The intent of the FY22 TBIPHRP CTA is to support the rapid implementation of clinical trials with the potential to have a significant impact on psychological health conditions and/or TBI through clinical applications, including healthcare products, technologies, and/or practice guidelines.
research can be aligned with TBI, psychological health, or both.Clinical trials may be designed to evaluate promising new products, pharmacologic agents (drugs or biologics), devices, therapies, clinical guidance, behavioral interventions, emerging approaches and technologies, and/or new indications for products currently FDA-approved or - cleared.Proposed projects may range from small proof-of-concept trials (e.g., pilot, first-in-human, phase 0) to demonstrate feasibility or inform the design of more advanced trials through large- scale trials to determine efficacy in relevant patient populations.
Proposals/applications proposing comparative effectiveness, implementation science, healthcare services research as the primary research objective should consider the FY22 TBIPHRP Patient-CenteredResearch Award (Funding Opportunity Number:
W81XWH-22-TBIPHRP-PCRA).A clinical trial is defined as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include a placebo or another control) to evaluate the effects of the interventions on biomedical or behavioral health-related outcomes.
Funded trials are required to post a copy of the Institutional Review Board (IRB)- approved informed consent form used to enroll subjects on a publicly available federal website in accordance with federal requirements described in Code of Federal Regulations, Title 32,Part 219 (32 CFR 219).
For more information, see the Human Subject Resource Document.Clinical research is defined as:
(1) Patient-oriented research.
Research conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects.
Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual.
Patient-oriented research includes:
(a) mechanisms of human disease, (b) therapeutic interventions, (c) clinical trials, and (d) development of new technologies; (2) epidemiologic and behavioral studies; and (3) outcomes research and health services research.
Studies that meet the requirements for IRB review Exemption 4 are not considered CDMRP-defined clinical research.
IRB Exemption 4 refers to research involving the collection or study of existing de- identified specimens or data, if these sources are publicly available.
Studies seeking to conduct clinical research only but not a clinical trial do not meet the intent of the award mechanism and will not be funded.This BAA may not be used to support studies requiring an exception from informed consent (EFIC).Funding from this award mechanism must support a clinical trial and cannot be used for animal studies.
Principal Investigators (PIs) seeking funding for a preclinical research project or a clinical research project that does not involve a clinical trial should consider one of applicable FY22 TBIPHRP program announcements or the other BAA being offered.If the proposed clinical trial involves the use of a drug that has not been approved by the FDA for the proposed investigational use, then an Investigational New Drug (IND) application to the FDA that meets all requirements under 21 CFR 312 may be required.
It is the responsibility of the applicant to provide evidence from the IRB of record or the FDA if an IND application is not required.
If an IND application is required, evidence that an IND application has been submitted or IND authorization without clinical hold status has been secured must be included in the FY22 TBIPHRP CTA proposal/application.
The IND application should be specific for the product (i.e., the product should not represent a derivative or alternate version of the investigational agent described in the IND application) and indication to be tested in the proposed clinical trial.
For more information on IND applications, the FDA has provided guidance at https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/ap provalapplications/investigationalnewdrugindapplication/default.htm.If the investigational product is a device, then an Investigational Device Exemption (IDE) application to the FDA that meets all requirements under 21 CFR 812 may be required.
It is the responsibility of the applicant to provide evidence if an IDE application is not required or thedevice qualifies for an abbreviated IDE application.
If an IDE application is required, evidencethat an IDE application submission or IDE authorization without clinical hold status has been secured must be included in the FY22 TBIPHRP CTA proposal/application.
The IDE application should be specific for the device (i.e., should not represent a derivative or modified version of the device described in the IDE application) and indication to be tested in the proposed clinical trial.If the proposed clinical trial of an investigational product will be conducted at international sites, evidence that an application to the relevant national regulatory agency of the host country(ies) has been submitted or approved must be included in the FY22 TBIPHRP CTA proposal/application.The following are important aspects of the FY22 TBIPHRP CTA:• The proposal/application must include Community-Based Participatory Research (CBPR) approaches in the development and execution of the clinical trial.
CBPR approaches should be documented in Attachments 12 and 1 3. • The proposed clinical trial is expected to begin no later than 6 months after the award date.• The proposed intervention(s) to be tested should offer significant potential impact for individuals affected by psychological health conditions and/or TBI.• Inclusion of preliminary data relevant to the proposed clinical trial is required.• The proposed clinical trial must be based on sound scientific rationale that is established through logical reasoning and critical review and analysis of the relevant literature.• The proposal/application should describe the planned indication for the product label, if appropriate, and include an outline of the product development plan required to support that indication.• The proposal/application should demonstrate the availability of and access to a suitable patient population that will support a meaningful outcome for the study.
The proposal/application should include a discussion of how accrual goals will be achieved and how standards of care may impact the study population.• The proposal/application should demonstrate documented availability of and access to the drug/compound, device, and/or other materials needed, as appropriate, for the proposed duration of the study.
