Department of Health and Human Services
Part 1. Overview Information

 

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Center for Complementary and Integrative Health (NCCIH)
National Center for Advancing Translational Sciences (NCATS)
National Cancer Institute (NCI)
National Eye Institute (NEI)
National Institute on Aging (NIA)
National Institute of Dental and Craniofacial Research (NIDCR)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute on Neurological Disorders and Stroke (NINDS)
National Institute on Minority Health and Health Disparities (NIMHD)
National Institute of Nursing Research (NINR)

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)

Funding Opportunity Title

HEAL Initiative: Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing (PRISM)(UG3/UH3 Clinical Trial Optional)

Activity Code

UG3/UH3 Exploratory/Developmental  Phased Award Cooperative Agreement

Announcement Type

New

Related Notices
  • January 4, 2019 - Notice of 3 Pre-Application Webinars for NCCIH HEAL Funding Opportunity Announcements. See Notice NOT-AT-19-019.
Funding Opportunity Announcement (FOA) Number

RFA-AT-19-004

Companion Funding Opportunity

RFA-AT-19-011, U24 Resource-Related Research Projects – Cooperative Agreements

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.213; 93.350, 93.393, 93.867, 93.866, 93.273, 93.846, 93.865, 93.121, 93.307, 93.853, 93.361

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) encourages UG3/UH3 phased cooperative research applications to conduct efficient, large-scale pragmatic or implementation trials to improve pain management and reduce the unnecessary use of opioid medications. Awards made under this FOA will initially support a one-year milestone-driven planning phase (UG3), with possible transition to an implementation phase (UH3) of up to 4 years duration (5 years total for the two phases). UG3 projects that have met the scientific milestone and feasibility requirements may transition to the UH3 phase. The UG3/UH3 application must be submitted as a single application, following the instructions described in this FOA.

The overall goal of this initiative is to support the "real world" assessment of health care strategies and clinical practices and procedures in health care systems that may lead to improved pain management along with a reduction in unnecessary opioid prescribing. This FOA requires that the intervention under study be embedded into health care delivery system, “real world” settings.  Studies can propose to integrate interventions that have demonstrated efficacy into health care systems; or implement health care system changes to improve adherence to evidence-based guidelines. Trials should be conducted across three or more health care systems (HCS) and will become part of and work with the NIH HCS Research Collaboratory supported through the NIH Common Fund. (See https://commonfund.nih.gov/hcscollaboratory).  The NIH HCS Research Collaboratory Program has established a Collaboratory Coordinating Center (CCC) that is providing national leadership and technical expertise in all aspects of research with HCS. Awarded applicants will work with the HCS CCC (http://rethinkingclinicaltrials.org/about-nih-collaboratory/) to facilitate further planning and refinement of the proposed study in partnerships with health care delivery systems.

Key Dates

 

Posted Date

December 10, 2018

Open Date (Earliest Submission Date)

January 08, 2019

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

February 08, 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.

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)

February 08, 2019, by 5:00 PM local time of applicant organization. All types of AIDS and AIDS-related applications allowed for this funding opportunity announcement are due on these dates.

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.

Scientific Merit Review

June 2019

Advisory Council Review

August 2019

Earliest Start Date

September 2019

Expiration Date

February 09, 2019

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow 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 the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.


Table of Contents

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information


Part 2. Full Text of Announcement
Section I. Funding Opportunity Description

Purpose

This Funding Opportunity Announcement (FOA) encourages UG3/UH3 phased cooperative research applications to conduct efficient, large-scale pragmatic or implementation trials to improve pain management and reduce the unnecessary use of opioid medications. Awards made under this FOA will initially support a one-year milestone-driven planning phase (UG3), with possible transition to an implementation phase (UH3). UG3 projects that have met the scientific milestone and feasibility requirements may transition to the UH3 phase. The UG3/UH3 application must be submitted as a single application, following the instructions described in this FOA.

The overall goal of this initiative is to support the "real world" assessment of health care strategies and clinical practices and procedures in health care system that may lead to improved pain management along with a reduction in unnecessary opioid prescribing. This FOA requires that the intervention under study be embedded into health care delivery system, “real world” settings.  Studies can propose to integrate interventions that have demonstrated efficacy into health care systems; or implement health care system changes to improve adherence to evidence-based guidelines. 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 supported through the NIH Common Fund. (See https://commonfund.nih.gov/hcscollaboratory).  The NIH HCS Research Collaboratory Program has established a Collaboratory Coordinating Center (CCC) that is providing national leadership and technical expertise in all aspects of research with HCS. Awarded applicants will work with the HCS CCC (http://rethinkingclinicaltrials.org/about-nih-collaboratory/) to facilitate further planning and refinement of the proposed study in partnerships with health care delivery systems.

Background

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 have been published by various government agencies, and clinical and professional societies now 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, therefore, are needed because policies, clinical practice guidelines, and tools and interventions have not been readily adopted and implemented by health care systems. However, compelling evidence suggests that this has not been the case. Research is needed to study strategies to most effectively, equitably, and efficiently implement evidence-based interventions and pain management guidelines.

The increased adoption of health information technology tools is not only changing how care is delivered but also providing opportunities for expanded participation of health care delivery organizations in research. Although the importance for biomedical research and strengthened 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 quality-controlled data from health care systems in understandable ways are not trivial. Research studies frequently use endpoints that are not part of the normal evaluation of patients during a routine visit or monitor the fidelity of intervention delivery in ways that are difficult in most care delivery settings, which may limit external validity. Education and engagement of providers and patients on the value of research in the care setting, and of researchers on the relevance of their work to health systems, are urgently needed to improve pain management for all people to decrease the reliance on opioid medications.

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.

For the purpose of this FOA, we define "embedded pragmatic clinical trial" and "implementation research", as follows:

Embedded pragmatic clinical trials are conducted within the health care delivery setting and are “primarily designed to determine the effects of an intervention under the usual conditions in which it will be applied”, which is in contrast with explanatory trials that “are primarily designed to determine the effects of an intervention under ideal circumstances” (http://www.bmj.com/content/350/bmj.h2147).  "There are “three key attributes of pragmatic clinical trials (PCTs): (1) an intent to inform decision-makers (patients, clinicians, administrators, and policy-makers), as opposed to elucidating a biological or social mechanism; (2) an intent to enroll a population relevant to the decision in practice and representative of the patients or populations and clinical settings for whom the decision is relevant; and (3) either an intent to (a) streamline procedures and data collection so that the trial can focus on adequate power for informing the clinical and policy decisions targeted by the trial or (b) measure a broad range of outcomes (http://rethinkingclinicaltrials.org/chapters/pragmatic-clinical-trial/what-is-a-pragmatic-clinical-trial-2/)."

