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.

Background

This study is part 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.

This initiative will expand upon the Health Care Systems Research Collaboratory Program that has been funded by the NIH Common Fund. The NIH Common Fund supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for transformation of research processes.

The overall goal of the NIH Health Care Systems (HCS) Research Collaboratory program is to strengthen the national capacity to implement cost-effective, large-scale research studies that engage health care delivery organizations as research partners. The HEAL Initiative supported a program entitled, “Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing (PRISM),” which issued two FOAs to support pragmatic trials conducted within the context of health care systems (RFA-AT-19-004 and RFA-19-005). Within those FOAs, NIH stated, “Trials or studies should be conducted across three or more health care systems (HCS) and will become part of and work with the NIH HCS Research Collaboratory.” The current FOA will support the expansion of the activities of the NIH HCS Research Collaboratory Program to provide a Resource Coordinating Center (RCC) for the additional trials supported through the HEAL PRISM initiative. Under this new award, the NIH expects to:

1. expand the activities of a Resource Coordinating Center that will provide national leadership and technical expertise in all aspects of pragmatic research with HCS ;
2. support the design and rapid execution of a set of high impact Pragmatic Studies that will conduct research studies in partnership with health care delivery systems to improve pain management and reduce unnecessary opioid prescribing;
3. make available data, tools and resources for HEAL PRISM and other projects to facilitate a broadened base of research partnerships with HCS to improve pain management across all HCS.

The aim of the HCS Research Collaboratory program is to provide a framework of implementation methods and best practices that will enable the participation of many health care systems in clinical research, not to support a defined health care research network. Health care systems have interest in participating in research that may potentially impact the pain care they deliver, including pragmatic clinical trials, longitudinal cohort studies, population-based studies, and studies addressing the incorporation of new technologies into care. Research conducted in partnership with health care systems is essential to strengthen the relevance of research results to ‘real world’ health practice. Successful approaches and best practices established through this initiative for research partnerships with health care systems will have a major impact on clinical research in the US. (See http://commonfund.nih.gov/hcscollaboratory/).

Although the importance for biomedical research to engage and strengthen partnerships with organizations that deliver health care is clear, many challenges exist, both cultural and practical. Many ethical and regulatory issues must be addressed to perform research in the health care delivery setting. Technical challenges to accessing and aggregating data from health care systems in understandable ways are not trivial. Health care providers’ focus is on providing the best treatment based on current knowledge whereas research studies have typically focused on studying which treatments work best in a precisely defined population. Research studies have frequently used endpoints that are not part of the normal evaluation of patients during a routine visit and interventions that are impractical in most care delivery settings. Policy issues can arise due to conflicts between the mission of delivering health care and that of generating new knowledge. Education and engagement of providers and patients on the value of research in the care setting are urgently needed. The NIH HCS Research Collaboratory program created a broad framework to tackle some of these major challenges and continued HEAL support will further address these issues.

More than 25 million Americans suffer from chronic pain, a highly debilitating medical condition that is complex and difficult to manage. In recent decades, there has been an over-reliance on the prescription of opioids for chronic pain, contributing to a significant and alarming epidemic of opioid overdose deaths and addiction. Extant data suggest that nonopioid pain management interventions show some efficacy for the treatment of acute and chronic pain. For example, the Agency for Healthcare Research and Quality (AHRQ) published a systematic review entitled, "Noninvasive nonpharmacological treatment for chronic pain: a systematic review." The results describe a number of nonopioid interventions improved function and reduce pain beyond the end of treatment for conditions such as chronic low back pain, chronic neck pain, knee osteoarthritis, hip osteoarthritis, fibromyalgia, and chronic tension headache.

In addition, several pain treatment guidelines published by government agencies, and clinical and professional societies recommend the use of nonpharmacologic approaches as first tier treatment for the management of pain. The Centers for Disease Control (CDC) guideline for prescribing opioids for chronic pain, for example, states that "nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain." The Clinical Practice Guideline from the American College of Physicians also recommends noninvasive, nonopioid treatments for acute, subacute, and chronic low back pain.

