It is critical that applicants follow the Multi-Project (M) 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 Funding Opportunity Announcement (FOA) invites research applications to plan and implement Interdisciplinary Mechanistic Research Centers (MRC) in Low Back Pain (LBP) with the NIH Back Pain Consortium (BACPAC) Research Program. BACPAC is a patient-centric research program focused on translational and clinical research for discovery of chronic low back pain (cLBP) mechanisms, and on identification and testing of new interventions targeted to individual patients. BACPAC will utilize novel analytics and technologies to extensively phenotype patients with low back pain, develop an integrated model of cLBP, produce new and improved diagnostic and treatment algorithms, and test new therapies in Phase 2 clinical trials. The MRCs will conduct translational and clinical research projects addressing critical gaps and opportunities in LBP with advanced analytics and approaches to improve understanding of disease and identify new targets for intervention. The MRCs will generate data for deep patient phenotyping and for the development of patient-based algorithms. The MRCs will conduct a collaborative, adaptive design, multimodal therapy study in cLBP with the aim of improving the use of therapies targeted to individual patients. The MRCs will run in parallel and synergize with projects supported in the BACPAC Data Integration, Algorithm Development and Operations Management Center, Technology Research Sites and Phase 2 Clinical Trials. BACPAC is part of the multi-pronged HEAL (Helping to End Addiction Long-term) Initiative, an aggressive effort to speed scientific solutions to stem the national opioid public health crisis (https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative). HEAL will build on extensive, well-established NIH research to address the opioid crisis and provide safer therapies for people with pain.

NIH has identified a set of research priorities reflecting urgent unmet needs across the lifespan along with areas of promising scientific opportunity in order to develop concrete strategies capable of providing rapid and durable solutions to the opioid crisis. This includes an improved understanding of the biological underpinnings of chronic pain and discovery and testing of new non-addictive pain treatments. The Federal Pain Research Strategy is a long-term strategic plan to guide the federal agencies and departments that support pain research and to advance the science to better understand pain and improve pain care. Overall, the priorities cover basic through clinical, dissemination, and implementation research to support the translation of scientific discoveries into clinical practice and improve the lives of people with pain. The strategy includes several priority recommendations regarding the evaluation of efficacy, safety and interactions of novel drugs and non-pharmacologic treatments for pain. https://iprcc.nih.gov/Federal-Pain-Research-Strategy/Overview.

Back pain is one of the most common forms of chronic pain among adults worldwide. According to National Health Interview Survey data, 20% of adults in the United States reported frequent back pain and 28% of adults experienced low back pain that lasted a whole day or more during the past three months. Out of all 291 conditions included in the Global Burden of Disease 2010 Study, low back pain ranked highest in terms of years lived with disability. Back pain is over-represented among women and in people with low socioeconomic status. Children are also affected, a recent study indicated that the prevalence of low back pain in adolescents increases with age and reaches the levels observed in adults by age 18. There are disparities in the treatment of pain between whites and racial/ethnic minorities.

In 2013, the NIH Pain Consortium established a Steering Committee for a Research Task Force (RTF) on Research Standards for cLBP. The RTF made recommendations for the use of a standardized consistent use of a definition of cLBP, a minimum dataset, and reporting outcomes. The RTF also made future research recommendations. They concluded that greater consistency in reporting should facilitate comparisons among studies and the development of disease phenotypes. https://www.ncbi.nlm.nih.gov/pubmed/24787228.

Despite the pipeline for new pharmacologic treatments for back pain which includes agents targeting inflammation, peripheral pain transmission or amplification, central sensitization, and descending modulation, there are currently no consistently effective and durable pharmacologic interventions for cLBP. This is also the case for non-pharmacologic interventions such as exercise, multidisciplinary rehabilitation, acupuncture, cognitive behavioral therapy (CBT), and mind-body practices. Clearly, more rigorous studies are needed that better integrate different modalities, and development of individualized treatment plans. In addition, a better means of identifying sources of pain in different individuals is a crucial need as is the need for patient stratification and improved outcomes measures.

Disease heterogeneity, lack of informative data for the management of patients with cLBP and the challenges of identifying the source of pain and assessing treatment response and disease modification necessitate the formation of a clinical program to undertake sequential, adaptive clinical trial design approaches to evaluate the safety and efficacy of targeted interventions. A translational research program can provide evidence to stratified patient populations, with specific phenotypes, and the use of predictive and monitoring algorithms will enhance the efficiency of trials as compared to single interventional approaches in large, heterogeneous patient populations. Novel designs that are paired with advanced diagnostic, imaging and robust outcome assessments and fully integrated mechanistic studies are needed to provide preliminary evidence of clinical effect and to design and launch exploratory trials. Clinical trials testing the efficacy and safety of novel agents, including pharmacologic and non-pharmacologic interventions are needed to advance effective therapies for cLBP.

The goal of the BACPAC Research Program is to probe the biomedical and biopsychosocial mechanisms of LBP using interdisciplinary methods and innovative technologies so that novel individualized targeted treatments can be developed, tested and combined for an integrated approach to treat cLBP. This highly collaborative research program will conduct research to deliver an integrated model of cLBP and patient-based algorithms to facilitate the identification of treatments tailored to the individual patient. The BACPAC Research Program will generate new knowledge regarding phenotypes, endotypes, mechanisms, diagnostics, trial outcomes, and therapeutic responsiveness. Data generated regarding disease phenotypes, endotypes, and treatment responses will be used to develop and test diagnostic, predictive and treatment algorithms and in multi-stage, adaptive study designs that may have the potential to determine the best therapeutic response of individual patients. BACPAC will aim to study low back pain in patients from diverse ethnic, racial, and socioeconomic groups and across the lifespan including adolescence.

Public Law 115-141, the Consolidated Appropriations Act of 2018 (signed March 23, 2018) includes a requirement that grantees from for-profit applicant organizations must provide a 50% match and/or in-kind contribution of all federally awarded dollars under the grant award (direct costs, as well as facilities and administrative costs) for research related to opioid addiction, development of opioid alternatives, pain management and addiction treatment.

Matching Requirement: A grantee from a for-profit organization funded under this announcement must match funds or provide documented in-kind contributions at a rate of not less than 50% of the total-Federally awarded amount, as stipulated by Public Law 115-141, the Consolidated Appropriations Act of 2018.The applicant will be required to demonstrate that matching funds and/or in-kind contributions are committed or available at the time of, and for the duration of, the award. Applications must identify the source and amount of funds proposed to meet the matching requirement and how the value for in-kind contributions was determined. All matching funds and/or in-kind contributions must be used for the portion of allowable project costs not paid by Federal funds under the grant award. NIH will not be the recipient, nor serve as a pass-through entity, of any such matching funds and/or in-kind contributions required under this announcement. See 45 CFR 75.306 for additional details.

The BACPAC Research Program consists of four primary components that will work collaboratively to achieve the overarching goals:

• A Data Integration, Algorithm Development and Operations Management Center (DAC). This Center will guide and coordinate all activities of the consortium and ensure communications, interactions, synergies and accountability. It will manage a core as a Consortium-wide registry, including patient reported outcomes and preferences. The DAC will include the BACPAC Systems Biology and Bioinformatics Group (SBG) to provide system level analysis for BACPAC generated multidimensional datasets to produce an integrated model of LBP. Using data from clinical studies across the Consortium, this Center will develop patient-centered algorithms for prediction of optimized therapeutic interventions.
• Interdisciplinary Mechanistic Research Centers (MRC) that will conduct translational research leading to further characterization of low back pain mechanisms and improved phenotyping of patients with chronic low back pain in clinical cohorts. Centers might conduct exploratory trials or innovative design clinical studies to obtain data for deep patient phenotyping or test new technologies.
• Technology Research Sites (Tech Sites) that will conduct technology development and deployment.

The Interdisciplinary Mechanistic Research Centers and the Technology Sites will interface with the Systems Biology and Bioinformatics Group for the first level of research data integration and modeling. Together the Centers, Sites and Group will explore linkages between specific structural, dynamic, cellular or molecular abnormalities to specific patient-reported symptoms and function.

• Phase 2 Clinical Trials (Phase 2CT). The goal of the Phase 2 CTs will be to test the safety and efficacy of non-addictive therapies for cLBP. These trials will be conducted in two phases. A planning phase (UG3) to be carried out collaboratively within the BACPAC Consortium in consultation with the Early Phase Pain Investigation Clinical Network: EPPIC-Net (formerly known as the Clinical Trial Network for Pain Research, CTNPR)
• (https://grants.nih.gov/grants/guide/notice-files/NOT-NS-18-058.html,
• https://grants.nih.gov/grants/guide/notice-files/NOT-NS-18-069.html, https://grants.nih.gov/grants/guide/notice-files/NOT-NS-18-057.html).
• The trial implementation phase (UH3) will be conducted within the EPPIC-Net Clinical Trial environment using the EPPIC-Net Trial Hubs, Clinical Coordinating Center (CCC) and Data Coordinating Center (DCC) infrastructure, services, operating and cost standards. Innovative trial designs will be used to test new non-addictive drugs, biologics, devices and complementary medicine approaches to relieve pain and improve physical function.

In addition to the component-specific projects, the BACPAC will conduct:

• A Collaborative Clinical Project to test at least one specific translational or clinical hypothesis on low back pain that builds on strengths of participating center(s) and engage other members of the BACPAC Research Program after award.
• Pilot Studies to be conducted either by the individual Centers, Sites or by the Consortium.
• Ancillary Studies linked to the trials to understand biological and biopsychosocial effects of the therapies or other aspects of the disease or treatment, to identify potential biomarkers and test new outcome instruments.

To manage the support for these projects, the DAC will establish a Funds Management Unit.

The Funds Management Unit (FMU) will administer, on behalf of the entire BACPAC Research Program, the Collaborative Research Fund for support of the Pilot and Ancillary Studies Projects and additional studies required for achieving the aims of the BACPAC Research Agenda. In addition, the FMU will manage funds to establish a future contract with EPPIC-Net.

BACPAC Governance Structure

The success of the BACPAC Research Program will require collaboration, cooperation, and extensive data and resource sharing among its component parts. It will also demand a commitment by all members to use common data, protocols and standards agreed upon by the Consortium. Therefore, participation in the BACPAC governance committees is an important responsibility. The governance structure will be finalized with the participant investigators and institutions after awards are made for the Mechanistic Centers, Technology Sites, Phase 2 Trials and the DAC.

These committees will include:

The BACPAC Steering Committee (BACPAC SC) will function as the governing body for the BACPAC Research Program. The BACPAC SC will have primary responsibility for developing a research agenda for the BACPAC Research Program to ensure that the work of the consortium leads to an integrated model of low back pain and to the development, testing and validation of patient-based diagnostic and treatment algorithms.

The BACPAC SC will:

• Provide scientific leadership for the BACPAC Research Program.
• Promote and ensure synergy, collaboration, and sharing of data and resources across the BACPAC components and among members.
• Formulate the BACPAC Research Program Agenda and approve the Collaborative Projects.
• Coordinate the BACPAC scientific agenda with EPPIC-Net and other funded components of the HEAL initiative.
• Disseminate information about the activities of the BACPAC Consortium.
• Report to the NIH and to the BACPAC Advisory Board appointed by NIAMS/NIH.

The BACPAC SC will establish Functional Working Groups to build synergies and facilitate interactions around specific research activities such as: 1) Mechanistic Research, 2) Systems Biology/Bioinformatics, 3) Technology Development Standards; and 4) Patient Reported Outcomes and Preferences.

The BACPAC Executive Committee (BACPAC EC) will direct the day-to-day administration and operations of the BACPAC Research Program. The BACPAC EC will be responsible for operationalizing the Research Agenda approved by the BACPAC SC. The EC will carry out a broad range of technical, operational and management functions to support the implementation of the BACPAC Research Program Agenda and for the day-to-day monitoring and coordination of BACPAC research projects.

The BACPAC EC will:

• Develop and execute a plan to implement the research priorities of the BACPAC Research Agenda.
• Coordinate the SC, Functional Working Groups, and Clinical Management Committee activities and deliverables.
• Disseminate the SC approved research plans, protocols and other relevant information to all BACPAC participating investigators and functional entities.
• Oversee planning of the collaborative project.
• Ensure the work of the Consortium is progressing along the agreed upon timelines and policies.

