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 Institute on Aging (NIA)

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

National Institute of Biomedical Imaging and Bioengineering (NIBIB)

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

National Institute of Dental and Craniofacial Research (NIDCR)

National Institute of Neurological Disorders and Stroke (NINDS)

National Center for Advancing Translational Sciences (NCATS)

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 Research on Women's Health (ORWH)

Funding Opportunity Title
HEAL Initiative: Developing Quantitative Imaging and Other Relevant Biomarkers of Myofascial Tissues for Clinical Pain Management (R61/R33, Clinical Trial Required)
Activity Code

R61/R33 Exploratory/Developmental  Phased Award

Announcement Type
New
Related Notices

None

Funding Opportunity Announcement (FOA) Number
RFA-AT-22-003
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.213, 93.853, 93.866, 93.846, 93.286, 93.121, 93.313, 93.350, 93.865
Funding Opportunity Purpose

The National Institutes of Health (NIH) intends to support the development of innovative quantitative imaging and other relevant biomarkers of myofascial tissues for pain management involving research participants using a two-phase grant funding mechanism. This effort is part of the NIH HEALSM (Helping to End Addiction Long-term) Initiative to speed the development and implementation of scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative is bolstering research across NIH to (1) improve treatment and prevention of opioid misuse and opioid use disorder and (2) enhance pain management. This funding opportunity announcement (FOA) seeks research applications to develop quantitative imaging biomarkers of myofascial tissues and assess their abilities to monitor responses and/or predict outcomes of a variety of pain management regimens. Candidates for the quantitative imaging biomarkers may include objective measures based on minimally invasive imaging technologies, electrophysiological recordings, integration of multiparametric imaging and electrophysiology approaches, or their integration with other markers (e.g., immune factors, genomic markers, physiological factors) through multiscale modeling or machine learning analysis. The first phase, funded by the R61, will provide funding for up to 3 years to develop quantitative measures that can differentiate abnormal myofascial tissue in latent versus active myofascial pain stages from healthy tissues using cross-sectional correlations with clinical signs/symptoms. In addition, the R61 phase should include planning activities for the R33 phase. The second phase, funded under the R33, will support to assess the abilities of the quantitative measures developed in the R61 phase to monitor responses and/or predict outcomes in response to specified therapies to relieve myofascial pain in longitudinal interventional studies. The combined R61/R33 should not exceed 5 years. Transition from the R61 to the R33 phase of the award will be administratively reviewed and will be determined based on successful completion of “Transition Milestones” that need to be clearly specified in the R61 phase application.

Key Dates

Posted Date
November 16, 2021
Open Date (Earliest Submission Date)
January 11, 2022
Letter of Intent Due Date(s)

January 11, 2022

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
February 11, 2022 Not Applicable Not Applicable May 2022 August 2022 September 2022

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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.

Expiration Date
February 12, 2022
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

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

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

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

The National Institutes of Health (NIH) intends to support the development of innovative quantitative imaging and other relevant biomarkers of myofascial tissues for pain management involving research participants using a two-phase grant funding mechanism. This effort is part of the NIH HEALSM (Helping to End Addiction Long-term) Initiative to speed the development and implementation of scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative is bolstering research across NIH to (1) improve treatment and prevention of opioid misuse and opioid use disorder and (2) enhance pain management. This funding opportunity announcement (FOA) seeks research applications to develop quantitative imaging biomarkers of myofascial tissues and assess their abilities to monitor responses and/or predict outcomes of a variety of pain management regimens. Candidates for the quantitative imaging biomarkers may include objective measures based on minimally invasive imaging technologies, electrophysiological recordings, integration of multiparametric imaging and electrophysiology approaches, or their integration with other markers (e.g., immune factors, genomic markers, physiological factors) through multiscale modeling or machine learning analysis. The first phase, funded by the R61, will provide funding for up to 3 years to develop quantitative measures that can differentiate abnormal myofascial tissue in latent versus active myofascial pain stages from healthy tissues using cross-sectional correlations with clinical signs/symptoms. In addition, the R61 phase should include planning activities for the R33 phase. The second phase, funded under the R33, will support studies to assess the ability of the quantitative measures developed in the R61 phase to monitor responses and/or predict outcomes in response to specified therapies to relieve myofascial pain in longitudinal interventional studies. The combined R61/R33 cannot exceed 5 years. Transition from the R61 to the R33 phase of the award will be administratively reviewed and will be determined based on successful completion of “Transition Milestones” that need to be clearly specified in the R61 phase application.

