Department of Health and Human Services

Participating Organization(s)
National Institutes of Health (NIH)
Components of Participating Organizations

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institute on Aging (NIA)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute on Drug Abuse (NIDA)
National Institute of Mental Health (NIMH)
National Institute of Neurological Disorders and Stroke (NINDS)
National Institute of Nursing Research (NINR)
National Institute on Minority Health and Health Disparities (NIMHD)
National Center for Complementary and Integrative Health (NCCIH)

All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers.  The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Behavioral and Social Sciences Research (OBSSR)
Office of Research on Women’s Health (ORWH)

Funding Opportunity Title
HEAL Initiative: Back Pain Consortium (BACPAC) Research Program Data Integration, Algorithm Development and Operations Management Center (U24 Clinical Trial Not Allowed)
Activity Code
U24 Resource-Related Research Projects – Cooperative Agreements
Announcement Type
New
Related Notices
  • December 13, 2018 - Notice of Pre-Application Webinars for the HEAL Initiative: Back Pain Consortium (BACPAC) Research Program. See Notice NOT-AR-19-031.
Funding Opportunity Announcement (FOA) Number
RFA-AR-19-027
Companion Funding Opportunity

RFA-AR-19-026 - U19 Research Program – Cooperative Agreements

RFA-AR-19-028 - UH2/UH3 Phase Innovation Awards Cooperative Agreement

RFA-AR-19-029 - UG3/UH3 Exploratory/Developmental Phased Award Cooperative Agreement

Number of Applications

Only one application per institution is allowed, as defined in Section III. 3. Additional Information on Eligibility

See Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)
93.846; 93.213; 93.866; 93.286; 93.865; 93.279; 93.242; 93.307; 93.853; 93.361; 93.313
Funding Opportunity Purpose

This funding opportunity announcement (FOA) invites applications for the NIH Back Pain Consortium (BACPAC) Research Program Data Integration, Algorithm Development and Operations Management Center.  BACPAC is a patient centric-research program that will focus 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 patient. The Research Program 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 will conduct traditional Phase 2 Clinical Trials as well as sequential, adaptive, phase 2/proof of concept clinical studies in stratified patient populations. 

BACPAC will include multiple Mechanistic Research Centers, Technology Research Sites, Phase 2 Clinical Trials (Phase 2CT) and a Data Integration, Algorithm Development and Operations Management Center (DAC). This FOA invites applications for the BACPAC Data Integration, Algorithm Development and Operations Management Center (U24) and runs in parallel with companion FOAs (RFA-AR-19-026) that invites applications for the BACPAC Mechanistic Research Centers, (RFA-AR-19-028) for the BACPAC Technology Sites, and (RFA-AR-19-029) for the Phase 2 Clinical Trials.

Posted Date

December 10, 2018

Open Date (Earliest Submission Date)
February 20, 2019
Letter of Intent Due Date(s)
February 20, 2019
Application Due Date(s)
March 20, 2019, by 5:00 PM local time of applicant organization.

No late applications will be accepted for this Funding Opportunity Announcement

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)
Not Applicable
Scientific Merit Review
June/July 2019
Advisory Council Review
August 2019
Earliest Start Date
September 20, 2019
Expiration Date
March 21, 2019
Due Dates for E.O. 12372
Not Applicable
Required Application Instructions
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from 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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.
  4. Table of Contents

Purpose

This funding opportunity announcement (FOA) invites applications for the NIH Back Pain Consortium (BACPAC) Research Program Data Integration, Algorithm Development and Operations Management Center. This patient-centric research program will focus on translational and clinical research for discovery of low back pain (LBP) mechanisms, and on identification and testing of new interventions targeted to individual patient. The Research Program will utilize novel analytics and technologies to extensively phenotype patients with low back pain, develop an integrated model of LBP, produce new and improved diagnostic and treatment algorithms, and will test new therapies for cLBP in traditional Phase 2 Clinical Trials as well as sequential, adaptive, phase 2/proof of concept clinical studies in stratified patient populations.

