized medicine. Each award will support the collection, storage, and characterization of patient data; and each awardee will work together with other PEPR awardees to build centralized methods and resources, such as common data standards and validated methods for use by all consortium investigators, and will contribute to the rapid dissemination of cPRO data to the wider scientific community through a publicly accessible PEPR Consortium data portal. Validation studies conducted in the context of extant clinical research cohorts are strongly encouraged. Leveraging existing cohorts of participants in a parent study or selected subsets, depending on the scientific questions posed and the sample size required to answer them is strongly encouraged. Collection of biospecimens is allowed when the collection is justified as a component of the clinical evaluation, when it complements or enhances the value or relevance of the cPROs collected, and if an infrastructure is in place to ensure the long-term storage and disposition of the specimens. The proposed studies may draw patients from two or more parent projects provided approval from these parent projects is obtained. This FOA will provide support for the recruitment of patients when an infrastructure is in place to ensure the rapid implementation of the protocol. This FOA encourages collaboration between clinical investigators and partnerships with private entities. In addition, this FOA encourages junior investigators to take a leading role in clinical research with the support and collaboration of senior investigators.

To promote rapid and transparent public access to PEPR-supported data and results, all Program Directors (PDs)/Principal Investigators (PIs) funded under this initiative will work closely with the lead Data Management Core to harmonize data submission and development of new systems for data integration, analysis, presentation, and visualization. All PEPR investigators will be expected to share their PEPR supported data publicly through a PEPR Consortium data portal approved by NIH partners. The privacy of participants will be safeguarded, and confidential and proprietary information will be protected. After award and prior to data collection, data set definitions and schedules for data sharing will be negotiated with NIH as appropriate, as will appropriate plans for other resource sharing.

This program is milestone-based and includes the flexibility to quickly redirect or replace research projects during the funding period. Funds available beyond the first year may be negotiated downward depending on the progress in meeting the data- and other resource-sharing milestones negotiated with NIH after award.

Applications including the following types of studies will be considered non-responsive and will not be reviewed:

• Projects that do not include an assessment of PROs in the context of pediatric chronic diseases or conditions in ongoing clinical cohorts.
• Projects primarily focused on psychometric analysis or modeling.
• Projects that do not include evaluation of PROMIS tools.
• Projects that include a clinical trial of a new intervention.
• Projects that propose to create item banks that do not conform to the PROMIS standards without an appropriate scientific rationale.

Required Organization Structure

The following must be included in the application: a minimum of two and a maximum of four Research Projects, an Administrative Core, a Data Management Core, and an Infrastructure and Opportunities Fund Management Core.

Research Projects

Each PEPR application must include a minimum of two and a maximum of four synergistic research projects in either (1) two or more pediatric chronic diseases, or (2) one pediatric disease validated in both the clinical research and the clinical care settings. The project should be organized around a central scientific theme related to clinical validation of existing or emerging PROMIS PROs, and/or new bank development focused on PROs and the impact of environmental stressors or exposures. Studies may propose validation in multiple cohorts with the same disease or with different diseases.

Administrative Core

The Administrative Core will support the coordination of efforts across the research projects and cores, and will support activities to advance integration into the broader PEPR Consortium. This core will be responsible for organization, management, decision-making, and periodic evaluations within the individual PEPR group, as well as protection of intellectual property, regulatory compliance, involvement of institutional and programmatic resources, and shared publications. This core is expected to create and implement administrative and leadership mechanisms that will foster effective interactions with other PEPR Consortium PDs/PIs and institutions as well as within the individual group to promote synergistic research efforts. A Steering Committee will be established and supported by Administrative Core of the center responsible for the IOF to serve as the governing board of the PEPR Consortium collaborative research program.

Data Management Core

This core will provide central data storage, data management and information security services to all researchers within the Consortium, and will be responsible for ensuring the timely submission of data and data analyses obtained under this award to the NIH designated PEPR Consortium data portal as appropriate. In addition, this core may include study design and statistical support for the researchers within the Consortium. After award, one institution will be chosen by NIH from successful applicants to provide coordination and oversight for consortium-wide data management activities.