Background

Myofascial pain—pain originating from muscles and/or associated soft tissues such as fascia—is likely an important component of many severe and chronic pain conditions, including chronic low back pain, temporomandibular disorders, chronic neck and shoulder pain, and headache. Like most painful situations, myofascial pain can be managed with existing non-opioid therapies and non-pharmacologic treatments. However, many potentially effective non-pharmacologic treatments are not reimbursed by insurance and are less accessible to economically disadvantaged populations. Furthermore, evidence on which treatments are effective for myofascial pain is limited, and patients often receive treatments that are not evidence based. In addition, clinicians would like guidance on how to treat this type of pain. The field of musculoskeletal pain has largely focused on the skeletal system (bones, joints, intervertebral discs) and central nervous system (brain and spinal cord) components. The contribution of myofascial tissues, especially fascia, and the interactions of fascia, muscles, and peripheral nerves are understudied and remain mostly unknown. Many chronic musculoskeletal pain patients do not respond to surgery (targeting joint and other skeletal pathology) or develop significant side effects from pharmacotherapy including non-opioid and opioid analgesics (targeting the nervous system). In addition, theories exist that, in part, these patients’ persistent pain may be due to ineffective treatment of the myofascial pain component of their pain. Therefore, there is a strong need to address the contributions of myofascial tissues and their interactions with the neural and immune systems that may contribute to chronic pain, as the myofascial tissues are among the last “unturned stones” of all the tissue types involved in musculoskeletal pain. Specifically, identifying and developing quantitative and innovative biomarkers involving myofascial tissues are critical for effective pain management regimens through a variety of therapeutic approaches, including non-pharmacologic therapies, and may also shed light on the transition from acute to chronic pain.

Ideal biomarkers for pain management are objective measurements that are noninvasive or minimally invasive, as well as capable of monitoring the responses to and predicting the clinical outcomes of a given treatment. In the field of pain, developing such biomarkers has been challenging for two reasons: first, pain is a symptom rather than a disease; and second, pathophysiological mechanisms leading to pain are complex, heterogeneous, and still poorly understood. Nevertheless, some biomarkers have proven useful in managing some types of pain, for example pain resulting from small fiber neuropathies. For many types of pain, however, developing useful biomarkers has been difficult. This is especially true for musculoskeletal pain involving the back, neck, shoulders, hips and extremities. For many years, structural imaging (X-rays, computed tomography [CT], magnetic resonance imaging [MRI]) of “hard” tissues (bones, cartilage, intervertebral discs) was the main tool to guide treatment decisions, including surgery. Over time, it became apparent that these biomarkers lacked sensitivity and specificity. Meanwhile, imaging and other objective measurements of “soft” tissues including muscles, and especially connective tissues or “fasciae,” lag far behind, and until recently, these tissues were not even considered as musculoskeletal pain biomarker candidates.

In parallel with the growing awareness of the limitations of single tissue-specific biomarkers, there has been an increasing appreciation of the neuroplastic, psychological and genetic components of pain. This led to the recognition that musculoskeletal pain is a complex, multifactorial bio-psycho-social phenomenon that needs a systems approach integrating multiple types of biomarkers to guide both diagnosis and treatment. Identifying and filling “biomarker gaps” is important and timely to ensure that models for back pain and other pain conditions such as neck pain, temporomandibular disorder, and headache are used to their fullest potential.

One component that remains to be integrated into musculoskeletal pain models is the “myofascial unit,” including muscles and associated connective tissues, nerves, blood vessels and lymphatics. Recent studies in animals and humans have demonstrated that the perimuscular fascia is richly innervated with small-diameter fibers whose receptive fields increase in the presence of inflammation. In response to these studies, myofascial tissues are now receiving long-overdue attention as possible “pain generators.” Since the 1960s, the clinical literature has included descriptions of “myofascial pain syndrome,” which is currently diagnosed based on signs and symptoms, including tender and indurated nodules termed myofascial “trigger points,” which are detected by palpation. This constellation of symptoms is distinct from those of fibromyalgia. Myofascial pain can affect both males and females and often presents in individuals with a sedentary lifestyle combined with intermittent repetitive physical exertion. It may be focal and episodic in nature and include both “active” and “latent” phases. During the active phase, the patient complains of spontaneous pain that limits the range of motion and has localized, tender indurated foci within myofascial tissues. Palpation of these nodules reproduces the patient’s pattern of local and/or radiating pain. During the latent phase, focal palpable nodules are present and may be tender to palpation but without spontaneous pain. The latent phase also includes myofascial dysfunction, including soft tissue stiffness and reduced range of motion (not associated with pain) in the affected area. There is currently no physiological explanation for these clinical findings, nor are there quantitative measurements to differentiate active versus latent phases. Thus, it remains unclear how a patient may transition from a painless latent state to a painful and often disabling active state. Quantifying the myofascial tissue abnormalities in both latent and active states and in comparison to a healthy state is a critical first step to develop clinically useful biomarkers and to optimize effective management for this prevalent and often debilitating problem.

