This technical assistance webinar was designed to aid potential grantees for RFA-AT-19-006: HEAL: BRIM.
RFA-AT-19-006: HEAL Initiative: Behavioral Research to Improve MAT: Behavioral and Social Interventions to Improve Adherence to Medication Assisted Treatment for Opioid Use Disorders (R61/R33 Clinical Trial Optional)
The purpose of this FOA is to solicit applications to examine the impact of adding behavioral and/or social interventions to Medication Assisted Treatment (MAT) for persons with Opioid Use Disorders (OUD). Applications are encouraged for fully powered effectiveness and/or implementation studies that will examine whether combining MAT with behavioral and/or social interventions (e.g., mindfulness meditation, cognitive behavioral therapy, or multi-disciplinary rehabilitation) can improve adherence to MAT and, at the same time, prevent substance abuse relapse and improve long-term abstinence from illicit opioids.
The videocast is archived.
Scientific Contact: Dr. Dave Clark
Summary of Questions and Answers From a Technical Assistance Videocast Held on January 18, 2019
Participating NIH Staff:
- Dr. Dave Clark, Program Director, Division of Extramural Research, National Center for Complementary and Integrative Health (NCCIH)
- Dr. Sarah Duffy, Deputy Branch Chief, Services Research Branch, National Institute on Drug Abuse (NIDA)
- Dr. Martina Schmidt, Chief, Office of Scientific Review, NCCIH
- Dr. Wendy Weber, Branch Chief, Clinical Research Branch, NCCIH
Note: The questions and answers below are in reference to BRIM-2 RFA-AT-19-006 (not BRIM-1 RFA-AT-19-007).
Q: If intervention implementation is planned at multiple clinical sites, do the stakeholders from each clinical site (e.g., multiple clinics in the same geographic area who collaborate but are part of different health systems) need to participate as key study personnel?
A: If, for example, you have a study with 20 different individual clinics, it’s not recommended to have each person at 10 percent total annual effort as a coinvestigator, especially considering the type of work that’ll be necessary on the coinvestigators’ part to ensure the study is done well. To include other people as relevant stakeholders and part of the project, consider designating them as consultants or a consultant group. The goal is to have them on at the appropriate level of effort to conduct the study.
Q: For the R61 phase, is it strongly recommended that there be an attention control group for the intervention?
A: It depends on the specific research questions that you are proposing and whether an attention control is the best comparison group for answering those questions. There needs to be a scientific justification for why your chosen comparison group or groups are appropriate to answer your research questions. The best comparison group might be treatment as usual, an attention control, or both.
Q: Is a control group necessary in an R61 phase versus the R33 phase? What activities are typical in an R61 versus what’s expected in an R33?
A: It depends. The R61 phase involves doing the preparatory work and demonstrating that you are ready to proceed to the R33 phase as soon as the transition happens (e.g., start recruiting almost on day 1). In doing the preparatory work, if you think it’s important or necessary to demonstrate that you can recruit and retain control group subjects, that’s a very good rationale for recruiting a control group during an R61 phase. But if you already have established successful recruitment/retention steps along with past experience, it may not be necessary to involve a control group in the R61 phase.
Depending on where you are in terms of the development of your intervention, it can help—if you don’t already have it—to have some kind of signal, especially in cases where you’re combining things. It’s not a phase I.
For projects that may be assigned to the NCCIH, we have a website that outlines what we consider appropriate use of pilot data: https://nccih.nih.gov/grants/whatnccihfunds/pilot_studies
Q: Are feasibility trials (to look at feasibility and acceptability of the intervention) allowable in an R61 phase?
A: Yes, that can be a great use of the R61 phase, especially in formative work. It’s important, however, to operationalize and carefully define what your thresholds are for feasibility and acceptability.
Q: Is it required that the study add a behavioral intervention to medication assisted treatment (MAT)? Could a behavioral intervention by itself be compared to an education-only control?
A: No, the intervention needs to be in combination with MAT. The point of the funding opportunity announcement (FOA) is to look at ways of increasing adherence to MAT to improve outcomes.