Implementation research seeks to understand the behavior of practitioners and support staff, organizations, consumers and family members, and policymakers in context as key influences on the adoption, implementation and sustainability of evidence-based health interventions and guidelines (e.g., Community Guide to Preventive Services, U.S. Preventive Services Task Force, and clinical and professional societies' recommendations and guidelines). Implementation research studies should not assume that effective interventions can be integrated into any service setting and for consumer groups and populations without attention to local context, nor that a unidirectional flow of information (e.g., publishing a recommendation, trial, or guideline) is sufficient to achieve practice change.

The awards supported by this initiative will utilize the existing coordinating center of the Health Care Systems Research Collaboratory. The overall goal of the NIH Common Fund 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 providers and delivery organizations and patients as research partners. The NIH HCS Research Collaboratory Program established a Collaboratory Coordinating Center (CCC) led by Duke University in 2012 (http://rethinkingclinicaltrials.org/about-nih-collaboratory/) that is providing national leadership and technical expertise. Awardees from this FOA will work with the NIH and CCC for both the planning and implementation of their pragmatic clinical trial or implementation study. All Projects must conduct research studies in partnership with at least three health care delivery systems, and work with the NIH and the CCC to ultimately make available data, tools, resources and lessons learned from Collaboratory research projects to facilitate a broadened base of research partnerships with HCS.

The HCS Research Collaboratory program encourages sharing of resources with broad availability of policies, practices, materials, and tools to facilitate collaboration, reuse, and replication. In addition, the HCS Research Collaboratory program encourages sharing of study data from Projects in a timely manner with appropriate privacy and confidentiality protections, in accordance with the Data Sharing Policy developed by the HCS Research Collaboratory Steering Committee (https://www.nihcollaboratory.org/Products/Collaboratory.DataSharingPolicy_June232014.pdf). Thus, the HCS Research Collaboratory program requires awardees to implement a Resources and Data Sharing Plan consistent with achieving these program goals. 

Research Objectives

This FOA solicits applications for UG3/UH3 exploratory/developmental phased award cooperative agreements for projects for large-scale pragmatic trials or implementation research trials to be implemented through at least three HCS. The design of the proposed project should maximize external validity of the study, by testing generalizability, feasibility and sustainability of findings across distinct health care settings, and diverse staff and patient populations.

The proposed pragmatic trials or implementation research studies must meet the following criteria:

  • The project must test an intervention, or coordinate several interventions (which can be treatments, preventive actions, or organizational changes) that are robust, apply broadly to pain patient populations and are suitable for use in multiple health systems, with the broad goal of determining whether the intervention(s) improves pain outcomes, and adds value to the utilization of the nation’s health care resources.
  • The question must be of public health importance.
  • The intervention(s) must be well-characterized and available such that it could be reliably delivered by clinical providers and/or HCS. If an intervention includes a drug, biologic or device, it must be a legally-marketed drug, biologic or medical device in the US, and used as approved/cleared for use by the Food and Drug Administration.
  • The intervention(s) must be reasonably simple and not require a complex structure for implementation or monitoring. System level interventions may be particularly suitable.
  • As in routine practice, the project must allow for interventions to be implemented with maximal flexibility and by all appropriate practitioners (not just those with high levels of training or competence).
  • The project must leverage opportunities made available through the health care systems and use outcomes that can be captured with passive follow-up by electronic health records, with minimal need for adjudication.  Augmentation of the electronic health record is allowable for patient reported data and outcomes, although this should be streamlined and collected only at necessary time points.
  • The project outcome measure(s) must be clinically meaningful and important to stakeholders including patients, providers, health care systems, and policy makers. Additional outcome measures such as use of health care services or medications, and other resources may be included. Outcome measures must provide useful information to medical decision makers, whether patients, care providers, health care systems or payers.
  • The project design must incorporate rigorous controls, prospectively identified, preferably by randomization. The design may incorporate novel randomization approaches, such as by cluster or timing of implementation. If another method is used to generate the comparison group, perhaps by staged assignment or staged implementation of the intervention, it should provide comparable rigor.
  • Proposed analytic plans for projects that proposed cluster-randomized trials must address adequacy of sample size and study power, and employ analytic strategies relevant for such pragmatic trial designs.  Applicants are strongly encouraged to consult Collaboratory Biostatistical Guidance documents (http://sites.duke.edu/rethinkingclinicaltrials/biostatistical-guidance-documents/) when developing pragmatic trial analytic plans.
  • The study must address, and potentially overcome, important barriers to research in the setting of HCS partnerships.
  • The project must enroll patients based on broad eligibility criteria to maximize diversity, and minimize intentional or unintentional exclusions based on risk, age, health literacy, demographics, or expected adherence.

Partnerships with health care delivery organizations will be critical in conducting this work. It is anticipated that the Projects will generally be performed with high volume electronically-supported integrated HCS to establish efficiencies. The HCS partnership must facilitate access to all data sources relevant to the project, which may include inpatient, outpatient, imaging, clinical laboratory, pharmacy and community data. Applicants, who may be from academic institutions or other organizations, must demonstrate experience in successful conduct of clinical or implementation research in partnerships with HCS. In general, applicants must identify at least three HCS as partners for the proposed Project. If an applicant identifies less than three HCS as partners for the proposed Project, they must provide a strong scientific rationale for limiting this aspect of the project and address generalizability and adequacy of sampling for the Project. 

These projects will be funded as phased awards with a one-year planning phase (UG3) and a two-to-four-year implementation phase (UH3). Activities in both phases will depend on the specific study (e.g. disease domains, type of interventions, experimental design, randomization strategy and proposed outcome measures).