Due to the lack of methods to objectively evaluate myofascial tissues, no biomarkers have been available either to study myofascial tissue pathophysiology or to test the effects of treatments. It is in this context that HEAL supported the 2020 workshop on “Quantitative Evaluation of Myofascial Tissues: Potential Impact on Musculoskeletal Pain Research,” which demonstrated that this situation is ripe for change. Several key consensus themes emerged from this workshop, pointing to a unique and transformative research opportunity for HEAL to combat the challenges of pain management and opioid addiction. Current hypotheses discussed at the workshop on the pathophysiology underlying myofascial pain syndrome include:

For the active painful phase

  • Motor endplate and or/ muscle spindle sensitization causing areas of focal persistent muscular contraction, local ischemia, acidosis and metabolic dysfunction
  • Activation of nociceptors, especially within the heavily innervated perimuscular fascia
  • Neurogenic inflammation and release of inflammatory cytokines in the myofascial milieu (muscle and/or fascia)

For the latent non-painful phase

  • Chronic inflammation and fibrosis of the myofascial unit that may also involve peripheral nerves and muscle spindles
  • Muscle atrophy, fatty infiltration, and fibrosis, causing motor weakness, abnormal (increased or decreased) muscle length and chronic muscle metabolic dysfunction
  • Abnormal proprioception involving deep sensory mechanoreceptors within myofascial tissues
  • Chronic segmental sensory, motor, and/or sympathetic dysfunction

The workshop outlined some specific state-of-the-art imaging technologies with some preliminary data on myofascial tissues, multiple types of technologies (e.g., imaging, electrophysiology, metabolic measurements) that have been used in musculoskeletal tissues but not yet applied to myofascial pain, and finally technologies used in other tissues (e.g., brain, liver) that could be applied to musculoskeletal tissues. There is an opportunity to harness these technologies for the development of quantitative predictive biomarkers of myofascial pain through a multidisciplinary approach. Since a substantial proportion of patients with “non-specific” low-back, neck, shoulder, or temporomandibular pain or headache and migraine may have myofascial contributions, research on myofascial pain will potentially greatly enhance therapeutic development in all of these areas. The video recordings (Day 1 and Day 2), executive summary, and detailed summary of the workshop can be found here: https://www.nccih.nih.gov/news/events/nih-heal-initiative-workshop-on-myofascial-pain. Investigating the contributions from myofascial tissues, in the context of their therapeutic potential, and identifying biomarkers that can predict pain treatment responses and outcomes remain urgent unmet needs as we strive to end the opioid addiction and pain management crises in this country.

This FOA will fill a significant research gap within the HEAL pain research portfolio as well as the entire NIH pain research portfolio because myofascial pain is an understudied area that has significant health and economic impacts. It also complements the ongoing HEAL Back Pain Consortium (BACPAC) Research Program, which focuses on an integrative approach to low-back pain yet does not include a myofascial tissue component, which remains a “black box” within the current back pain models. In addition, this FOA intends to increase knowledge about other important pain conditions involving myofascial tissues, such as temporomandibular disorders, and chronic neck and shoulder pain, as well as headache. Most importantly, it aims to accelerate and enhance our development of predictive biomarkers that can guide our choices of effective pain management and reduce opioid addiction long term.

HEAL Initiative

This FOA is part of the NIH HEAL (Helping to End Addiction Long-term) Initiative to speed the development and implementation of scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative is bolstering research across NIH to (1) improve treatment for opioid misuse and addiction and (2) enhance pain management. More information and periodic updates about HEAL are available at: https://heal.nih.gov/.

