Research Proposal Questions

1. Should I apply for the RFA-AT-22-005 or RFA-AT-22-004 funding opportunity?

Title HEAL Initiative: Sickle Cell Disease Pain Management Trials Utilizing the Pain Management Effectiveness Research Network Cooperative Agreement (UG3/UH3, Clinical Trial Required) RFA-AT-22-005 HEAL Initiative: Pragmatic and Implementation Studies for the Management of Sickle Cell Disease Pain (UG3/UH3, Clinical Trials Optional) RFA-AT-22-004

Appropriate types of studies

  • Effectiveness research trials.
  • Studies need to randomize participants individually, collect in-person measures for research purposes (such as specified clinical laboratory tests, observed studies of mobility or other measures of function), or deliver an intervention in a standardized fashion.
  • Embedded pragmatic trials or implementation trials.
  • Interventions under study must be embedded into health care delivery systems in real-world settings.
  • Pragmatic trial models collect most data needed for analysis of the research question as part of clinical care, and it is expected that these data will be obtained primarily through the electronic records of the health care system.
  • Implementation trials have implementation-focused main outcomes that are most likely at a system or individual provider level. Patient-level implementation outcomes may be possible if they are not focused on health but on use of the targeted intervention.

Infrastructure

  • Clinical trials will be conducted within the infrastructure of the NIH HEAL ERN.
  • Awardees will work with the National Center for Advancing Translational Sciences (NCATS) Trial Innovation Network (TIN, trialinnovationnetwork.org) for clinical, biostatistical, and recruitment support.
  • Clinical trials will be conducted within the infrastructure of the NIH HEAL Initiative Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing (PRISM) Program Coordinating Center.
  • Awardees will work with the Health Care Systems (HCS) Research Collaboratory Coordinating Center (CCC, rethinkingclinicaltrials.org) to facilitate further planning and refinement of the proposed trial in partnerships with health care delivery systems.

2. Does my study design meet your criteria as an effectiveness trial?

Refer to the definition of effectiveness research in the FOA and design your study in the context of this definition. You should ensure that your control arm is justified.

3. Should the effectiveness research clinical trials in the UG3/UH3 enroll patients at more than one institution/center?

To enhance the generalizability of study results, applications must have participation of three or more clinical sites in the study. This will also increase the pool of possible participants, accelerate recruitment, and increase sample diversity and representation.

4. Does the NIH HEAL Pain Management Effectiveness Research Network (HEAL ERN) already exist?

Yes. The NIH HEAL Pain Management Effectiveness Research Network (HEAL ERN) is composed of the existing NCATS Clinical and Translational Science Award (CTSA) Program TIN, including the CTSA Program hubs and additional clinical sites identified by the awardees. As the funded trials progress, the TIN will seek additional clinical sites from the currently funded CTSA Program hubs if needed to meet recruitment goals of the individual trials. Applicants also should check the NIH HEAL Initiative website (heal.nih.gov/funding/awarded) to ensure their proposed trial does not overlap significantly with currently funded NIH HEAL Initiative studies.

5. Should I contact the Trial Innovation Network (TIN) centers before I apply?

You do not need to contact the TIN awardees regarding their level of interest in your application or its content. You do not need to set up an agreement with the TIN centers prior to submitting your application. The NCATS TIN centers will serve as clinical, data, and biostatistical coordinating and recruitment centers and, if needed, will provide additional recruitment sites for the NIH HEAL Initiative Pain Management ERN clinical trials.

6. What type of resources will the TIN provide for my trial?

The TIN will provide data coordination services, clinical coordination services, single Institutional Review Board (IRB) functions, biostatistical support, and recruitment and retention support for awarded studies. Those submitting applications in response to RFA-AT-22-005 do not need to request these resources or include costs for these resources in their budgets. Please refer to RFA-AT-22-005 for information regarding resources provided to all NIH HEAL ERN awardees.

7. How do I find CTSA sites for my study?

A list of TIN points of contact at the individual CTSA institutions can be found at trialinnovationnetwork.org/liaison-teams/?key-element=1601. They will help you find a local principal investigator, if available, for your SCD pain trial application at the clinical sites.

8. Should the budget include the level of effort for the principal investigator and study coordinator at each CTSA site, or will each CTSA site get a per-patient reimbursement?

Generally, budgets for the individual sites are based on per-patient reimbursement. However, the final budget for each site is established through negotiations between the principal investigator’s institution and the participating sites.