During the UG3 or planning phase activities will generally include, but are not limited to:

  • Identify project staff that will participate in the Collaboratory Work Groups (see Section I.5 Additional Information https://www.nihcollaboratory.org/cores/Pages/default.aspx), which will develop guidelines and practices to be implemented across projects.
  • Work with the Collaboratory to implement approved guidelines and practices for electronic data extraction and quality control methods and tools, as well as for electronic data sharing. In the planning phase, this will include developing and validating all electronic data methods and tools within the HCS needed for the Project (e.g. electronic health records, electronic methods for patient identification and outcomes assessment, patient reported data, biospecimens, images, high-throughput genomic data, family history data, data abstraction and survey instruments) and complete quality control testing at all sites. 
  • Assess adequacy and finalize clinically relevant outcome measures with other Collaboratory investigators. Awarded applicants will work with other Collaboratory investigators and NIH to identify common outcome measures (pain severity, pain interference, and pain functioning, as well as others); and will work with the CCC and NIH to develop metrics for resource utilization for planning and implementing Collaboratory pragmatic trials.  If an award is made, NIH and CCC staff will work with the Program Directors/Principal Investigators to facilitate coordination among projects.
  • Refine estimates of requirements with guidance from NIH and the CCC, for sample size, numbers of sites, site to site heterogeneity, and implementation timetable based on data derived from the partnering HCS.
  • In general, all studies must use at least three HCS for implementation, unless a specific rationale for limiting this aspect of the project is provided.
  • Develop detailed plans for site implementation, including site staff, method of identification, randomization (as applicable) and participant recruitment and acquisition and administration/implementation of the intervention if applicable.
  • Address all ethical issues and issues related to human subject safety oversight for the Project, including development of informed consent documents or opt-out consent if applicable, and finalizing site of IRB review. Applicants must propose a consolidated or centralized IRB approach for trial oversight, to facilitate both appropriate and timely study implementation.
  • Address all potential regulatory elements of the proposed trial (if applicable).
  • Develop a detailed budget for conduct and completion of the Project, including preparation of a final study report.
  • Finalize detailed plans for data coordination and quality control for the UH3 phase. The CCC will not provide these functions for individual Projects. Data coordinating activities for individual Projects must be separately budgeted as part of the UH3 budget.

Project Implementation Phase (UH3): The objective of the two-to-four-year UH3 implementation phase is to conduct the Project in accordance with activities planned in the UG3 phase. Implementation activities will depend upon the study, but in general the following goals should be achieved:

  • Each project is expected to implement all aspects of the proposed pragmatic trial or implementation research study– including the identification and recruitment of proposed sample sizes of patients, practice sites, and clinicians, the execution of the intervention and its implementation, and the assessment of outcomes.
  • Each project is expected to provide complete assessment of all issues related to patient, clinician and site identification, and EHR tools used in these steps.
  • Each project is expected to provide definitive information about the execution of the intervention at all sites.
  • Each project is to provide detailed and definitive testing of the validity of methods used for monitoring and outcome assessment.

Milestones and UG3/UH3 Transition

Utilization of milestones is a key characteristic of this FOA. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity. This FOA will utilize a two-phase, milestone-driven cooperative agreement (UG3/UH3) mechanism consisting of a start-up phase of up to one year (UG3) and a full enrollment and clinical or implementation trial execution phase (UH3).  Projects should include well-defined milestones for the planning phase (UG3) and annual milestones for the implementation phase (UH3).   It is understood that the proposed milestones for the UH3 phase will be revised as activities in the UG3 phase progress. In the event of an award, the PD/PI and NIH staff will negotiate a final list of milestones for each year of support.

At the completion of the UG3 planning phase, the applicant will be required to submit a detailed transition request for the UH3 Project implementation phase. UH3 transition requests will undergo an administrative review to determine whether the Project will be awarded the implementation phase (UH3). All regulatory approvals should be obtained prior to the end of the UG3 award. Training of intervention providers, comparison group providers, or other resources should be planned at the start of the UH3 award to allow for the successful launch and execution of the proposed pragmatic trial or implementation study in the UH3 phase. Prospective applicants should note that initial funding of the UG3/UH3 Phase Innovation cooperative agreement does not guarantee support of the UH3 Project implementation phase.  Applicants should understand that transition to the UH3 phase of the project will occur only if an administrative review process recommends that the UG3 planning milestones have been successfully met, that the UH3 phase can proceed with confidence of success, and availability of funds. Continuation of the award is conditional upon satisfactory progress and subject to availability of funds. If, at any time, recruitment falls significantly below the projected milestones for recruitment, the NIH will consider ending support and negotiating an orderly phase-out of the award and retains, as an option, periodic external peer review of progress. NIH staff will closely monitor progress at all stages, milestones, accrual, and safety.

Research Areas of Interest

Applicants should propose a pragmatic or implementation trial to address one or more critical research questions important for improved pain management within health care systems. The following list provides examples of some of the potential research questions that might be addressed by such pragmatic trials:

  • Studies to test the effect of system level innovations to improve implementation of established guidelines for nonopioid approaches to pain management and comorbid conditions;
  • Assessment of the effectiveness of integrating evidence-based pain management strategies into health care delivery to reduce the transition from acute to chronic pain, for example in the peri-operative period;
  • Comparative effectiveness studies utilizing different combinations of pain management treatments for chronic pain within health care systems
  • Studies of implementation strategies to support the adoption and integration of effective pain management treatments, clinical procedures or guidelines into existing care systems;
  • Studies to identify effective implementation strategies for integrating multiple evidence-based practices within community or clinical settings to meet the needs of pain patients and diverse systems of care;
  • Studies testing the effectiveness and impact on utilization of health care services of implementation strategies to reduce health disparities and improve quality of pain management among rural, minority, low literacy and numeracy, and other underserved populations

National Center for Complementary and Integrative Health (NCCIH)

The mission of NCCIH is to define, through rigorous scientific investigation, the usefulness and safety of complementary and integrative health interventions and their roles in improving health and health care.  In the context of this FOA, NCCIH is particularly interested in encouraging applications that will study the integration of complementary health approaches into health care delivery, for those interventions that already have demonstrated efficacy or effectiveness in fully powered randomized controlled trials. In addition, NCCIH encourages applications that will study methods to improve adherence to evidence-based pain management guidelines that include complementary and integrative health approaches to reduce the unnecessary use of opioids, and ultimately reduce the occurrence of opioid use disorder.  Applicants are encouraged to discuss applications the NCCIH contact listed in Section VII. Agency Contacts.

