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 Mental Health (NIMH)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute on Drug Abuse (NIDA)
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: Phase 2 Clinical Trials (UG3/UH3 Clinical Trial Required)
Activity Code
UG3/UH3 Exploratory/Developmental Phased Award Cooperative Agreement
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-19-029
Companion Funding Opportunity
Catalog of Federal Domestic Assistance (CFDA) Number(s)
93.846; 93.213; 93.866; 93.865; 93.279; 93.242; 93.307; 93.853; 93.361; 93.313
Funding Opportunity Purpose
This Funding Opportunity Announcement (FOA) invites research applications to plan and implement Phase 2 clinical trials (Phase 2CT) in chronic Low Back Pain (cLBP) with the NIH Back Pain Consortium (BACPAC) Research Program.  BACPAC will carry out a patient centric-research program focused on translational and clinical research for discovery of chronic low back pain mechanisms, and on identification and testing of new interventions targeted to individual patients. BACPAC will utilize novel analytics and technologies to extensively phenotype patients with low back pain, develop an integrated model of cLBP and produce new and improved diagnostic and treatment algorithms.  BACPAC Phase 2 clinical trials (Phase 2CT) will evaluate interventions including medications, biologics, procedures, medical and assistive devices and technologies, diagnostic testing, behavioral change, rehabilitation strategies, complementary therapies for cLBP. The studies will use randomized trial design as well as adaptive, phase 2/proof of concept design studies in stratified patient populations. Clinical trials may be conducted within the infrastructure of the Early Phase Pain Investigation Clinical Network (EPPIC-Net) (formerly known as the Clinical Trial Network for Pain Research CTNPR). The Phase 2CTs will run in parallel and will synergize with projects supported in the BACPAC Mechanistic Research Centers, the Data Integration, Algorithm Development and Operations Management Center and the Technology Research Sites. 
 

Posted Date

December 10, 2018

Open Date (Earliest Submission Date)
January 26, 2019
Letter of Intent Due Date(s)
January 26, 2019
Application Due Date(s)
February 26, 2019 , by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.

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
May/June 2019
Advisory Council Review
August 2019
Earliest Start Date
September 20, 2019
Expiration Date
February 27, 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 research applications to plan and implement Phase 2 clinical trials (Phase 2CT) in chronic Low Back Pain (cLBP) with the NIH Back Pain Consortium (BACPAC) Research Program. 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 the individual patient. The Research Program will utilize novel analytics and technologies to extensively phenotype patients with low back pain (LBP), 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 Phase 2 Clinical Trials UG3/UH3, and runs in parallel with companion FOAs (RFA-AR-19-026) the BACPAC Mechanistic Research Centers, (RFA-AR-19-027) Data Integration, Algorithm Development and Operations Management Center, and (RFA-AR-19-028) for the BACPAC Technology Sites.

BACAC 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 across the lifespan including adolescence.

This study is part of the of the NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative will bolster research across NIH to (1) improve treatment for opioid misuse and addiction and (2) enhance pain management. More information about the HEAL Initiative is available at:  https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative.

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) will be conducted within the EPPIC-Net Clinical Trial environment using the EPPIC-Net Trial Hubs, Clinical Coordinating Center (CCC) and Data Coordinating Center (DCC) infrastructure, services, operating and cost standards. Innovative trial designs will be used to test new non-addictive drugs, biologics, devices and complementary medicine approaches to relieve pain and improve physical function.

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

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

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

The Funds Management Unit (FMU) will administer 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, 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 (estimated to be summer 2019-summer 2020) 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 studies 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 summer 2020, immediately after the planning year. In July 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.

Phase 2 Trials

Research Objectives

The purpose of this FOA is to facilitate the planning and execution of phase 2 clinical trials that are part of the larger BACPAC Initiative. The Phase 2CT proof-of-concept trials are intended to test the efficacy and safety of repurposed or novel, non-addictive therapies (e.g. drugs, biologics, devices, CAM) for patients with non-specific cLBP. where other etiologies such as malignancy or infection have been eliminated. High impact chronic pain often limits daily activities of life. Therefore, it will be important to conceptualize and execute these trials with a biopsychosocial perspective to ensure physical, mental and social aspects of cLBP are fully addressed.