BACPAC will include multiple Mechanistic Research Centers, Technology Research Sites, Phase 2 Clinical Trials (Phase 2CT) and a Data Integration, Algorithm Development and Operations Management Center (DAC). This FOA invites applications for the BACPAC Data Integration, Algorithm Development and Operations Management Center (U24) and runs in parallel with companion FOAs (RFA-AR-19-026) BACPAC Mechanistic Research Centers, (RFA-AR-19-028) BACPAC Technology Sites, and (RFA-AR-19-029) 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.

Background and Objectives of the BACPAC Research Program

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 that work. 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, 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 comprehensive information about patient phenotypes to stratify patient populations, 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. Clinical trials with 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 efficacy trials.

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 funding opportunity 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.

Components of the BACPAC Research Program

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 SBG 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.

The trial implementation phase (UH3) may 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 after award, on behalf of the entire BACPAC Research Program, two funds: the Collaborative Clinical Fund for support of the Collaborative Clinical Projects and 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.

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.

The composition of the various committees and the meeting frequency are described in the Table below. 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 and 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.

U24 Research Approach

Over the project period, the BACPAC consortium will conduct three types of clinical and translational studies in LBP. Clinical cohorts established and characterized at the MRCs Clinical Cores (CC) will provide demographic, clinical and laboratory data at enrollment. Subjects enrolled in those cohorts may participate in mechanistic research projects conducted at the MRCs or Tech Sites or in clinical trials. The BACPAC will also conduct a Collaborative Clinical Project using sequential, adaptive trial designs involving subjects enrolled in all the MRCs Clinical Cores.

The DAC will establish a central database system for the BACPAC Research Program that includes clinical and research data and will ensure data accessibility, archiving and transfer.

The DAC will have a dual coordination/support and research role in BACPAC in the following five areas:

Clinical Registry, Data Integration and Coordination

Areas of responsibility include:

  • Providing scientific and operational support to the CMC during the development of the BACPAC Consensus Plan for case definition, minimal dataset, and outcomes measures
  • Providing the necessary operational, material and training support to the clinical sites to facilitate the adoption of the consensus plan for uniform collection of common data elements.
  • Establishment and maintenance of a secure, efficient, and easily accessible electronic database for storage and interrogation of clinical study data. It is anticipated that data will include demographics, medical history, medications, results of clinical laboratory tests, findings from physical examination and other diagnostic procedures, and responses to questionnaires and patient-centric diaries.
  • Development of a flexible approach, in collaboration with the DAC SBG, to support the integration of mechanistic data with clinical datasets. The first level of integrative analysis of research data generated from the mechanistic studies will be carried out by the ICs in the MRCs.
  • Development and Implementation of standard operating procedures for data curation, quality control and quality assurance of data entry to facilitate downstream data integration and algorithm development.
  • Monitoring and evaluation of protocol execution, subject accrual, data quality received from the CCs, and provide relevant reports to the SC, DSMB and NIH.
  • Initiation of changes in training/procedures in response to issues/protocol changes that emerge during trials.
  • Managing a central IRB for the BACPAC Consortium Research Program
  • Preparation of datasets for deposition into public data repository for broad sharing.

Adaptive Design, Patient Reported Outcomes (PRO) and Biostatistics

The DAC will play a major research role in the development of the Collaborative Clinical Project protocol(s), together with the BACPAC CMC. The DAC Adaptive Design Expert Group will have responsibility over interim and final analysis of data. This group is expected to include expertise in integration of multi-stage testing in targeted, adaptive clinical trial designs, and the combination of individual patient data to give group treatment effect estimates. There needs to be expertise with PRO and Patient Preferences (PPR) instruments and methodology so that they can be integrated into clinical protocols.

Areas of responsibility include:

  • Participation in all parts of protocol development, execution, and final analyses to help determine the optimal selection of predictive outcomes for use in specific patient phenotyping, development and statistical modeling, analysis of early responsiveness, formulation of stopping rules, and final analysis of composite biologic and clinical outcomes as well as group effect analyses.
  • Working with the BACPAC CMC, EC and SC to finalize a Consensus Plan for the overall study during the first year of award, including the development of common data elements, common protocol elements, metadata and data sharing agreements as appropriate.
  • Development of a plan for appropriate selection of PRO instruments to be included as part of the core element data collection, and working with all BACPAC Research Sites, the CMC and the SC to devise the final plan for the optimal collection and analysis of PRO and PPR core element data.
  • Advising and facilitating appropriate selection of PRO instruments as part of evaluation of outcomes in specific clinical cohorts to maximize the transfer of PRO and PPR data into a common, harmonized and standardized metric.
  • Performing initial quality control and quality assessment of raw clinical, PRO and PPR data and working with research sites to resolve issues of missing data, etc.
  • Contributing to overall data analysis and interpretation, and preparation of publications and resources originating from BACPAC.