Pragmatic trials and implementation studies, therefore, are needed because policies, clinical practice guidelines, and tools and interventions have not been readily adopted and implemented by health care systems for the management of pain. Research is needed to study strategies to most effectively, equitably, and efficiently implement evidence-based interventions, and pain management guidelines to further assess their effectiveness in “real world” settings..

Pragmatic Studies will be selected based both on the importance of the scientific questions and the potential to improve pain management within health care delivery organizations. The NIH anticipates funding an additional seven - ten Pragmatic Studies in addition to the ongoing projects. New Pragmatic Studies will utilize a phased award UG3/UH3 mechanism, with a planning (UG3) and an implementation (UH3) phase.

During the UG3 phase the Pragmatic Study teams in cooperation with the Coordinating Center will develop detailed plans for site implementation; determine resource needs; test data extraction methods for patient identification and outcome assessment; test methods for outcome assessment augmentation beyond the EHR; review study design, statistical analytic plans, and study power; and develop plans for all aspects of ethical and regulatory oversight and protection of human subjects. All projects will be milestone-driven, and not all planning grants will necessarily move to the implementation phase.

The companion FOAs (RFA-AT-19-004 and RFA-AT-19-005), solicited Pragmatic Clinical Trials or Implementation Studies as part of the NIH HEAL PRISM Initiative.

Coordinating Center Overview

The PRISM Resource Coordinating Center will build upon their overall national leadership for the NIH Health Care Systems (HCS) Research Collaboratory program and expand its activities to support pragmatic trials supported through the NIH HEAL PRISM initiatives. The Coordinating Center will: 1) further develop, adapt, and adopt technical and policy guidelines and best practices for the effective conduct of research in partnership with health care systems; 2) work collaboratively with each Pragmatic Study team supported through the Collaboratory program, including their partnering health care systems, to develop, test, and implement the proposed Pragmatic Studies while providing technical, design, and coordination support for the pain management studies; 3) learn and disseminate the best strategies for engaging health care systems as research partners to improve health and care delivery of pain management; and 4) learn, develop, and disseminate the best means of conducting pragmatic clinical trials in health care systems to improve the scientific community’s ability to perform future pragmatic trials. Overall, the Coordinating Center will also serve as the central resource for NIH HEAL PRISM Initiatives, coordinating activities and providing administrative support for the Working Groups, Steering Committee and its subcommittees, leveraging existing Collaboratory expertise and resources

As the national leader for the NIH HEAL PRISM program in cooperation with NIH, the Program Director/Principal Investigator(s) of the Coordinating Center is expected to have broad experience in working collaboratively with a variety of health care systems on issues related to the planning and implementation of pragmatic trials; and in extracting health care data for research and in managing the related regulatory, ethical, and policy issues. The ability to work collaboratively with multiple communities while providing strong leadership is a requirement. In addition to a strong leader, the Coordinating Center must include individuals with broad experience (as detailed below) and ability to communicate clearly with all relevant stakeholders and work to find common ground.

The Coordinating Center is expected to have significant experience and knowledge in the following areas; the application should highlight the depth of experience and how it will be provided by the proposed team and structure.

• Extracting information from electronic health records and relevant clinical systems for research; experience with multiple health care systems and EHRs is preferred
• Knowledge of the latest regulatory requirements for conduct of research and for use of health care data for research and experience in conducting research that complies with the current and new regulations related to pain management, opioid medication, and opioid use disorder
• Experience with the ethical issues related to clinical research, clinical care, quality improvement, population health, surveillance, and their boundaries
• Conduct of multisite research studies with participation by multiple health care delivery organizations and various private and public health care payers
• Working collaboratively with others including patients, research participants, practitioners, researchers, hospital and research informatics and technical personnel, and senior managers of health care and research organizations
• Workflows and practices of health care systems and their practitioners
• Workflows and practices of research teams; experience in workflow for design and implementation of randomized studies should be highlighted
• Knowledge, including an understanding of the strengths and weaknesses, of current data models, algorithms, and approaches used by various networks and studies to define clinical phenotypes, extract information, define endpoints, and discover errors in data from health care systems
• Project management experience in taking a research question from idea through implementation to completion
• Study design and statistical expertise, particularly in novel study designs and methods for pragmatic clinical trials
• Creativity and innovation in solving technical and project challenges that respect and promote participation by all relevant communities
• Reusable and sustainable models for incorporation of patient reported outcomes and patient reported assessments in health care EHRs and research study management tools, including augmentation of EHRs via streamlined tools to gather patient reported outcomes, and use of smart phone or sensor data collection to enhance information available for pragmatic trials.