Phase 2CTs will utilize not only extant patient phenotypes and/or endotypes as well as predictive biomarkers or profiles and mechanistic targets that already exist, but they will leverage mechanistic and other important insights from real time results that will emerge from the U19 mechanistic research centers (link) as well as the aggregate BACPAC Initiative. The Phase 2 CTs data will also facilitate the development of algorithms that will clinically meaningfully make a difference in the personalized/targeted therapy and care of patients with cLBP.

The goal of the Phase 2 CT will be to generate data on safety and efficacy of new interventions using the most scientifically rigorous approaches. In addition to the traditional randomized controlled trial approach, the use of novel, efficient study designs including adaptive and platform designs is encouraged in this FOA. This may include designs that may be modified from their original UG3 planned format based on new information or mechanistic targets established early in the Initiative. Other more complex strategies such as adaptive designs that employ Bayesian approaches and master protocols that could include umbrella or platform designs may also be proposed.

UG3/UH3 Approach

Each UG3/UH3 Clinical Trial Implementation Cooperative Agreement application can propose the planning and implementation of only one clinical trial. The PI of the Phase 2 T will lead the design, planning, implementation and data analysis of the study working collaboratively with BACPAC, EPPIC-Net and NIH.

NIH is interested in supporting clinical trials that are designed to answer questions based on a strong scientific premise and are carried out through a robust approach. To adequately plan and finalize the details for implementation of the clinical trials, investigators, in coordination with the BACPAC CMC and the EPPIC-Net Clinical Coordinating Center (CCC) and Data Coordinating Center (DCC) need time to prepare. Therefore, the UG3 component of the award will support up to a two year planning phase. Applicants and recipients of UG3 funding should note that the UG3 award does not guarantee subsequent UH3 funding for implementation of the clinical trial. Only those trials that successfully meet the scientific milestones and feasibility requirements for transition will be funded to move to the trial implementation phase (UH3).

The UG3 award supports the planning period and is not designed for the collection of preliminary data (neither clinical nor pre-clinical studies) about the efficacy or effectiveness of an intervention, or the collection of prospective data to support the rationale for a clinical trial. Awardees will develop their protocols and associated study documents with the BACPAC CMC and the EPPIC-Net CCC and DCC in conjunction with NIH project scientists and other NIH staff assigned to the projects.

Examples of activities supported during the UG3 phase include, but are not limited to:

  • A final clinical protocol developed in cooperation with EPPIC-Net and approved by the BACPAC SC.

  • The Manual of Procedures (MOP) including a detailed description of study procedures and process details;

  • The final statistical analysis plan developed in collaboration with the EPPIC-Net and BACPAC DAC;

  • The consent form(s) or, if applicable, permission and assent form(s),

  • A plan for the administration of study agent(s), if applicable;

  • Detailed description of Roles and Responsibilities of study personnel;

  • The final quality management and data management plans;

  • Strategies to put in place should enrollment or retention not meet specified metrics.

The final protocol must be accepted by NIH and receive approval by the BACPAC single IRB and the Data and Safety Monitoring Board (DSMB).

The planning phase will be followed by up to four additional years of higher funding levels, during which the study will be implemented. The duration of the combined proposed UG3/UH3 project cannot exceed five years.

Clinical Trial Implementation Phase (UH3):

The objective of the up to 4-year UH3 implementation phase is to conduct the clinical trial in accordance with activities planned in the UG3 phase. The trial outcome measure(s) must be clinically meaningful and important to stakeholders including patients and health care providers. The NIH expects clinical trials supported during the UH3 phase to be hypothesis driven, milestone-defined, and have the potential for high impact within the research mission of the BACPAC initiative. The clinical trial must meet all applicable NIH, Food and Drug Administration (FDA), and Office of Human Research Protections (OHRP) regulatory and policy requirements. Applicants should propose the most appropriate primary outcome for the trial question. Standardized pain measures and functional outcomes are strongly encouraged to ensure that data is translatable across all BACPAC studies. Secondary outcomes, including selected patient reported outcomes will be added to the protocol during the UG3 protocol development phase. A final list of these required measures will be developed by the CMC, and the SC.

Applicants are strongly encouraged to consider using the PROMIS domains (http://nihpromis.org) related to pain, such as pain interference, physical function and depression instruments, as measures in their studies.