The BACPAC Clinical Management Committee (BACPAC CMC) will lead the development of a plan for BACPAC clinical common data and protocol elements for approval by the BACPAC SC.

The BACPAC CMC will:

• Develop a BACPAC Clinical Consensus Plan for a) cLBP case definition, b) a minimum dataset to be obtained in all participants, and c) outcomes measures that will be used across all projects. The Consensus Plan will be reviewed and approved by the SC.
• Serve as the Clinical Expert Group for the DAC activities around Clinical Registry, Data Integration and Coordination, and for the Phase 2CTs.
• Serve as the Clinical Expert Group for the DAC activities around Algorithm Development, Testing, and Validation to ensure algorithms are developed in the relevant clinical context.
• Design the Collaborative Clinical BACPAC Study in collaboration with the DAC Adaptive Design Expert Group.

An External Scientific Advisory Group (ESAG) will be constituted by NIH to provide advice and recommendations on research priorities, specific projects/analyses, project-transition and future directions.

Membership and meeting frequency for the SC, EC, CMC and the ESAG are outlined in the table entitled "BACPAC Governance Committees". BACPAC SC meetings may include other ad hoc participants, such as research team members from the MRCs, Tech Sites or Phase 2CT. The Chair or co-Chairs of the BACPAC SC will be selected by NIAMS for the first year of award. The SC members will nominate candidates for Chair or Co-Chairs for NIAMS/NIH approval in years 2-5.

Table: BACPAC Governance Committees

Committee	Membership	Meetings
Steering Committee	MRC PIs, Tech Sites PIs, Phase 2 Trial PIs, BACPAC DAC PI (s), SBG PI, NIH Official	Monthly by phone or webinar Twice per year face to face meetings (at least one in the Washington DC metro area)
Executive Committee	DAC PD/PI (chair), MRC PI, Tech site PI, BACPAC Program Manager, NIH Official	Weekly by phone or webinar
Clinical Management Committee	MRC Clinical Cores PIs, Phase 2CT PIs, DAC PI or designee (Chair), BACPAC Program Manager, NIH Official	Twice a month by phone or webinar, adjusted by activity and needs of the studies.
External Scientific Advisory Group	4 external experts from academia and federal agencies and 1 NIH official	As needed, but at least one annual face-to-face meeting together with a BACPAC SC meeting and once a year by phone or webinar.

Timeline

The first year of the program will include significant planning activities during which limited funds will be available to awardees for all four FOAs. In this year, the Steering Committee will be established, the consortium will develop the clinical protocols, standard operating procedures, staff training plans, recruitment plans, electronic health record standardization, safety standards, and regulatory processes, identify biospecimen types and amounts to be collected, and develop biospecimen collection and storage protocols if needed. A systems biology analysis plan and an integrated clinical data analysis plan will be developed.

The planning year will be followed by up to four additional years (duration varies across awards) of higher funding levels, during which the study will be implemented. It is anticipated that patient enrollment for the Collaborative Clinical Project and for the Implementation Phase of the Phase 2CTs to begin in Fall 2020, immediately after the planning year. In Fall 2021, an assessment will be performed to determine whether the rate of patient enrollment and retention is adequate to meet the assumptions of the power analysis. In the event of lower than expected enrollment or poor retention of patients, the BACPAC Steering Committee will make recommendations to NIH to either increase enrollment or terminate the study. NIH will make the final determination.

The MRCs will conduct translational research studies designed to address fundamental questions about back pain. Translational research is defined here as applied and clinical scientific research that is directed towards testing the validity and limits of applicability of knowledge derived from basic science and bioengineering to the understanding of human diseases and health. It could be research involving living human subjects (i.e., clinical), but it might also be non-clinical involving the study of human genes, tissues, specimens, or cells. The objective is to improve the understanding of disease, generate new information that contributes to accurate patient phenotyping and identify novel pathways and targets for intervention. The MRCs will also use adaptive novel study designs and multimodal therapies to understand the basis for patient treatment responses and improve the targeting of effective treatment to individual patients.

The investigator has the flexibility to design a BACPAC Mechanistic Center with optimal structure to foster synergistic interactions or maximize integration and productive interdisciplinary collaborations. There are 4 required components of a BACPAC Mechanistic Center. Required components include:

1. A strong research program focused on back pain:

Each MRC will consist of one or more translational Research Projects and one or more Research Cores carried out by a multi, inter or transdisciplinary team focused on the translation of new scientific findings and technological development into better approaches for improving the lives of patients with chronic back pain. The research should be conceptualized and executed with a biopsychosocial perspective to ensure physical, mental and social aspects of cLBP are fully addressed. The focus of the research could be either:

a) a back pain-targeted translational research theme addressed by synergistic Research Projects with support from the Research Cores; or

b) a back pain-related critical challenge addressed through a single Research Project enabled by several highly interactive Research Cores whose work is integrated over time during the development and implementation of the Project.

Research Projects within each Center should be linked to a cohort or a trial and designed such that at a minimum, the data generated will contribute directly to either an integrated model of back-pain or to improving patient phenotyping.

The research data generated by projects and cores in the MRC will be shared with the DAC SBG to carry out systems-level analyses of multi-dimensional datasets. The goal is to identify pathways involved in disease, integrate them with clinical and other patient-based data, and define how they differ between patients with different clinical characteristics.

2. A Clinical Core that includes:

a) an existing, ongoing well characterized back pain cohort with the capacity to rapidly expand enrollment.

b) a strong approach to operationalize and/or develop a working definition of cLBP, for a minimal common dataset and for the outcomes measures that will be used in all patients enrolled at the Center the Research Project(s) and can be shared with other Centers and sites across the BACPAC Research Program.

c) current approaches and potential capacity for rapidly expanding phenotyping and deep patient phenotyping within the Center and to other MRCs, Tech Sites and Phase 2CTs.

d) approaches and capacity for conducting studies using multimodal therapies for cLBP and adaptive design studies.

e) a strong approach to data management and data sharing with the BACPAC DAC.

f) evidence for capacity to implement mechanistic studies deployed across the consortium, whether initiated by another MRC or by the Tech Site.

3. An Administrative Core:

The Center must have an Administrative Core with an Advisory Committee that includes scientific and lay members. Each Center must have a Director and Associate Director, one of whom is a clinical investigator and is responsible for fostering clinical translation and assuring a mutually supportive interaction between investigators of the clinical discipline and those of other research disciplines. The Director of the Center is responsible for the organization and overall operation of the Center. The Center Director, the Associate Director and the Advisory Committee should have the collective expertise to assure focused development and implementation of high quality and meaningful translational research.

4. An Informatics Core (IC):

The core will conduct data collection/management activities to support the clinical and research activities of the MRC, with the option to propose to extend the services and support to the other centers and projects within the BACPAC consortium. This Core will directly interact with the BACPAC DAC and SBG.

Research topics that will NOT be considered responsive to this FOA:

• Phase 3 clinical trials.
• Animal studies are allowed but the model and/or data will have to demonstrate immediate relevance and applicability to human disease.

Pre-Application Webinar

NIAMS will hold a pre-application informational webinar for this FOA. The date, time, and other details for the webinar and BACPAC FAQs will be posted at NIAMS website, https://www.niams.nih.gov/grants-funding/funded-research/nih-back-pain-consortium-bacpac-research-program.

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

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

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) 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 to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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.

For grantees from a for-profit organization, this FOA does require cost sharing, as defined in the NIH Grants Policy Statement. More information on cost matching requirements is in Section IV.2 R&R or Modular Budget

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).

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

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, 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.

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:

Robyn Bent, M.S.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
One Democracy Plaza, Suite 800
Bethesda, MD 20892
Telephone: 301-594-5055
Email: [email protected]

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	30
Admin Core	6
Research Project	12
Research Core	12
Informatics Core	6
Clinical Core	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
• Administrative Core: required
• Research Projects: at least one required*
• Research Core: at least one required*
• Informatics Core: required
• Clinical Core: required

*To be considered complete, a Center application will need a minimum of three Research Cores or Projects, in any combination, in addition to the required Administrative, Clinical and Informatics Cores.

When preparing your application, use Component Type Overall .

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

Cost Matching Requirement for For-profit Applicants

Cost matching or documented in-kind contributions is required for for-profit organizations responding to this FOA. The for-profit awardee is required to match funds or provide at least a 50% matching of funds or documented in-kind contributions at a rate of not less than 50% of the for the total-Federally awarded amount (direct costs, as well as facilities and administrative costs), as stipulated by Public Law 115-141, the Consolidated Appropriations Act of 2018.

Federal funds may not be used as a source of matching funds. Generally, cost matching requirements may not be met from the following sources:

a) Costs borne by another Federal grant or sub award;

b) Costs or contributions toward cost sharing on another Federal grant, a Federal procurement contract, or any other award of Federal funds;

c) Cost of services or property financed by income earned by contractors under a contract from the recipient (or sub recipient);

(d) Program income; and

(e) Patient incentives.

The for-profit organization will be required to demonstrate that matching funds and/or in-kind contributions are committed or available at the time of, and for the duration of, the award. Applicants must submit budgets that clearly document the total costs, the source and amount of matching funds, and how valuation was determined in the case of in-kind contributions, as well as the Federal and Institutional (non-Federal) components of the budget. All matching funds and/or in-kind contributions must be used for the portion of allowable project costs not paid by Federal funds under the grant award. NIH will not be the recipient, nor serve as a pass-through entity, of any such matching funds and/or in-kind contributions required under this announcement. See 45 CFR 75.306 for additional details.

Budget Justification: All for-profit applicants must document the matching (non-Federal) component and the federal (non-matching) component in the total project budget. That is, the requested budget plus the cost-matching budget must be detailed in tabular format to document the cost-matching (non-Federal) component and the federal (non-cost matching) component. The amount of matching is subject to adjustment based on total allowable costs incurred. All costs and contributions used to satisfy the matching requirement must be documented by the recipient, including how the value for in-kind contributions was determined, and are subject to audit. The cost matching requirement is not negotiable for for-profit organizations.

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.

Other Attachments:

Applicants may propose one or more concepts for future Pilot Research Projects and Ancillary Studies. Label the file "Pilot.pdf".

Present a brief description of the goals, significance and feasibility for each of the proposed concepts, indicating whether it will be associated with one or more or the components of the BACPAC Research Consortium. Details on the technical approach and a detailed budget should not be included. Each concept description should not exceed one page. Concepts may propose exploring a research question or applying the applicants analytic or technology in a different experimental model, system or population elsewhere in the BACPAC research Program sites and Centers.

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.

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 broad long-term objectives and goals of the proposed Mechanistic Center. Include the objectives for each of the Research Projects, Research Cores, the Clinical Core, the Informatics Core and the Administrative Core.

Research Strategy:

The Research Strategy section of the Overall Component serves to introduce the proposed Center, to state the objectives, and to identify either the research theme or the research challenge that the Center proposes to address. This section also provides reviewers with a sense of the overall significance of the BACPAC Mechanistic Center, i.e., how the Center and the unique research approaches proposed will advance translation of knowledge to improve our understanding of the mechanisms of back pain and lead to new therapeutic, diagnostic or prevention strategies or other tangible products or deliverables for back pain.

The Research Strategy section of the Overall component should be organized in the following fashion:

Overview

Each BACPAC Mechanistic Center application should have an Overview section. This section should describe the goals of the Center, the disciplines brought together and explain the strategy for achieving the objectives of the overall program. Describe the scientific, organizational and management structure of the Center and how they relate to either the selected research theme or research challenge. Include the leadership structure of the Center and the various Research Components and Cores. It is important to emphasize the events that have led to the current application, and especially to describe the anticipated unique opportunities for translational research within the proposed Center. Briefly describe each of the proposed project(s), and how the project(s) address the overarching theme or challenge in back pain. Briefly describe any research cores that are included in the application and how each core will support the proposed project(s). Address how the research contributes to 1) improved patient phenotyping, 2) an integrated model of LBP, 3) development of new and improved algorithms, and/or 4) identification of new targets for intervention.