It is expected that the Coordinating Center, as national leader in pragmatic trials, will continue to engage the US communities and stakeholders working in similar areas and stay abreast of emerging experience, regulations, and technical advances that impact the ability of research to be conducted in health care settings. This could include NIH funded projects that are also part of the NIH HEAL Initiative, such as the Pain Effectiveness Research Network and the Early Phase Pain Investigation Clinical Network. In addition, it is likely that this program will work with other NIH supported projects including but not limited to eMERGE, PROMIS, CTSAs, and other federally and privately funded efforts, including Query Health and other programs supported by the Office of the National Coordinator for Health Information Technology (ONC), PCORNet and PCORI.

Specific Objectives of this Coordinating Center

The specific objectives of the Coordinating Center are to:

1. further develop, adapt, and adopt technical and policy guidelines and best practices for the effective conduct of research studies in partnership with health care systems;
2. work collaboratively with each Pragmatic Study team supported through the NIH HEAL PRISM program, including their partnering health care systems, to develop, test, and implement the proposed Pragmatic Studies while providing technical, design, and coordination support for the pain management studies;
3. learn and disseminate the best strategies for engaging health care systems as research partners to improve health and care delivery of pain management; and
4. learn, develop, and disseminate the best means of conducting pragmatic clinical trials in health care systems to improve the scientific community’s ability to perform future pragmatic trials.

This FOA will expand the HCS Research Collaboratory Work Groups and allow the creation of new ones to achieve the collaborative activities of this program. The Work Groups will play a vital role in achieving the goals of the program. Activities to support the above four objectives could include, but are not limited to:

• Building on the technical and policy experience of the many health care systems and researchers that have conducted studies that leverage electronic health record data and health care settings to address a variety of research questions
• Articulating basic requirements, including technical, policy, and workflow practices, for participation by health systems in pain management research
• Defining clearly the requirements for research that can be conducted in partnership with various health care systems so researchers better understand the types of research that can be done in these settings
• Developing clear guidance and model agreements for addressing in uniform manner regulatory requirements for pain management studies conducted in single and multiple health care systems
• Defining processes and best practices for ethical conduct of research in health care settings
• Enabling input from health care system leadership, patients, family members, providers, researchers, and staff on research questions and study conduct to ensure feasibility.
• Collaborating with related HEAL initiatives to share learnings and contribute to complementary efforts that support the conduct of research with health care systems
• Developing short training modules/materials, methods and tools to widely disseminate Collaboratory endorsed policies, practices, and lessons learned, to inform best practices for the conduct of pragmatic clinical trials. Including presentation of resources and tools at national conferences and seminars.
• Developing guidance and best practices about how to implement successful interventions from pragmatic clinical trials into other health care systems to improve pain management nationally, and, when necessary, how to de-implement unsuccessful interventions.
• Further developing tools and metrics that can be used to manage and track the quality and efficiencies of pragmatic clinical trials
• Developing approaches to facilitate sharing of data and metadata (how the data are generated and coded) to improve the quality of analyses.
• Developing guidance for engaging a wide range of health care systems, patients, payers, and clinicians in pragmatic clinical trials
• Collaborating with other HEAL pain clinical trials to determine the appropriateness and possible implementation of common data elements for the databases of the Pragmatic Studies and a minimal data set for pain outcomes and common co-occurring conditions
• Participating in occasional NIH HEAL initiative meetings and updates to the NIH HEAL Multi-Disciplinary Working Group if requested

The exact boundaries of the activities of the Coordinating Center, the Pragmatic Studies, and NIH are not possible to predict at this time and will depend in large part on the capacities and experience of the Pragmatic Study teams selected.