Applicants should make note of the following:

The BACPAC research program will use the infrastructure of the EPPIC-Net to provide scientific guidance and coordination of the BACPAC Phase 2 trials to ensure high quality Phase 2CT clinical trials to test novel therapeutics for pain. EPPIC-Net personnel will participate on study teams of projects selected for UG3/UH3 funding during the planning and implementation phases and will provide Clinical Coordination Center (CCC), Data Coordinating Center (DCC) services, and recruitment and retention services (Clinical Hubs), and biostatistical support. Further information can be found at NOT-NS-18-057, NOT-NS-18-058, and NOT-NS-18-069

Specific EPPIC-Net functions in support of BACPAC include but are not limited to:

  • Developing the final study protocol with the principal investigator(s) and other investigators on the study team and with the BACPAC CMC;
  • Providing study design support, statistical analysis and interpretation of results for manuscripts and publications;
  • Finalizing recruitment and retention plans with the individual investigators before initiation of the trial;
  • Developing associated trial documents, including the Manual of Procedure or Standard Operating Procedures; materials for site investigators, case report forms and training materials for study personnel with the study team and the DAC.
  • Training clinical site investigators and staff for the individual trials. Training areas include, but are not limited to, regulatory requirements, Good Clinical Practice (GCP), adverse event reporting, human subject protections, informed consent, and NIH policies and procedures;
  • Developing and maintaining a data management system for trial data collection and storage and adverse event reporting;
  • Providing randomization support;
  • Providing clinical operations and monitoring support. Includes project management, to oversee and coordinate activities associated with the clinical trials, study implementation, from study start-up through site selection, enrollment, site management, study monitoring and close out.
  • Monitoring enrollment and retention at the individual sites and working with sites that fail to meet their enrollment targets;
  • Preparing reports for the Data and Safety Monitoring Boards;
  • Working with the DAC and awardees to execute the Master Clinical Trial Agreement to the individual clinical sites.

NIH Resources: As appropriate, applicants are encouraged to make use of the following resources for clinical research including:

(a) Clinical and Translational Science Award (CTSA) program (https://www.ctsacentral.org );

(b) NIH Toolbox (http://www.nihtoolbox.org );

(c) PROMIS (http://www.nihpromis.org ); and

(d) NINDS Common Data Elements (http://www.commondataelements.ninds.nih.gov ).

Milestones and UG3/UH3 Transition

  • Applications must include well-defined milestones for the planning phase (UG3) and annual milestones for the clinical trial implementation phase (UH3). Prior to a pending award, the PD/PI and NIH will negotiate a final list of milestones for each year of support. The proposed milestones for the UH3 phase may be revised during the award period in coordination with NIH staff, the CCC and DCC, as activities in the UG3 phase progress.
  • Four months before completion of the UG3 planning phase or if possible sooner, the applicant will be required to submit a detailed transition proposal for the UH3 clinical trial implementation phase. The UH3 transition proposal will undergo an administrative review to determine whether the study will be awarded the implementation phase (UH3). The review will determine if the UG3 planning milestones have been met, and that the UH3 phase can successfully test the chosen hypothesis in a timely fashion.

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 the 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?
Required: Only accepting applications that propose clinical trial(s)

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NIAMS intends to commit $1.3M to fund up to 8 awards in Phase I in FY2019. NIAMS expects to support up to five UH3 awards.

Award Budget

Application budgets are limited to $200,000 Direct Costs for the entire UG3 planning phase. Application budgets for the UH3 phase are not limited but need to reflect the actual needs of the proposed project.

Award Project Period
The scope of the proposed project should determine the project period.  The maximum project period for the UG3 phase is two years, and the maximum project period for the UH3 phase is four years. The duration of the combined UG3/UH3 award cannot exceed five 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)
  • Eligible Agencies of the Federal Government

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

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

Foreign Institutions

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


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


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

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

 

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

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

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

Applicant organizations may submit more than one application provided that each application is scientifically distinct.

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.

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.

Applications that are missing The Clinical Trial Experience are considered incomplete and will be withdrawn.

Other Attachments: 

1.    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 conducting clinical trials of similar complexity in back pain or musculoskeletal chronic pain conditions. The table should be labelled as "Clinical Trial Experience.pdf" and may not exceed 3 pages.

The table columns must include:

Column A: clinical trial title  

Column B: applicant's role in the trial 

Column C: a brief description of the trial design

Column D: planned enrollment

Column E: actual enrollment

Column F: number of sites

Column G: whether the trial(s) were completed on schedule or not

Column H: publication reference(s)

2.    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. 

