DoD Prostate Cancer, Translational Science Award

The FY23 PCRP Translational Science Award mechanism supports advanced translational research that will foster transformation of promising ideas in prostate cancer into clinical applications, ultimately providing a solution to one or more of the FY23 PCRP Overarching Challenges. Translational research may be defined as an integration of basic science and clinical observations. Observations that drive a research idea may originate from a laboratory discovery, population-based studies, or a clinician’s firsthand knowledge of patient care. Principal Investigators (PIs) should not view translational research as a one-way continuum from bench to bedside but can include a reciprocal flow of ideas and information between basic science and clinical science (bench to bedside and/or bedside to bench).

New for FY23! The intent of the Translational Science Award is expanded for FY23 to include support for implementation science studies that will bridge the gap between clinical research and real-world implementation. Even after information, tools, and interventions have been successfully evaluated in their intended populations, the development of knowledge to support their broader dissemination and implementation has often remained outside the scope, limiting the impact on the intended patient population(s). As part of the TSA, implementation science studies are expected to bridge the gap between research, practice, and policy by building a knowledge base on how interventions, clinical practices/guidelines, tools, and policies can be deployed to targeted populations at the appropriate time and point of need. An implementation science study is defined as the scientific study of the use of strategies to adopt and integrate evidence-based health interventions into clinical and community settings in order to improve patient outcomes and benefit population health.

This mechanism is intended to fund a broad range of translational studies including, but not limited to, the following:

• Advanced preclinical studies aimed at translating results from animal studies to applications with human samples/cohorts (the Translational Science Award is not intended to support initial mechanistic studies of a new target)

• Late-stage preclinical work leading to/preparing for a clinical trial, e.g., an Investigational New Drug application submission

• Correlative studies that are associated with an open/ongoing or completed clinical trial, e.g., projects that utilize biospecimens from clinical trials to improve clinical management of prostate cancer and/or define new areas of research

• Projects that develop endpoints for clinical trials

• Analysis of existing data, resources, or clinical tools to inform clinical practice and/or maximize patient-relevant outcomes

• Small-scale clinical trials with implementation science focus

• Comparative effectiveness research establishing the benefits and harms of emerging or standard-of-care interventions and strategies to prevent, diagnose, treat, and monitor health conditions in real-world settings

• Development and evaluation of strategies to overcome barriers to the adoption, adaptation, integration, scale-up, and sustainability of evidence-based interventions, tools, policies, and guidelines.

Preliminary data to support the scientific rationale and feasibility of the research approaches are required. The inclusion of additional preliminary data to support the clinical relevance of the idea is strongly encouraged.

Applications should carefully consider study sample size to ensure that the study results will be able to support valid conclusions and further translation toward clinical application. It is the applicant’s responsibility to demonstrate access to the required resources or populations necessary for the study and to provide sufficient evidence that the sample size is appropriate to meet the objectives of the study. Additional guidance regarding statistical rigor for preclinical studies is provided at the end of Translational Science Award Information section.

As the ultimate goal of translational research is to move a concept or observation forward into clinical application and/or the patient community, applications must include a detailed research transition plan that articulates the pathway to moving the project’s findings to the next phase of development after successful completion of the award. Research transition plans are encouraged to consider not just the pathway to developing tangible products (e.g., drugs or diagnostic assays) into clinical testing, but also the implementation of research findings and other evidence-based practices into clinical practice and patient communities.

Partnering PI Option: The FY23 PCRP Translational Science Award encourages applications that include meaningful and productive collaborations between investigators. The PIs may have expertise in similar or disparate scientific disciplines, but each PI is expected to bring distinct contributions to the application; collaborations between basic science and clinical researchers are highly encouraged. The Partnering PI Option is structured to accommodate two PIs. One PI will be identified as the Initiating PI and will be responsible for the majority of the administrative tasks associated with application submission. The other PI will be identified as a 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. If recommended for funding, each PI will be named to an individual award within the recipient organization. For individual submission requirements for the Initiating and Partnering PI, refer to Section II.D.2, Content and Form of the Application Submission.

A congressionally mandated Metastatic Cancer Task Force was formed with the purpose of identifying ways to help accelerate clinical and translational research aimed at extending the lives of advanced state and recurrent patients. As a member of the Metastatic Cancer Task Force, CDMRP encourages applicants to review the recommendations (https://health.mil/Reference-Center/Congressional-Testimonies/2018/05/03/Metastatic-Cancer-Research) and submit research ideas to address these recommendations provided they are within the limitations of this funding opportunity and fit within the FY23 PCRP priorities.

Collaborations between researchers at military or Veteran institutions and non-military institutions are strongly encouraged. These relationships can leverage knowledge, infrastructure, and access to unique clinical populations that the partners bring to the research effort, ultimately advancing cancer research that is of significance to the Warfighter, military families, and the American public.

The types of awards made under the program announcement will be assistance agreements. An assistance agreement is appropriate when the federal government transfers a “thing of value” to a “state, local government,” or “other recipient” to carry out a public purpose of support or stimulation authorized by a law of the United States instead of acquiring property or service for the direct benefit and use of the U.S. government. An assistance agreement can take the form of a grant or cooperative agreement. The level of involvement on the part of the Department of Defense (DOD) during project performance is the key factor in determining whether to award a grant or cooperative agreement. If “no substantial involvement” on the part of the funding agency is anticipated, a grant award will be made (31 USC 6304). Conversely, if substantial involvement on the part of the funding agency is anticipated, a cooperative agreement will be made (31 USC 6305), and the award will identify the specific substantial involvement. Substantial involvement may include, but is not limited to, collaboration, participation, or intervention in the research to be performed under the award. The award type, along with the start date, will be determined during the negotiation process.