Significance of the Mechanistic Center

This section should succinctly present the areas of back pain research focus and explicitly state and clearly describe the premise or the rationale for the proposed Center. The section should indicate the significance of the proposed work with respect to the research activities of the community and field(s), the unique and scientific, clinical, technical and informatics aspects of the Center, any critical resources such patient cohorts, indicating the degree to which the Center is expected to accelerate scientific and translational progress in back pain.

Innovation of the Mechanistic Center

Describe the innovation brought by the Mechanistic Center. Address how the proposed research will advance or change current research or clinical practice paradigms by using novel theoretical concepts, approaches or methodologies, instrumentation, or interventions. Describe how the research integrates current biomedical and psychosocial approaches to the study of back pain. Describe the potential of any interdisciplinary collaboration and synergistic interactions within the BACPAC consortium that will bring innovation to the Center and to the back-pain research field. Describe how the innovation in the Center can be shared with other MRCs, Tech Sites and Phase 2CTs in the BACPAC Research Program.

Approach of the Mechanistic Center

Summarize the overall strategy and the unique research approaches or any unique cohorts proposed that will accomplish the specific aims of the Mechanistic Center and accelerate discovery and translation of knowledge to improve our understanding of human pathobiology and lead to new therapeutic, diagnostic or prevention strategies in back pain. Describe any anticipated problems, alternative strategies and benchmarks for success. Indicate how the Center will leverage existing resources within the BACPAC to advance the goals and objectives of the proposed Center.

Describe the strategy and approaches that the proposed Center will employ in bringing together all the individual elements into a functional and cohesive unit such that the whole is greater than the sum of its parts. If more than one project is proposed, describe strategies and approaches used to stimulate and foster synergistic interactions among projects. If a single project is proposed with two or more research cores, describe how the proposed research cores serve as an integral part of the Center and are essential to the accomplishment of the translational objectives of the research project. This section should include a description of ways, type and frequency of interactions designed to maximize integration of cores with the project and present an integrated list of milestones and combined timeline. The approaches for the components of the MRC are expected to be focused in cLBP, the inclusion of studies using small cohorts with related conditions, such as acute back pain, must be justified scientifically, and the applicant needs to clearly explain how the results and data directly relate to the scientific goals and objectives of BACPAC.

Role and Contributions of the Mechanistic Centers to the BACPAC

Describe how the Center can contribute to the overall goals of the BACPAC Research Program. Describe any unique capabilities and resources that can be shared across the Consortium to and contribute to the BACPAC Research Agenda. Describe the capacity of the MRC to implement collaborative mechanistic studies and collaborative clinical adaptive design studies. Explain how the Clinical Core will contribute to the collaborative clinical adaptive multimodal study and how the Informatics Core and other research cores will share data with other MRCs and with the DAC Data Integration and the Systems Biology and Bioinformatics Groups.

Letters of Support:

For-profit applicants must include a letter(s) of support confirming that the required secured cost matching (cash; in-kind commitments such as salary, consultant costs, equipment) is available and confirm that the essential personnel have the authority within the organization to allocate resources.

Provide letters of support from outside consultants or collaborators that will contribute to the project or provide resources necessary to carry out the proposed research. Applications that do not include the letters of support will be considered incomplete and will be withdrawn without review.

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:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

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

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

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

When preparing your application, use Component Type Administrative 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.

Applications must include an Intellectual Property (IP) strategy. Applicants are encouraged to prepare this attachment section in consultation with their institution's technology transfer officials. The section should be labeled "Intellectual Property Strategy. pdf" and may not exceed 3 pages. Include the Attachment even if IP issues are not a consideration for the project. Indicate: IP issues are not applicable and explain why.

This section should describe a dissemination plan that involves patent protection and commercialization:

• Describe the IP landscape surrounding their model system. Applicants should describe any known constraints that could impede sharing of their model system (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar model systems that are under patent protection and/or on the market, etc.) and how these issues could be addressed with achieving the goals of this program.
• Include a letter from any entity who has ownership of the IP indicating whether they will provide the technology, if there are any limitations on the studies that can be performed with that technology, agreement about public disclosure of results (including negative results), and whether there is an agreement already in place.
• If patents pertinent to the technology being developed under this application have been filed, the applicant should indicate the details of filing dates, what type of patents are filed, and application status, and associated US Patent and Trademark Office links, if applicable.
• Describe future IP filing plans. For a multiple-PD/PI, multiple-institution application, applicants should describe the infrastructure of each institution for bringing the technologies to practical application and for coordinating these efforts (e.g., licensing, managing IP) among the institutions.
• State how IP will be shared or otherwise managed if multiple PD/PIs and institutions are involved, consistent with achieving the goals of the BACPAC Research Program.

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 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.

The MRC Director is expected to make a commitment of at least 3 person months (PM) to the overall administration of the MRC and activities of the BACPAC Research Program, Committees and Functional Groups. The Associate Director is expected to commit at least 1.5 PM to administration. Administrative support personnel may be requested at no more than 1.5 full time equivalent (FTE) which may be divided among one or more positions.

In addition, administrative support for the management of funds for the Collaborative Clinical Research Project to be carried out by the Clinical Core must be included. In the budget justification, describe whether the support can be extended to manage the funds, subcontracting and other arrangements necessary for managing the aggregate (all MRC Clinical Cores' Collaborative project funds combined) total funds for the collaborative project. Funding of the collaborative project is expected to begin in year 2.

Applications should include yearly travel expenses in the Administrative Core to pay for the MRC Director, Associate Director and one other individual to attend two 2-day meetings related to the BACPAC Research Program.

Pilot and Ancillary studies, if proposed, must be budgeted under the Administrative Core beginning in Year 2.

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

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: The Administrative Core provides overall coordination, management support, and planning for the center, and the aims of the core should show the elements by which those goals will be achieved.

Research Strategy: The Administrative Core is responsible for the planning, development, coordination, and overall administration of the Mechanistic Center. Applicants are encouraged to organize the Research Strategy section of the Administrative Core along the following headings.

Leadership

Define the responsibilities of the Center Director and Associate Director, Advisory Committee, institution officials and other involved parties. Describe in detail, and by diagram if appropriate, the line of authority or chain of responsibility for decision-making and administration. Include to whom the Center Director reports and the administrative structure as it relates to the investigators responsible for the research projects and research cores.

The Administrative Core will also manage interactions with the Center Advisory Committee. Describe the plans and procedures for nominating and selecting members of this committee. Describe the expected composition of the Advisory Committee (number of members, types of expertise, etc.), but do NOT name the members of the committee who are not from the Mechanistic Center Institution in the application so as not to limit the pool of potential reviewers. The Advisory Committee should consist of three to six members including scientists both from the parent and from other research institutions, and one or more lay members who can bring the patient perspective about the disease to the group. Their collective expertise should reflect key issues addressed in the translational theme and target disease areas of the Center.

Management

The Administrative Core is responsible for coordinating and integrating the Mechanistic Center components and activities. Describe the management plans for the Center, including fiscal administration, procurement, property and personnel management, planning, budgeting, etc. If the Center will involve more than one institution, it may be necessary to explain how the management plans will coordinate activities at each of these sites. Describe capacity to coordinate consortium-wide collaborative studies. Describe plans for the management of conflict of interest relating to intellectual property (when applicable).

Include a Milestone and a Deliverables list for the Overall Center. The lists may include anticipated interactions and synergies within the Center and with other components of BACAPAC including the DAC Integration and Systems Biology Groups.

A Center should conduct ongoing evaluation and assessment of its activities, scientific progress of the research projects and whether the Center is meeting the goals and expected outcomes, milestones or deliverables in a timely fashion set forth in the grant application. These evaluations should also include use of the Research Cores, the quality and efficiency of the services and resources provided to the research projects in accomplishing the proposed specific aims. Describe how the Center Directors plan to make decisions if necessary to adjust the focus or direction of the initially proposed research core based on the results of the Center research to provide more effective services and approaches in support of the translational progress of the research projects.

The Advisory Committee should be actively involved in the evaluation and planning process of the Center. The Advisory Committee should meet formally at least annually to assist the Center Directors in evaluating the scientific progress and optimizing strategies to meet its overall translational goals over the course of the grant award. Indicate the format of the Advisory Committee meetings; describe any reports on Center activities that will be provided to the committee members and how the committee may convey comments and recommendations back to the Center Directors. Describe how the recommendations from this committee will be integrated into the planning and management of the Center over the course of the award.

Communication

A key role of the Administrative Core is to foster productive interactions and promote synergistic collaborations to enhance innovative interdisciplinary research. Describe the plans for maintaining effective communication and cooperation among the Center investigators and the plans for communication with the investigators of the research community as well as those in the BACPAC consortium. This plan should take into consideration the geographic distribution of Center investigators. Explain how the communication plans will help to coordinate and integrate the investigators and the activities of the Center to enhance the research environment and promote the goals of the Mechanistic Center. The Administrative Core is responsible for the planning, development, coordination, and overall administration of the Mechanistic Center.

Letters of Support: Provide letters of support from outside consultants or collaborators that will contribute to the project or provide resources necessary to carry out the proposed research. If these documents are included in the Overall component, please state so.

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:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

When preparing your application, use Component Type Research Project (s).

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

SF424 (R&R) Cover (Research Project(s))

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 Project(s))

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project(s))

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 Project(s))

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 Project(s))

ASSIST will default to Project Lead . If you would like to use a different category, then replace Project Lead below with a different Category (e.g., Core Lead).

• 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 Project(s))

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

Applications should include yearly travel expenses for the PD/PI and one other individual to attend two 2-day meetings related to the BACPAC Research 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.

For Applications proposing a clinical trial:

• The applicants should include a full budget for all the activities related to the planning and implementation of the clinical trial however, some or all of the clinical coordination, data management and clinical site operations may be subcontracted out to the EPPIC-Net. Applicants are instructed to review the EPPIC-Net FOAs to understand what functions they provide. The decision will be made at the time of the award, and budgets will be adjusted accordingly.
• Costs at the clinical sites must include a trial infrastructure component that includes salary support for the PI and study coordinator only.
• Trial costs should be budgeted on a per-subject or per-procedure basis. Applicants should provide a breakdown of the total per subject costs as part of the budget justification and should indicate how the cost for an item or procedure was determined. These costs should be calculated and presented taking into consideration that NIAMS anticipates that enrollment and follow-up for the proposed trial should be completed within 24 months after the opening date of enrollment.
• Costs for collection, analysis, shipping, and/or storage of biospecimens during the study should be included as a separate item in the budget. Specimens collected beyond that needed for the study or remaining at the close of study will be stored in the NIH EPPIC-Net Biorepository. Costs for shipping to the repository should be included in the budget. Costs for long-term storage in the EPPIC-Net repository will be covered through HEAL funds.
• Costs to support the DSMB will be covered by the NIAMS.
• If some trial costs are to be borne by sources other than NIH, these contributions must be presented in detail in the budget justification. These costs borne by third parties do not constitute cost-sharing as defined in the current NIH Grants Policy Statement and should not be presented as part of the requested budget.

PHS 398 Research Plan (Research Project(s))

The most commonly referenced Research Plan attachments are listed below for your convenience. FOA specific instructions are required for the Specific Aims and the Research Strategy in each component. FOA-specific instructions are optional for Letters of Support. Delete Letters of Support if there are no FOA-specific instructions.

Specific Aims: For each Research Project, clearly state the broad long-range goals and the expected outcome(s). Concisely describe the specific objectives of the research proposed and the specific aims to be accomplished by the project. Applications that choose to address a back-pain-related critical translational research question, rather than a back-pain-targeted translational theme, with a single collaborative project enabled by highly interactive cores may use a single set of specific aims repeated in every individual research component, provided that each component includes a distinct Research Strategy based on the unique discipline and technologies represented by the investigators conducting the research component.

Research Strategy: Use this section to describe in more detail how the proposed research project will contribute to meeting the goals and objectives of the Mechanistic Center and explain the rationale for the proposed approach, methodologies, technologies, and/or analyses to accomplish the specific aims.

Organize the Research Strategy in the order specified in the SF 424 (R&R) Application Guide. Make sure to start each section with the appropriate section heading in order, Significance, Innovation, and Approach.