Research Objectives and Requirements

This FOA aims to achieve two major objectives using the R61/R33 phased approach.

Objective 1 (R61 Phase): Observational Studies and Planning for the R33 Phase (up to three years)

The primary objective of the R61 phase is to identify and develop quantitative measures for research participants that can differentiate abnormal myofascial tissues in latent versus active pain stages from healthy tissues in observational study designs and through cross-sectional correlations with clinical signs/symptoms. In addition, the investigators should include efforts directed towards the team building and planning for the R33 phase clinical trial during this first phase.

Potential quantitative technologies for developing such quantitative measures include, but are not restricted to:

1) Structural imaging (e.g., magnetic resonance [MR], ultrasound), addressing improved spatial resolution needed to visualize micro-structures such as muscle spindles that may be involved in myofascial pain

2) Functional assessments (e.g., elastography) to quantify soft tissue mobility and biomechanical properties (e.g., stiffness, viscosity, shear plane mobility)

3) Quantitative evaluation of tissue metabolism, perfusion, oxygenation, and fatty infiltration (e.g., positron emission tomography [PET], optical, photoacoustic, or MR spectroscopic imaging or electrophysiological measurements of muscle, sensory, motor, and autonomic peripheral activity)

4) Multimodal, multiparametric, and multiscale approaches integrating different types of measurements, including dynamic changes of tissue targets

No preliminary data are required for the R61 phase. However, feasibility may be demonstrated through literature citations or preliminary data in animal studies or human subject studies. Investigators may choose one type of technology or multiple types of technologies described above to develop the quantitative measures to assess the "myofascial unit," which includes muscles and associated connective tissues, nerves, blood vessels, and lymphatics. Thresholds or metrics for the quantitative measures should be hypothesized and described to distinguish healthy versus latent versus active painful states with a reasonable degree of fidelity.

For the R61 phase, combining expertise in minimally invasive imaging technology, quantitative analysis and/or computational modeling, and myofascial pain will be strongly encouraged. The R61 phase should also include a brief plan to extend the investigator team with additional expertise in clinical trials and nonpharmacologic or integrative pain management and develop a clinical study protocol for the R33 phase. For example, in a collaborative team pain experts and clinicians may help define clinical criteria for myofascial pain; technology developers may facilitate the development and testing of objective quantitative measurements associated with different clinical conditions of myofascial pain, including patient reported outcomes; and interventionists may be important for the proper design and analysis of the R33 phase.

Objective 2 (R33 Phase): Interventional Studies

The primary objective of the R33 phase is to build on the quantitative measures identified and developed in the R61 phase to test their abilities to monitor responses and predict outcomes, including patient reported outcomes, in response to existing and putative treatments to relieve myofascial pain in randomized, controlled longitudinal interventional studies of patients with pain. Specifically, potential biomarkers should be measured at baseline and during and after treatments to measure changes in response to interventions. In addition, baseline biomarker levels of the quantitative measures should be determined for their abilities to identify or predict patients who are more likely to have pain relief or better pain relief and other favorable effects after the intervention. Also, clinical pain measures should be assessed before (at baseline) and after the interventions.

The sensitivity and specificity of these putative biomarkers to monitor treatment response or predict treatment outcomes should be assessed in the R33 phase.

Current empirical treatment of myofascial pain includes acupuncture or “dry needling,” injections (lidocaine, glucose or saline solutions), and manual therapies, while additional putative treatment may include drugs and devices, or other non-pharmacologic approaches. For this FOA, applicants are required to choose one or more of the following treatments or therapies for the R33 study:

  1. Physical force-based manipulations, such as manual therapies (e.g., massage therapy, soft tissue mobilization, strain-counterstrain techniques, joint mobilization, muscle energy techniques, high-velocity/low-amplitude thrusting, spinal manipulation, osteopathic manipulation, gua sha) and stretching-based physical activities (e.g., yoga, tai chi, dance therapy)
  2. Dry needling or acupuncture
  3. Thermotherapies (e.g., heating or cooling/cryotherapy)
  4. Local chemical-based injection therapies (e.g., lidocaine injection therapy)

Applicants are not expected to provide efficacy data to justify the choice of the intervention/treatment for the R33 phase.

R61 to R33 Transition Criteria and Process

Investigators are expected to describe a set of “Transition Criteria” in the form of quantitative milestones (please see Section IV.2 “Research Plan” for detailed instructions) that will allow for a definitive assessment of whether the R61 phase provides sufficient evidence to support the R33 phase of biomarker development studies.