Infrastructure and Opportunities Fund Management Core

An Infrastructure and Opportunities Fund (IOF) will be made available to support resources that provide additional assistance and/or technical expertise for projects undertaken by PEPR investigators. One institution will be chosen by NIH after award from the successful applicants to manage the IOF for the entire Consortium. This institution must agree to take responsibility for managing the IOF, including disbursement, administration, and reports.

Management of the IOF will involve:

• Establishing an administrative structure to manage the IOF
• Disbursing and tracking IOF funds under the advice of the Steering Committee
• Implementing plans for interacting with the institutions that will receive IOF funds
• Establishing procedures, formats, and timelines for reporting on the status of IOF projects and expenditures to the NIH and the PEPR Consortium Steering Committee.

All projects supported by the IOF must be within the scientific scope of the investigators awards and the short-and long-term goals of the Consortium. The PEPR Steering Committee will make recommendations to the awardee of the IOF Management Core as to the goals, priorities, and evaluation criteria for the use of the IOF. These recommendations should include: the size and content of the applications; the frequency of applications; the timeline from solicitation to funding; and the process to be used to evaluate the applications. Resources supported by the fund may be housed at a particular PEPR awardee institution, or may be supported by subawards, to other facilities, and may include Consortium coordinating and data management activities. Any activities funded through the IOF must comply with NIH policies. Monitoring compliance is the responsibility of the IOF Management Core and NIH program staff.

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are 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.

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

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).

Applicants can access 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.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

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 and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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:

Jennifer Chi, MHS
Clinical Operations Manager
Division of Skin and Rheumatic Diseases
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5592
Fax: 301-480-1284
Email: PEPR@mail.nih.gov

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core	6
Core (Data Management Core and IOF Management Core)	6
Project (Use for Research Projects)	12

Additional page limits 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 a multi-component application.

The application should consist of the following components:

• Overall: required, 1
• Administrative Core: required, 1
• Data Management Core, required, 1
• IOF Management Core: required, 1
• Research Projects: required, 2-4

Note: Cores and Projects will be listed in the final application in the order in which they were entered in ASSIST.

When preparing your application in ASSIST, use Component Type Overall .

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

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

Applicants should provide evidence that demonstrates the PD/PI's abilities and capabilities to provide leadership, guidance and direction over the proposed project. The PD/PI of the U19 should be a recognized leader in clinical pediatric research and patient care with demonstrated expertise in clinical management and evaluation of chronic disease in children. He/she must have demonstrated expertise in leading large clinical collaborative efforts, recruiting and retaining cohort(s) of high quality, and for considering quality of life issues in his/her research.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Specific Aims: Describe the central scientific theme of the proposed research program, and list in priority order the broad, long-range objectives and goals of the proposed overall program.

Research Strategy:

This section summarizes the overall research strategy for the multi-component application and explains how the proposed program satisfies the purpose and objectives of this FOA as delineated in Section I. Applications responding to this FOA should describe the central theme of the proposed program and explain how the proposed research projects are synergistic and fit under the overarching program theme. The application should be viewed as a confederation of interrelated projects, each capable of standing on its own scientific merit, but complementary to one another. This is an important section for it provides the group of investigators an opportunity to give conceptual wholeness to the overall program by giving a statement of the general problem area and by laying out a broad strategy for attacking the problems. As the strategy develops, each project and core should be cited briefly as to its place in the overall scheme. Summarize the special features in the environment and/or resources that make this application strong or unique. Describe the synergy and collaborations that occurred among the applicant and proposed collaborators. If there was no prior experience of collaboration among the investigators, explain why the proposed investigator collaborations will result in synergy.

Letters of Support: Provide any institutional letters of support specific to the Overall Component.