Under Significance, include a paragraph that clearly describes how the research project contributes to the translational theme of the Mechanistic Center or addresses the critical challenge identified by the Center to advance the overall translational objectives as a whole. Further, describe how this project relates to other projects or research cores, and when appropriate, how the outcomes of this will inform the other projects proposed in the Center and the consortium. If it is a basic research project, describe the rationale of including it as a basic research project within the theme of the Center. Describe how the project contributes to the objectives of the BACPAC Research Program to produce an integrated model of LBP, develop new and improved approaches and information for patient phenotyping, identify new targets for intervention or develop new algorithms for treatment or diagnosis.

Letters of Support: Provide letters of support from outside consultants or collaborators that will contribute to the project or provide resources necessary to carry out the proposed research. If these documents are included in the Overall component, please state so.

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.

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

PHS Human Subjects and Clinical Trials Information (Research Project(s))

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Section 3 - Protection and Monitoring Plans

3.3 Data and Safety Monitoring Plan

Note that if an application is awarded, the NIAMS will organize an independent Data and Safety Monitoring Board or appoint an independent Safety Officer based on the risk and complexity of the trial. For more information about NIAMS requirements for Data and Safety Monitoring, please see: https://www.niams.nih.gov/grants-funding/conducting-clinical-research/data-safety-guidelines-policies.

Section 4 - Protocol Synopsis

4.2.a Narrative Study Description

As applicable, state how the following resources for clinical research will be utilized:

NINDS Common Data Elements (https://www.commondataelements.ninds.nih.gov/#page=Default);

NeuroQOL (http://www.healthmeasures.net/explore-measurement-systems/neuro-qol);

NIH Toolbox (http://www.healthmeasures.net/explore-measurement-systems/nih-toolbox); and

PROMIS (http://www.healthmeasures.net/explore-measurement-systems/promis).

4.4 Statistical Design and Power

Applicants should provide a Statistical Analysis Plan (SAP) including details on the analyses specified in the study protocol, including a description of how the statistical analysis of the primary, secondary and other endpoints will be performed, how the sample size was determined, study power, how missing data will be handled, plans for interim analyses for safety and futility, plans for recalculation of the sample size midway through the trial (if applicable), etc. If computer simulations were used to investigate the operating characteristics of complex clinical trial designs (such as adaptive designs), to choose between alternative outcome measures, or to determine sample size, accounting for the impact of noncompliance, missing data, subject eligibility criteria, etc., sufficient details about the simulations should be provided if the SAP. It is particularly important to discuss the range of conditions that were considered in the simulation and why this range was considered appropriate, how robust the findings were across the range of conditions considered, and how the study will adjust for any design deficiencies (e.g., bias, loss of power) the simulations revealed.

The final SAP will be developed with statistical guidance of the BACPAC DAC.

4.6 Will the study use an FDA-regulated intervention?

4.6.a. If yes, describe the availability of Investigational Product (IP) and Investigational New Drug (IND)/Investigational Device Exemption (IDE) status.

4.7 Dissemination Plan

U19 applicants proposing a clinical trial must submit a plan for the dissemination of NIH-funded clinical trial information that will address how the expectations of the NIH Policy on the Dissemination of NIH-funded Clinical Trial Information will be met. Responsibility for adhering to this policy lies with the U19 grantee institution.

Section 5 - Other Clinical Trial-related Attachments

5.1 Other Clinical Trial-Related Attachments

The application must contain the following information, according to the instructions below, to provide evidence that the investigator(s) has planned a feasible clinical trial. The information provided here supports the Research Strategy and should not duplicate it. The following documents must be uploaded as separate pdf files with the names indicated below.

1. Clinical Monitoring and Data Management Plan: The Clinical Monitoring and Data Management Plan is a required attachment and must use the filename "Clinical Monitoring and Data Management Plan.pdf" appended with 1, 2, 3, etc., as needed. Applications lacking this attachment will be considered incomplete and will not be reviewed. Each Clinical Monitoring and Data Management Plan includes 2 parts: (A) The Clinical Monitoring Plan for the quality assurance of the proposed clinical trial through clinical data monitoring activities, and (B) the Data Management Plan for the quality controls proposed through data management activities.

Part A: The purpose of the Clinical Monitoring Plan is to verify that the clinical trial is being conducted, and documented in accordance with the Protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s):

Describe the persons/entity responsible for conducting the clinical monitoring (e.g., contracted Clinical Research Associate, Data Coordinating Center, Independent study monitor from the Clinical Coordinating Center);

• Describe the frequency of planned monitoring activities (e.g., Study Initiation, Interim Visits, Study Close Out), locations where the monitoring will occur (e.g., participating clinical sites, data center, clinical coordinating center) and what data will be reviewed;
• Provide an overall description of the monitoring plan to ensure adherence to the protocol, adequate documentation of the consenting process, and the quality and consistency of the study intervention(s), including fidelity monitoring for behavioral interventions. Include methods to monitor study data collected and systems to record and manage exceptions and deviations. If applicable, describe monitoring of participating facilities, such as labs or pharmacies for adequate handling and storage of investigational product(s) and study specimens. Include a description to assure that the investigational product(s) accountability and reconciliation are performed adequately during and at the end of the trial per applicable regulatory requirements;
• Describe plans for handling any deficiencies that are uncovered and in cases of serious deficiencies the appropriate reporting to relevant authorities, including but not limited to the IRB of record, DSMB if one is assigned, FDA if applicable, institutional officials and the NIH.

Part B: The purpose of the Data Management Plan is to ensure that validated systems and controls are in place to assure the integrity of the clinical research data being collected for the proposed study:

• Describe methods and systems for data collection (e.g., Case Report Forms/CRFs), data entry, data verification and data validation. Describe the data query process and frequencies and any planned mitigation strategies in the event of noncompliance;
• Describe methods and systems to ensure data confidentiality and subject privacy;
• Describe process for locking the final trial datasets and the planned procedures on data access and sharing, as appropriate.

The NIAMS requirements for clinical monitoring and data management for clinical trials as described above are in addition to the application's Data and Safety Monitoring Plan (DSMP) provided in section 3.3 of FORMS-E, which describes how research participant safety and data in the trial will be monitored by an independent monitoring and oversight entity.

2. Intervention Documents: The Intervention Documents attachment is required and must use the filename "Intervention Documents.pdf" appended with 1, 2, 3, etc., as needed. Applications that lack an Intervention Document attachment will be considered incomplete and will not be reviewed. The Intervention Documents should include one of the following documents according to the type of intervention(s) to be used in the proposed clinical trial:

• Investigator's Brochure or Product Label/Package Insert (provide for trials in which the intervention is a device, drug, or a biologic): A compilation of the clinical and nonclinical data on the investigational product(s) that are relevant to the study of the product(s) in human subjects and provides information on the risk of the intervention;
• Intervention Monitoring Manual(s): (provide for trials in which the interventions are behavioral or social). A document that describes in detail the content and delivery of the intervention, the intervention manual should describe how to conduct the intervention, how to train the interventionists, how to monitor fidelity in delivering the intervention, and the rationale for the specified intervention.

Delayed Onset Study

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

When preparing your application, use Component Type Research Core(s)'.

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

SF424 (R&R) Cover (Research Core(s))

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 Core(s))

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Core(s))

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.

Application guide states that Project Narrative is required. However, it is only required for the Overall component. If you would like the applicant to provide a project narrative for this component, update the above instructions accordingly. Specific names provided for Other Attachments must be no more than 50 characters including spaces.

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

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 Core(s))

ASSIST will default to Project Lead . If you would like to use a different category, then replace Project Lead below with a different Category (e.g., Core Lead).

• 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 Core(s))

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

Applications should include yearly travel expenses for the Core Director and one other individual to attend two 2-day meetings related to the BACPAC Research Program.

For applications proposing a clinical trial:

• The applicants should include a full budget for all the activities related to the planning and implementation of the clinical trial however, some or all of the clinical coordination, data management and clinical site operations may be subcontracted out to the EPPIC-Net. Applicants are instructed to review the EPPIC-Net FOAs to understand what functions they provide. The decision will be made at the time of the award, and budgets will be adjusted accordingly.
• Costs at the clinical sites must include a trial infrastructure component that includes salary support for the Core Director and study coordinator only.
• Trial costs should be budgeted on a per-subject or per-procedure basis. Applicants should provide a breakdown of the total per subject costs as part of the budget justification and should indicate how the cost for an item or procedure was determined. These costs should be calculated and presented taking into consideration that NIAMS anticipates that enrollment and follow-up for the proposed trials should be completed within 24 months after the opening date of enrollment.
• Costs for collection, analysis, shipping, and/or storage of biospecimens during the study should be included as a separate item in the budget. Specimens collected beyond that needed for the study or remaining at the close of study will be stored in the NIH EPPIC-Net Biorepository. Costs for shipping to the repository should be included in the budget. Costs for long-term storage in the EPPIC-Net repository will be covered through HEAL funds.
• Costs to support the DSMB will be covered by the NIAMS.
• If some trial costs are to be borne by sources other than NIH, these contributions must be presented in detail in the budget justification. These costs borne by third parties do not constitute cost-sharing as defined in the current NIH Grants Policy Statement and should not be presented as part of the requested budget

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 Core(s))

Specific Aims: For each Research Core, describe the broad, long-term objectives, and describe concisely the specific aims to be accomplished. Include research to enhance the capabilities of the core. Mechanistic Center applications that choose to address a critical research challenge in back-pain- translational research with a single collaborative research project enabled by highly interactive research cores may use a single set of specific aims repeated in every individual research component, provided that each component includes a distinct Research Strategy based on the unique discipline and technologies represented by the investigators conducting the research component. Research Cores are encouraged to leverage existing resources, such as existing patient registries, existing clinical cohorts, and existing datasets.

Research Strategy: Explain how the research core is justified by the scientific and translational needs of the Mechanistic Center. Describe the expected contributions of the core such as technical support and services or other resources to accelerate progress and promote innovative and more effective approaches to enhance the likelihood of success of the research project(s) in achieving the overall translational objectives of the center, and how the research core is likely to promote interdisciplinary team approach to the Center. For a Research Core that by its nature is not innovative, describe why it is essential to advance the translational theme or objectives of the Center.

Describe in detail the techniques or services or any unique resources such as patient back pain cohort(s) or banked tissues and cells provided by the proposed core to support research project(s) within the Mechanistic Center. A core may be a unit designed just for the Center projects or may be an existing institutional core. However, funds may only be requested for Center project use. Explain why support for the service or resource through the Center provides added value beyond that which would be provided through a fee for service or access, especially where support is proposed for an existing resource. Describe plans and procedures for quality control and cost-effectiveness of the services and resources provided by each Core to the Center investigators. The Core should also include sections on plans for data management and data analysis and integration with the MRC Informatics Core and the relevant BACPAC DAC components and groups.

Include plans to develop new and/or unique state-of-the-art core services during the tenure of the Center through technology development and/or adaptation of technologies to meet the translational research needs of the Center. It is expected that the services and resources provided by the Research Core will not only evolve with the science conducted by the Center investigators, but they are also likely to drive the science with increasingly sophisticated and powerful technologies. Explain how those could be shared and have synergies with projects that may be carried out at the BACPAC research Program level. The Core should propose main approaches, metrics for go/no-go decisions, and options for alternative approaches to enhance the effectiveness of services to support the progress of the proposed research project(s). Describe any interactions with the Center leadership and other lead investigators in the Center in formulating an ongoing evaluation plan and development of metrics for go/no-go decisions.

In the application, the PD(s)/PI(s) should describe the initial research cores proposed and how they plan to adjust direction if necessary based on the results of their research and input form the BACPAC Steering Committee and Functional Groups. Each Core should propose main approaches, metrics for go/no-go decisions, and options for alternative approaches.

Describe any special arrangements to effectively leverage other existing resources at this or another institution. If any research core is located at a different institution separated geographically, describe the processes that will be in place to facilitate coordination, distribution and accessibility to the services, facilities or resources that the core proposes to provide.

Organize the Research Strategy in the order specified in the SF 424 (R&R) Application Guide. Make sure to start each section with the appropriate section heading in order, Significance, Innovation, and Approach.

Letters of Support: Provide letters of support from outside consultants or collaborators that will contribute to the project or provide resources necessary to carry out the proposed research. If these documents are included in the Overall component, please state so.