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

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

Applications that are missing The Clinical Trial Experience, and the Intellectual Property Strategy are considered incomplete and will be withdrawn.

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

 

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

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

Cost Matching Requirement for For-profit Applicants

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

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

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

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

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

(d) Program income; and

(e) Patient incentives.

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

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

The budget for the entire UG3 planning phase should not exceed $200,000 direct costs. The budget justification must include:
  • The applicants should include a full budget for all of the activities related to the planning and implementation of the clinical trial. However, some or all of the clinical coordination, data management, and clinical site operations may be subcontracted out to EPPIC-Bet.  Applicants are instructed to review the EPPIC-Net FOAs to understand what functions they provide.  The decision will be made at the time of the UH3 award, and budgets will be adjusted accordingly.
  • Costs at the clinical sites must include a trial infrastructure component that includes salary support for the PI and study coordinator only. 
  • Trial costs should be budgeted on a per-subject or per-procedure basis. Applicants should provide a breakdown of the total per subject costs as part of the budget justification and should indicate how the cost for an item or procedure was determined. These costs should be calculated and presented taking into consideration that NIAMS anticipates that enrollment and follow-up for the proposed Phase 2 trials should be completed within 24 months after the opening date of enrollment. 
  • Costs for collection, analysis, shipping, and/or storage of biospecimens during the study should be included as a separate item in the budget.  Specimens collected beyond that needed for the study or remaining at the close of study will be stored in the NIH EPPIC-Net Biorepository.  Costs for shipping to the repository should be included in the budget.  Costs for long-term storage in the EPPIC-Net repository will be covered through HEAL funds. 
  • In addition, applicants should budget for two annual two day, in-person investigator meeting and should budget to allow up to 4 persons from the investigator team to attend.  (The expenses of the meeting room rental will be covered separately.)
  • Costs to support the DSMB will be covered by the NIAMS.
  • If some trial costs are to be borne by sources other than NIH, these contributions must be presented in detail in the budget justification. These costs borne by third parties do not constitute cost-sharing as defined in the current NIH Grants Policy Statement and should not be presented as part of the requested budget.
  • The release of funds will be milestone-driven, according to milestones pre-specified in the Notice of Award.

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:
Significance and Clinical Relevance: Describe the significance of the proposed efficacy/safety/ POC clinical trial in the context of the status of current interventions for pain management and improvement of physical function and prevention of disability in cLBP. Describe the risks and benefits of the proposed study interventions. Discuss how the trial will test the hypotheses proposed and how the results of the trial (positive or negative) will advance the field. Applicants are encouraged to include evidence such as letters or references that relevant stakeholders (e.g. potential subjects, referring and treating physicians, patient organizations, or professional organizations) view the question to be important.

Previous Studies: Present the major findings and discuss the strength of the evidence that support the biological and/or clinical premise of the study. Ensure that the data supporting the proposed trial meet the NIH scientific rigor guidelines (see https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-103.html). Preliminary data supporting efficacy of the proposed intervention may come from the applicant’s previous work or from published literature.

Investigator(s): Describe the expertise of the study team in the conduct of multi-center trials and the team’s ability to plan and implement the proposed study. 

Approach: 
The approach should clearly justify the clinical relevance for the length of observation for the pain outcome and the additional outcomes. It should also describe known side effects and risk benefit analysis of the proposed intervention. 
The Approach section should have a clear demarcation of the UG3 and UH3 portions of the application. 

For the UG3 phase:

•   Describe the study development activities planned for the UG3 phase. 

For the UH3 phase, include the following: 

•    An assessment of the feasibility of recruiting participants who are eligible for the proposed research.
•    An overview of the proposed study design that must justify the selected trial elements provided in the Protocol Synopsis, including: 

o    Rationale for the selected trial design (e.g., single-group, parallel, cross-over, factorial) and allocation method.
o    Rationale for selection of the intervention to be tested and a description of how and at what frequency the intervention will be administered.
o    For behavioral interventions, strategies that will be used to deliver the intervention with fidelity.
o    Justification for selection of the primary and secondary outcome measures and a description of how the outcome variables will be collected and the criteria for measuring the outcomes and plan for modification following input from the BACPAC and EPPIC-Net relevant committees. 
o    Description of the study population, including the sample size, pertinent demographic information, required health status or disease condition, and geographic location. Explain why the study population is an appropriate group to address the study objectives. Do not duplicate information described in Section 2 (Study Population Characteristics) of the Study Record: PHS Human Subjects and Clinical Trials Information form. Describe whether the trial proposed may use the EPPIC-Net Clinical Hubs, if appropriate. 
o    Description of the study duration. Provide a justification if the trial duration is expected to exceed 24 months from the date when enrollment opens until the last observation is obtained in the last patient enrolled.  