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, 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 preparing your application in ASSIST, use Component Type Admin Core.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The PD/PI of the application must serve as the Leader of the Administrative Core. If multiple PD(s)/PI(s) are proposed, the PD(s)/PI(s) must select one PD/PI from amongst themselves to serve as the Administrative Core Leader

Budget forms appropriate for the specific component will be included in the application package. The budget request should include travel funds for the PD(s)/PI(s) and Project and Core Leaders to participate in the semi-annual PEPR Consortium Steering Committee meetings.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: List in priority order the proposed activities and services of the Administrative Core. Concisely and realistically describe the work to be completed to address issues of program coordination, communication, and management.

Research Strategy: Applicants should provide a staffing and administrative plan that includes a discussion of the structure and roles of administrative and scientific staff for the core, including: the functions to be performed; and how resources will be prioritized, allocated, and managed. Provide a management plan for fiscal accountability and communication within the program.

Applicants should provide a detailed plan describing how they will manage the Program-specific activities related to the Steering Committee functions, meetings, and administration.

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:

• Generally, Resource Sharing Plans are expected, but they are not applicable for this component.

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.

When preparing your application in ASSIST, use Component Type Core.

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

SF424 (R&R) Cover (Data Management Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Data Management Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Data Management Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components

Project /Performance Site Location(s) (Data Management Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Data Management Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The core is expected to include designated personnel with the expertise to enable compliance with the data- and other resource-sharing policies, consistent with achieving the goals of the program.

Budget (Data Management Core)

Budget forms appropriate for the specific component will be included in the application package. The budget request for this core should include funds for personnel, equipment, supplies and services to support central data storage, data management, and information security services to all researchers within the applicant group; and to support the timely submission of data and data analyses to the NIH designated database as appropriate. The core is expected to include designated personnel with the expertise to enable compliance with the data- and other resource-sharing policies, consistent with achieving the goals of the program.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Data Management Core)

Specific Aims: List in priority order the broad, long-range activities and services of the proposed core, indicating the core’s relationship to the program’s goals.

Research Strategy: Use this section to explain how the core will serve the proposed research projects. For example, describe core activities to support: study design; data collection, cleaning, and tracking; database infrastructure; information management and monitoring; management of complex cross-sectional or longitudinal data; data sharing; sample size and power calculations; and statistical analysis methods.

Letters of Support: Provide any letters of support from collaborators that are specific to the Data Management Core.

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, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• All PEPR investigators will be expected to share their PEPR supported data publicly through a PEPR Consortium data portal designated by NIAMS.

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.

Planned Enrollment Report (Data Management Core)

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

PHS 398 Cumulative Inclusion Enrollment Report (Data Management Core)

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

When preparing your application in ASSIST, use Component Type Core.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (IOF Management Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (IOF Management Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (IOF Management Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (IOF Management Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (IOF Management Core)

Budget forms appropriate for the specific component will be included in the application package.

The budget for the Infrastructure and Opportunity Fund Management Core should not exceed $150,000 Direct Costs per year. The budget request for this core should include the costs of administrative staff to manage the IOF and any needed supplies or services. This core budget may be modified by NIAMS after award, but for purposes of the application, assume that: one part time administrator will be needed; modest oversight effort will be needed from the PD/PI or other senior staff; and 5-10 post-award subawards will be issued by this core during the life of the project. Note that individual Subaward Budget Attachments should not be provided for these post-award subawards at the time of application.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (IOF Management Core)

Specific Aims: List in priority order the proposed activities and services of the IOF Management Core. Concisely and realistically describe the work to be completed to address issues of program communication and fiscal management.

Research Strategy: Use this section to describe how the IOF Management Core will operate to serve the PEPR Consortium, including descriptions of: (1) an administrative structure that includes an experienced administrator; (2) methods of communication with the Steering Committee regarding the disbursement and tracking of IOF funds; and (3) methods for reporting on the status of IOF funds to NIAMS. Also describe plans and procedures to ensure that all projects supported from the IOF will comply fully with all applicable Federal regulations, policies, and guidelines for research involving human subjects, including the evaluation of risks and protections in projects and appropriate ethical oversight.