Key evidence in the “Transition Criteria” should include thresholds for the quantitative measures in the R61 phase to differentiate different states related to myofascial pain (e.g., healthy, latent, and active states). If multiple thresholds are proposed, prioritization should be provided to determine which measure(s) would be moved forward into the R33 for biomarker development. Alternatively, the threshold of a composite measure may be described and proposed for R33 phase biomarker development if multidimensional measures are assessed in the R61 phase. Examples of such quantitative milestones may include cumulative variance of data at a specified threshold (>90%) or statistical difference among the three conditions (healthy, latent, and active states).

Progress under the R61 phase will be administratively reviewed by the HEAL program team. Funding for and transition to the R33 phase are contingent on the following: 1) meeting the “Transition Criteria” approved by NIH prior to the initial R61 award, 2) NIH HEAL approval of the planned R33 research activities and investigator team, and 3) the availability of funds. If a device or a drug is proposed in the R33 phase, investigators are encouraged to communicate with the U.S. Food and Drug Administration (FDA) prior to the R33 award for determination about whether the R33 trial will need to be conducted under an Investigational New Drug (IND) application or Investigational Device Exemption (IDE).

Scope and Priorities

This FOA supports the identification and development of biomarkers including quantitative assessments of myofascial tissues in healthy subjects and patients with relevant pain conditions. Both phases must include appropriate human subject research. Animal model studies are not allowed in response to this FOA.

All applications must include quantitative assessments of at least one component of the myofascial unit in both the R61 and R33 phase studies using minimally invasive or non-invasive technologies. If an application does not include any quantitative assessment of the myofascial component, it would be deemed non-responsive to this FOA.

Highly invasive technologies and biomarkers will be deprioritized. The R61/R33 award is primarily intended to stimulate the development and adaptation of innovative imaging technologies and other quantitative assessment methods to differentiate the healthy, latent, and active states of myofascial tissues involved in pain in human subjects. Consequently, strong applications are expected to propose a well-conceived plan for up to 3 years focusing on research activities developing these technologies and quantitative assessment methods in the R61 phase. The description of the R33 phase may be brief and should specify the intended interventions and clinical pain population to be studied to test the biomarkers developed in the R61 phase. However, the R33 phase research plan may be modified based on the outcomes of the R61 study and approval by the HEAL program team.

Research applications submitted under this FOA are likely to cover a large and diverse group of pain conditions involving myofascial tissues. Examples of potentially suitable pain conditions include but are not limited to:

  • Chronic low back pain
  • Shoulder, neck, arm, leg, or pelvic pain
  • Temporomandibular disorders
  • Headache
  • Sickle cell disease pain

Non-responsiveness criteria:

  • An application not proposing quantitative assessment of at least one component of the myofascial unit will not be responsive to the FOA
  • Applications not proposing one or more of the following treatments or therapies for the R33 study will be considered not responsive to the FOA:
    • Physical force-based manipulations,
    • Dry needling or acupuncture
    • Thermotherapies
    • Local chemical-based injection therapies

Consultation With NIH

Applicants are encouraged to consult with NIH Scientific Contacts listed in the FOA before they begin developing their applications (see Section VII, Agency Contacts). This early contact will provide an opportunity to clarify whether the research topic is a fit with the FOA’s purpose and priorities.

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

Section II. Award Information

Funding Instrument

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed
New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

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

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The NIH HEAL Initiative intends to commit at least $5 million total costs in FY 2022 to fund at least 5 - 8 awards.

Award Budget

TheR61 budget should not exceed $500 K in direct cost per year. The R33 budget maynot exceed $700 K in direct cost per year if 3 years are proposed for the R33 phase. If a 2-year R33 phase is proposed, the R33 budget maynot exceed $800 K in direct cost per year.

Award Project Period

The scope of the project should determine the project period for each phase. The maximum period of the combined R61 and R33 phases is 5 years, with up to 3 years for the R61 phase.

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:

  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)

Local 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)

Federal Governments

  • 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 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.
  • 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.

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, per 2.3.7.4 Submission of Resubmission Application. 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

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

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:

Diane Joss, PhD
Telephone: 240-549-9868

Email: myofascial_pain_heal@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.

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.

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:

Specific Aims should include brief descriptions of both the R61 phase and R33 phase as well as the transition criteria.

