Stimulating T4 Implementation Research to Optimize Integration of Proven-effective Interventions for Heart, Lung, and Blood Diseases and Sleep Disorders into Practice (STIMULATE) (R01 Clinical Trial Not Allowed)

A.1.  NIH Definition of a Clinical Trial:

A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include a placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavior outcomes.

• The simplified case studies apply the following four questions to determine whether NIH would consider the research study to be a clinical trial:

1. Does the study involve human participants?
2. Are the participants prospectively assigned to an intervention?
3. Is the study designed to evaluate the effect of the intervention on the participants?
4. Is the effect being evaluated a health-related biomedical or behavioral outcome?

If the answer to all for questions is “yes,” then the clinical study would be considered a clinical trial according to the NIH definition.

• The Electronic Forms-E walks you through the steps of determining if you proposed grant includes a clinical trial, at the point of entering your grant application in to the system.

• You are strongly encouraged to review NIH policy on clinical trials and case studies for reference.

• A Walk-through of the PHS Human Subjects and Clinical Trials Information Form
  Link to Non-U.S. Government Site - Click for Disclaimer (Video, 9 min.)
   

A.2. Applicants are encouraged to select the best FOA and research and analytical plans to address their research questions.  Based on information and guidance from https://grants.nih.gov/policy/clinical-trials.htm a few examples of types of research designs anticipated include:

• Research study using  focus groups to identify information to design an intervention (NIH CT #27)
• Collecting follow-up data to determine if impact of original intervention persists (NIH CT, NIDA Case Ex 1)
• Secondary data analyses and follow up data to explore impact of two or more previously deployed implementation strategies
• Natural experiments  examining different implementation strategies when the intervention “assignments” have been made by policy or other means (i.e., not assigned by the study design (NIH CT Case #19)
• Systems science and simulation modeling scenarios of complex interrelationships that can help adjust and refine research designs for future consideration.
• Prospective observational studies assessing non-biological/non-behavioral outcomes of the implementation (NIH CT Case #29)

A. 3 You are encouraged to apply to the FOA for which your research project is best aligned.  The RFA-HL-19-014 funding has specified research objectives and set aside resources to fund meritorious applications to conduct non-clinical trial research which is designed to identify strategies to enhance sustainable uptake of proven-effective interventions to prevent and/or manage heart, lung, and blood diseases and/or sleep disorders (HLBS conditions), explicitly. Other Funding Opportunity Announcements such as the PAR-18-007 (Dissemination and Implementation Research in Health (R01 Clinical Trial Optional); Single-Site Clinical Trial PAR-18-406 Single-Site Investigator -Initiated Clinical Trials (R61/R33 Clinical Trial Required); or, Multiple Site Clinical Trial PAR-18-407 Clinical Coordinating Center for Multi-Site Investigator-Initiated Clinical Trials (Collaborative UG3/UH3 Clinical Trial Required).

A.4. Focus of changes in FORMS-E (Clinical Trial is not allowed):

• Consolidation of human subjects, inclusion enrollment, and clinical trial information previously collected across multiple agency forms
• Incorporation of recent Grants.gov changes to R&R Budget and SBIR/STTR Information forms
• These changes will be implemented with application form packages identified with a Competition ID of "FORMS-E" and associated application guide instructions. See High-level Summary of Form Changes in FORMS-E Application Packages for a full list of changes
• Annotated Form Sets, FORMS-E:
  • Annotated Form Set for NIH Grant Applications - FORMS-E Series (PDF - 2 MB)
  • Preview of FORMS-E Grant Application Form Changes (PDF – 4 MB)

A.5. Yes. Multiple PIs are allowed.

A.6. Yes.

A.7. Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply. Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

A.8. Please refer to Section V (Application Review Information) in the funding opportunity announcement (https://grants.nih.gov/grants/guide/rfa-files/RFA-HL-19-014.html). Review criteria are specified in that section. 

NIH’s Office of Extramural Research webpage, https://grants.nih.gov/policy/peer/index.htm, provides a variety of resources on policies and practices of peer review.

A.9. The NIH recognizes the importance of training and cultivating future generations of researchers.  Early stage investigators (ESIs) are encouraged to review policy and resources at the https://grants.nih.gov/policy/early-investigators/index.htm. ESI clinicians are encouraged to consider applying to HL-19-015, Physician-Scientist (PS) Research Award for Early Stage Investigators (ESIs) (R01 - Clinical Trial Optional)

A.10. At this time, the Office of Extramural Review plans to review STIMULATE applications via a special emphasis panel.

A.11. This is a critical objective. Meritorious applicants must provide a compelling case that they would  generate research and insights that would illuminate the “how and why” these multi-level strategies work. Such insights are to be garnered based on the objective that an implementation strategy be developed and detested to demonstrate sustainable approach(es) beyond a grant funding period, and, that approaches could be replicable elsewhere. As such, a blend of qualitative and quantitative assessment which account for community needs and contexts, which account for cultural and organizational are anticipated. Data on mechanisms of action, moderators, and mediators of dissemination and implementation strategies will greatly aid decision-making on which strategies work for different settings, community priorities, and populations. 

A.12.

• Patient(s), family(ies)
• Primary care team
• Healthcare specialists, pharmacists
• Community-based organizations
• Population at large

A.13. Applications that propose:   

a. Clinical Trials.

b. To use out-dated evidence-based practice guidelines (as applicable) 

c. To test new intervention(s) (i.e., that have not been proven to be effective) 

d. To test the implementation strategy within only one social ecologic level

A.14. At the time of submission of your proposal, it is incumbent on the applicant to select  appropriate guideline and demonstrate relevancy. For purposes of determination of responsiveness, if a particular organization’s guideline is selected by the applicant it must be the most recent version of that organization’s guideline. 

A.15. Projects are anticipated to use validated organizational and other outcome measures which assess readiness for and impact of the implemented intervention(s) or guideline (e.g., acceptability, adoption, appropriateness, affordability, costs, feasibility, fidelity, penetrance, and sustainability in the selected context beyond the project.)

A.16. Yes.

A.17. If a pragmatic study pragmatic design is used to test the effectiveness of an intervention in broad routine clinical practice, and all four of the questions below would be yes, then it would not be responsive to STIMULATE:

a. Does the study involve human participants?

b. Are the participants prospectively assigned to an intervention?

c. Is the study designed to evaluate the effect of the intervention on the participants?

d. Is the effect being evaluated a health-related biomedical or behavioral outcome?

A.18. In the grant application, the applicant need to present a compelling justification as to how the intervention has already been proven to be effective. The FOA does not require a specific study design used to determine the effective intervention.

A.19. More than one proven-effective intervention can be studied.

A.20. The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. NHLBI anticipates funding up to 5 new awards in years FY2019, FY2020, FY2021.

A.21. You may wish to consider the following recurring FOAs:

• PAR-18-007 Dissemination and Implementation Research in Health (R01 Clinical Trial Optional) (recommended as first FOA for consideration)
• Physician-Scientist (PS) Research Award for Early Stage Investigators (ESIs) (R01 - Clinical Trial Optional)
• Single-Site Clinical Trial PAR-18-406 Single-Site Investigator-Initiated Clinical Trials (R61/R33 Clinical Trial Required)
• Multiple Site Clinical Trial PAR-18-407 Clinical Coordinating Center for Multi-Site Investigator-Initiated Clinical Trials (Collaborative UG3/UH3 Clinical Trial Required)