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases. In the context of this FOA, the NIAMS is interested in pragmatic clinical trials that reduce the burden of pain while reducing the unnecessary usage of opioids, improve physical function and prevent disability in children and adults with acute and chronic diseases and conditions within the NIAMS mission. Pragmatic clinical studies may include testing of evidence-based interventions of non-opioid medications, biologics, procedures, medical or assistive devices and non-pharmacologic approaches to improve decision-making in the management of back pain, OA pain, and post-surgical pain. Applicants are encouraged to discuss applications with the NIAMS contact listed in Section VII. Agency Contacts.”

National Institute of Dental and Craniofacial Research (NIDCR)
NIDCR is interested in clinical trials aimed at reducing the burden of pain associated with acute and chronic oral and craniofacial diseases and conditions including temporomandibular joint disorders (TMD), trigeminal neuropathies, burning mouth syndrome, oral cancer pain, dental pain and other conditions. Examples of research topics that would be appropriate to the NIDCR include: 1) Clinical studies to test the implementation of effective opioid use disorder (OUD) screening and referral to treatment models in dental care settings; 2) Pragmatic clinical trials to test evidence-based clinical tools and/or interventions designed to modify dental practitioner opioid prescribing behaviors, especially for adolescent and young adult patients; and 3) Pragmatic clinical studies to test the implementation of evidence-based opioid risk mitigation strategies in dental practice settings. Applicants are encouraged to discuss applications the NIDCR contact listed in Section VII. Agency Contacts.

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

A significant portion of individuals with chronic pain consume alcohol in a manner or quantity that adversely impacts their experience of pain and the effect of medications or other treatments intended to address pain.  For example, current or past heavy drinking or alcohol dependence occurs in 16% to 25% of chronic pain patients.  Thus, NIAAA has a particular interest in studies that address alcohol use in the context of pain management and its implications for the delivery and effectiveness of evidence-based pain management practices.

National Institute of Nursing Research (NINR)
The mission of the NINR is to promote and improve the health and quality of life of individuals, families, and communities. In the context of this FOA, NINR is interested in non-pharmacologic strategies with established efficacy for management of pain. Of particular interest are self-management approaches that are guided by an interdisciplinary team to address both the clinical and biopsychosocial aspects of persistent pain and which can be tested in real world settings. Outcomes of interest include psychological well-being, self-efficacy, and functionality for the affected individual and characteristics of patient/provider relationships that signify sustained pain management.  

National Institute on Minority Health and Health Disparities (NIMHD)

The mission of NIMHD is to lead, conduct and support scientific research to improve minority health and reduce health disparities. In the context of this FOA, NIMHD is particularly interested in encouraging applications that could include, but are not limited to: address the intersection of chronic pain management and opioid use disorder (OUD): ways to maintain continuity of care in patients with chronic pain, and strategies to improve services; research on the outcomes of implementation of the CDC Guidelines on management of opioid prescribing in treatment of chronic pain disorders; conduct subgroup analysis to determine which interventions work best for specific population groups, including medically underserved and under-represented groups with the intent to focus on reduction of Opioid prescribing. We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

National Cancer Institute (NCI)

NCI is interested in pragmatic clinical trials aimed at reducing the burden of pain associated with cancer (metastatic bone pain, visceral pain, and neuropathic pain [plexopathies, radiculopathies]) and/or its treatment (post-surgical phantom limb pain, radiation induced plexopathies, mucositis, aromatase inhibitors, and chemotherapy induced peripheral neuropathy).  Within the context of these pain conditions, NCI is interested in applications that will study the integration of guideline driven cancer pain management approaches into health care delivery. In addition, NCI encourages applications that will study methods to reduce the inappropriate or unnecessary use of opioids in patients experiencing pain arising from cancer and/or its treatment. For these types of trials, NCI encourages approaches that seek to improve adherence to evidence-based pain management guidelines, patient-provider communication, shared decision-making and incorporation of the EMR system.   Applicants are encouraged to discuss applications with the NCI contact listed in Section VII. Agency Contacts

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

In the context of this FOA, NICHD is particularly interested in exploring the implementation of evidence-based pre-surgical education and training in pain management in the treatment of gynecologic disorders or after gynecologic surgery to reduce the unnecessary use of opioids and ultimately reduce the occurrence of opioid use disorder. Further NICHD is interested in implementation trials of evidence-based post-cesarean pain management approaches which reduce opioid prescription and increase the use of non-opioid alternatives to reduce the occurrence of opioid use disorder. Additionally, NICHD encourages applications for pragmatic trials to improve methods of referral and adherence to behavioral or rehabilitation approaches to pain which have demonstrated efficacy or effectiveness in fully powered randomized controlled trials in pediatric populations or for individuals with disability. NICHD is interested in research that includes the populations mentioned in the specific priorities indicated above and which include health disparity populations to the extent possible (i.e., diverse race/ethnicity, sexual and gender minorities, and underserved/low-resource communities).

National Institute of Neurological Disorders and Stroke (NINDS)

The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.  Pain is a frequent component of many neurological disorders including those involving traumatic injury to the central nervous system, as well as neurodegenerative and neuroinflammatory conditions.  In the context of this FOA, NINDS is interested in pragmatic clinical trials of evidence-based interventions to reduce the burden of pain associated with neurological disorders and their treatment, as well as to prevent the transition from acute to chronic pain in these conditions.  Interventions may include non-addictive drugs, biologics, natural products, devices, surgical procedures, motor training, brain stimulation, and behavioral strategies.  Additionally, NINDS is interested in research on the use of strategies to adopt and integrate evidence-based interventions into clinical and community settings to improve patient outcomes.

Office of Behavioral and Social Sciences Research (OBSSR)

Although OBSSR does not accept assignment of applications or manage awards that are funded through this announcement, OBSSR does encourage applications relevant to the OBSSR mission and may provide co-funding support to ICs that do manage the awards.  OBSSR is specifically interested in studies that apply evidence-based approaches for behavioral change (e.g., provider prescribing practices, adherence to treatment and management guidelines for both the practitioner and patients, provider/patient communications, among other topics) to improve outcomes that include mitigating the transition from acute to chronic pain and enhancing effective management for those with persistent and chronic pain. Additionally, approaches to identifying characteristics of individuals most likely to benefit from evidence-based nonpharmacologic approaches for pain management are of interest to OBSSR.