Research Strategy section should provide diagrams and describe the study designs as well as analytic plans for the R61 phase and the R33 phase separately. This section should also provide quantitative details of the R61 to R33 Transition Criteria as well as timeline for completing the R61 and the R33 phases. It is anticipated that the R61 study should be completed within 32 months post award to allow for a timely submission of transition request to the R33 phase.

R61 phase: (up to 3 years)

The R61 Phase may choose to study the myofascial unit in one of the following clinical populations:

  • Chronic low back pain
  • Shoulder, neck, arm, leg, or pelvic pain
  • Temporomandibular disorders
  • Headache
  • Sickle cell disease pain

If another pain condition not listed above is chosen, application should describe evidence supporting the relevance of myofascial unit in such a pain condition.

The R61 phase may choose to employ one or multiple of the following technologies with minimal invasiveness to develop quantitative measures or integrate these measures with other markers (e.g., immune factors, genomic markers, physiological factors) through multiscale modeling or machine learning analysis to differentiate healthy, latent, and active states of the myofascial units in the chosen clinical pain condition:

1) Structural imaging (e.g., MR, ultrasound), addressing improved spatial resolution needed to visualize microstructures such as muscle spindles that may be involved in myofascial pain

2) Functional assessments (e.g., elastography) to quantify soft tissue mobility and biomechanical properties (e.g., stiffness, viscosity, shear plane mobility)

3) Quantitative evaluation of tissue metabolism, perfusion, oxygenation, and fatty infiltration (e.g., PET, optical, photoacoustic, or MR spectroscopic imaging or electrophysiological measurements of muscle, sensory, motor, and autonomic peripheral activity)

4) Multimodal, multiparametric, and multiscale approaches integrating different types of measurements, including dynamic changes of tissue targets

The R61 phase must also include a plan to develop a detailed research study and clinical study protocol with appropriate expertise for the R33 phase for the HEAL program team to review and approve.

R61-to-R33 Transition Criteria:

The criteria must include quantitative milestones to specify the threshold(s) to be used to differentiate healthy, latent, and active states of myofascial units in a chosen clinical pain population using the proposed technological measures. It should also include a timeline to complete the R61 phase within 32 months of time post award to ensure timely requests for transition to the R33 phase.

R33 phase: (R61/R33 combined cannot exceed 5 years)

The R33 phase should be brief and must choose one or more of the following treatments or therapies along with an appropriate control group (minimally a time control group) to conduct a randomized clinical trial.

  1. Physical force-based manipulations, such as manual therapies (e.g., massage therapy, soft tissue mobilization, strain-counterstrain techniques, joint mobilization, muscle energy techniques, high-velocity/low-amplitude thrusting, spinal manipulation, osteopathic manipulation, gua sha) and stretching-based physical activities (e.g., yoga, tai chi, dance therapy)
  2. Dry needling or acupuncture
  3. Thermotherapies (e.g., heating, or cooling/cryotherapy)
  4. Local chemical-based injection therapies (e.g., lidocaine injection therapy)

The quantitative measure(s) developed in the R61 phase should be assessed in the R33 phase at baseline and at the end of the intervention as well as at a specified frequency during the intervention to monitor the ability of such measure(s) to assess responses to the intervention. An appropriate clinical pain assessment should also be performed at baseline and at the end of the intervention to assess the ability of the R61 quantitative measure(s) to predict clinical outcomes of the chosen intervention. The R33 phase should also propose to calculate the sensitivity and specificity of the R61 quantitative measures to monitor the treatment response and predict the clinical outcomes.

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

The following modifications also apply:

HEAL Data Sharing

NIH intends to maximize the impact of HEAL Initiative-supported projects through broad and rapid data sharing. Consistent with the HEAL Initiative Public Access and Data Sharing Policy (https://heal.nih.gov/about/public-access-data), all applications, regardless of the amount of direct costs requested for any one year, are required to include a Data Management and Sharing Plan outlining how scientific data and any accompanying metadata will be managed and shared. The plan should describe data types, file formats, submission timelines, and standards used in collecting or processing the data. It is expected that data generated by HEAL Initiative-funded projects will be submitted to study-appropriate domain-specific or generalist repositories in consultation with the HEAL Data Stewardship Group to ensure the data is accessible via the HEAL Initiative Data Ecosystem.