Letters of Support: Provide any letters of support from collaborators that are specific to the IOF Management Core.

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:

• Generally, Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and GWAS Sharing Plan) are expected, but they are not applicable for this component.

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.

Planned Enrollment Report (IOF Management Core)

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

PHS 398 Cumulative Inclusion Enrollment Report (IOF Management Core)

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

When preparing your application in ASSIST, use Component Type Project.

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

Applications must include a minimum of 2 and may include a maximum of 4 research projects organized around a central scientific theme. The application should include at least one project that conducts validation in two diseases, or at least two projects each focused on a different chronic disease.

SF424 (R&R) Cover (Research Projects)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Research Projects)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Projects)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Research Projects)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Research Projects)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Research Projects)

Budget forms appropriate for the specific component will be included in the application package.

In cases where data for the proposed PRO studies are to be collected from an independently-funded clinical trial, applicants can include in their budgets the costs of additional clinical trial-related activities such as the costs of re-consenting study participants, preparation of protocol or IND amendments, and additional data collection, preparation, and management.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Research Projects)

Specific Aims: List the broad, long-range objectives and goals of the proposed project. Concisely and realistically describe the work to be completed. In addition, state the individual project’s relationship to the program’s goals and how the project relates to other projects or cores to create synergy.

Research Strategy: Each project should address a common theme related to the chronic diseases, the PRO selected for study or both. Synergy should be clearly evident among all the proposed research projects. Each project must include proposed studies with clearly defined pediatric patient cohorts. Describe how the proposed research will contribute to meeting the program’s goals and objectives and explain the rationale for selecting the approach and methods to accomplish the specific aims. In addition to stating the significance for clinical research and care, indicate the project’s relevance to the primary theme of the application and how it will synergize with the other projects. Results from preliminary work should be included as part of the approach section, and must be contained within the page limits of the Research Strategy section.

Required Elements: Applications that do not meet these requirements will be considered incomplete and will not be reviewed.

• Each proposed project must involve the validation of one or more PROMIS instruments/banks in an ongoing pediatric cohort in either 1) a clinical research setting such as that of a longitudinal observational study or a clinical trial, (2) a clinical care setting provided that patients are followed under shared or common protocols that allow for the collection of reliable, interpretable data with significant common elements to ensure a robust sample size. Sample size justification must include a description of the population and subpopulations required to conduct analysis by sex, ethnic, racial and underrepresented groups if scientifically appropriate. Sample sizes should also be appropriate to address the goals of the project.
• The application must include a synopsis of the protocol(s) used in any independently-funded clinical trial(s) from which data will be obtained for this program

Recommended Elements: It is strongly recommended that applications include the following elements to enable comprehensive evaluation by the review panel:

• Strong rationale for selection of the subject population(s) to be studied, the data collection times, and the data analysis plan to be used.
• Clear description of the availability of study subjects, justification of the number of subjects to be studied, statement of the numbers of visits/data points for each study, and concise description of the statistical design for each study and the computational methods to be used for data analysis.
• Concise description of the data management and quality control systems and procedures to be used,
• Each project proposed, where appropriate, should include comparisons of the PROMIS item banks/instruments to clinical gold standard measures of the construct, or to study/validate item banks in special populations. Both types of trials may address proof-of-concept issues, especially for early domain validation efforts and should help provide a sufficient base of validity data for adoption into clinical trials and/or as the basis of support for further hypothesis testing of the domain of interest;
• Projects may also propose to expand existing or new domains relevant to the central theme of the application, but this is optional

Although clinical trials of new interventions will not be supported under this initiative, cohorts may be developed with individuals participating in clinical trials that are funded by independent mechanisms, or cohorts from independently-funded trials in humans. Applications must not propose any new clinical trials. See the following link for the NIH definition of a clinical trial: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-015.html

Protection of Human Subjects: For projects proposing the use of human subjects, provide the information described in the SF424 (R&R) Application Guide.