Types of Clinical Trials Not Responsive to this FOA

The following types of clinical trials are not responsive to this FOA and applications proposing such activities will be deemed non-responsive and will not be reviewed:

  • Phase I (first-in-human) trials whether single or multi-site
  • Single site trials
  • Studies to understand the mechanism of the intervention
  • Studies to assess initial feasibility of an intervention
  • Drug or device safety trials
  • Studies that propose to conduct studies in animals or in vitro studies

Opportunities to submit other types of pain clinical trials for NIH support:

The Early Phase Pain Investigation Clinical Network (EPPIC-Net) will provide infrastructure for the rapid design and performance of high-quality Phase 2 clinical trials to test promising novel therapeutics for pain.  This network will support exploratory clinical trials of investigational drugs and biologics, investigational devices, natural products, and surgical procedures for the treatment of pain. These trials may include deep phenotyping, validation of biomarkers, and proof of mechanism, to support justification and provide the data for designing a future Phase 3 trial.  The specific pain conditions of interests for EPPIC -Net include well-defined conditions with high unmet therapeutic needs in patients across the lifespan. Further information can be found at NOT-NS-18-057, NOT-NS-18-058, and NOT-NS-18-069.

The Pain Effectiveness Research Network will support cooperative agreement applications that propose clinical trials to establish the effectiveness of existing therapies and approaches for prevention and management of pain while reducing the risk of addiction. The studies must address questions within the mission and research interests of participating NIH Institutes and Centers and evaluate preventive strategies or interventions  in well controlled trials  The overall goal is to inform clinicians about the effectiveness of interventions or management strategies that reduce the risk of addiction that will improve functional outcomes and reduce pain across the continuum of acute to chronic pain associated with many types of diseases or conditions or pain presenting as a disease itself. Clinical trials will be conducted within the infrastructure of the HEAL Pain Effectiveness Research Network.

Additional Information

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

HCS Research Collaboratory Work Groups have been established by the CCC and the NIH as the core collaborative activity of this program. The Work Groups 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 have been established in the following areas: Electronic Health Records, Regulatory /Ethics, Biostatistics & Study Design, Health Care Systems Interactions, and Patient Reported Outcomes (http://rethinkingclinicaltrials.org/cores-and-working-groups/).  Additional Work Groups may be identified as the HCS Research Collaboratory expands with new projects as part of this initiative. Work Groups will comprise individuals from each of the Projects, the Coordinating Center, and staff from the NIH. PD/PIs must identify study staff or investigators that will participate in Collaboratory Work Groups.

A Steering Committee has been established by the CCC to address issues that span all projects, provide input into the policies and processes of the HCS Collaboratory, and assist in dissemination of policies and processes that enable research in healthcare systems, involving their patients, and practitioners. At a minimum, the Steering Committee will have one representative from each of the Projects, one representative from each Work Group, one representative from the Coordinating Center, NIH Program Officers and Project Scientists for the CCC and Projects. All members are expected to actively participate in all Steering Committee activities.  The combined vote of NIH membership may never exceed 40 percent. NIH may convene an external panel of experts to provide advice on the overall program progress.

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

Section II. Award Information
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?

Optional: Accepting applications that either propose or do not propose clinical trial(s)

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NIH HEAL Initiative intends to commit $4,500,000 in FY 2019 to fund 6-7 awards.

Award Budget

The application budget for the UG3 phase is limited to $500,000/year in direct costs. Costs for each year of the UH3 phase are limited to $1 million/year in direct costs.

Award Project Period

The UG3 phase is limited to up to one year and the UH3 phase can request up to four years of support. The total project period for an application submitted in response to this FOA may not exceed 5 years.

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

Section III. Eligibility Information
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:

o   Hispanic-serving Institutions

o   Historically Black Colleges and Universities (HBCUs)

o   Tribally Controlled Colleges and Universities (TCCUs)

o   Alaska Native and Native Hawaiian Serving Institutions

o   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
Foreign Institutions

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

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.

 Personnel of the NIH HCS Research Collaboratory Coordinating Center must not be named as PDs/PIs on applications submitted in response to this FOA.

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

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).
Section IV. Application and Submission Information
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

It is critical that applicants follow 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.

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
Telephone: 301-594-3456
Email: SchmidMa@mail.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.

Facilities and Other Resources: The application should provide sufficient rationale for the proposed HCS(s) for the Project. Applicants should provide a description of successfully conducted clinical studies within the partnering HCS, and describe the infrastructure and expertise (e.g. clinical investigators, informaticists) to implement the proposed pragmatic trial within all proposed HCSs

SF424(R&R) Senior/Key Person Profile

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

R&R Budget

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

Budgets for both phases (UG3/UH3) should be included; the UH3 budget will undergo reassessment during the UG3 planning phase.

Minimum effort of personnel: The PD/PI must devote a minimum level of effort of 20% annually (2.4 -person months) to the project. There must be an appropriate mix of time allocated for senior and junior scientists to ensure the successful conduct of the study. Budgeted effort of other personnel must be appropriate to the needs of the project. The budget must include personnel at all participating HCS with expertise relevant to the project, which might include a health informatics expert, clinical investigators and staff with expertise in the administrative aspects of clinical trials oversight.

Applications should budget for study personnel to participate in each of the Work Groups.

Applications must budget for project PD(s)/PI(s) travel to attend two, one-and-a-half-day Health Care Systems Research Collaboratory program meetings in the first year, and an annual meeting in subsequent years in the greater Washington D.C. area

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: 

To clearly distinguish between the two phases, applicants should specify separate UG3 and UH3 information in each subsection (Specific Aims and Research Strategy) of the PHS 398 Research Plan as appropriate. Activities in both phases will depend on the specific study (e.g. specific pain population, type of interventions, experimental design, randomization strategy and proposed outcome measures). In preparing the application, investigators should consider the fact that applications will be assigned a single impact score for both UG3 and UH3 phases.

Specific Aims: Applicants should address the scientific questions to be answered, what specifically will be done during the proposed funding periods and the impact of addressing the research question on public health. Specific aims should be scientifically appropriate for the distinct phases of the project. Include separate aims, within the designated page limit, for both the UG3 and UH3 phase, and clearly label them as UG3 specific aims and UH3 specific aims.