The Coordinating Center will be responsible for facilitating harmonization and sharing of tools, guidance documents, best practices, and approaches within and across Pragmatic Studies in this collaborative program and as possible with other HEAL initiatives.

Administrative Support for HCS Research Collaboratory Program

Administrative activities of the CCC to expand the HCS Research Collaboratory program to support the NIH HEAL PRISM Program could include but are not limited to:

• provision of a public website for communication and sharing of activities, events, and resources of the program
• private collaboration space for the Pragmatic Studies during the planning phase of their projects
• organizational and logistical support for facilitating the activities of the HCS Research Collaboratory Work Groups, Steering Committee and designated sub-committees,
• supporting standards and mechanisms for publicly sharing data, resources, phenotype definitions and algorithms, and code developed and utilized in HCS Research Collaboratory projects and by the Coordinating Center
• organizing and supporting the logistics of face to face meetings of the HCS Research Collaboratory Work Groups and Steering Committee in the Bethesda MD area of a kick off and one annual meeting for one and half days in the first year of the competing award and annual meetings of similar length in following years

HCS Research Collaboratory and NIH HEAL PRISM Program Governance

The awards funded under this FOA and the companion FOA will be cooperative agreements (see Section VI.2 Cooperative Agreement Terms and Conditions of Award). Close interaction with the NIH and with the awardees under the companion FOA will be required to accomplish the goals of this program.

HCS Research Collaboratory Work Groups will be expanded and if needed new ones established as the core collaborative activity of this program. The Work Groups will provide a forum for discussion of challenges and solutions across projects; harmonized and standardized policies and processes will be vetted in these groups. Work Groups are expected to be established to cover the following topic areas (one work group could cover more than one topic area): Ethics and Regulatory; Biostatistics and Study Design; Patient-Reported Outcomes; Healthcare Systems Interaction; and Electronic Health Records. Work Groups will be open to participation by individuals from all funded Pragmatic Studies, the Coordinating Center, and the NIH. Workgroups should capture solutions and disseminate their findings via appropriate means such as peer reviewed publications, the Knowledge Repository, or white papers.

An HCS Research Collaboratory and NIH HEAL PRISM Steering Committee will be established to address issues that span all projects, provide input into the policies and processes of the HCS Research Collaboratory, and assist in dissemination of policies and processes that enable research in partnership with health care systems, their patients, and practitioners. Either a new Steering Committee can be proposed or the existing HCS Collaboratory Steering Committee could be expanded to include the new projects. At a minimum, the Steering Committee will be composed of one representative from each of the Pragmatic Studies, one representative from each Work Group, one representative from the Coordinating Center, the NIH Program Coordinator, and representatives from various NIH ICs. All members are expected to actively participate in all Steering Committee activities. The combined vote of NIH membership may never exceed 1/3 of the total committee membership.

Program Resources, Data, and Software Sharing

The HCS Research Collaboratory program encourages sharing of resources with broad availability of policies, practices, materials, and tools to facilitate collaboration, reuse, and replication. The NIH HEAL PRISM program will have similar goals related to resources, data, and software sharing. In addition, the program encourages sharing of study data from Pragmatic Studies in a timely manner with appropriate privacy and confidentiality protections to facilitate further research, reuse of data, and replication. Thus, the program expects grantees to implement a Resources and Data Sharing Plan consistent with these program goals.