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:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Research Core(s))

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Section 3 - Protection and Monitoring Plans

3.3 Data and Safety Monitoring Plan

Note that if an application is awarded, the NIAMS will organize an independent Data and Safety Monitoring Board or appoint an independent Safety Officer based on the risk and complexity of the trial. For more information about NIAMS requirements for Data and Safety Monitoring, please see: https://www.niams.nih.gov/grants-funding/conducting-clinical-research/data-safety-guidelines-policies.

Section 4 - Protocol Synopsis

4.2.a Narrative Study Description

As applicable, state how the following resources for clinical research will be utilized:

NINDS Common Data Elements (https://www.commondataelements.ninds.nih.gov/#page=Default);

NeuroQOL (http://www.healthmeasures.net/explore-measurement-systems/neuro-qol);

NIH Toolbox (http://www.healthmeasures.net/explore-measurement-systems/nih-toolbox); and

PROMIS (http://www.healthmeasures.net/explore-measurement-systems/promis).

4.4 Statistical Design and Power

Applicants should provide a Statistical Analysis Plan (SAP) including details on the analyses specified in the study protocol, including a description of how the statistical analysis of the primary, secondary and other endpoints will be performed, how the sample size was determined, study power, how missing data will be handled, plans for interim analyses for safety and futility, plans for recalculation of the sample size midway through the trial (if applicable), etc. If computer simulations were used to investigate the operating characteristics of complex clinical trial designs (such as adaptive designs), to choose between alternative outcome measures, or to determine sample size, accounting for the impact of noncompliance, missing data, subject eligibility criteria, etc., sufficient details about the simulations should be provided if the SAP. It is particularly important to discuss the range of conditions that were considered in the simulation and why this range was considered appropriate, how robust the findings were across the range of conditions considered, and how the study will adjust for any design deficiencies (e.g., bias, loss of power) the simulations revealed.

The final SAP will be developed with statistical guidance of the BACPAC DAC.

4.6 Will the study use an FDA-regulated intervention?

4.6.a. If yes, describe the availability of Investigational Product (IP) and Investigational New Drug (IND)/Investigational Device Exemption (IDE) status

4.7 Dissemination Plan

U19 applicants proposing a clinical trial must submit a plan for the dissemination of NIH-funded clinical trial information that will address how the expectations of the NIH Policy on the Dissemination of NIH-funded Clinical Trial Information will be met. Responsibility for adhering to this policy lies with the U19 grantee institution.

Section 5 - Other Clinical Trial-related Attachments

5.1 Other Clinical Trial-Related Attachments

The application must contain the following information, according to the instructions below, to provide evidence that the investigator(s) has planned a feasible clinical trial. The information provided here supports the Research Strategy and should not duplicate it. The following documents must be uploaded as separate pdf files with the names indicated below.

1. Clinical Monitoring and Data Management Plan: The Clinical Monitoring and Data Management Plan is a required attachment and must use the filename "Clinical Monitoring and Data Management Plan.pdf" appended with 1, 2, 3, etc., as needed. Applications lacking this attachment will be considered incomplete and will not be reviewed. Each Clinical Monitoring and Data Management Plan includes 2 parts: (A) The Clinical Monitoring Plan for the quality assurance of the proposed clinical trial through clinical data monitoring activities, and (B) the Data Management Plan for the quality controls proposed through data management activities.

Part A: The purpose of the Clinical Monitoring Plan is to verify that the clinical trial is being conducted, and documented in accordance with the Protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s):

Describe the persons/entity responsible for conducting the clinical monitoring (e.g., contracted Clinical Research Associate, Data Coordinating Center, Independent study monitor from the Clinical Coordinating Center);

• Describe the frequency of planned monitoring activities (e.g., Study Initiation, Interim Visits, Study Close Out), locations where the monitoring will occur (e.g., participating clinical sites, data center, clinical coordinating center) and what data will be reviewed;
• Provide an overall description of the monitoring plan to ensure adherence to the protocol, adequate documentation of the consenting process, and the quality and consistency of the study intervention(s), including fidelity monitoring for behavioral interventions. Include methods to monitor study data collected and systems to record and manage exceptions and deviations. If applicable, describe monitoring of participating facilities, such as labs or pharmacies for adequate handling and storage of investigational product(s) and study specimens. Include a description to assure that the investigational product(s) accountability and reconciliation are performed adequately during and at the end of the trial per applicable regulatory requirements;
• Describe plans for handling any deficiencies that are uncovered and in cases of serious deficiencies the appropriate reporting to relevant authorities, including but not limited to the IRB of record, DSMB if one is assigned, FDA if applicable, institutional officials and the NIH.

Part B: The purpose of the Data Management Plan is to ensure that validated systems and controls are in place to assure the integrity of the clinical research data being collected for the proposed study:

• Describe methods and systems for data collection (e.g., Case Report Forms/CRFs), data entry, data verification and data validation. Describe the data query process and frequencies and any planned mitigation strategies in the event of noncompliance;
• Describe methods and systems to ensure data confidentiality and subject privacy;
• Describe process for locking the final trial datasets and the planned procedures on data access and sharing, as appropriate.

The NIAMS requirements for clinical monitoring and data management for clinical trials as described above are in addition to the application's Data and Safety Monitoring Plan (DSMP) provided in section 3.3 of FORMS-E, which describes how research participant safety and data in the trial will be monitored by an independent monitoring and oversight entity.

2. Intervention Documents: The Intervention Documents attachment is required and must use the filename "Intervention Documents.pdf" appended with 1, 2, 3, etc., as needed. Applications that lack an Intervention Document attachment will be considered incomplete and will not be reviewed. The Intervention Documents should include one of the following documents according to the type of intervention(s) to be used in the proposed clinical trial:

• Investigator's Brochure or Product Label/Package Insert (provide for trials in which the intervention is a device, drug, or a biologic): A compilation of the clinical and nonclinical data on the investigational product(s) that are relevant to the study of the product(s) in human subjects and provides information on the risk of the intervention;
• Intervention Monitoring Manual(s): (provide for trials in which the interventions are behavioral or social). A document that describes in detail the content and delivery of the intervention, the intervention manual should describe how to conduct the intervention, how to train the interventionists, how to monitor fidelity in delivering the intervention, and the rationale for the specified intervention.

Delayed Onset Study

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

When preparing your application, use Component Type Informatics Core(s)'.

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

SF424 (R&R) Cover (Informatics Core(s))

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 (Informatics Core(s))

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Informatics Core(s))

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.

Application guide states that Project Narrative is required. However, it is only required for the Overall component. If you would like the applicant to provide a project narrative for this component, update the above instructions accordingly. Specific names provided for Other Attachments must be no more than 50 characters including spaces.

Project /Performance Site Location(s) (Informatics Core(s))

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 (Informatics Core(s))

ASSIST will default to Project Lead . If you would like to use a different category, then replace Project Lead below with a different Category (e.g., Core Lead).

• 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 (Informatics Core(s))

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

Applications should include yearly travel expenses for the Core Director and one other individual to attend two 2-day meetings related to the BACPAC Research 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 (Informatics Core(s))

Specific Aims: Describe the broad, long-term objectives, and describe concisely the specific aims to be accomplished. Include research to enhance the capabilities of the core. The IC is encouraged to leverage existing resources, such as existing patient registries, existing clinical cohorts, and existing datasets and locally available bioinformatics resources and support.

Research Strategy: Explain how the approaches, services, expertise and resources are justified by the scientific and translational needs of the Mechanistic Center.

• Describe the expected contributions of the IC such as technical support and services or other resources to accelerate progress and promote innovative and more effective approaches to enhance the likelihood of success of the research project(s) in achieving the overall translational objectives of the center, and how the research core is likely to promote interdisciplinary team approach to the Center. If the IC will deliver services and support that are not innovative, describe why the approach is essential to advance the translational theme or objectives of the Center. Describe specialized statistical expertise and services, if applicable to the scope of the research projects and cores.
• Provide a description of the current data collection/management activities to support the Mechanistic Center. Describe plans and procedures for quality control and cost-effectiveness of the services and resources provided by the Core.
• Explicitly define the capabilities of the Informatics Core to aid in the generation of new and/or modification of existing algorithms.
• Describe in detail the techniques or services or any unique resources and capabilities of the IC. Explain why support for the service or resource through the Center provides added value beyond that which would be provided through a fee for service or access, especially where support is proposed for an existing resource.
• Include plans to develop new and/or unique state-of-the-art core services during the tenure of the Center through technology development and/or adaptation of technologies to meet the translational research needs of the Center. Explain how those could be shared and have synergies with projects that may carried out at the BACPAC Research Program level.
• Describe proposed approaches for interaction with the other Research Project(s) and Core(s) in the Center, other U19 Centers and with the BACPAC U24 DAC. Describe whether the services and activities of the IC can be extended to other Centers or projects within BACPAC. The organization and interactivity of the IC are essential, and the investigative team should present evidence to support the likelihood that they will have effective interactions with research sites and investigators outside the MRC.
• The Core should propose main approaches, metrics for go/no-go decisions, and options for alternative approaches to enhance the effectiveness of services to support the progress of the proposed research project(s). Describe any interactions with the Center leadership and other lead investigators in the Center in formulating an ongoing evaluation plan and development of metrics for go/no-go decisions.
• In the application, the PD(s)/PI(s) should describe how the initial informatics proposed might be adjusted if necessary based on the input from the BACPAC Steering Committee and Functional Groups. The IC should propose main approaches, metrics for go/no-go decisions, and options for alternative approaches.
• Describe any special arrangements to effectively leverage other existing resources at this or another institution. If the IC is located at a different institution separated geographically, describe the processes that will be in place to facilitate coordination, distribution and accessibility to the services, facilities or resources that the core proposes to provide.

Organize the Research Strategy in the order specified in the SF 424 (R&R) Application Guide. Make sure to start each section with the appropriate section heading in order, Significance, Innovation, and Approach.

Letters of Support: Provide letters of support from outside consultants or collaborators that will contribute to the project or provide resources necessary to carry out the proposed research. If these documents are included in the Overall component, please state so.

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:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Informatics Core(s))

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

When preparing your application, use Component Type Clinical Core.

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

SF424 (R&R) Cover (Clinical 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 (Clinical Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Clinical 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) (Clinical 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 (Clinical Core)

ASSIST will default to Project Lead . If you would like to use a different category, then replace Project Lead below with a different Category (e.g., Core Lead).

• 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 (Clinical Core)

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

Budget for travel for key personnel to two 2-day meetings of the BACPAC SC, CMC or Functional Group Meetings.

The total direct costs for the Clinical Core annual budget should not exceed $1.5M in the first year of award.

For Research Project applications proposing a clinical trial:

• The applicants should include a full budget for all the activities related to the planning and implementation of the clinical trial however, some or all of the clinical coordination, data management and clinical site operations may be subcontracted out to the EPPIC-Net. Applicants are instructed to review the EPPIC-Net FOAs to understand what functions they provide. The decision will be made at the time of the award, and budgets will be adjusted accordingly.
• Costs at the clinical sites must include a trial infrastructure component that includes salary support for the PI and study coordinator only.
• Trial costs should be budgeted on a per-subject or per-procedure basis. Applicants should provide a breakdown of the total per subject costs as part of the budget justification and should indicate how the cost for an item or procedure was determined. These costs should be calculated and presented taking into consideration that NIAMS anticipates that enrollment and follow-up for the proposed trials should be completed within 24 months after the opening date of enrollment.
• Costs for collection, analysis, shipping, and/or storage of biospecimens during the study should be included as a separate item in the budget. Specimens collected beyond that needed for the study or remaining at the close of study will be stored in the NIH EPPIC-Net Biorepository. Costs for shipping to the repository should be included in the budget. Costs for long-term storage in the EPPIC-Net repository will be covered through HEAL funds.
• Costs to support the DSMB will be covered by the NIAMS.
• If some trial costs are to be borne by sources other than NIH, these contributions must be presented in detail in the budget justification. These costs borne by third parties do not constitute cost-sharing as defined in the current NIH Grants Policy Statement and should not be presented as part of the requested budget

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 (Clinical Core)

Specific Aims: Describe the broad, long-term objectives, and describe concisely the specific aims to be accomplished by the clinical core. Include research and activities to enhance the recruitment, enrollment and or phenotyping capabilities of the core. MRC applications that choose to address a disease-related critical translational research question, rather than a disease-targeted translational theme, with a single collaborative project enabled by highly interactive research cores may use a single set of specific aims repeated in every individual research component, provided that each component includes a distinct Research Strategy based on the unique discipline and technologies represented by the investigators conducting the research component.

