Frequently Asked Questions: HEAL Initiative— Toward 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®, has committed an estimated total of $4 million in FY 2024 to fund up to five awards. Awards pursuant to this funding opportunity are contingent upon NIH appropriations and the submission of a sufficient 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 RFA-AT-24-003, 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 your application should include clear bolded headings on the Specific Aims page and in the Research Strategy Section for:

- R61 Phase
- R61 to R33 Transition Criteria
- R33 Phase

The budget for all R61 phases cannot exceed $500K 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 $800K 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 $700K 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 NOFO.

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. Preferred metrics include effect sizes (e.g., Cohen’s d > 0.5), average area under the curve (e.g., AUC or ROC of 0.7), or other metrics of classification accuracy (e.g., sensitivity and specificity metrics of 70 percent). Please note that the R61 to R33 transition criteria may be further negotiated with NIH program officials after review and prior to funding.

The NOFO primarily focuses on developing and testing quantitative technologies and measures and their abilities to accurately assess myofascial tissue properties, including the ability to differentiate among pathophysiological states of myofascial tissue in different types of chronic pain conditions. The primary goal is not to develop or test new/emerging interventions or a combination of existing interventional approaches to treat myofascial pain. However, in the R33 phase, applicants will propose to use at least one of the five listed types of interventions specified in the NOFO to test whether the quantitative measures developed in the R61 phase predict or respond to the proposed intervention.

The key for the NOFO 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 NOFO in the R33 phase, it would be responsive to this NOFO.

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 quantitative measures to study myofascial tissue pathophysiology. If there are painful myofascial tissue changes in patients with carpal tunnel syndrome, then it could be a relevant model for MPS.

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

Evidence supporting myofascial tissue changes associated with pain in the proposed sports-related injury/injuries would be needed as one of the scientific premises.

The primary emphasis of the NOFO 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 NOFO 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 at the tissue level) is not aligned with the goals of this NOFO.

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. 

No late applications will be accepted for this NOFO.

Post-submission materials are allowed by this NOFO but have to be submitted no later than 30 calendar days prior to the peer review meeting. Allowable post-submission materials are listed in NOT-OD-19-083. They require concurrence from your Authorized Organization Representative and must follow other instructions in the notice. 

Please note that applicants are no longer able to submit a one-page update with preliminary data as post-submission material (per NOT-OD-23-106).

Reviewers will provide only one overall impact score for both phases R61 and R33 together, which will reflect the 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.