In addition, the program encourages sharing of software and code that are developed or modified to accomplish aims of this program. This may include, but is not limited to, software, tools, or code sets for extraction or definition of data from EHRs, clinical systems, and other health care data systems; implementation of new workflows for research studies; analytic and analysis programs; and tools for incorporation of patient input. The goals of software sharing under this program include 1) broad availability to biomedical researchers, health care delivery organizations, research institutions, and government health care systems and researchers; 2) terms that permit the dissemination and commercialization of enhanced or customized versions of the software, or incorporation of the software or components of it into other software packages; and 3) terms of software availability that include the ability of individuals outside the applicant institution and its collaborating organizations to modify the source code and to share modifications with others. While software development is not the primary goal of this program, it is expected that software or sets of code may be developed under this program by the Coordinating Center or the Pragmatic Studies, thus, grantees and their sub-contractors are expected to implement software sharing plans consistent with the goals of this program.

Coordinating Center Director Effort

The NIH HEAL PRISM Research Collaboratory Coordinating Center Director is the person(s) responsible for the overall management of the Resource Coordinating Center and coordination with each of the Pragmatic Studies. The relationship between the Coordinating Center and the Pragmatic Studies should be one of equal partners in the planning and implementation phases. The Coordinating Center Director (or team of multiple PD/PIs) must devote at least 20% effort (2.4 person months) to the HEAL PRISM Resource Coordinating Center (the effort must be in addition to the existing required effort to the HCS Collaboratory program).

1. Eligible Applicants

Eligibility is limited to awardees of RFA-RM-16-018. This limited competition will allow new consortium agreements to bring in needed expertise.

Applicant organizations

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

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

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

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

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.

In terms of experience and expertise, in addition to a strong experienced leader, the Coordinating Center PD/PI(s) should have the following qualities:

• Technical expertise in accessing and extracting information from electronic health records (EHRs) of the health care systems that deliver care .
• Knowledge of the regulatory requirements for conducting pragmatic clinical trials including knowledge of policies and procedures for the use of health care data for research purposes and experience in conducting research that complies with clinical practice and research regulations for these systems.
• Experience with the ethical issues related to pragmatic clinical trials, clinical care, quality improvement, population health, and surveillance. Specifically, knowledge of the human subjects protection requirements.
• Ability to provide technical support for multisite pragmatic clinical trials involving multiple health care delivery organizations.
• Experience working with a variety of stakeholders including patients, research participants, practitioners, researchers, hospital and research informatics and technical personnel, senior managers of health care and research organizations, and public and private payers.
• Knowledge of workflows and research team practices in design and implementation of pragmatic clinical trials.
• Knowledge of current data models, algorithms, and approaches used by the various eligible networks and practices to define clinical phenotypes, extract information, define endpoints, and discover errors in data.
• Knowledge of privacy regulations related to health care systems.
• Project management experience in taking a research question from idea, through implementation, to completion.
• Study design and statistical expertise, particularly in pragmatic clinical trial methodology, including cluster randomization and stepped-wedge designs.
• Ability to solve technical challenges effectively and respectfully with all relevant communities.
• Knowledge of patient reported outcomes and patient reported assessments in health care EHRs of health care systems, research study management tools, including electronic transfer of information from mobile and other devices.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications  

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

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

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

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace 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

Letter of Intent  

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:

Martina Schmidt, Ph.D
National Center for Complementary and Integrative Health (NCCIH)
6707 Democracy Blvd.
Suite 401, MSC 5475
Bethesda, MD 20892-5475 (For FedEx, etc., use 20817)
Telephone: 301-594-3456
Email: SchmidMa@mail.nih.gov

, with the following exceptions or additional requirements: For this specific FOA, the Research Strategy section is limited to 30 pages.

Biographical Sketches should reflect how the investigator team, collaborators, and other personnel are well suited to the project. The team should include expertise and experience in non-pharmacological approaches to pain management and comorbidities, including but not limited to, experience with data extraction in meaningful ways from EHRs and other clinical systems, experience with ethical issues related to research and care boundaries, experience in design, conduct, and analysis of pragmatic clinical trials, and experience in collaborative research with a variety of stakeholders.

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

The Coordinating Center Director (or team of multi-PI/PDs) must be able to devote at least 20% effort (2.4 person months) to this program in addition to the required effort contributed to the HCS Collaboratory Coordinating Center.