The anticipated direct costs budgeted for the entire period of performance for an FY23 PCRP Translational Science Award should not exceed $900,000. Refer to Section II.D.5, Funding Restrictions, for detailed funding information.

Awards will be made no later than September 30, 2024. For additional information refer to Section II.F.1, Federal Award Notices.

The CDMRP expects to allot approximately $7.2M to fund approximately five Translational Science Award applications. Funding of applications received is contingent upon the availability of federal funds for this program as well as the number of applications received, the quality and merit of the applications as evaluated by scientific and programmatic review, and the requirements of the government. Funds to be obligated on any award resulting from this funding opportunity will be available for use for a limited time period based on the fiscal year of the funds. It is anticipated that awards made from this FY23 funding opportunity will be funded with FY23 funds, which will expire for use on September 30, 2029.

Research Involving Human Data, Human Anatomical Substances, Human Subjects, or Human Cadavers: All DOD-funded research involving new and ongoing research with human data, human anatomical substances, human subjects, or human cadavers must be reviewed and approved by the USAMRDC Office of Human and Animal Research Oversight (OHARO), Office of Human Research Oversight (OHRO), prior to research implementation. This administrative review requirement is in addition to the local Institutional Review Board (IRB) or Ethics Committee (EC) review. Local IRB/EC approval at the time of application submission is not required; however, local IRB/EC approval is necessary prior to OHRO review. Allow up to 3 months to complete the OHRO regulatory review and approval process following submission of all required and complete documents to the OHRO. Refer to the General Application Instructions, Appendix 1, and the OHARO web page https://mrdc.health.mil/index.cfm/collaborate/research_protections/hrpo for additional information.

As of January 20, 2020, U.S. institutions engaged in non-exempt cooperative research must rely on a single IRB to review and approve the portion of the research conducted at domestic sites in accordance with Code of Federal Regulations, Title 45, Part 46.114(b) (45 CFR 46.114[b]). If the proposed, non-exempt research involves more than one U.S.-based institution, a written plan for single IRB review arrangements must be provided at the time of application submission or award negotiation. The lead institution responsible for developing the master protocol and master consent form should be identified and should be the single point of contact for regulatory submissions and requirements.

New for FY23: The Clinical Trial Option allows for studies proposing small-scale clinical trials that focus on implementation science. 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.

Studies that do not seek to measure safety, effectiveness, and/or efficacy outcome(s) of an intervention are not considered clinical trials.

Clinical research encompasses research with patient samples, data, and interaction with patients that may or may not be considered a clinical trial. For the purposes of this funding opportunity, research that meets the definition of a clinical trial is distinct from clinical research. Clinical research is observational in nature and includes: (1) Research that does not seek to evaluate the effects of interventions. Research conducted with human subjects (or on material of human origin such as data, tissues, specimens, and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects, but does not seek to assess the effects of an intervention, qualifies as clinical research. Patient-oriented research may include but is not limited to: (a) mechanisms of human disease, (b) diagnostic or detection studies (e.g., biomarker or imaging), (c) health disparity studies, and (d) development of new technologies. (2) Epidemiologic and behavioral studies that do not seek to study the safety, effectiveness, and/or efficacy outcomes of an intervention. (3) Outcomes research and health services research that do not fit under the definition of clinical trial. Excluded from the definition of clinical research are in vitro studies that utilize human tissues that cannot be linked to a living individual. Note: Studies that meet the requirements for exemption under §46.104(d)(4) of the Common Rule are not considered clinical research as defined by CDMRP. Exemption category 4 refers to secondary research for which consent is not required.

Use of DOD or Department of Veterans Affairs (VA) Resources: If the proposed research involves access to active-duty military and/or VA patient populations and/or DOD or VA resources or databases, the application must describe the access at the time of submission and include a plan for maintaining access as needed throughout the proposed research. Refer to Section II.D.2.b.ii, Full Application Submission Components, for detailed information. Refer to the General Application Instructions, Appendix 1, for additional information.

Research Involving Animals: All research funded by the FY23 Translational Research Award involving new and ongoing research with animals must be reviewed and approved by the USAMRDC OHARO Animal Care and Use Review Office (ACURO), in addition to the local Institutional Animal Care and Use Committee (IACUC) of record. IACUC approval at the time of submission is not required. Allow at least 3 to 4 months for ACURO regulatory review and approval processes for animal studies. Refer to the General Application Instructions, Appendix 1, for additional information.

All projects should adhere to a core set of standards for rigorous study design and reporting to maximize the reproducibility and translational potential of preclinical research. The standards are described in SC Landis et al., 2012, A call for transparent reporting to optimize the predictive value of preclinical research, Nature 490:187-191 (www.nature.com/nature/journal/v490/n7419/full/nature11556.html). While these standards are written for preclinical studies, the basic principles of randomization, blinding, sample-size estimation, and data handling derive from well-established best practices in clinical studies. Projects that include research on animal models are required to submit Attachment 10, Animal Research Plan, as part of the application package to describe how these standards will be addressed. Applicants should consult the ARRIVE guidelines 2.0 (Animal Research: Reporting In Vivo Experiments) to ensure relevant aspects of rigorous animal research are adequately planned for and, ultimately, reported. The ARRIVE guidelines 2.0 can be found at https://arriveguidelines.org/arrive-guidelines.