Q: Would reviewers be enthusiastic about an application with stress as the primary outcome and adherence as the secondary outcome?
A: Reviewers are primarily interested in adherence. A very strong case supported by the literature would need to be made by the applicant for why stress should be the primary outcome, such as how stress is directly related to adherence.
Q: In addition to adherence to MAT, what are other relevant potential primary outcomes, such as other opioid abuse disorder outcomes? What is the expected duration of followup?
A: Claims data and other data suggest that people don’t stay on MAT for long. We are lacking scientific evidence on the ideal amount of time for MAT, but observational data show that in many cases, at least 1 year or more is beneficial. Primary outcomes will depend on the population, what you think the deficit is, and what you think can help.
You will need to justify that a rigorous and scientific examination of the outcomes you’re proposing will answer your research questions. The justification should include length of follow-up. The outcomes need to relate directly to the aims that you’re proposing. Examples of potential primary outcomes in addition to adherence include abstinence from illicit opioid use and time to relapse.
Q: How many grants are expected to be awarded?
A: It’s anticipated that six to eight applications will be funded.
Q: Does the principal investigator of an application have to come from an academic institution?
A: No. Entities eligible to apply include academic institutions but are not limited to them. See the FOA’s Part 2. Full Text of Announcement / Section III. Eligibility Information / 1. Eligible Applicants for a complete list of eligible organizations.
Q: Does each coinvestigator listed in the application need to submit a letter of support?
A: Generally, coinvestigators do not need to submit letters of support because their input is already listed in the application. You may use the coinvestigator’s biographical sketch to describe their role and contribution to the project. Letters of support usually come from consultants whose work is not otherwise described in the application.
If an involved person is elevated to the level of coinvestigator, they will be submitting a biographical sketch and other information, which will help to outline their level of support and contribution to the proposal. A person listed as a consultant can be listed as key personnel, in which case they would submit a biographical sketch. But they also can be listed in a letter of support and named as a consultant, in which case they would not submit a biographical sketch.
Q: How important is it that the projects leverage state funding support from the Substance Abuse and Mental Health Services Administration (SAMHSA) initiative?
A: For BRIM-2 (RFA-AT-19-006), there is no requirement that you be aligned with the SAMHSA State Targeted Response (STR) projects, but it is allowed and encouraged. Leveraging ongoing resources and activities that states are implementing and then conducting your research around those activities to make your budget go further would be a wonderful use of research dollars.
Q: Is it okay to do a clinical trial in the R61 phase and then not do a clinical trial in the R33 phase?
A: More details on your specific aims would be needed to answer this question. Keep in mind that this specific funding opportunity limits the R61 phase to no more than 2 years, which is likely insufficient to conduct a fully powered effectiveness or implementation science study. There may be situations where what you are doing in the R61 or R33 phase might not technically meet the NIH definition of a clinical trial.
Q: If the studies that are proposed meet the definition of an NIH clinical trial, should a study record be included for one or both of the proposed studies?
A: Each study that meets the definition of a clinical trial needs its own study record. A study record needs to be submitted for an R33 phase that meets the NIH clinical trial definition. A separate study record would need to be submitted if the R61 phase also meets the NIH clinical trial definition.
Q: Do you expect to have additional submission deadlines for this RFA? Do you anticipate the RFA being reissued or will there be receipt dates later this year?
A: No. At this point, we don’t have any available public information regarding future plans to reissue this RFA. If you’re unable to submit an application by the deadline for this funding opportunity, there are other funding opportunities toward which we can potentially guide you. Even though this RFA will have only a single receipt date, it doesn’t mean that your research ideas can be submitted only at that one time.
Q: Does the proposed intervention or behavioral intervention have to be a complementary or integrative health approach?
If you want to have your grant application stay with NCCIH, then the answer is yes. NCCIH, however, is one of seven participating institutes and centers (ICs). Your research idea should align with at least one of the seven participating ICs. You can find brief descriptions within the RFA about the priority areas of each of the participating ICs. If you are still uncertain which IC aligns best with your research idea or you have more specific questions, see the Scientific/Research Contact(s) list in Section VII toward the bottom of the RFA for someone to contact.