9. Does the TIN help with recruitment?

Yes, the TIN will help each individual trial with recruitment. The TIN will assist principal investigators with the development of a recruitment plan during the UG3 planning phase and monitor recruitment and retention carefully throughout the UH3 trial implementation phase.

10. What information do I need from the clinical sites that agree to participate in my study?

Sites within the CTSA consortium, outside the consortium, or in other, nonconsortium networks can be included in the trial. Per the FOA, applicants should state how many sites will be needed and survey the potential clinical sites to ensure that study recruitment targets can be met. Include any survey results in the application. The survey questions will depend on the nature of the trial and the protocol-specified screening procedures and might include availability of needed resources, number of eligible patients seen monthly, and projected enrollment. Include a description of how additional clinical sites not named in the application will be selected to implement the trial. The plan also should include a contingency plan for adding new sites if enrollment falls below targets or if enrollment of new participants is discontinued at sites that do not meet individual goals.

11. Where can I find more information about the TIN central IRBs?

Please see trialinnovationnetwork.org/elements/central-irb for more information about the TIN central IRBs and the process of central IRB review.

12. Where can I find more information about the Master Clinical Trial Agreement?

Please see trialinnovationnetwork.org/elements/fdp-ctsa-trial-innovation-standard-agreement for more information about the Master Clinical Trial Agreement that will be used to pay sites for each enrolled participant.

13. Are dosing and efficacy studies responsive to the FOA?

Yes, provided the trial does not need an Investigational New Drug (IND) for testing. For example: If you are testing a drug that is already approved at one dose for a particular pain condition, you could propose a dosing trial if the study’s maximum dose does not exceed the dose approved for use.

14. Can a drug approved by the U.S. Food and Drug Administration (FDA) for other purposes be tested for SCD pain in a trial under this FOA?

This FOA will not support studies of interventions or investigational products that require an IND application. The principal investigator is responsible for acquiring study drugs. The principal investigator is responsible for ensuring that the drug is available and approved for the study. The investigator team is responsible for contacting the FDA to determine if an IND is required. We encourage principal investigators to contact the FDA soon if they have a question.

15. We are using two approved devices in a combined sensor. Each device has FDA approval. Does this satisfy FDA requirements?

If you are comparing two different FDA-approved (or exempt) devices, the grant application is responsive to the FOA. However, you should contact the FDA to ask if the combined sensor requires approval or is exempt.

16. What activities should be carried out in the UG3 phase?

During the UG3 or planning phase, investigators will work with the TIN centers to develop the following types of study documents:

  • A final clinical protocol developed in cooperation with the CCC, data coordination center, and biostatistical core, following International Conference on Harmonization E6 Good Clinical Practice consolidated guidance, prepared using the standard interventional protocol template provided by the NIH HEAL ERN.
  • A manual of procedures developed in collaboration with the NIH HEAL ERN data coordination center and study site investigators, including a detailed description of study procedures and process details.
  • Staff training and recruitment plans in collaboration with the CCC and the Recruitment Innovation Center.
  • A final statistical analysis plan, which will be developed in collaboration with the NIH HEAL ERN biostatistical core.
  • The electronic data capture system, which will be developed and maintained by the TIN data coordination center as the central NIH HEAL ERN data capture system.
  • Consent forms or permission and assent forms (if applicable), which will be developed with assistance from the NIH HEAL ERN CCC and data coordination center.
  • Safety standards and regulatory processes.
  • Plans for biospecimen collection (if appropriate) and storage protocols.
  • A plan for the administration of study agents (if applicable). 
  • Detailed description of roles and responsibilities of study personnel developed in conjunction with the NIH HEAL ERN CCC.
  • The final quality management and data management plans developed with the NIH HEAL ERN CCC and data coordination center.
  • Strategies if enrollment or retention do not meet specified metrics.

17. Can NIH provide additional guidance on including milestones in the application?

Milestones are intermediate steps toward the completion of concrete goals and must include clear and quantitative criteria for success. Yearly quantitative milestones are required to provide clear indicators of a project’s continued success or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of noncompeting award years. The application must include clearly specified, well-defined milestones; quantitative go/no-go decision points; and timelines for assessing progress. Applicants must provide a timeline and detailed annual quantitative milestones spanning the funding period. If selected for funding, applicants will work with NIH staff to develop more granular quarterly milestones for each year of funding.

18. What are some examples of quantitative milestones?

Examples of quantitative milestones include but are not limited to enrollment numbers, completion of enrolled patient follow-up, and publication of results. Note that prior to an award, NIH staff and the applicants will finalize an agreed upon set of milestones that will be included in the notice of grant award.