Research Strategy: Within the Research Strategy, applicants should first describe the UG3 Phase and then the UH3 Phase. The Research Strategy section should have a clear demarcation of the UG3 and UH3 phases of the application. It is not necessary to repeat background information or details of methods in the UH3 portion that were provided in the UG3 portion. The UH3 Phase must be described in sufficient detail to permit reviewers to assess significance and innovation of the proposed work and the strength of the experimental design. Address how the research question serves the goals of the overall Collaboratory program and addresses the urgent need for better pain management. Applications should describe details for the proposed pragmatic trial or implementation research study including projections for recruitment, attrition and effect size estimations. Investigators are encouraged to describe how the approaches, measures, design and outcomes proposed are pragmatic or utilize implementation research methods.

The application should describe the health care system partners and the investigative team's experience conducting pragmatic trials within health care systems. In general, all studies must use at least three HCS for implementation, unless a specific rationale for limiting this aspect of the project is provided, which must be identified in the application. The application must provide a rationale for the HCS selected for the Project and provide a description of the infrastructure and expertise to implement the proposed pragmatic trial within all proposed HCS.

Both the UG3 and the UH3 phases of the Research Strategy must include a summary of the proposed Milestones Plan that is a required Other Clinical Trial-related attachment. The summary should describe the key milestones that need to be met for each phase of the application (UG3 and UH3) to ensure its success; the methods that will be used to reach the milestones; and a timetable identifying when each of these key milestones will be met.

Collaboratory Work Groups include participation by individuals from all funded Projects, the CCC, and the NIH. Applicants should describe how project personnel would participate in the Collaboratory Work Groups (Electronic Health Records, Regulatory /Ethics, Biostatistics & Study Design, Health Care Systems Interactions, and Patient Reported Outcomes http://rethinkingclinicaltrials.org/cores-and-working-groups/). Applicants must describe their willingness to comply with policies, guidelines and practices developed by the Work Groups, and to work with the CCC in providing relevant information and materials.

Applicants must not propose work that duplicates efforts already funded or underway. Although novel theoretical approaches and methodologies may be needed, when possible applicants should leverage, adopt or adapt resources from ongoing NIH-supported efforts in informatics as well as other national efforts including but not limited to the many federal investments in the HMO Research Network, the CTSAs, REDCap, PROMIS, NIH Toolbox, Health Care Innovation Awards, DEcIDE, eMERGE, other networks, CERTs, SHARP, Vaccine Safety Datalink, the Sentinel Initiative.

Letters of Support

Applications must include a strong letter of support from each of the HCS partners that relates their commitment to the proposed research and outlines how the project fits with organizational priorities, the quality of the proposed EHR and data systems and the commitment of their IT staff to the project. The letter must provide a description of how the project would directly impact delivery of healthcare within their organization and indicate level of intention to sustain the intervention(s) based upon results. The application is expected to include letters from the officials responsible for intellectual property issues at the applicant institutions (including sub-contractor institutions) stating that the institution supports and agrees to abide by the Resources and Data Sharing Plan put forth in the application. These letters should be clear expressions of commitment consistent with achieving the goals of the program

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, must include a Data Sharing Plan. Applicants must provide a description of the resources that will be made broadly available including policies, practices, materials, and tools to facilitate collaboration, reuse, and replication of the project.  Applications should provide descriptions of how privacy and confidentiality will be maintained.  The plan must include a description of how data will be shared to allow for transparency and reproducibility of study findings (e.g. access to data, data enclave, or data repository).

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:

If the application includes human subjects, it must include at least one human subjects study record for the activities of the UH3 project.  If the UG3 will include any human subjects research a separate study record should be included for the UG3 human study(ies).  As stated in the instructions, investigators must submit a study record for each clinical trial proposed in the application.

Section 2 - Study Population Characteristics

2.4 Inclusion of Women, Minorities, and Children
Describe the safeguards for vulnerable populations that may be participants in the research as appropriate (e.g., children, pregnant women, prisoners).
 
2.5 Recruitment and Retention Plan
Describe the following: 1) the planned recruitment methods including use of contact lists (participants and/or sites) databases or other pre-screening resources, advertisements, outreach, media / social media and referral networks or groups; 2) if there are known participant or study-related barriers to accrual or participation (based on literature or prior experience), please list these barriers and describe plans to address them to optimize success; 3) contingency plans for participant accrual if enrollment significantly lags behind accrual benchmarks; 4) participant retention and adherence strategies; and 5) possible competition from other trials for study participants.
 
Applicants must provide strong evidence of the availability of appropriate institutional resources, and suitable patient populations, providers, clinics, or facilities (depending on unit of randomization). Documentation of availability of eligible participants, clinic sites, or units of randomization, presented in tabular format must be provided. The application must include relevant information that addresses the feasibility of recruiting participants who are eligible for the pragmatic trial implementation study. Specifically, applicants must provide evidence that each recruiting center in the study or trial has access to a sufficient number of participants who meet the eligibility criteria as defined in the submitted protocol. For multisite applications, information must be provided for each participating site.
 

Section 3 - Protection and Monitoring Plans

 
3.3 Data and Safety Monitoring Plan
In addition to the NIH application requirements for a data and safety monitoring for clinical trials, Applicants should refer to NIH’s policy on data and safety monitoring (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html). 
 

Section 4 - Protocol Synopsis

  
4.7 Dissemination Plan
Describe how the investigators will facilitate and support timely publication and dissemination of results and developed tools as appropriate and consistent with achieving the goals of the program.

Section 5 - Other Clinical Trial-related Attachments

 
5.1 Other Clinical Trial-related Attachments
The following attachments must be included as a part of the cooperative agreement application.  Attachments permit expansion of certain elements that cannot be appropriately described in the Research Strategy. All attachments listed below must be provided or the application will not be peer reviewed.
 
1. Clinical Trial Experience  
Applicants must provide a detailed table listing the characteristics of trials that demonstrate Key Personnel experience in trial or implementation study coordination in the last 5 years. The table must be provided as an attachment called "Clinical Trial Experience.pdf", appended with 1, 2, 3, etc. as needed, and must not exceed 3 pages.
The table columns should include:

Column A: clinical trial or implementation study 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. Milestones Plan
 
A Milestones Plan must be provided as an attachment called "Milestones Plan.pdf" , appended with 1, 2, 3, etc as needed, and must not exceed 3 pages.
 