•    Discuss potential biases or challenges in the proposed trial and how they will be minimized and/or addressed.

Those planning Phase 2 clinical trials that require investigational new drug (IND) or investigational device exemption (IDE) applications should provide elements that are consistent with the requirements of the Food and Drug Administration (FDA) IND or IDE. A protocol template for such studies can be found at https://osp.od.nih.gov/clinical-research/clinical-trials/. Applications proposing to test products must contain information ensuring that the products are produced according to Good Manufacturing Practice (GMP), a system for ensuring that products are consistently produced and controlled according to quality standards. 

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 with the following additional instructions:

Section 2 - Study Population Characteristics

2.5 Recruitment and Retention Plan
Applicants should state how many sites will be needed and survey the potential clinical sites to ensure that recruitment targets can be met. Present the survey results using a table where the rows represent potential clinical sites and the columns include responses to questions from the survey. The survey questions will depend on the nature of the trial and the protocol-specified screening procedures but might include these:

o Has the site PD/PI previously recruited individuals with this disease into a clinical trial?
o Does this site have all necessary equipment to complete eligibility evaluations?
o What is the total number of individuals with this disease seen at this site in the past 12 months?

Existing other networks sites suitable to answer the study question such as EPPIC-Net may also be used. If the plan is to add more clinical sites after the award, specify the criteria for selecting additional sites.

The plan should also include a contingency plan for adding new sites if enrollment falls behind targets or discontinuing enrollment of new participants at sites that do not meet individual goals.

Section 3 - Protection and Monitoring Plans

3.3 Data and Safety Monitoring Plan

Applicants should refer to the NIAMS Data and Safety Monitoring Guidelines (https://www.niams.nih.gov/grants-funding/conducting-clinical-research/data-safety-guidelines-policies) when developing their DSMP.

A Clinical Site Monitoring Plan will be developed with the EPPIC-Net CCC and BACPAC DAC during the first year of the study. This will include how site adherence to the protocol and consenting process will be ensured, who is responsible for site monitoring, the frequency of planned monitoring activities, and the plan for handling deficiencies. Plans for training and, if needed, certifying site personnel to complete study procedures will be developed by the PD/PI and the EPPIC-Net DCC and CCC during the UG3 phase of the study.

A detailed Data Management Plan, including the methods and systems for data collection and quality control, and for ensuring data confidentiality and privacy, and the process for locking the final dataset will be developed by the PD/PI and the EPPIC-Net DCC and the BACPAC DAC during the UG3 phase of the study.

Describe the plans, if any, to use non-traditional data collection approaches (e.g., digital/mobile/sensor technologies and web-based systems) and why these are appropriate.

Section 4 - Protocol Synopsis

4.2.a Narrative Study Description

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

o NINDS Common Data Elements (https://www.commondataelements.ninds.nih.gov/#page=Default);
o NeuroQOL (http://www.healthmeasures.net/explore-measurement-systems/neuro-qol);
o NIH Toolbox (http://www.healthmeasures.net/explore-measurement-systems/nih-toolbox); and
o PROMIS (http://www.healthmeasures.net/explore-measurement-systems/promis).

4.4 Statistical Design and Power

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

The final SAP will be developed with statistical guidance of the EPPIC-Net DCC and the BACPAC DAC.

4.6 Will the study use an FDA-regulated intervention?

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

4.7 Dissemination Plan
UG3/UH3 applicants must submit a plan for the dissemination of NIH-funded clinical trial information that will address how the expectations of the NIH Policy on the Dissemination of NIH-funded Clinical Trial Information will be met. Responsibility for adhering to this policy lies with the UG3/UH3 grantee institution.

Section 5 - Other Clinical Trial-related Attachments

5.1 Other Clinical Trial-related Attachments

Additional Instructions: The information provided here will be considered by reviewers and is meant to supplement, not duplicate, information provided in the Research Plan. The following documents must be uploaded as separate pdf files with the names indicated below.