To maximize discoverability and value of HEAL datasets and studies, and facilitate data integration and collaboration, applications submitted in response to this FOA are strongly encouraged to incorporate standards and resources where applicable:

  • Applicants are encouraged to ensure that data collected by the study conform to Findable, Accessible, Interoperable, and Reusable (FAIR) principles.
  • Applicants are specifically encouraged to incorporate into their planning, an alignment with the guidelines, principles and recommendations developed by the HEAL Data Ecosystem, including but not limited to preparing data to store in selected specified repositories, applying minimal metadata standards, use of core HEAL Clinical Data Elements (CDEs, https://heal.nih.gov/data/common-data-elements), and other necessary requirements to prepare data to connect to the HEAL Data Ecosystem.
  • All new HEAL clinical pain studies are required to submit their case-report forms/questionnaires to the HEAL Clinical Data Elements (CDE) Program. The program will create the CDE files containing standardized variable names, responses, coding, and other information. The program will also format the case-report forms in a standardized way that is compliant with accessibility standards under Section 508 of the Rehabilitation Act of 1973 (29 U.S.C § 794 (d)), which “require[s] Federal agencies to make their electronic and information technology accessible to people with disabilities.” HEAL Initiative clinical studies that are using copyrighted questionaries are required to obtain licenses for use prior to initiating data collection. Licenses must be shared with the HEAL CDE team and the program officer prior to use of copyrighted materials. For additional information, visit the HEAL CDE Program.

The NIH notices referenced below provide additional NIH guidance that should be considered in developing a strong data management and sharing plan. The list is instructive but not comprehensive.

  • Elements of an NIH Data Management and Sharing Plan (NOT-OD-21-014)
  • NIH has provided guidance around selecting a repository for data generated by NIH-supported research and has developed desirable characteristics for all data repositories (NOT-OD-21-016).
  • NIH encourages the use of data standards including the PhenX Toolkit (www.phenxtoolkit.org) (for example, see NOT-DA-12-008, NOT-MH-15-009)
  • NIH encourages researchers to explore the use of the HL7 FHIR® (Fast Healthcare Interoperability Resources) standard to capture, integrate, and exchange clinical data for research purposes and to enhance capabilities to share research data (NOT-OD-19-122). The FHIR® standard may be particularly useful in facilitating the flow of data with EHR-based datasets, tools, and applications.
  • NIH encourages clinical research programs and researchers to adopt and use the standardized set of data classes, data elements, and associated vocabulary standards specified in the United States Core Data for Interoperability (USCDI) standards, as they are applicable (NOT-OD-20-146). Use of the USCDI can complement the FHIR® standard and enable researchers to leverage structured EHR data for research and enable discovery.

Awardees conducting research that includes collection of genomic data should incorporate requirements under the NIH Genomic Data Sharing Policy (NOT-OD-14-124, NOT-OD-15-086).

Appendix:

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

  • No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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.

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

 

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.

For this particular announcement, note the following: This FOA is primarily focused on developing and/or adapting innovative technologies to assess the myofascial units in appropriate clinical pain populations for diagnostic purpose as proposed in the R61 phase. Secondarily, the R33 phase must choose from one of the specified treatments and therapies listed in the RFA to test whether the technological measures developed in the R61 phase can monitor the treatment responses and predict treatment outcomes of the chosen intervention. The priority of this FOA is the technological development in the R61 phase and the ability of the proposed technology or method to differentiate the healthy, latent, and active states of myofascial tissues in a chosen painful condition.

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

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

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

 

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

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

For this particular announcement, note the following

Are the chosen technologies for both phases considered minimally invasive or non-invasive? How well would the proposed quantitative biomarkers allow differentiation of the healthy, latent, and active states of myofascial tissues in a chosen painful condition? How is the proposed technology relevant to the myofascial units?

 

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

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

For this particular announcement, note the following

Has a multidisciplinary team been proposed to cover the technology, myofascial pain, clinical pain, and pain management/treatment aspects of the application? Is the R61 planning appropriate to ensure adequate areas of expertise for the R33 phase?

 

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

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

For this particular announcement, note the following

How innovative are the proposed technology and technological measures to differentiate healthy, latent, and active states of the chosen clinical pain condition?

 

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?

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?
 

For this particular announcement, note the following

Are the chosen quantitative technologies well justified for developing quantitative measures to differentiate healthy, latent, and active states of the myofascial units?

Is the analytical plan for the R61 phase appropriate?