The quality and stability of the product should be documented and commensurate with current FDA manufacturing standards applicable to the type and phase of product being developed (i.e., Quality System Regulation, Good Manufacturing Practice [GMP] guidelines).• The proposal/application should reflect the study team’s experience interacting with the FDA, including previous FDA submissions, if applicable.• The proposed clinical trial design should include clearly defined objectives and appropriate endpoints/outcome measures, and comply with current Good Clinical Practice (GCP) guidelines.• The proposal/application should include a clearly articulated statistical analysis plan, appropriate statistical expertise on the research team, and a power analysis reflecting sample size projections that will answer the objectives of the study.• The proposal/application should include a clearly articulated data management plan and use of an appropriate database to safeguard and maintain the integrity of the data.
If FDA- regulated, the trial must use a 21 CFR 11-compliant database and appropriate data standards.• The proposal/application should include a clearly articulated safety management plan outlining how safety pharmacovigilance will be conducted, as applicable.• The proposal/application should include a clearly articulated clinical monitoring plan outlining how the study will be monitored for GCP compliance.• The proposal/application should include a study coordinator(s) who will guide the clinical protocol through the local IRB of record and other federal agency regulatory approval processes, coordinate activities from all sites participating in the trial, and coordinate participant accrual.• The proposal/application should include a Transition Plan (including potential funding and resources) as Attachment 10 showing how the product will progress to the next clinical trial phase and/or delivery to the market after the successful completion of the FY22 TBIPHRP CTA.• The proposal/application should clearly demonstrate strong institutional support and, if applicable, a commitment to serve as the FDA regulatory sponsor, ensuring all sponsor responsibilities described in 21 CFR 312, Subpart D, are fulfilled.• Funded trials are required to post a copy of the informed consent form used to enroll subjects on a publicly available federal website in accordance with federal requirements described in 32 CFR 21 9. Research Scope:
The following are general descriptions, although not all-inclusive, of the scope of research projects that would be appropriate to propose under the current BAA.
Selection of the appropriate FY22 TBIPHRP CTA Research Level is the responsibility of the applicant:• Research Level 1:
Research Level 1 is intended to support proof-of-principle pilot studies, phase 0/small phase 1 trials, correlative studies related to an intervention, and other innovative, exploratory clinical trials.
The period of performance of Research Level 1 awards will be 3 years.
The anticipated direct cost budgeted for an FY22 TBIPHRP CTA Research Level 1 award will not exceed $500,00 0. ○ Early-Career Investigator Partnering Option:
The FY22 TBIPHRP encourages proposals/applications that include meaningful and productive collaborations between investigators.
The FY22 TBIPHRP CTA (Research Level 1 only) includes an Early- Career Investigator Partnering Option that is structured to accommodate two PIs, one of whom is an Early-Career Investigator.
The combined Initiating and Partnering organizations’ budgeted direct costs approved by the government will not exceed$500,00 0. The PIs may have experience in similar or disparate scientific disciplines, but each PI is expected to bring distinct contributions to the proposal/application.
One PI will be identified as the Initiating PI and will be responsible for the majority of the administrative tasks associated with proposal/application submission.
The other investigator will be the Partnering PI.
One of the named PIs on an application submitted under the Early-Career Investigator Partner Option must be an Early- Career Investigator who may be either the Initiating or Partnering PI.
Both PIs should contribute significantly to the development of the proposed research project, including the Project Narrative, Statement of Work (SOW), and other required components.
The proposal/application is expected to describe how the PIs’ unique experience/expertise combined as a partnership will better address the research question, how the unique experience/expertise that each individual brings to the proposal/application is critical for the research strategy and completion of the SOW, and why the work should be done together rather than through separate efforts.
If recommended for funding, each PI will be named to an individual award within the recipient organization.
For individual DOD FY22 TBIPHRP submission requirements for the Initiating and Partnering PI, refer to Section II.D.2, Content and Form of the Proposal/Application Submission.• Research Level 2:
Research Level 2 is intended to support phase 1 and more advanced clinical trials for promising interventions.
The period of performance of Research Level 2 awards will be 4 years.
The anticipated direct costs budgeted for an FY22 TBIPHRP CTA Research Level 2 award will not exceed $2M.• Research Level 3:
Research Level 3 is intended to support larger-scale clinical trials that demonstrate efficacy in relevant patient populations.
The period of performance of Research Level 3 awards will be 4 years.
The anticipated direct costs budgeted for an FY22 TBIPHRP CTA Research Level 3 award will not exceed $4M.Funded studies are required to register the study in the National Institutes of Health (NIH) clinical trials registry, www.clinicaltrials.gov, prior to initiation of the study.
Refer to the General Submission Instructions, Appendix 1, Section D, for further details.Refer to Section II.D.6, Funding Restrictions, for detailed funding information.Awards will be made no later than September 30, 202 3. For additional information refer to .F.1, Federal Award Notices.