Frequently Asked Questions: HEAL Initiative—Developing Quantitative Imaging and Other Relevant Biomarkers of Myofascial Tissues for Clinical Pain Management (R61/R33, Clinical Trial Required)

The National Institutes of Health (NIH) Helping to End Addiction Long-term^® Initiative, or NIH HEAL Initiative^®, office has set aside at least $5 million to support at least five to eight awards for this RFA. The actual amount may increase or decrease, depending on the number of meritorious applications. 

Yes. You have to describe both the R61 and R33 phases, as well as the R61 to R33 transition criteria, both on the Specific Aims page and in the Research Strategy Section. Every applicant is strongly encouraged to read and follow the guidance described in the RFA Section IV. Application and Submission Information, 2. Content and Form of Application Submission, under PHS 398 Research Plan. This section includes explanations of critical information that you must include in your application. (See excerpt below.) It is highly advised that both on the Specific Aims page and in the Research Strategy Section, your application should include clear bolded headings for “R61 Phase,” “R61 to R33 Transition Criteria,” and “R33 Phase.” 

The budget for all R61 phases can NOT exceed $500 K direct cost per year. If an application proposes 3 years for the R61 phase and 2 years for the R33 phase, the budget limit for the 2-year R33 phase is $800 K direct cost per year. If an application proposes 2 years for the R61 phase and 3 years for the R33 phase, the budget limit for the 3-year R33 phase is $700 K direct cost per year. We are trying to make the total cost across the 5 years comparable for both options. Please note that a 1-year R61 proposal is highly discouraged for this RFA. 

Applications should propose to test whether the proposed quantitative measure(s) can differentiate the healthy, latent, and active pain states of the myofascial tissues in a chosen pain condition. However, the minimum transition criterion is the ability to differentiate the healthy from the active painful states of the myofascial units. Please note that the R61 to R33 transition criteria will be assessed during review and may be renegotiated with NIH program officials after review and prior to funding. 

No. Both the R61 and R33 phases are exploratory clinical studies. There is no requirement for either phase to be fully powered for clinical efficacy of the proposed intervention. For the R61 phase, statistical methods should be proposed and described in the application to support interpretations that the proposed quantitative measure(s) would be able to differentiate the healthy from the active painful state of the myofascial units with a reasonable level of specificity and sensitivity. Again, please note that the R61 to R33 transition criteria may be renegotiated with NIH program officials after review and prior to funding. 

The RFA primarily focuses on developing and testing quantitative technologies and measures and their abilities to accurately assess myofascial tissue properties, and more specifically, the ability to differentiate the different states of pathophysiology of the myofascial units. It is not about developing or testing new/emerging interventions or a combination of existing interventional approaches for myofascial pain. However, in the R33 phase, applicants must propose one of the four types of interventions specified in the RFA to test whether the quantitative measures developed in the R61 phase predict or respond to the proposed intervention. 

While the focus should be on MPS, the key for the RFA is the quantitative evaluation of myofascial tissues. If a team of investigators proposes to develop and evaluate the applicability of a technique or technology to evaluate the muscle pain (myalgia) side of fibromyalgia in the R61 phase and apply the technology for myofascial tissue characterization in response to one of the treatments specified in the RFA in the R33 phase, it would then be responsive to the RFA. 

The focus is not on developing neuroimaging techniques. NIH has a large portfolio in this area and has invested heavily already. The key purpose of this funding initiative is to challenge the technology development community to address a very specific need identified by this myofascial pain workshop held in 2020.

The pathological condition causing the pain is not the focus of the project. The focus of the proposal should be to develop a technology to differentiate between painful and nonpainful myofascial tissues. If there are painful myofascial tissue changes in the upper extremity in patients with carpal tunnel syndrome, then it could be a relevant model for MPS. 

As the title of the RFA indicates, quantitative measures are desired. An application with only qualitative measures likely will not be well aligned with the RFA. 

Evidence to support that myofascial tissue changes are associated with pain in the proposed sports-related injuries would be needed as one of the scientific premises. 

The primary emphasis of the RFA is on developing and testing quantitative measures to differentiate the myofascial tissue changes associated with pain, using one or more of the treatment methods listed in the RFA in the R33 phase to test responsiveness of the quantitative measure to treatment. Developing various methods for scoring/indexing patients’ level of pain (but not on the tissue level) is not aligned with the goals of this RFA.

It is up to applicants to explain the relevance of the myofascial unit in any proposed pain condition in the application.

It is up to applicants to explain the relevance of the myofascial unit in any proposed pain condition in the application. 

Yes. The RFA has not opted out of late submission, so late submission within a 2-week window of consideration is allowed. Late applications are accepted only in extenuating circumstances. If an application is submitted late, a cover letter explaining the reasons for the delay must be included with the signed, completed application. Late applications are evaluated on an individual basis considering the reasons provided by the Center for Scientific Review’s Division of Receipt and Referral based on NOT-OD-15-039 or NOT-OD-20-082.

Post-submission materials are allowed by this RFA but have to be submitted no later than 30 calendar days prior to the peer review meeting. They require concurrence from your Authorized Organization Representative and must follow other instructions in the notice. Allowable post-submission materials are listed in NOT-OD-19-083. Additionally, NOT-OD-22-047 applies, allowing applicants to also submit a one-page update with preliminary data, in addition to the materials specified in NOT-OD-19-083, as post-submission materials if needed.

As part of the COVID-19 flexibility policy, for applications submitted to this RFA, a one-page update with preliminary data will be accepted as post-submission materials (NOT-OD-22-047) and should follow the instructions for post-submission materials. 

Reviewers will provide only one overall impact score for both phases together, the R61 and the R33 phase, reflecting their combined evaluation of both phases.

Yes. Milestones are an additional reviewer criterion, like study timeline and protection of human subjects. This criterion will be factored in along with the scored criteria to produce the overall impact score. How this is balanced is dependent on reviewers’ judgment.