Algorithm Development, Testing and Validation

The DAC will conduct de novo modeling, using systems and machine learning approaches to improve current diagnostic and treatment algorithms.

Areas of responsibility include:

  • Generation of improved and new algorithms to incorporate new phenotypic data obtained by the research sites in the clinical cohorts.
  • Utilization of real-time information from clinical and biologic data generated from the BACPAC Research program to model new algorithms to project treatment responses. These data will be used to inform SC evaluation and recommendation of protocol modifications about specific phenotypes, biomarkers, and/or interventions that may need to be added or eliminated for successful execution of the protocol.
  • Working with the DAC Clinical Registry, Data Integration and Coordination group and the Systems Biology and Bioinformatics group to integrate clinical and mechanistic data.
  • Working with the DAC Clinical Registry, Data Integration and Coordination group, the MRC Clinical Cores and the CMC to conduct testing and validation of new algorithms.

Systems Biology and Bioinformatics

The goal is to conduct data integration and systems-level analyses of multi-dimensional datasets generated by the research projects at the MRCs, the Tech Sites and the clinical projects. Areas of responsibility include:

  • Applying existing bioinformatics tools to analyze and interpret BACPAC generated data.
  • Devising new software and advanced tools for systems level analysis to produce an integrated model of how abnormalities in different tissue interact to produce altered physical function and pain.
  • Establishing a central database system to facilitate data standardization, data accessibility, archiving and transfer.
  • Implementing a BACPAC Portal to facilitate data sharing and dissemination.
  • Working with the DAC Clinical Registry, Data Integration and Coordination group as well as the Algorithm Development, Testing and Validation group to support the integration of mechanistic data with clinical datasets.
  • Providing scientific, technical support and training about analytical strategies to the Network and to individual MRCs and Tech Sites.
  • Preparation and submission of large genomic dataset to the NIH designated database for public sharing when applicable.

Operations Management

Areas of responsibility include:

  • Providing support to the SC, the EC, the CMC and Functional Working Groups including planning and arranging meetings for the various committees and groups.
  • Oversight of the budget for the BACPAC Collaborative Research Project and Ancillary and Pilot Projects.
  • Administration of the EPPIC-Net fees and negotiation of clinical agreements and budgets with the EPPIC-Net and PIs for the Phase 2CTs.
  • Establishing and maintaining effective communications across BACPAC to ensure the members of the consortium understand their roles and responsibilities, adhere to the SC approved policies and procedures, and are kept abreast of the scientific and procedural development in the Research program.
  • Development and maintenance of a secure portal for the distribution of study documents, forms, and information, including metrics (textual and graphical) of study progress and performance (e.g., expected versus actual subject accrual indexed by the CCs) across the BACPAC components.
  • Development and maintenance of an open-access web site to provide information about BACPAC to the public and prospective research subjects. The public web site must comply with all applicable Federal regulations, including Section 508 of the Rehabilitation Act of 1973 (29 USC 794d). See http://www.section508.gov and http://www.nih.gov/icd/od/ocpl/resources/wag/.
  • Providing support for obtaining IRB approvals, IND and/or IDE approval from FDA; establishing subcontract to potential external laboratories/biospecimens repositories; coordinating with suppliers of drugs and arrange for the preparation and packaging of medications for delivery to CCs for the Phase 2CTs and the Collaborative Clinical Research Project.
  • Development of a comprehensive framework for evaluating the effectiveness of BACPAC, including the identification of specific metrics for assessment of the BACPAC in achieving the proposed goals.
  • Preparation of public-use files for disseminating research resources, such as methods, standard procedures, study manuals, case-report form templates, patient-centric diary templates, and phenotype ascertainment instruments.
  • Registration and updating of protocols at ClinicalTrials.gov.
  • Submission of manuscripts accepted for publication to PubMed Central according to Federal and NIH policy (http://publicaccess.nih.gov/). Tracking of progress of publications, including PubMed Central reference number, and presentations of findings.
  • Conducting additional activities aimed at maximizing the utility and successful adoption of BACPAC Algorithms.
  • Developing training seminars or instruction manuals for using the BACPAC Algorithms.
  • Based on experience and feedback from trainees, developing a set of training materials (e.g. slides sets, manuals, handouts), an interactive web training program, and an algorithm users’ demo that will provide training on algorithm application and uses.
  • Providing user support for both inside and outside of the BACPAC Research Program.