When possible, it is strongly recommended that informed consent/assent be used that allows the broadest use of de-identified stored samples and de-identified data for future studies, beyond the scope of the study; including genetic studies and unrestricted sharing of the samples and data for use by other researchers, subject to IRB approval.

For projects proposing the use of human data to be obtained from independently-funded clinical trials, supporting documents should be uploaded in the Appendix as described in the instructions for the Appendix section below.

Letters of Support: Provide any letters of support from collaborators that are specific to the research project.

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, 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.

For projects proposing the use of data to be obtained from independently-funded clinical trials, the following materials should be included:

• synopsis of the parent clinical trial protocol
• informed consent/assent forms for the parent clinical trial
• reference to the ClinicalTrials.gov citation, if applicable
• table of events and other studies for the PRO project
• memorandum of understanding from the clinical trial sponsors, IND holders, and Principal Investigators. The applicant should provide a memorandum of understanding signed by the applicant, an appropriate representative of the applicant institution, the PD/PI of the parent clinical trial and his or her academic institution, an appropriate representative of the sponsor of the parent clinical trial and holder of the IND, if applicable and not one of the above. This memorandum will confirm agreement among the various parties and will outline their expectations of the agreement in the following areas: (1) ownership, analysis, access, and release of data from the proposed PRO studies; (2) access to the data from the parent clinical trial (how/when) that is needed to analyze the data generated by the proposed PRO studies, including procedures for prevention of unmasking of the parent trial; (3) documentation of quality assurance procedures for both the parent clinical trial and the proposed PRO studies, and documentation of data and safety monitoring procedures for the parent clinical trial, especially for efficacy trials; (4) intellectual property management; and (5) publication of the proposed profiling study results
• To the extent permitted by applicable laws and regulations, NIH will treat as confidential trial information that the trial sponsor deems proprietary.

Planned Enrollment Report (Research Projects)

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

PHS 398 Cumulative Inclusion Enrollment Report (Research Projects)

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

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

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. 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.

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.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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) and component Project Leads 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.

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 (SAM). 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 NIAMS Referral Office by email at linh1@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

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

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

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 and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

• Are the overall program goals and scientific questions appropriate for the PEPR program?
• Will important scientific gains and synergy be achieved by combining the component projects and cores into a multi-project program?
• Will the scientific gains be beyond those achievable if each project were pursued independently?
• Is the program cohesive in terms of the research projects and cores fitting into a common theme?
• Does the PD/PI have sufficient experience on chronic pediatric diseases clinical research and care, leadership ability, and scientific talent to develop a program of integrated research projects with a well-defined central research focus?
• Is there evidence of unique features in the environment and resources and of institutional support?

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 Research 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?

Are the Project Lead(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? Are the designated personnel sufficient to enable compliance with the data- and other resource-sharing policy?

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?

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

If the project involves 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?

In each Research Project, are the human subject cohorts to be analyzed well characterized, available in sufficient numbers, and appropriate for the stated goals? Are adequate resources available to conduct the proposed studies, including a local database and bioinformatics expertise, sample repository, and statistical capability? Will data collection and analysis methods be appropriate in terms of quantitation, controls, and management? If proposed for development, are new assays or statistical or bioinformatics tools scientifically sound?

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?

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the core to exert a sustained, powerful influence on the research field(s) involved.

Reviewers will consider each of the review criteria below, as appropriate for the individual core, in the determination of scientific merit and provide an overall impact score for each Core, but will not give separate scores for these items.

• Are the staffing and administrative plans appropriate to facilitate attainment of the objectives of the proposed program?
• Are the experience, level of commitment, and availability of the Core Leader adequate to manage the core and the overall program?
• Is the plan to organize communications, group meetings, and teleconferences adequate and appropriate?
• Are the plans for coordination, problem identification and resolution, and establishment of a strong collaborative environment for the program appropriate?
• Are the plans for resource allocation within the program adequate and appropriate?
• Is the management plan for fiscal accountability and communication within the program appropriate?
• Are the plans for communication and collaboration with other PEPR awarded programs adequate?