Q: Does the medication for opioid use disorder need to be a specific type, such as methadone or buprenorphine?
A: It can be any U.S. Food and Drug Administration (FDA)-approved medication for the treatment of opioid use disorder. It can be a single medication or multiple medications.
Q: Are there any restrictions on foreign aspects of the application? Are foreign applications, foreign components, or non-U.S. citizens allowed?
A: Foreign institutions, non-domestic (non-U.S.) components, and foreign components, as defined in the NIH Grants Policy Statement, are not allowed for this funding opportunity. Non-US citizens are allowed if they are from an eligible institution as defined in Part 2. Full Text of Announcement / Section III. Eligibility Information / 1. Eligible Applicants in the FOA.
Q: For multimodal interventions, do you prefer or expect investigators to assess which components of the multiple-component intervention work best, or do you want to know whether the intervention as a whole works effectively? What is the general goal of the FOA?
A: The more we can understand the mechanisms within an intervention, the better. This RFA, however, is not designed to look only at mechanisms. The RFA’s focus is on effectiveness and implementation studies rather than basic and efficacy studies.
Q: Can piloting of the intervention be done in the R33 phase, or does that need to be completed in the R61 phase?
A: Generally, R33s are comparable to R01s, for which reviewers want to see that the preliminary work is already done. Last-minute refinement in the R33 phase might be fine, but piloting to determine if an intervention actually works likely would not be okay. It’s best to contact the IC about this.
Q: If I haven’t already sent in a letter of intent, should I still send one in?
A: Yes, you can still send in a letter of intent. It’s helpful for NCCIH to receive letters of intent as they act as a preview of what’s to come. A letter of intent is not, however, required or binding. If you do not send one, your application will still be accepted.
Q: During the planning phase, it seems possible that some aspects of the trial might change, which in turn might influence the budget or how the trial is implemented in the R33 phase. Can adjustments be made to the budget at the time of the transition request? Can money be moved between different budget categories? Can the total budget be changed?
A: Staying budget-neutral and moving money within different budget categories is likely a nonissue. Increasing the total budget is not something that the ICs anticipate doing and would require a discussion with the administering IC.
Q: For the clinical trial experience table that’s required as part of the application, is that only for the principal investigator or for all key personnel?
A: It is for all key personnel.
Q: What personnel should be listed in the application? Who should be omitted from the application?
A: Whom you list depends on the level of contribution to your application. List those who provide a significant contribution to your application. Do not include people on advisory board committees.
Q: Given the scope and budget, what sample sizes might you anticipate for the R61 and R33 phases?
A: It will depend on the anticipated effect size, the number of covariables, and other factors. The R33 phase needs to be adequately powered to answer the question in a scientific and rigorous manner. If the R61 phase is meant to provide preliminary efficacy data, it might also need to be similarly powered. Consider how much evidence will be needed to provide a signal that the trial can proceed. It is highly encouraged that you involve a biostatistician as part of your project.
Q: What is the anticipated scientific expertise of the review panel?
A: The review panel will include people with expertise in biostatistics, clinical trials, and key aspects specific to the FOA. Cover letters and letters of intent from applicants are helpful to NCCIH for ensuring the types of expertise necessary to do a fair review of your application.
Q: Can the R61 phase be 18 months and not 1 year or 2 years?
A: Yes. The R61 phase is limited to 2 years, with a range of 1 to 2 years, so 18 months is fine.
Additional detailed questions will be answered in direct responses to the individuals who submitted them.
Dr. Clark: Thank you for your interest. If you have additional questions about this funding opportunity or general questions about ideas that might work with my portfolio outside of the HEAL Initiative, please email me.
Dr. Duffy: Thank you for your interest in this initiative. We look forward to seeing great applications and receiving any questions before then.
Dr. Schmidt: We are looking forward to seeing your application and having it in review.