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.

Pre-Application Webinar

NIAMS will hold a pre-application informational webinar for this FOA. 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.

Funding Instrument
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.
Application Types Allowed
New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Clinical Trial?
Not Allowed: Only accepting applications that do not propose clinical trials

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

NIAMS intends to commit up to $6 million in Fiscal Year 2019, to fund one to two awards.

Award Budget
Application budgets are limited to $3.6 million direct costs in Year 01.
Award Project Period
The maximum project period is 5 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

1. Eligible Applicants

Eligible Organizations

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)

  • 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

Foreign Institutions

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


Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.


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

Required Registrations

Applicant organizations

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

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

Eligible Individuals (Program Director/Principal Investigator)
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.

2. Cost Sharing

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

3. Additional Information on Eligibility

 

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101)

1. Requesting an Application Package

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

 

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

  • Descriptive title of proposed activity
  • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
  • Names of other key personnel
  • Participating institution(s)
  • Number and title of this funding opportunity

The letter of intent should be sent to:

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: robyn.bent@nih.gov

 

Page Limitations

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

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

Instructions for Application Submission
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
SF424(R&R) Cover
All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations
All instructions in the SF424 (R&R) Application Guide must be followed.

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

Other Attachments: 

1.    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. 


2.    Applicants may propose one or more concept(s) for future Pilot Research Projects and Ancillary Studies.
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. 

SF424(R&R) Senior/Key Person Profile
All instructions in the SF424 (R&R) Application Guide must be followed.

The DAC must have key investigators (PDs/PIs) with sufficient effort the following areas of expertise: 1) management of complex clinical trials and studies in back pain or musculoskeletal chronic pain conditions, 2) back pain phenotyping and biomarker signatures or profiles, and 3) the design and analysis of predictive, multi-stage, adaptive clinical trials. 4) bioinformatics, biomedical informatics, biostatistics, or related quantitative sciences (computer sciences, mathematics, physics and engineering, 5) evidence at a senior level of experience and expertise in integrating and interpreting large datasets of biomedical data, such as genomics, proteomics, metabolomics, imaging data and clinical study data; and 6) in-depth technical knowledge and experience of in programming, systems and database architecture, high performance computing and networking technologies.

The DAC must include a qualified full-time Project Manager and an administrator for the Funds Management Unit (FMU) which 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.

 

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

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 documented in-kind contributions at a rate of not less than 50% of 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.

To justify the personnel included in the budget, in addition to the standard biosketches including the tailored individual statement for key personnel, include a table outlining the expertise and effort proposed for the DAC. Relevant expertise includes, but not limited to, biostatistics in predictive modeling, bioinformatics and machine learning, bioinformatics, biomedical informatics, or related quantitative sciences, design and execution of predictive, sequential, adaptive clinical trials, PRO and PPR instruments, management of complex clinical trials or studies in back pain or musculoskeletal chronic pain conditions, back pain phenotyping and biomarker signatures/profiles, project management, computer expertise including database creation and management, and website development.

Include budget for key personnel travel to attend up to two face-to-face SC meetings with at least one to be held in the Bethesda, Maryland or Washington, DC general geographic area. Include a budget for a two-day meeting that includes the travel expenses of 20-30 experts to discuss a working definition of chronic low back pain and elements of a common data set.

The budget must include a separate item in years 1-5 to support the central database system for the BACPAC Research Program and the BACPAC Portal to facilitate data sharing and dissemination.

The budget must include a separate item of an intent to establish a future subcontract with the EPPIC-Net CCC in support of services for Phase 2CTs and other BACPAC collaborative clinical projects for a total of $4M/year in years 2 through 4 and for a total of $3.5M in year five. These costs should be placed in the Subawards/Consortium/Contractual Costs category.