The milestones should be well described, quantifiable, and scientifically justified to allow an assessment of progress. For UG3 milestones, applicants should delineate what they propose to achieve in order to proceed to the UH3 phase. The milestones should also include a timeline, a discussion of the suitability of the milestones for assessing success in the UG3 Phase, and a discussion of the implications of successful completion of these milestones for the proposed UH3 Phase. Annual milestones for the Project implementation (UH3) phase should also be included in the application, although it is understood that timelines and milestones for implementation in the UH3 phase that are proposed in the application will evolve as activities in the UG3 phase progress, if an Award is made.
 
All applicants must use the following definition of a milestone in their application: a scheduled event in the project timeline that signifies the completion of a major project stage or activity. Milestones must be relevant, achievable, and measurable. Milestones should address overall recruitment and retention goals.  The Terms and Conditions under this FOA will include a milestone plan that is mutually agreed upon by the investigators and NIH.

Delayed Onset Study

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

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

PHS Assignment Request Form

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit 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.

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.

Section V. Application Review Information
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.

In addition, for applications involving clinical trials:

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

For this particular announcement, note the following:

This FOA includes Additional Review Criteria on Milestones, which require comment by reviewers and which are to be considered when determining the overall impact score.

 
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.

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?

In addition, for applications involving clinical trials

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

Specific to this FOA:

Will this project develop effective methods at the health care system level to improve the management of pain and reduce the unnecessary use of opioid medications? For studies that integrate an intervention into health care delivery, how strong is the evidence of efficacy or effectiveness for the intervention? For studies that propose to improve adherence to established guidelines, how strong is the evidence for the guidelines that are being used? Is the proposed pragmatic trial or implementation study addressing a major public health issue focused on pain management and comorbidities? How will the completion of the proposed pragmatic trial change the management of pain in health care systems? How will potential outcomes provide clinically meaningful information to stakeholders? Is there a strong likelihood that the UG3 planning activities and subsequent Project implementation in the UH3 phase achieve significant advances in the ability to perform large-scale pragmatic clinical trials or implementation research? 

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?  

In addition, for applications involving clinical trials

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

Specific to this FOA:

Do interdisciplinary teams include necessary expertise to conduct the trial and appropriate collaborators from the participating HCS? Do the PD(s)/PI(s) and key personnel have the necessary expertise in design and implementation of large-scale clinical studies within a HCS?  For example, do they have expertise in using electronic health records for recruitment and outcomes assessment?  Do the PD(s)/PI(s) have extensive experience in performing proposed Planning Phase activities, and do they have a track record of successful recruitment and retention in prior studies, investigative collaborations or partnerships with (within) health delivery organizations in conducting clinical studies within a HCS?  

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? 

In addition, for applications involving clinical trials

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

Specific to this FOA:

Does the application challenge and seek to impact current conventional approaches to pain management studies by utilizing novel approaches or methodologies for a pragmatic trial or implementation research that will allow it to be successfully implemented in a HCS environment? Is a refinement, improvement or new strategy of approaches proposed? Does the application include mechanisms for leveraging novel collaboration and study oversight strategies? 

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? 

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

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

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

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable:

Study Design

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

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

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

Data Management and Statistical Analysis

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

Specific to this FOA:

Will proposed planning activities (including plans for identifying a sufficiently large target patient population), allow for implementing the Project? Are the projections for recruitment, ongoing engagement, attrition and effect size estimations based on data in the proposed HCS or similar settings? Is the degree of pragmatic aspects of the approaches, measures, design and outcomes well justified for the design elements of the proposed study? Will the results provide relevant information and adequate data for other potential adopting HCS settings to determine applicability? Will rigorous controls be included in the design?  Will broad but adequate eligibility criteria be used, as proposed? Can interventions be easily implemented?  How will the approaches proposed overcome barriers to research in the HCS setting? Are the goals of the UG3 phase reasonable and if accomplished will they provide the basis for the proposed UH3 phase? 

Environment

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

In addition, for applications involving clinical trials

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

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

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

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

Specific to this FOA:

Does the application provide sufficient rationale for the HCS (s) selected for the Project? Is commitment from the HCS to the project evident? Has/have the HCS (s) successfully conducted clinical studies, such that there are sufficient infrastructure and expertise (e.g. clinical investigators, informaticists) to implement the proposed pragmatic trial within all proposed HCSs? 

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

Specific to applications involving clinical trials

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

Milestones

Are the steps and milestones clearly defined? Are the milestones feasible, well developed and quantifiable with regard to specific goals and accomplishments? Are adequate criteria provided for the UG3 phase that will be utilized in determining milestone completion before proceeding to the next phase of the project? Are the UH3 milestones appropriate for the next phase of the project?

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.

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.

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.

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.

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 appropriate National Advisory Council or Board. 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.

Section VI. Award Administration Information
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). 

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.

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

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

Cooperative Agreement Terms and Conditions of Award

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

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

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

  • Overseeing the overall budget, activities and performance of the Project. The PD(s)/PI(s) must devote a minimum level of effort of 20% annually (2.4 calendar months) to the project. If a project includes multiple PIs, the total annual PI effort must be at least 20%.  The institution must obtain appropriate prior approval for any change in PI effort.
  • Accepting the participatory and cooperative nature of the collaborative research process and complying with policies and practices developed by the NIH HCS Research Collaboratory governing structure.
  • Sharing data and resources according to the approved sharing policies for the NIH HCS Research Collaboratory program.
  • Participating in all meetings of the HCS Research Collaboratory Steering Committee. Identifying study team members with relevant expertise to participate in program-wide Work Groups and sub-committees (as appropriate).
  • Cooperating with the NIH HCS Research Collaboratory Steering Committee, Collaboratory Coordinating Center, research partners, and NIH staff in the design and conduct of protocols, analysis of data, and reporting of results of research.
  • Agreeing to accept close coordination, cooperation and management of the project with NIH, including those outlined below under "NIH Responsibilities."
  • Submitting materials to the NIH Program Director, Coordinating Center, and/or Steering Committee as requested.  This will include regular reports of accomplishments and roadblocks, conference and meeting summaries, and other reports as requested.
  • Materials submitted will meet all subject and formatting requirements.
  • Awardees will submit a detailed transition request for the UH3 Project implementation phase, outlining UG3 progress, how negotiated UG3 Milestones have been met, as well as detailed plans, budget and annual milestones for the UH3 implementation phase.  Note that, funding of the UG3 Project planning phase cooperative agreement does not guarantee support of the UH3 Project implementation phase.
  • Any of the above function may be performed by the applicant organization or by subcontract to the applicant organization.