Research Strategy:

Describe how the Clinical Core will contribute to the overall goals of the Mechanistic Center.

Explain how the Clinical core is justified by the scientific and translational needs of the Mechanistic Center. Describe the expected contributions of the core such as technical support and services or other resources to accelerate progress and promote innovative and more effective approaches to enhance the likelihood of success of the research project(s) in achieving the overall translational objectives of the Center, and how the research core is likely to promote interdisciplinary team approach to the Center.

Describe how the patients, services, expertise and resources of the Clinical Core will be used in the conduct of research by the MRC Research Projects and Cores.

Include a detailed description of a prospective observational study using an ongoing back pain clinical cohort that includes a minimum of 100 patients. Include a description of the disease definition, elements of the dataset generated for the study and outcomes being used in the cohort. Include a plan to enhance enrollment to a minimum of 400 patients by the end of Year 2.

If the application includes the expansion or utilization of an existing back pain or back pain related cohort, describe current accessibility and use of the data. The data collected by the individual Clinical Cores at all funded MRCs using common data elements are expected to be used in the generation, testing and validation of algorithms leading to the further characterization of back pain mechanisms and improved phenotyping of patients with low back pain in clinical cohorts.

A description of the current approaches to patient phenotyping and capacity to expand patient phenotyping in the Clinical Core and to transfer current phenotyping approaches to other MRCs, Tech Sites and Phase 2CTs.

Must propose, if not currently used, methods for obtaining patient reported outcomes (PROs) and patient reported preferences and values related to treatments, healthcare states and outcomes.

A description of the patient populations, multimodal therapy approaches and types of adaptive design that the Clinical Core may propose to contribute to a future BACPAC collaborative clinical study. The future clinical study will be planned/designed and implemented using non-traditional randomized approaches such as adaptive or SMART designs that include multimodal treatments aimed at improving patient treatment responses and providing data on patient-based treatment responses that contribute to building the phenotyping database and algorithms.

Include a discussion of the premise of the future study and how it supports the need to test the intervention; the premise should be well supported by preliminary data, information in the literature or knowledge of biological mechanisms.

Include any potential ethical issues surrounding the future study; and describe any special arrangements to effectively leverage other existing resources within the BACPAC Consortium.

Describe a plan for making the MRC clinical cohorts, including the mechanistic studies, available to other BACPAC Centers.

Describe current methodologies and technologies utilized for data collection and management, stressing common data elements and outcomes. Describe limitations and pitfalls of the approach to share the data with the BACPAC U24 Data Management Center.

Organize the Research Strategy in the order specified in the SF 424 (R&R) Application Guide. Make sure to start each section with the appropriate section heading in order, Significance, Innovation, and Approach.

Applicants are strongly encouraged to consult the Draft FDA Guidance "Adaptive Designs for Clinical Trials of Drugs and Biologics Guidance for Industry," https://www.fda.gov/downloads/drugs/guidances/ucm201790.pdf for current definitions, implementation and statistical considerations on adaptive design.

Letters of Support: Provide letters of support from outside consultants or collaborators that will contribute to the project or provide resources necessary to carry out the proposed research. If these documents are included in the Overall component, please state so.

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:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Clinical Core)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Section 3 - Protection and Monitoring Plans

3.3 Data and Safety Monitoring Plan

Note that if an application is awarded, the NIAMS will organize an independent Data and Safety Monitoring Board or appoint an independent Safety Officer based on the risk and complexity of the trial. For more information about NIAMS requirements for Data and Safety Monitoring, please see: https://www.niams.nih.gov/grants-funding/conducting-clinical-research/data-safety-guidelines-policies.

Section 4 - Protocol Synopsis

4.2.a Narrative Study Description

As applicable, state how the following resources for clinical research will be utilized:

NINDS Common Data Elements (https://www.commondataelements.ninds.nih.gov/#page=Default);

NeuroQOL (http://www.healthmeasures.net/explore-measurement-systems/neuro-qol);

NIH Toolbox (http://www.healthmeasures.net/explore-measurement-systems/nih-toolbox); and

PROMIS (http://www.healthmeasures.net/explore-measurement-systems/promis).

4.4 Statistical Design and Power

Applicants should provide a Statistical Analysis Plan (SAP) including details on the analyses specified in the study protocol, including a description of how the statistical analysis of the primary, secondary and other endpoints will be performed, how the sample size was determined, study power, how missing data will be handled, plans for interim analyses for safety and futility, plans for recalculation of the sample size midway through the trial (if applicable), etc. If computer simulations were used to investigate the operating characteristics of complex clinical trial designs (such as adaptive designs), to choose between alternative outcome measures, or to determine sample size, accounting for the impact of noncompliance, missing data, subject eligibility criteria, etc., sufficient details about the simulations should be provided in the SAP. It is particularly important to discuss the range of conditions that were considered in the simulation and why this range was considered appropriate, how robust the findings were across the range of conditions considered, and how the study will adjust for any design deficiencies (e.g., bias, loss of power) the simulations revealed.

The final SAP will be developed with statistical guidance of the BACPAC DAC.

4.6 Will the study use an FDA-regulated intervention?

4.6.a. If yes, describe the availability of Investigational Product (IP) and Investigational New Drug (IND)/Investigational Device Exemption (IDE) status

4.7 Dissemination Plan

U19 applicants proposing a clinical trial must submit a plan for the dissemination of NIH-funded clinical trial information that will address how the expectations of the NIH Policy on the Dissemination of NIH-funded Clinical Trial Information will be met. Responsibility for adhering to this policy lies with the U19 grantee institution.

Section 5 - Other Clinical Trial-related Attachments

5.1 Other Clinical Trial-Related Attachments

The application must contain the following information, according to the instructions below, to provide evidence that the investigator(s) has planned a feasible clinical trial. The information provided here supports the Research Strategy and should not duplicate it. The following documents must be uploaded as separate pdf files with the names indicated below.

1. Clinical Monitoring and Data Management Plan: The Clinical Monitoring and Data Management Plan is a required attachment and must use the filename "Clinical Monitoring and Data Management Plan.pdf" appended with 1, 2, 3, etc., as needed. Applications lacking this attachment will be considered incomplete and will not be reviewed. Each Clinical Monitoring and Data Management Plan includes 2 parts: (A) The Clinical Monitoring Plan for the quality assurance of the proposed clinical trial through clinical data monitoring activities, and (B) the Data Management Plan for the quality controls proposed through data management activities.

Part A: The purpose of the Clinical Monitoring Plan is to verify that the clinical trial is being conducted, and documented in accordance with the Protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s):

Describe the persons/entity responsible for conducting the clinical monitoring (e.g., contracted Clinical Research Associate, Data Coordinating Center, Independent study monitor from the Clinical Coordinating Center);

• Describe the frequency of planned monitoring activities (e.g., Study Initiation, Interim Visits, Study Close Out), locations where the monitoring will occur (e.g., participating clinical sites, data center, clinical coordinating center) and what data will be reviewed;
• Provide an overall description of the monitoring plan to ensure adherence to the protocol, adequate documentation of the consenting process, and the quality and consistency of the study intervention(s), including fidelity monitoring for behavioral interventions. Include methods to monitor study data collected and systems to record and manage exceptions and deviations. If applicable, describe monitoring of participating facilities, such as labs or pharmacies for adequate handling and storage of investigational product(s) and study specimens. Include a description to assure that the investigational product(s) accountability and reconciliation are performed adequately during and at the end of the trial per applicable regulatory requirements;
• Describe plans for handling any deficiencies that are uncovered and in cases of serious deficiencies the appropriate reporting to relevant authorities, including but not limited to the IRB of record, DSMB if one is assigned, FDA if applicable, institutional officials and the NIH.

Part B: The purpose of the Data Management Plan is to ensure that validated systems and controls are in place to assure the integrity of the clinical research data being collected for the proposed study:

• Describe methods and systems for data collection (e.g., Case Report Forms/CRFs), data entry, data verification and data validation. Describe the data query process and frequencies and any planned mitigation strategies in the event of noncompliance;
• Describe methods and systems to ensure data confidentiality and subject privacy;
• Describe process for locking the final trial datasets and the planned procedures on data access and sharing, as appropriate.

The NIAMS requirements for clinical monitoring and data management for clinical trials as described above are in addition to the application's Data and Safety Monitoring Plan (DSMP) provided in section 3.3 of FORMS-E, which describes how research participant safety and data in the trial will be monitored by an independent monitoring and oversight entity.

2. Intervention Documents: The Intervention Documents attachment is required and must use the filename "Intervention Documents.pdf" appended with 1, 2, 3, etc., as needed. Applications that lack an Intervention Document attachment will be considered incomplete and will not be reviewed. The Intervention Documents should include one of the following documents according to the type of intervention(s) to be used in the proposed clinical trial:

• Investigator's Brochure or Product Label/Package Insert (provide for trials in which the intervention is a device, drug, or a biologic): A compilation of the clinical and nonclinical data on the investigational product(s) that are relevant to the study of the product(s) in human subjects and provides information on the risk of the intervention;
• Intervention Monitoring Manual(s): (provide for trials in which the interventions are behavioral or social). A document that describes in detail the content and delivery of the intervention, the intervention manual should describe how to conduct the intervention, how to train the interventionists, how to monitor fidelity in delivering the intervention, and the rationale for the specified intervention.

There is no page limit for these attachments. Do not circumvent page limits by including irrelevant information that belongs in another section of the application in these attachments.

Delayed Onset Study

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

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.

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

Important reminders:

All PD(s)/PI(s) 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 NIAMS, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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

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

In addition, for applications involving clinical trials:

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Mechanistic Center 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 Mechanistic Center 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 Mechanistic Center that by its nature is not innovative may be essential to advance a field.

Does the Mechanistic Center address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the Mechanistic Center 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?

Specific to this FOA:

Is the Center poised to contribute to an integrated model of back pain or to improve patient phenotyping or contribute to algorithm development in a significant way?

Does the application present a compelling case for the research focus, and for the approaches that the Center will use to address a critical issue in back pain research?

In addition, for applications involving clinical trials:

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Center? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific for this FOA:

Is there evidence of experience and commitment to participate in collaborative projects, Networks or Consortia?

Have the Center Director and Associate Directors ensured that the Cores and Projects are designed so that they can maximize the opportunities for resource and data sharing within the MRC and with other entities in BACPAC?

In addition, for applications involving clinical trials:

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

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?

Specific for this FOA:

Are novel theoretical concepts, methodologies, instrumentation, or interventions proposed?

Is there evidence of synergy or integration between the cores and projects?

In addition, for applications involving clinical trials:

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

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Center? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the Mechanistic Center involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific for this FOA:

Is there a comprehensive plan for interactions among investigators within the center and with the consortium to maximize a collaborative environment, and sharing of ideas and resources?

Is there a well-organized management structure for the Center?

In addition, for applications involving clinical trials:

Does the application adequately address the following, if applicable?

Study Design

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

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

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

Data Management and Statistical Analysis

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

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?

Specific for this FOA:

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

In addition, for applications involving clinical trials:

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

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

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

Reviewers will consider the following criteria in the determination of an overall impact score for Administrative Core, although scores for the individual criterion will not be provided.

Leadership

Do the Center Director and Associate Director have the leadership and research qualifications to lead a Mechanistic Center? Do the proposed Director and Associate Director have the collective expertise and leadership to identify and focus research projects on clinically relevant issues? Are appropriate and well-defined responsibilities described for the Director and Associate Director, Internal Advisory Committee, Resource Core Directors, institution officials and other involved parties? Have the scientific and administrative leadership committed adequate time and effort for the effective management of the Mechanistic Center? Are there adequate plans for establishing the Internal Advisory Committee and for the Director and Associate Director to communicate regularly with the committee? Are the composition and plans for selecting the members of the committee appropriate?