The applicant must include funds for the Coordinating Center PD/PI and key personnel to support and attend two, one-and-half day Collaboratory program meetings in the first year and an annual one-and-half-day meeting in subsequent years in the greater Washington D.C. area. Funds need to be included for the coordinating center to host the meetings, including the meeting room and all other expenses. Pragmatic Study staff will travel their own people on their budgets.

The budget justification should describe how the applicants will leverage the existing resources of the HCS Collaboratory Coordinating Center and add to that infrastructure with the additional funds provided through this RFA to support the NIH HEAL PRISM Initiative pragmatic trials. If more funds are requested in some years, the budget justification should describe why additional resources are needed in those years.

Research Strategy: Resource coordinating center applicants must indicate their willingness to cooperate with Pragmatic Study teams in the development and design of research approaches, methods, processes, policies, and tools used in this program.

The Resource Coordinating Center will have five to seven Work Groups that will work with the Pragmatic Studies to assist with optimizing the design and implementation; gathering lessons learned across projects; and developing guidance and best practice documents. The application must provide details of how the existing HCS Work Groups will be expanded to accommodate the new HEAL PRISM trials, including additional staffing, planned activities, and deliverables. For example, the application must describe how Coordinating Center Work Groups will review the study design and biostatistical assumptions of the proposed Pragmatic Studies; work with the Pragmatic Study teams to develop detailed plans for site implementation, determine resource needs, test data extraction methods for patient identification and outcome assessment; and review plans for all aspects of ethical and regulatory oversight and protection of human subjects. Applicants should note if any additional Work Groups will be added to the current HCS Collaboratory.

To meet the needs and responsibilities of the NIH HEAL PRISM Resource Coordinating Center, applicants should describe their group expertise and prior experience working collaboratively in research consortia and other collaborative projects to accomplish shared goals for the team as a whole, without repeating information on individual biosketches. Additionally, applications should describe the team's experience conducting pragmatic trials in health care settings such that they can provide technical expertise to other investigators proposing to do pragmatic trials in these settings. A description of the team's ongoing record of accomplishment in support of coordination, collaboration, and communication of large national-level inclusive networks or consortia should be provided.

The applicant should also describe the specific tasks and accomplishments needed to meet the objectives of the Collaboratory Coordinating Center, which could include, but are not limited to:

• Provide national leadership and engage all stakeholders in advancing policies and practices that enhance the broad participation of researchers and health care systems in research focused on improving pain management
• Improve the capability, methods, and technologies used in addressing research important to effect health improvement regarding pain management
• Specific tasks and accomplishments of the Coordinating Center and associated Work Groups
• Approaches that allow the use of patient reported outcomes or other descriptive protocols, and algorithms developed elsewhere to address questions relevant to the NIH HEAL PRISM initiative
• Basic requirements for technical, policy, and workflow practices, needed for health systems participation in research
• Defining the needs, requirements and approaches to conduct pragmatic clinical trials to improve pain management and other comorbid conditions in partnership with eligible health care systems
• Processes and agreements needed to address regulatory requirements for single and multiple health care systems
• Processes and best practices for ethical conduct of pragmatic clinical trials in eligible health care settings that obtain input from health care system leadership, patients, family members, providers, researchers.
• Mechanisms for leveraging novel collaboration and communication strategies, as well as creativity and flexibility to innovate on an ongoing basis

Contingency Plan: The HCS Coordinating Center has NIH funding support through FY2021. The applicant should provide a description of how they will continue their Resource Coordination activities for the NIH HEAL PRISM program regardless of whether there is additional support from NIH for the HCS Coordinating Center.

The following modifications also apply:

Similar to the HCS Research Collaboratory, the NIH HEAL PRISM Initiative will encourage sharing of resources with broad availability of policies, practices, materials, and tools to facilitate collaboration, reuse, and replication. In addition, the program encourages sharing of study data from Demonstration Projects in a timely manner with appropriate privacy and confidentiality protections to facilitate further research, reuse of data, and replication. Thus, the program expects grantees to implement a Resources and Data Sharing Plan consistent with achieving these program goals.