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

  • The NIH Project Scientist will work with the PD(s)/PI(s) and the Steering Committee to ensure the objectives of the program are being met.  The primary responsibility for the program resides with the awardee, although specific tasks and activities will be shared among the awardee and the NIH Project Scientist.
  • NIH staff will interact with the PD(s)/PI(s) on a regular basis to monitor progress. Monitoring may include: regular communication with the PD(s)/PI(S) and his/her staff, periodic site visits for discussion with the awardees’ research team, observation of field data collection and management techniques, fiscal reviews, and other relevant stewardship activities.
  • The NIH reserves the right to terminate or curtail the award (or an individual component of the award) in the event of inadequate progress or data reporting.
  • Additional NIH staff may participate in all Work Groups, implementation teams and committees, including the Steering Committee, as appropriate. NIH may designate staff from other federal agencies to participate, if advantageous to facilitate the activities of the program.
  • NIH staff will act as a resource and facilitator for activities of the awardee with non-NIH HCS researchers and other NIH, DHHS, or other federally-sponsored research networks that may be relevant to this effort.
  • NIH staff will provide input, expert advice, and suggestions in the design, development, and coordination of the infrastructure development and implementation efforts.
  • NIH staff will report periodically on progress of the program to the NIH Common Fund, NIH and Departmental leaders. NIH may convene an external panel of experts to provide advice on program progress.
  • NIH staff will conduct an administrative review of the UH3 transition request to determine whether the Project will transition to UH3 funding and be implemented.  Criteria for transition to the UH3 phase used in the NIH administrative review include: successful achievement of the UG3 milestones, potential for successfully meeting the UH3 implementation phase plans and milestones, demonstrated ability of the team to work within the consortium arrangement, and the availability of funds.
  • Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

  • Ensuring that NIH HCS sites and investigators as well as NIH and other research partners fully comply with federal regulatory requirements.  This includes but is not limited to those relating to human subjects protections, informed consent, and reporting of adverse events.
  • Jointly developing appropriate confidentiality procedures for data collection, processing, storage and analysis to ensure the confidentiality of data on individual health care provider organization patients, health care providers and other institutions involved in any Collaboratory research projects.
  • Participating in the HCS Research Collaboratory Steering Committee 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.  At a minimum, the Steering Committee will be composed of one representative from each of the Projects, one representative from each Work Group, one representative from the CCC, the NIH Program Coordinator, and representatives from various NIH ICs and the Common Fund.  The combined vote of NIH membership may never exceed 40 percent of the total committee membership.
  • Participating in the HCS Research Collaboratory Work Groups that have been established as the core collaborative activity of this program. The Work Groups 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 have been established in the following areas: Electronic Health Records, Regulatory /Ethics, Biostatistics & Study Design, Health Care Systems Interactions, and Patient Reported Outcomes (http://rethinkingclinicaltrials.org/cores-and-working-groups/).  Additional Work Groups may be identified as the HCS Research Collaboratory expands with new projects. Work Groups are open to participation by individuals from all funded Projects, the CCC, and the NIH.
  • Awardees will work with other Collaboratory investigators and NIH to identify common clinical outcome measures (such as measures of quality of life, physical function, pain or fatigue). NIH and CCC staff will work with the Principal Investigators to facilitate this aspect of the Projects.o
  • Establishing and adherence by each Project Team (Project grantee, CCC grantee, and NIH staff) to a written plan of engagement, with timelines, to ensure timely delivery of the tested implementation plan. 
  • Working together with the CCC through all phases of the projects, including the implementation and close out, to assure all resources, materials, protocols, data, best practices, program policies, and lessons learned are disseminated broadly through the CCC, to inform researchers and health care systems engaged in research in health care settings.

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 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.

Section VII. Agency Contacts

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 submission by the due date, and post-submission issues)

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

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

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

Patricia Jones DrPH, MPH
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0792
patricia.jones@nih.gov

Houmam Araj, Ph.D.
National Eye Institute (NEI)
Telephone: 301-451-2020
Email: arajh@nei.nih.gov

Marcel Salive, M.D, M.P.H.
National Institute on Aging (NIA)
Telephone: 301-496-6761
Email: marcel.salive@nih.gov

Lori Ducharme, Ph.D. 
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-451-8507
Email: lori.ducharme@nih.gov

Shahnaz Khan, M.P.H
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Phone: 301-451-9893
Email: Shahnaz.Khan@nih.gov

Jennie Conroy Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-594-0331
Email: jennie.conroy@nih.gov

Dena Fischer, D.D.S, MSD, M.S.
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4876
Email: dena.fischer@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

Karen Huss, Ph.D., R.N.
National Institute of Nursing Research (NINR)
Telephone: 301-594-5970
Email: hussk@mail.nih.gov

Wendy B. Smith, M.A., Ph.D., BCB
Office of Behavioral and Social Sciences Research (OBSSR)
Telephone: 301-435-3718
Email: smithwe@mail.nih.gov

Diane St. Germain M.S., R.N., CRNP
ational Cancer Institute (NCI)
Telephone: 240-276-7050
Email: dstgermain@mail.nih.gov

Peter R. Gilbert
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone:  301-496-9135
Email:  gilbertp@ninds.nih.gov

Peer Review Contact(s)

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

Financial/Grants Management Contact(s)

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

Stacia Fleisher
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0851
Email: stacia.fleisher@nih.gov


Tijuanna Decoster
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: decostert@mail.nih.gov

Karen Robinson-Smith
National Eye Institute (NEI)
Telephone: 301-451-2020
Email: Karen.Robinson.Smith@nei.nih.gov

Lesa McQueen
National Institute on Aging (NIA)
Telephone: 301-496-1472
Email: mcqueenl@mail.nih.gov

Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: jfox@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 Clark, M.B.A.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: clarkb1@mail.nih.gov

Diana Rutberg, M.B.A.
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
Email: rutbergd@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

Ronald Wertz
National Institute of Nursing Research (NINR)
Telephone: 301-594-2807
Email: wertzr@mail.nih.gov

Amy Bartosch
National Cancer Institute (NCI)
Telephone: 240-276-6912
Email: amy.bartosch@nih.gov

Section VIII. Other Information

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.

NIH Office of Extramural Research Logo
Department of Health and Human Services (HHS) - Home Page
Department of Health
and Human Services (HHS)
USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.