Management

Is the management proposed appropriate for scientific administration as well as fiscal administration, procurement, property and personnel management, planning, budgeting, etc.? Is the management plan appropriate for fiscal administration, procurement, property and personnel management, planning, budgeting, etc.? Are the individual budgets appropriate for the proposed work to be done in Clinical and Research Core(s) and projects, and for any other proposed programs in relation to the total Center? Are there adequate plans for objectively evaluating the functioning of the Center by the Director and Associate Director, with input from the BACPAC Advisory Committee?

Communication

Are there adequate plans for the establishment and maintenance of effective internal communication and cooperation among the Center investigators, Core personnel, leadership of the Center, Internal Advisory Committee and the Center Advisory Committee? If the Center will involve multiple sites or institutions, is there a detailed plan of the communication strategies aimed to integrate the distant components and investigators into a coordinated entity?

Environment

Is the environment for the Administrative Core adequate and appropriate to support the overall Mechanistic Center as proposed? Is there evidence of institutional support for the management of Center?

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

Significance

Does the project address an important problem or a critical barrier to progress in the back-pain field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice related to back pain be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigators

Are the project leads, collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-lead, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

In addition, for applications involving clinical trials

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

Innovation

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

In addition, for applications involving clinical trials

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

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable?

Study Design

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

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

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

Data Management and Statistical Analysis

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

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

In addition, for applications involving clinical trials

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

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

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

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

Reviewers will consider the following criteria in the determination of an overall impact score for the Research Core, although scores for the individual criterion will not be provided.

Significance

Does the Research Core provide technical support and services or other resources to meet the scientific and translational needs of the Mechanistic Center? Does the Research Core have the potential to accelerate progress, and promote innovative and more effective approaches to enhance the likelihood of success of the research project(s) in achieving the overall objectives of the Center?

Specific to this FOA:

Is the proposed IC Core well matched to the needs of the overall Center? Do the services offered best fit within a core structure? If this is an add-on to a preexisting core, what is the benefit to the Mechanistic Center over direct purchase of services from the existing core?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigators

Are the qualifications, experience, and commitment of the Research Core Director and his/her collaborations with Center investigators appropriate to the proposed technical area and/or shared resource?

In addition, for applications involving clinical trials

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

Innovation

Are there plans to develop new and/or unique state-of-the-art core services during the tenure of the Center through technology development and/or adaptation of technologies to meet the translational research needs of the Center? Will the services and resources provided by the Research Core not only evolve with the science conducted by the Center Investigators, but are they also likely to drive the science with increasingly sophisticated and powerful technologies? Is the Research Core likely to promote interdisciplinary team approach to the Center? For a Research Core that by its nature is not innovative, is it essential to advance the objectives of the Center?

In addition, for applications involving clinical trials

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

Approach

Are the technical services and resources of the Research Core of high quality? Does support for the service or resource through the Center provide added value beyond that which would be provided through a fee for service or access, especially where support is proposed for an existing resource? Are there procedures for quality control of the services and resources for each Core? Is the Research Core cost-effective in providing services and resources to the Center investigators? Do the Research Cores effectively leverage existing resources at this or another institution? Is there a plan to share Core resources and technologies with other MRCs, Tech Sites and Phase 2 CTs?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable?

Study Design

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

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

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

Data Management and Statistical Analysis

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

Environment

What is the overall quality of the environment for the Research Core? Is there adequate institutional commitment to the Research Core, including physical space, lines of accountability regarding management of the Research Cores, and commitment to the individuals responsible for conducting essential core functions?

In addition, for applications involving clinical trials

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

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

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

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

Reviewers will consider the following criteria in the determination of an overall impact score for the Systems Biology/Informatics Core, although scores for the individual criterion will not be provided.

Significance

Does the IC provide services and/or resources to meet the scientific needs of the research community? Will the Core provide a unique and necessary component to enhance existing or stimulate new clinical research? What is the likelihood that the IC will increase efficiency, accelerate progress and promote new research directions and meaningful collaborations among community of clinical investigators?

Investigators

Are the qualifications, experience, and commitment of the IC Director and his/her collaborations with Center investigators appropriate to the proposed clinical area and/or shared resource? Are other key personnel adequate and appropriate for providing the proposed facilities or services?

Innovation

Are there plans to develop new and/or unique state-of-the-art core services during the tenure of the Center through technology development and/or adaptation of technologies to meet the needs of the clinical research community? Will the services and resources provided by the IC not only evolve with the science conducted by the Center Investigators, but are they also likely to drive the science with increasingly sophisticated and powerful technologies? Is the Informatics Core likely to promote interdisciplinary research? For an IC that by its nature is not innovative, is it essential to advance clinical research in the field?

Approach

Are the services and resources of the IC of high quality? Are there procedures for quality control of the services and resources for the Core? Is the IC cost-effective in providing services and resources to the MRC? Does the IC effectively leverage existing resources within the institution? Are there plans to share data, resources and approaches with the BACPAC consortium? What is the overall quality of the proposed informatics services? Is a plan provided to orchestrate the collection and dissemination of the data from this MRC to other Centers and the BACPAC DAC?

Environment

What is the overall quality of the environment for the IC? Is there adequate institutional commitment to the Center, including physical space, if required, for the IC? Are there lines of accountability regarding management of the IC Core and commitment from the Mechanistic Center to the individuals responsible for conducting essential core functions?

Reviewers will consider the following criteria in the determination of an overall impact score for the Clinical Core, although scores for the individual criterion will not be provided.

Significance

Does the Clinical Core provide services and/or resources, such as back pain cohorts, well matched to the scientific needs of the research community? Are unique services offered? If these services duplicate or overlap with existing institutional resources, how will this be addressed? Will the Core be used by multiple investigators? Is the process for maintenance of data integrity and assistance with development of safety plans for the projects supported by the Core adequately addressed? Is there evidence that the Clinical Core can and will support clinical research projects in low back pain?

Specific to this FOA:

Is the proposed Clinical Core well matched to the needs of the overall Mechanistic Center?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigator(s)

Are the qualifications, experience, and commitment of the leader of the Clinical Core and other key personnel adequate and appropriate for providing the proposed services?

In addition, for applications involving clinical trials

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

Innovation

Are there plans to develop and establish unique state-of-the-art core services for clinical research and innovative design clinical trials during the tenure of the Mechanistic Center? Will efforts be made to develop and/or adapt emerging methodologies to meet the needs of the clinical research community? Will the services and resources provided by the Clinical Core not only evolve with the clinical research conducted by the Center Investigators, but will these services and resources be developed to drive the clinical approaches with increasingly sophisticated and powerful technologies? Is the Clinical Core likely to promote collaboratory research with the other U19 Centers?

In addition, for applications involving clinical trials

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

Approach

Is there demonstrated capacity to enroll a large number of patients in the proposed project period? Are the plans to expand capacity to enroll larger numbers of patients well delineated? Are the services and resources (clinical cohorts) of the Clinical Core of high quality and unique to the needs of the Mechanistic Center?

Are the current approaches to phenotyping scientifically sound? Are the proposed enhancements to phenotyping of patients with back pain well described?

Are the plans to include PROs, patient preferences and patient phenotyping well described? What is the overall quality of the proposed core services, including the proposed definition for cLBP, common dataset and outcomes measures? Is there a scientifically sound and clearly described plan to incorporate PROs and PPrs into all clinical studies and projects at the Center? Are adequate quality control processes proposed for the services provided by the Clinical Core (including procedures, techniques, and quality control)? What are the criteria for prioritization and usage of Core products and/or services? Will the CC provide opportunities such as webinars, online courses, or other computer-based training to enhance the capabilities of faculty, staff, students and fellows associated with the Mechanistic Center to conduct clinical research using a wide range of rigorous approaches?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable?

Study Design

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

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

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

Data Management and Statistical Analysis

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

Environment

Is the environment for the Clinical Core adequate and appropriate to support the Mechanistic Center as proposed? Are the physical space, facilities and equipment adequate and appropriate? Is there evidence of institutional support or commitment?

In addition, for applications involving clinical trials

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

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

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

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

As applicable for the Center, projects, and cores 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.

Study Timeline

In addition, for applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project/cores involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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

Not Applicable

Not Applicable

Not Applicable

As applicable for the center, projects, and cores 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.

Intellectual Property

If applicable, is the IP Strategy adequate? Does it include descriptions of the IP landscaping surrounding the proposed model system, letters from IP owners, information about patents filed or to be filed? Does it address issues that may affect sharing of the model? Is the dissemination plan that involves patent protection and commercialization acceptable? If not applicable, does applicant provide an acceptable justification?

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 Data Sharing Plan .

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

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

Specific to this FOA:

If applicable, how likely is it that the plans for cost matching will be adequate?

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

• 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 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.

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

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

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

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

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

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

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

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

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols. Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

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

Additional language:

Special award condition specific to this FOA: A grantee from a for-profit organization funded under this announcement must match funds or provide documented in-kind contributions at a rate of not less than 50% of the total-Federally awarded amount, as stipulated by Public Law 115-141, the Consolidated Appropriations Act of 2018. See 45 CFR 75.306 for additional details. Matching funds must be non-Federal funds set aside for this project and are available from the source(s) identified in the application, as committed to by the recipient. Cost matching will be evaluated by the awarding office to ensure that this requirement is being met. Compliance with the matching requirement must be verified on an annual basis and must be documented in the annual and final FFR.

Awardee-selected projects that involve {clinical trials or studies involving greater than minimal risk to human subjects} require prior approval by NIH prior to initiation.

• The awardee institution will provide NIH with written study protocols that address risks and protections for human subjects in accordance with NIH s Instructions for Preparing the Human Subjects Section of the Research Plan.
• The awardee institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

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

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

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR 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.

By accepting an award, the PI and Institution agree to become part of the Back Pain Consortium Research Program (BACPAC). The work to be carried out under the award will be conducted collaboratively with other members of the consortium and the NIH and will be subject to review and approval by the BACPAC Steering Committee prior to full implementation as specified in this RFA.

ROLES AND RESPONSIBILITIES

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

Advancing and coordinating the activities at their Center (Site), scientifically and administratively;

Serving as a voting member of the Steering Committee;

• Participating actively in the formulation and implementation of the BACPAC Research Program Agenda;
• Actively participate in BACPAC Functional Working Groups;
• Implementing common data elements, protocols, standards and policies approved by the Steering Committee or required by NIH/NIAMS;
• Providing the BACPAC Data Integration, Algorithm Development and Operations Management Center (DAC) with all clinical study data for management, quality control, and analysis, using procedures and standards determined by the BACPAC Steering Committee (SC), and the Executive Committee (EC) and the DAC;
• Providing the BACPAC Systems Biology and Bioinformatics Group with all research study data for systems level analysis, using procedures and standards determined by the BACPAC Functional Working Group, SC, EC and DAC;
• Sharing data publicly through dbGAP or other public portals designated by NIH, as appropriate and consistent with achieving the goals of the program;
• Establishing procedures within the Center and affiliated sites to ensure that all members of that center are aware of, and conform to, the data sharing and other resource-sharing plans;
• Establishing procedures within the center to ensure that all members of that center, including any scientists added via FMU support, share data with the BACPAC Systems Biology and Bioinformatics Group and conform to the data sharing and other resource-sharing plans.

The NIH Project Scientist(s) will have substantial involvement that is above and beyond the normal stewardship role in awards, as described below:

• Cooperation and coordination with recipients in performance of project activities;
• Facilitate collaborations with and access to other NIH-supported research resources including those supported by HEAL projects;
• Share information regarding promising new agents, strategies, and developments when appropriate;
• Identify scientific gaps and organize meetings to facilitate exchange of scientific and regulatory information;
• Serve as liaison/facilitator among awardees and with the data portals such dbGAP;
• Participate on the Steering Committee as voting members and help coordinate Steering Committee activities and implementation of its recommendations, decisions, and policies.