  1. Schedule of Events. The filename "Schedule of Events" should be used to name this attachment. Provide a schematic, table, or text description of the protocol-specified schedule of events for an individual study participant. It should capture each study visit/assessment time point and planned activity(ies) for each time point.  Applications that are missing the schedule of events are considered incomplete and will be withdrawn.
  2. Milestone Plan. The filename "Milestone Plan" should be used to name this attachment.

The Milestone Plan must describe separate milestones for the UG3 and UH3 phases.

  • Applicants are required to provide detailed project performance and timeline objectives. This attachment must include two sections: those milestones to be completed during the UG3 planning phase and those to be completed during the UH3 phase. The plan should present an overview of the project timeline to achieve the following general milestones, as applicable:
  • Milestones to be completed during the UG3 phase:
    • Finalization of plans to obtain study agent(s), if applicable
    • Finalization of clinical sites, demonstration that the necessary study population is available at the clinical sites, and finalization of plans to add or drop clinical sites if needed
    • Finalization of agreements for use of resources available within EPPIC-Net, CTSAs, practice-based research networks, patient registries, etc.
    • Finalization of clinical protocol
    • Regulatory approvals (IRB and applicable oversight committees)
    • Completion of the data management system
    • Finalization of all documents necessary to implement the trial, such as case report forms and
    • Registration of clinical trial in ClinicalTrials.gov
    • Participation in consortium and common data elements development process
    • Approval by the BACPAC SC
  • Milestones to be completed during the UH3 phase:
    • Site activation
    • Enrollment of the first subject
    • Enrollment and randomization, if applicable, of 25%, 50%, 75% and 100% of the projected study population
    • Completion of data collection time period
    • Completion of primary endpoint and secondary endpoint data analyses
    • Completion of final study report
    • Reporting of results in ClinicalTrials.gov per the NIH policy on Dissemination of NIH-Funded Clinical Trial Information.

Milestones and timelines will be refined and finalized in consultation with the BACPAC CMC, DAC, and Program staff at the time of award.

Applications that lack the Milestone Plan attachment are considered incomplete and will be withdrawn.

Applicant are strongly encouraged to refer to the NIAMS webpage for additional information, policies and resources for clinical trials. (https://www.niams.nih.gov/grants-funding/conducting-clinical-research/trial-policies-guidelines-templates.

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.

 

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

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.

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

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

 

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?

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

Specific for this FOA:

Does the applicant demonstrate experience in conducting clinical trials of similar complexity?

 

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

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

 

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

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?

UG3 Planning Phase Specific
Are there clear plans to obtain any study agents?  Are there clear plans for developing a final clinical protocol and associated documents? Are there appropriate plans for the final selection of the clinical sites and necessary populations for the future study? Is there an adequate discussion of potential challenges that are anticipated during planning and study implementation, and how they will be addressed? Is there evidence the investigators will work with the consortium to finalize the UH3 study plans?

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

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

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

Data Management and Statistical Analysis 

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

 

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

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

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

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

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

 

Specific to the FOA:

Does the application provide sufficient rationale for the settings selected for the UH3 effectiveness trial?

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.

Study Timeline

Is the study timeline proposed for the UH3 described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

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

Specific for this FOA:

Are appropriate, evaluative milestones clearly defined for the UH3 phase? Are the milestones feasible and quantifiable with regard to specific aims and timeline?

 

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?

 

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

 

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

 

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

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

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

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

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

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. See45 CFR 75.306for 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 participate in BACPAC Functional Working Groups;
  • Implementing common data elements, protocols, standards and policies approved by the Steering Committee or required by NIH/NIAMS;
  • Providing the BACPAC Data Integration, Algorithm Development and Operations Management Center (DAC) with all clinical study data for management, quality control, and analysis, using procedures and standards determined by the BACPAC Steering Committee (SC), and the Executive Committee (EC) and the DAC;
  • Providing the BACPAC Systems Biology 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:
    

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


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

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

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

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

Trial Monitoring. The NIAMS Program Official or designee will oversee clinical site monitoring that evaluates Good Clinical Practice regulatory compliance, protocol implementation, internal quality assurance, and test article accountability at the 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 2T (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.

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)

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

James Witter, M.D., Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Tel: (301) 594-5055
Email:BACPAC-NIH@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.gov

Lois A. Tully, PhD
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

Wendy Weber, ND, PhD, MPH
National Center for Complementary and Integrative Health (NCCIH)
301-402-1272
weberwj@mail.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)
301.594.3788
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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