The budget must include a separate item of an intent to establish future subcontracts with BACPAC recipient institutions in support of future Pilot and Ancillary Studies. These costs should not exceed a total of $1M per year in years 2 through 5. These costs should be placed in the Subawards/Consortium/Contractual Costs category.

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

PHS 398 Cover Page Supplement
All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Research Plan
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy: In lieu of a standard Approach section as described in the SF424 (R&R) Application Guide, the applicant must present a discussion of the planned activities to carry out functions in the following areas. The applicant must describe:


Clinical Registry, Data Integration and Coordination

  • Approach to develop and finalize a consensus plan for case definition, minimal dataset, outcomes measures, and provide site training to facilitate adoption of the consensus plan for uniform data collection of common data elements.
  • Capacity to establish and maintain a secure and efficient electronic database to host and harmonize a large amount of various clinical data, and offer easy access for data integration, analyses, modeling, and algorithm development and testing.
  • Plan to collaborate with the DAC SBG to devise a strategy to support integration of biological and other types of datasets generated from the mechanistic studies with clinical datasets.
  • Approach for data curation, quality control and quality assurance of clinical data entry to facilitate downstream data integration and analyses.
  • Strategy for monitoring and improving subject enrollment and retention.
  • Plans for oversight of protocol execution, subject accrual, the quality of data received from the CCs, and safety monitoring, staff training, and drug preparation.
  • Plans to respond to issues/protocol changes that emerge during trials and initiate timely changes to training/procedures.
  • A detailed plan for data sharing within the consortium.
  • Applicants must provide a table detailing the characteristics of clinical trials or studies with longitudinal components in the last 5 years that demonstrate experience in coordination of multi-center clinical trials of similar complexity in back pain or musculoskeletal chronic pain conditions, including: clinical trial title, applicant's role in the trial, a brief description of the trial design, planned enrollment, actual enrollment, number of sites, whether the trial(s) were completed on schedule or not, publication reference(s).

Adaptive Design, Patient Reported Outcomes (PRO) and Biostatistics

  • Capacity to improve current and develop novel predictive, targeted, adaptive clinical trial designs and predictive statistical modeling and analysis of data.
  • Use of predictive data items, monitoring biomarkers, and early stopping rules with crossover to subsequent intervention(s), and modeling of group effect data. Approaches described should be flexible and able to adapt to interim analyses results such that phenotypes and/or individualized interventions can be added and/or eliminated.
  • Capabilities to advise and facilitate appropriate selection of PRO and PPR instruments and experience with other large collaborative efforts.

Algorithm Development, Testing and Validation

  • Capabilities for de novo modeling that combines individual patient data to give group treatment effect estimates using systems and machine learning approaches
  • Approach toward and capacity to develop improved algorithms to incorporate new LBP phenotyping data, biomarker signatures/profiles, and other biological data to project treatment responses.
  • Plans and clinical cohorts used for validation of new or improved algorithms.
  • Capacity to acquire and process data from very large databases, such as those that can be extracted from electronic medical records.
  • Applicants must also provide a table that documents experience in clinical data integration, de novo modeling, and patient-based algorithm development using systems and machine learning approaches, including: study title, study objectives, applicant's role in the study, types of clinical data analyzed, types of modeling and algorithms developed, and publications or websites where the algorithms are shared and validated.