The NIH Program Official will be named in the Notice of Award and will be responsible for the normal scientific and programmatic stewardship of the award, as described below:

• The Program Official will interact with the PI(s) on a regular basis to monitor progress. Monitoring may include: regular communication with the PI and their staff, periodic site visits for discussion with the awardee research team, observation of field data collection and management techniques, fiscal reviews, and other relevant stewardship matters.
• Work with the PIs to develop performance milestones for the individual awards.
• Provide oversight for human subject protections and provide monitoring for any studies that involve more than minimal risk for participants or that involve vulnerable populations;
• Aid the Steering Committee in the development of procedures for evaluating the performance of research studies and monitoring any Clinical Trials;
• Oversee clinical site operations to include development of template informed consent documents as well as site specific consents for IRB submission, operational activation of clinical sites, and review and evaluation of site monitoring reports.

The Program Official may also identify other extramural staff who have appropriate experience and expertise to assist with the management and proper stewardship of the award.

Monitoring of Mechanistic Research Centers/Technology Sites Clinical Study/Clinical Trials

Trial Monitoring. The NIAMS Program Official or designee will oversee clinical site monitoring that evaluates Good Clinical Practice regulatory compliance, protocol implementation, internal quality assurance, and test article accountability at the consortium clinical sites. The site monitors, with or without accompanying NIAMS staff, will visit MRC and Tech Sites clinical sites periodically to review selected protocols, provide training on general protocol conduct, review internal QA/QC plans, and audit pharmacies.

Protocol review. The NIAMS Program Official or designee will review all clinical trial protocols and approval is required for initiation. The Project Scientist or designee will return comments and recommendations to the protocol team after review. The protocol team must address in writing all safety, regulatory, ethical, and conflict of interest concerns raised by NIAMS to the satisfaction of NIAMS before participant enrollment can begin. If a protocol is disapproved, NIAMS will not permit expenditure of NIH funds for the proposed investigation. If a protocol is not initiated within six months of NIAMS approval, re-review and approval by NIAMS will be required.

Safety Monitoring. The NIAMS Program Official or designee will participate in the development of appropriate safety monitoring plans for all planned clinical studies/trials and must approve the plan for all trials involving investigational drugs, devices, biologics, or other clinical interventions. The frequency and intensity of safety monitoring will be based on individual study characteristics and past experience with study products and may require review by an Independent Safety Monitor, Safety Monitoring Committee (SMC) or Data and Safety Monitoring Board (DSMB). Approval of the final monitoring plan, including the composition of the review committee, by NIAMS is required prior to study initiation. NIAMS independently supports Data and Safety Monitoring Boards (DSMB) that oversee clinical trials.

NIAMS reserves the right to terminate or curtail a clinical study (or an individual component of the award) in the event of inadequate progress, data reporting, or insufficient use of this resource. Examples include, but are not limited to, risks to subject safety, failure to achieve recruitment goals, and reaching a major study endpoint substantially before schedule with persuasive statistical significance.

Clinical Data Access. NIAMS has the right of access to all clinical data generated (raw and analyzed) and may periodically review it. This includes data as recorded on the case report forms and in the central databases, and external checking against the original source documentation as required by federal regulation and NIH.

Phase 2 Clinical Trials

Trial Monitoring. The NIAMS Program Official or designee will oversee clinical site monitoring that evaluates GCP, regulatory compliance, protocol implementation, internal quality assurance, and test article accountability at the Phase 2 clinical sites. The EPPIC-Net Clinical Coordinating Center will coordinate site monitoring, with or without accompanying NIH staff, to review selected protocols, provide training on general protocol conduct, review internal QA/QC plans, and audit pharmacies.

Protocol review. The NIH Program Official or designee will review all clinical trial protocols and approval is required for initiation. The Project Scientist or designee will return comments and recommendations to the protocol team (composed by Trial PI, EPPIC-Net CCC and DCC PIs or designees) after review. The protocol team must address in writing all safety, regulatory, ethical, and conflict of interest concerns raised by NIH to the satisfaction of NIH before participant enrollment can begin. If a protocol is disapproved, NIAMS will not permit expenditure of NIH funds for the proposed investigation. If a protocol is not initiated within six months of NIAMS approval, re-review and approval by NIAMS will be required.

Safety Monitoring. The NIH Program Official or designee will oversee the development of appropriate safety monitoring plans for all planned clinical studies/trials and must approve the plan for all trials involving investigational drugs, devices, biologics, or other clinical interventions. The NIH EPPIC-Net CCC and DCC will work with the Phase 2CT PI to determine the frequency and intensity of safety monitoring based on individual study characteristics and experience with study products and may require review by an Independent Safety Monitor, Safety Monitoring Committee (SMC) or Data and Safety Monitoring Board (DSMB). Approval of the final monitoring plan, including the composition of the review committee, by NIAMS is required prior to study initiation. Independently supported Data and Safety Monitoring Boards (DSMB) to oversee BACPAC Phase 2CT will be arranged through the NIH EPPIC-Net.

The NIAMS reserves the right to terminate or curtail a clinical study (or an individual component of the award) in the event of inadequate progress, data reporting, or insufficient use of this resource. Examples include, but are not limited to, risks to subject safety, failure to achieve recruitment goals, and reaching a major study endpoint substantially before schedule with persuasive statistical significance.

Clinical Data Access. NIAMS has the right of access to all clinical data generated (raw and analyzed) and may periodically review it. This includes data as recorded on the case report forms and in the central databases, and external checking against the original source documentation as required by federal regulation and NIH.

An NIH Grants Management Official will be responsible for the normal monitoring of administrative and other non-programmatic aspects as described in the NIH Grants Policy Statement and will be named in the Notice of Award.

This monitoring may include: periodic site visits, review of grant management systems, fiscal reviews, and other relevant stewardship matters. In addition, the Grants Management Official or designee may attend Steering Committee meetings as a non-voting observer.

Areas of Joint Responsibility include:

Steering Committee

The voting members of the Steering Committee include a single PD/PI from each: MRC (U19), Tech Site (UH2), each Phase 2CT (UG3), one Systems Biology and Bioinformatics Group PI, the DAC (U24) PI, and a minimum of four NIH Officials. Note that although UH2, UG3 and the U24 may choose to utilize the multi-PI mechanism, each U19, UH2 and UG3 will have only one vote in all SC and relevant subcommittee meetings. Each member of the Steering Committee will have one vote. NIH representatives will be voting members, but will not serve as the Chair of the Steering Committee, or in aggregate represent more than forty percent of the total voting membership of the SC. All major scientific decisions will be determined by majority vote of the SC. All participants in the BACPAC Research Program are bound by the policies and procedures developed by the Steering Committee.

The Steering Committee responsibilities include:

• Compose, review and approve within three months after award a BACPAC Research Agenda establishing priorities for the entire program term. The Agenda will represent an integrated, synergistic view of individual center and technology site research projects, and the Clinical and Collaborative Projects but may include additional plans to foster collaborations among all the members of the BACPAC. The Agenda will include objectives, outputs, benchmarks and timelines that are linked to the overall goals of the BACPAC Program and can be clearly mapped back to the overall goals of
• Improved understanding of the mechanisms of low back pain
• Create an integrated model of LBP
• Produce rigorous, reliable patient based diagnostic and treatment algorithms
• Advance new therapies for LBP into Phase 3 clinical trials
• Oversee the development and implementation of the Clinical Projects at the MRCs and Tech Sites, including the associated mechanistic studies and the BACPAC Collaborative Project(s);
• Approve final Consensus Clinical Plans for common data and protocol elements and standardized processes and operating procedures for the BACPAC Research Program;
• Review and approve the plans for program-wide clinical and laboratory research data integration and analysis and ensure synergy with Center- and Site- level data analysis;
• Oversee the policies for use of the BACPAC Project Fund and the BACPAC Collaborative Research Fund;
• Review and approve data sharing and publication policies;
• Review and recommend to NIH/NIAMS new and transitioning projects.

Executive Committee

The members of the Executive Committee include the PI of the DAC, who will serve as the Chair, one MRC PI, one Tech Site PI, the BACPAC Program Manager from the U24 DAC, and one NIAMS Project Scientist. The MRC PI representative to the EC will be selected by vote of the MRC PIs. Similarly, the Tech Site PI representative to the EC will be selected by vote of the Tech Site PIs. The Executive Committee responsibilities include:

• Support the development of the Research Agenda by the BACPAC SC;
• Develop an implementation plan for the BACPAC Research Agenda;
• Support the CMC development of a Clinical Consensus Plan;
• Review of MRC and Tech Sites research projects together with the Functional Working Groups to identify synergies in accordance with criteria established by the SC and provide recommendations to the SC with respect to building synergies and interactions among the proposed research projects;
• Monitoring of BACPAC Research Projects along established timelines and milestones and ensure consistent adherence to common study protocols and standards across all participating research centers and sites;
• Prepare and present to the SC periodic reports on study progress, identifying problems/obstacles and making recommendations for their resolution, and implement corrective/remedial actions as directed by the SC;
• Serve as the central point of contact for submission of proposals for new and transitioning research projects in accordance with policies, procedures and necessary documentation established by the BACPAC SC.

Data Sharing:

• The data sharing plan will be referenced as a term and condition of award. Applicant organization must comply with the Public Health Service (PHS) policies relating to distribution of unique research resources produced with PHS funding and sharing of research data and other research resources, as well as the grantee’s data sharing plan subject to decisions of the BACPAC Steering Committee. For further information, see the NIH Data Sharing Policy at https://grants.nih.gov/grants/policy/data_sharing/.
• The effectiveness of the data sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report.
• The NIH intends for the resource sharing plans for the data generated under the BACPAC Research Program to follow the policy and goals stated in the BACPAC FOAs. Specifically, consistent with achieving the goals of the BACPAC Research Program, all data generated (including clinical data, imaging data, patient-reported data, laboratory data, processed/analyzed data, standard protocols, forms and procedures, and algorithms and methods developed, etc.) are expected to be deposited into the BACPAC designated central database in a timely fashion for access by the BACPAC investigators, consistent with applicable laws, regulations, and policies and unencumbered by any intellectual property claims. The NIH, in consultation with the BACPAC Steering Committee, will make all final decisions concerning data deposition and data access policies, and all policies are subject to change by the NIH as deemed necessary to sustain program principles and priorities, or to ensure the highest standards for responsible research conduct within the program.
• Applicant organization will comply with and implement the recommendations and decisions of the NIH and the BACPAC Steering Committee with respect to the sharing of information, data, protocols, resources, and methods developed by BACPAC investigators under the BACPAC Research Program.

Dispute Resolution:

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

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

A final Research Performance Progress Report (F-RPPR), invention statement, and the expenditure data portion of the Federal Financial Report, including Federal and non-Federal share for cost matching, are required for closeout of an award, as described in the NIH Grants Policy Statement.

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

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

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

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

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Basil Eldadah, M.D., Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-6761
Email: [email protected]

Charles H. Washabaugh, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Telephone: 301-594-5050
Email: [email protected]

Susan Marden PhD., RN
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6838
Email: [email protected]

David A. Thomas, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-435-1313
Email: [email protected]

Jeremy Brown, M.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-827-8375
Email: [email protected] ?

Lois A. Tully, PhD
National Institute of Nursing Research (NINR)
Telephone: 301-594-5968
Email: [email protected]

Benyam Hailu, M.D., M.P.H.
National Institute on Minority Health and Health Disparities (NIMHD)
Telephone: 301-594-8696
Email: [email protected]

Wen G. Chen, MMSc., Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
301-451-3989
[email protected]

Lisa Begg, Dr.P.H., RN
NIH Office of Research on Women’s Health
Telephone: 301/496-3975
Email: [email protected]

Kathy Salaita, Sc.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5033
Email: [email protected]

John Bladen
National Institute on Aging (NIA)
Telephone: 301-402-7730
Email: [email protected]

Erik Edgerton
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: (301) 594-7760
Email: [email protected]

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

Pam Fleming
National Institute on Drug Abuse (NIDA)
Telephone: 301-480-1159
Email: [email protected]

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

Randi Freundlich
National Institute of Nursing Research (NINR)
Telephone: 301-594-5974
Email: [email protected]

Priscilla Grant, J.D.
National Institute on Minority Health and Health Disparities (NIMHD)
Telephone: 301-594-8412
Email: [email protected]

Shelley Carow
National Center for Complementary and Integrative Health (NCCIH)
301.594.3788
[email protected]

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

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