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the core to exert a sustained, powerful influence on the research field(s) involved.

Review Criteria Data Management Core

Reviewers will consider each of the review criteria below in the determination of scientific merit and provide an overall impact score for the Data Management Core, but will not give separate scores for these items.

• Are the experience, level of commitment, and availability of the Core Leader adequate to manage the core?
• Are there sufficient effort and expertise dedicated to both data management and data sharing policies?
• Is there sufficient bioinformatics infrastructure to support the proposed activities?
• If support is proposed for study design and statistical analyses, are sufficient effort and expertise included in the core?

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.

IOF Management Core

• Is provision of the proposed core services to the program described in sufficient detail?
• Is sufficient justification provided for the management methods proposed?
• Are the personnel charged with managing the IOF appropriate?
• Are adequate plans and procedures proposed by the applicant to assure compliance with relevant federal regulations and NIH policies for the protection of human research participants, including the evaluation of risks and protections in project proposals, appropriate ethical oversight of funded projects, and plans for monitoring data and safety in clinical research projects?

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; and 3) 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 NIAMS in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• Will receive a written critique.

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council (NAMSAC). 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.
• Compliance with data- and resource-sharing policies.

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

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

• Defining the details and goals of the project as a whole within the guidelines of this FOA.
• Overseeing/performing the scientific activities.
• Administratively managing the U19 grant.
• One PD/PI from each U19 award will be a voting member of the Steering Committee; will participate in all Steering Committee activities, meetings and teleconferences; and will follow the policies and procedures developed by majority vote of the Steering Committee.
• The PD/PI will accept close coordination, cooperation, and participation of NIH staff in the scientific, technical, and administrative management of the PEPR program.
• While safeguarding the privacy of participants and protecting confidential and proprietary information, the PD/PI will be expected to make data publicly available. The timeline will be negotiated at the time of Award and included as a Term and Condition of Award. Data set definitions will be negotiated with NIAMS as part of the data-sharing plan for the awardee.
• The PD/PI will ensure successful completion of the data- and other resource-sharing plans negotiated with NIAMS. Sharing plans represent a commitment by the applicant institution (and its subcontractors, if any) to support and abide by the plan.
• The PD/PI will establish procedures within the program to ensure that all members of that program, including any scientists added via IOF support, conform to the data-sharing and other resource-sharing plans. The final versions of NIAMS-approved sharing plans will become a condition of the award. Note that funding beyond the first year may be subject to downward negotiation depending on the progress made in meeting negotiated milestones within the data- and other resource-sharing plans.
• Infrastructure and Opportunities Fund (IOF) management: after all grants have been awarded, one U19 awardee institution will be selected by NIAMS to manage the IOF for the entire consortium. This institution must agree to take responsibility for managing the funds, including the disbursement, administration, and reporting on the use of such funds as recommended by the Steering Committee and approved by NIAMS. Management of the IOF will involve:
  • Establishing an administrative structure to manage the IOF.
  • Disbursing and tracking IOF funds under the direction of the Steering Committee.
  • Implementing plans for interacting with the institutions that will receive IOF funds.
  • Establishing procedures, formats, and timelines for reporting on the status of IOF projects and expenditures to the NIAMS and the PEPR Steering Committee.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

NIH Project Scientists will have substantial programmatic involvement as described below:

• Provide input into the design of research activities.
• Play a key role in coordinating research efforts.
• Coordinate NIAMS staff assistance, including participation in periodic on-site monitoring with respect to compliance with Federal regulations, quality control, accuracy of data recording, sample accrual, etc.
• Evaluate the adequacy of data-sharing and other resource-sharing plans when making funding recommendations. NIAMS program staff may negotiate modifications of sharing plans with the applicant.
• Ensure that all PEPR investigators conform to the data-sharing and other resource-sharing policies.
• Participate in investigator and Steering Committee meetings.
• Facilitate collaborations with and access to other NIH-supported research resources and services.
• Facilitate negotiations with companies interested in participating in clinical studies with investigators.
• Advise in project management and technical performance.
• Serve as a resource for scientific and policy information related to the goals of the awardees research.
• Have confidential access to data generated under this Cooperative Agreement, for use in the preparation of internal reports on the activities of the awardees.
• Provide assistance to the Steering Committee in the development of procedures for evaluating the performance of research studies and monitoring any clinical studies developed via the IOF.
• Promote coordination of Steering Committee activities and implementation of its recommendations, decisions, and policies.
• Provide guidance to the awardees with regard to:
  • Compliance with Federal regulations
  • Oversight and monitoring of collaborative research
  • Feasibility of timely completion
  • Plans for incorporation of new technologies or other resources

After award of the grants, the NIAMS may establish an External Advisory Board (EAB) to advise NIAMS by reviewing, evaluating, and prioritizing the scientific progress of the individual awardees and the Consortium. EAB members will be selected by NIAMS and applicants should NOT contact any individuals for the purpose of serving on this EAB, nor should they identify any such individuals in their applications.

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

• Steering Committee membership: the PEPR Consortium will be governed by a Steering Committee to coordinate and facilitate research activities for the overall program; to facilitate compliance with the data- and other resource-sharing policies; and to promote optimal research flexibility, synergy, and efficiency.
• Steering Committee responsibilities will include:
  • Evaluate progress of the individual research projects and provide guidance
  • Establish protocols for the review and modification of ongoing studies, which may include recommendations for new collaborations or resource allocations among the PEPR members
  • Coordinate resource sharing among the programs
  • Assist as required in preparing formal reports summarizing activities and/or progress within the PEPR Consortium
  • Make recommendations to support specific applications through the IOF, recommend budget allocations for each IOF project, and monitor the progress of funded projects
  • Define needs for centralized resources such as standardized assays, bioinformatics expertise, or sample repositories
  • Review schedules for submission of PEPR generated data and data analyses from each PEPR program for public dissemination
  • Promote compliance of consortium members with the schedules for data- and other resource-sharing
  • Define procedures for the publication and/or oral presentation of results or data collected collaboratively within the PEPR Consortium
  • Meet by teleconference on a periodic basis to discuss business issues and exchange scientific advances
  • All PEPR investigators will be required to accept and implement policies approved by the Steering Committee.
• The Steering Committee will include one PD/PI from each awarded U19 as a voting member, and two NIH Project Scientists as voting members.
• Research Project and Core Leaders and other consortium investigators may serve as non-voting members, as determined by the Steering Committee. NIAMS may also appoint additional staff to serve on the Steering Committee as non-voting members, including representatives from the National Institutes of Environmental Health Sciences, the FDA and the CMS.
• The Steering Committee will establish subcommittees and working groups with discrete responsibilities and authorities to promote comprehensive data reporting, uniformity of practices for validation and standardization, data and sample sharing, and priority setting.

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.

Progress reports for multi-year funded awards are due annually on or before the anniversary of the budget/project period start date of award. The reporting period for multi-year funded award progress report is the calendar year preceding the anniversary date of the award. Information on the content of the progress report and instructions on how to submit the report are posted at http://grants.nih.gov/grants/policy/myf.htm.

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

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

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: http://grants.nih.gov/support/index.html
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-710-0267

James Witter, M.D., Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5055
Email: witterj@mail.nih.gov

Wm. Phil Tonkins Jr., M.S., Dr.PH
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301- 594-4979
Email: tonkinsw2@mail.nih.gov

Kathy Salaita, Sc.D.
National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5033
Email: Kathy.salaita@nih.gov

Andrew Jones
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-435-0610
Email: jonesan@mail.nih.gov

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

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