Is the chosen intervention proposed by the application to be studied in the R33 phase well justified to assess the abilities of the quantitative measures developed in the R61 phase to monitor responses and/or predict outcomes in response to specified therapies to relieve myofascial pain in longitudinal interventional studies?

Is the R33 phase proposing to collect both the proposed R61 quantitative measures and clinical pain outcomes at baseline, during the intervention, and at the end of the intervention?

Does the R33 phase assess the ability of the quantitative measures to monitor treatment responses and predict clinical outcomes?

How well does the Data Management and Sharing plan address the requirements of the HEAL Public Access and Data Sharing Policy?

 

 

 

 

 

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

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

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.

 

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)?

Does the study timeline described allow for timely completion of the proposed R61 research activities and the planning of the R33 phase research and team building?

 

For research that involves human subjects but does not involve one of the  categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the  categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

 

When the proposed project 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.

 

Not Applicable.

 

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

 

Not Applicable.

 

Not Applicable.

 

Not Applicable.

 

Does the application include “Transition Criteria” with appropriate quantitative milestones? Are quantitative criteria pre-specified and rigorously defined to assess milestone achievement and operational feasibility relevant to advancing from the R61 to the R33 phase? Are the milestones feasible, well developed and quantifiable to differentiate healthy, latent, and active states of a myofascial unit in a chosen clinical pain population using the proposed technological measures? Specifically, will the milestones aid investigators and HEAL program officials in determining whether the project succeeded in achieving its R61 phase goals? Does the application provide sufficient justification for the specific conditions under which the projects would not proceed to the R33 phase? Have the investigators adequately described anticipated problems?

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.

 

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

 

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

 

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

 

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

 

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

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 will receive a written critique.

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.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to NCCIH. 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 recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. 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 and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient 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, Recipients, and Activities, including of note, but not limited to:

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

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.

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.

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 and 2 CFR Part 200.206 “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

Not Applicable

3. Reporting

When multiple years are involved, recipients 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 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. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All recipients 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 the threshold.  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 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 and 2 CFR Part 200 – Award Term and Condition 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)

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

Melissa M Ghim, PhD
National Institute Of Dental & Craniofacial Research (NIDCR)
Phone: (301) 529-6570
E-mail: ghimm@mail.nih.gov

Devon Oskvig, Ph.D.
National Institute on Aging (NIA)
Phone: 301-827-5899
Email: devon.oskvig@nih.gov

Leslie K Derr, PhD
National Institute Of Arthritis And Musculoskeletal And Skin Diseases (NIAMS)
Phone: (301) 594-8174
E-mail: derrl@mail.nih.gov

Susan F Marden, PhD RN
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Phone: 301-435-7767
E-mail: mardens@mail.nih.gov

Bobbieann Mount
National Center For Advancing Translational Sciences (NCATS)
Phone: 301-435-0824
E-mail: bobbieann.mount@nih.gov

Guoying Liu
National Institute Of Biomedical Imaging And Bioengineering (NIBIB)
Phone: (301) 594-5220
E-mail: liug@mail.nih.gov

Michael L. Oshinsky, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9964
Email: michael.oshinsky@nih.gov
 

David A Thomas
Office Of Research On Women's Health (ORWH)
Phone: 301-435-1313
E-mail: david.thomas@nih.gov

 

Elena K Gorodetsky
Office Of Research On Women's Health (ORWH)
Phone: (301) 594-9004
E-mail: egorod@mail.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 Headley
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3788
Email: headleysm@mail.nih.gov

Diana Rutberg, MBA
National Institute Of Dental & Craniofacial Research (NIDCR)
Phone: (301) 594-4798
E-mail: dr258t@nih.gov

Paolo Arguinzoni-Urrutia
National Institute on Aging (NIA)
Phone: 301-827-5985
Email: paolo.arguinzoni-urrutia@nih.gov

Erik Edgerton
National Institute Of Arthritis And Musculoskeletal And Skin Diseases (NIAMS)
Phone: 301-594-7760
E-mail: erik.edgerton@nih.gov

Margaret A Young
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Phone: 301-642-4552
E-mail: margaret.young@nih.gov

Lauren Kristina Massey
National Center For Advancing Translational Sciences (NCATS)
Phone: 301-496-1240
E-mail: lauren.massey@nih.gov

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: ChiefGrantsManagementOfficer@ninds.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 and 2 CFR Part 200.

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