A Resources and Data Sharing Plan should be included in the application

Software Sharing Plan

The program encourages sharing of software and code that are developed or modified to accomplish aims of this program. This may include, but is not limited to, software, tools, or code sets for extraction or definition of data from EHRs, clinical systems, and other health care data systems; implementation of new workflows for research studies; analytic and analysis programs; and tools for incorporation of patient input. While software development is not the primary goal of this program, it is expected that software or sets of code may be developed under this program by the Resource Coordinating Center or the Demonstration Projects, thus, grantees and their sub-contractors are expected to implement a Software Sharing Plan consistent with achieving the goals of this program.

A Software Sharing Plan, with appropriate timelines, is expected in the application. There is no particular software dissemination license required for this program. However, NIH does have goals for software sharing and reviewers will be instructed to evaluate the sharing plan relative to the following goals:

• The software should be freely available to biomedical researchers, health care delivery systems, research institutions, and government health care systems and researchers.
• The terms should also permit the dissemination and commercialization of enhanced or customized versions of the software, or incorporation of the software or components of it into other software packages.
• The terms of software availability should include the ability of individuals outside the applicant institution and its collaborating organizations to modify the source code and to share modifications with other colleagues.

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:

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

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.

Since these awards will be issued as a multiyear award, with the budget and project period from the same fiscal year, the grantee will not have any authority for an automatic extension nor will one be permitted with NIH prior approval. Funds will not be available for expenditure beyond September 30th of the 5th fiscal year after the period of availability. Thus, extensions of the budget/project period will not be allowed beyond June 30th of the fifth fiscal year

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

In order to expedite review, applicants are requested to notify the NCCIH Referral Office by email atSchmidMa@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

1. Criteria

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

Significance  

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?

Specific to this FOA:

Will the Resource Coordinating Center provide national leadership and engage all appropriate stakeholders in advancing policies and practices that enhance the broad participation of researchers and health care systems in research focused on improving approaches to pain management? If the aims of the center are achieved, how will clinical research, translation of research into practice, and participation by relevant health care delivery organizations in research be improved? How will successful completion of the aims change the capability, methods, and technologies used in addressing research important to effect health improvement?

Investigator(s)  

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?

Innovation  

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

Specific to this FOA:

Does the application include mechanisms for leveraging novel collaboration and communication strategies? Does the application indicate creativity and flexibility to innovate on an ongoing basis?

Approach  

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

Specific to this FOA:

Will the proposed activities facilitate flexible, modular, and scalable policies, practices, algorithms, protocols, and tools to enable broad collaboration and participation? Will the proposed approach allow efficient management upkeep of a public website? Will the proposed approach allow for the Resource Coordinating Center personnel and collaborative tools to enable speedy Pragmatic Study team planning and implementation? Is the plan for administrative support of the NIH HEAL PRISM program synergistic with the proposed plan for support of the Pragmatic Studies and will it add to the productivity of the program?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Environment  

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

Protections for Human Subjects  

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

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

Inclusion of Women, Minorities, and 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.

Vertebrate Animals  

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.

Biohazards  

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.

Resubmissions  

Not Applicable.

Renewals  

Not applicable.

Revisions  

Not Applicable.

Applications from Foreign Organizations  

Not Applicable.

Select Agent Research  

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).

Resource Sharing Plans  

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).

Authentication of Key Biological and/or Chemical Resources:  

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.

Budget and Period of Support  

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

2. Review and Selection Process

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

• 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.

• 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.
• Willingness of the PD(s)/PI(s) to collaborate with the NIH.

3. Anticipated Announcement and Award Dates

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

1. Award Notices

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.

2. Administrative and National Policy Requirements

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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

3. Reporting

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

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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.

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: 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

Wendy Weber, N.D., Ph.D., M.P.H.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-402-1272
Email: weberwj@mail.nih.gov

Martina Schmidt, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3456
Email: schmidma@mail.nih.gov

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