Systems Biology and Bioinformatics

  • Strategy for the development and testing of tools and software for the integration, annotation, analysis, retrieval, and presentation of data and meta-data from BACPAC clinical and analytic studies. Consider building flexibility to allow incorporation of new and diverse data types.
  • Approach for assessing the application of existing bioinformatics tools to analyze and interpret BACPAC Research Program systems-level data.
  • Plans to establish and maintain a technologically up-to-date toolset that can be readily used for systems-level analyses of data generated by the Consortium. Emphasis should be given to systems biology and other emerging computational approaches that can contribute to understanding, visualization, integration and analysis of multi-dimensional data, envisaged to be essential for the goals of the BACPAC Research Program.
  • Approaches to advanced integrative analyses of high-throughput data sets generated by the Network. This includes established methodologies for statistical genetics and transcriptomics analysis (e.g., principal components analysis, data normalization, smoothing, clustering, association testing, eQTL mapping etc.). Examples of the types of analyses include: pipelines for genome-wide analysis and interpretation of RNA-seq and single cell RNA-seq data; pipelines and methods for interpretation of mass cytometry data, MRI and other imaging modalities, etc.
  • Novel approaches to perform systems-level analyses of multiple different datasets (e.g., genetic, epigenetic, imaging, proteomic or clinical) and define clinically relevant modules and nodes, and integrate the data into a multi-scale model of LBP.
  • Development and maintenance of a highly efficient database or highly efficient interoperable databases for storage and retrieval of data generated by the Network. The database must be able to store multi-dimensional data, such as image, numerical and multi-omics, and integrate those data with experimental (protocol) and clinical descriptive data as well as other existing datasets and to facilitate correlational and meta-analyses.
  • Development of criteria or templates for uniform data collection, quality control and assurance, curation, standardization, and exchange and integrative modeling across multiple data types.
  • Applicants must include a description of Database Building Capacity. The section should provide descriptions for the following:
    • Proposed database capacity for storage and retrieval of various types of data.
    • Proposed database capacity, types of data and multi-dimensional data, such as image, numerical and multi-omics data.
    • Proposed database capacity for integration of clinical, experimental and system biology data.
    • Proposed database capacity to include and integrate patient reported outcomes and patient preferences data, as well as other existing datasets and to facilitate correlational and meta-analyses.
    • Examples of criteria or templates for uniform data collection, data standardization, data exchange and integrative modeling across multiple data types. Consider use of existing biological ontologies as the basis for defining data standards.

Operations Management

  • Approaches to support the BACPAC SC, EC, CMC and Functional Groups activities including organization of meetings, conference calls, webinars and generation of meeting minutes.

  • Capabilities to provide funds management and oversight for the BACPAC Collaborative Research Projects, and ancillary and pilot projects, and negotiate clinical agreement and budgets with EPPIC-net and PIs of the Phase 2CTs.

  • An administrative structure of the proposed DAC and how this structure facilitates communication and cooperation across BACPAC and with the NIH. Explain how the proposed structure will be able to react quickly to unexpected events.

  • Capabilities for public and private website creation and maintenance.

  • Past experience in obtaining regulatory approvals from local institution and the FDA.

  • Institution's willingness to participate in a cooperative, central, or shared IRB.

  • Capabilities to negotiate and execute agreements, subcontracts, with academic institutions and for-profit organizations for drug supplies and potential biospecimen handling.

  • Plans for outreach and dissemination of BACPAC information and sharing of resources.

  • Plans including specific metrics for evaluation of effectiveness of the BACPAC in achieving proposed goals.

  • A detailed timeline for the planned activities.

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.

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.

The following modifications also apply:

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

Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information
When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) 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 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.

PHS Assignment Request Form
All instructions in the SF424 (R&R) Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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.

7. Other Submission Requirements and Information

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NIAMS, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Post Submission Materials
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.

1. Criteria

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

Overall Impact
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Scored Review Criteria
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

 

Does the project address an important problem or a critical barrier to progress in the field? Is 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 be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

 

Are the PD(s)/PI(s), 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-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific to this FOA: 

Do key personnel have appropriate expertise and experience in the analysis of clinical data and the use of bioinformatics and computational approaches to achieve the scientific objectives of the BACPAC program?

 

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

 

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

Specific to this FOA:

Have the investigators included plans to address Clinical Registry, Data Integration and Coordination? Is there a clear and well-organized plan to support the development of common protocol elements? Is there evidence demonstrating the capacity to establish and maintain a secure and efficient electronic database to host and harmonize a large amount of various clinical data?

Have the investigators included plans to address Adaptive Design, Patient Reported Outcomes and Biostatistics? Is there evidence in the application of capacity to improve current and develop novel predictive, targeted, adaptive clinical trial designs and predictive statistical modeling and analysis of data from BACPAC?

Have the investigators included plans to address Algorithm Development, Testing and Validation? Are the approaches for and capacity to develop improved algorithms to incorporate new LBP phenotyping data, biomarker signatures/profiles, and other biological data to project treatment responses clearly presented and feasible? Is there a clear plan for development of algorithm users training materials?

Have the investigators included plans to address Systems Biology and Bioinformatics? Does the application propose a sound strategy for the development and testing of bioinformatics tools and software for the integration, annotation, analysis, retrieval, and presentation of data and meta-data from BACPAC clinical and analytic studies, including production of an integrated, multi-scale model of LBP? Is there a strong plan to establish and maintain a technologically up-to-date toolset that can be readily used for systems-level analyses of data generated by the BACPAC? Do the proposed computing infrastructure and administration plans provide for sufficient system security, long-term maintenance and survival of data and the data system, computing power and data transfer capacity?

Have the investigators included plans to address Operations Management? Is there a clear plan to support BACPAC Research Program-wide projects, activities and procedures? Does the approach suggest that the investigators will have sufficient interactions with the other components of the BACPAC program such as the MRC, the Tech Sites, and the Phase 2CT to successfully complete the objectives of the BACPAC program?

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?

 

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?

Additional Review Criteria
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

 

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

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

 Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of 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

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

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?

 

Not Applicable

 

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

 

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

 

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: How likely is it that the plans for cost matching will be adequate?

2. Review and Selection Process

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

3. Anticipated Announcement and Award Dates

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.

1. Award Notices

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.

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.

2. Administrative and National Policy Requirements

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.

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.

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75 and other HHS, PHS, and NIH grant administration policies. 

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

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 participating 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 Core 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 Informatics Core 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:
    

  • Cooperate and coordinate 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 network 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.

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.  
    
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 DMC 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 DMC will work with the Phase 2T 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 2T 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 will attend all 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/Informatics Core 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
  • Improve 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 Official. 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.

 

3. Reporting

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 .

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

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

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

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

Application Submission Contacts
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten on-time submission, 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 processes and NIH grant resources)
Email: GrantsInfo@nih.gov (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: support@grants.gov

Scientific/Research Contact(s)

Wen G. Chen, MMSc, PhD
National Center for Complementary and Integrative Health (NCCIH)
Telephone: Email: 301-451-3989
chenw@mail.nih.gov

Basil Eldadah, M.D., Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-6761
Email:eldadahb@mail.nih.gov

Yan Wang, M.D., Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5032
Email: BACPAC-NIH@mail.nih.gov

Grace Peng, Ph.D.
National Institute of Biomedical Imaging and Bioengineering (NIBIB )
Telephone:301-451-4778
Email: penggr@mail.nih.gov

Susan Marden PhD RN
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6838
Email:mardens@mail.nih.gov

David A. Thomas, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-435-1313
Email:dthomas1@nida.nih.gov

Jeremy Brown, M.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-827-8375
Email:Jeremy.Brown@nih.go

Lois A. Tully, Ph.D.
National Institute of Nursing Research (NINR)
Telephone: 301-594-5968
Email:tullyla@mail.nih.gov

Benyam Hailu, M.D., M.P.H.
National Institute on Minority Health and Health Disparities (NIMHD)
Telephone: 301-594-8696
Email:benyam.hailu@nih.gov

Lisa Begg, Dr.P.H., RN
NIH Office of Research on Women’s Health (ORWH)
Telephone: 301-496-3975
Email:beggl@od.nih.gov

Peer Review Contact(s)
Kathy Salaita, Sc.D. 
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5033
Email: Kathy.Salaita@nih.gov
Financial/Grants Management Contact(s)

John Bladen
National Institute on Aging (NIA)
Telephone: 301-402-7730
Email: jbladen@mail.nih.gov

Erik Edgerton
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301- 594-7760
Email: edgertont@mail.nih.gov

Bryan S. Clark, MBA
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email:clarkb1@mail.nih.gov

Pam Fleming
National Institute on Drug Abuse (NIDA)
Telephone: 301-480-1159
Email: pfleming@mail.nih.gov

Tijuanna Decoster, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email:tijuanna.decoster@nih.gov

Randi Freundlich
National Institute of Nursing Research (NINR)
Telephone: 301-594-5974
Email:Freundlichr@mail.nih.gov

Priscilla Grant, J.D.
National Institute on Minority Health and Health Disparities (NIMHD)
Telephone: 301-594-8412
Email:grantp@mail.nih.gov

Shelley Carow
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3788
Email:carows@mail.nih.gov

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

Authority and Regulations
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.


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