Ethical Issues in Translational Science Research (R01 Clinical Trial Optional)

Ethical Issues in Translational Science Research (R01 Clinical Trial Optional) is sponsored by National Institutes of Health (NIH). This funding opportunity supports research to address ethical issues in translational science research. Collaboration among bioethicists, legal scholars, social scientists, and translational research scientists is encouraged.

Expired RFA-TR-20-001: Ethical Issues in Translational Science Research (R01 Clinical Trial Optional) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Center for Advancing Translational Sciences ( NCATS ) Funding Opportunity Title Ethical Issues in Translational Science Research (R01 Clinical Trial Optional) R01 Research Project Grant October 28, 2021 - Reminder: FORMS-G Grant Application Forms & Instructions Must be Used for Due Dates On or After January 25, 2022 - New Grant Application Instructions Now Available.

See Notice NOT-OD-22-018 . September 13, 2021 - Updates to the Non-Discrimination Legal Requirements for NIH Recipients. See Notice August 5, 2021 - New NIH "FORMS-G" Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2022.

See Notice NOT-OD-21-169 . August 5, 2021 - Update: Notification of Upcoming Change in Federal-wide Unique Entity Identifier Requirements. See Notice NOT-OD-21-170 April 20, 2021 - Expanding Requirement for eRA Commons IDs to All Senior/Key Personnel.

See Notice NOT-OD-21-109 October 5, 2021 - Notice of Change to Key Dates for RFA-TR-20-001, Ethical Issues in Translational Science (R01 Clinical Trial Optional) . See Notice NOT-TR-22-001 March 10, 2020 - Reminder: FORMS-F Grant Application Forms & Instructions Must be Used for Due Dates On or After May 25, 2020- New Grant Application Instructions Now Available. See Notice NOT-OD-20-077 .

July 26, 2019 - Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-128 August 23, 2019 - Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-137 Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity See Section III.

3. Additional Information on Eligibility . Catalog of Federal Domestic Assistance (CFDA) Number(s) Funding Opportunity Purpose The purpose of this Funding Opportunity Announcement is to support research to address ethical issues in translational science research.

Collaboration between bioethicists, legal scholars, social scientists, and translational research scientists is encouraged. The focus is to develop knowledge to inform the ethical development, modification, or application of novel findings, technologies, and approaches to improve human health, including their impact on individuals, families, communities, and society.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) February 6, 2020, October 6, 2020, and October 6, 2021, February 8, 2022 All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date. No late applications will be accepted for this Funding Opportunity Announcement.

AIDS Application Due Date(s) June 2020, February 2021, February 2022, June 2022 August 2020, May 2021, May 2022, October 2022 September 2020, July 2021, July 2022, December 2022 New Date February 9, 2022 per issuance of NOT-TR-22-001 Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide ,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV . When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review. Part 1. Overview Information Part 2.

Full Text of Announcement Section I. Funding Opportunity Description Section II. Award Information Section III.

Eligibility Information Section IV. Application and Submission Information Section V. Application Review Information Section VI.

Award Administration Information Section VII. Agency Contacts Section VIII. Other Information Part 2.

Full Text of Announcement Section I. Funding Opportunity Description The National Center for Advancing Translational Sciences mission is to catalyze the generation of innovative methods and technologies that will enhance the development, testing and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions.

Translation is the process of turning observations in the laboratory, clinic and community into interventions that improve the health of individuals and the public from diagnostics and therapeutics to medical procedures and behavioral changes.

NCATS focuses on research that impacts systemic change across the entire translational spectrum from basic research, pre-clinical research, clinical research, clinical implementation, and public health. NCATS encourages innovative approaches to systemic change and is disease and science domain agnostic.

Novel discoveries, methods, and technologies frequently come with questions and concerns about their ethical development, application, and use as well as their broader impact on societal norms. Potential for harms as well as improvements of health of individuals, communities, and society can arise related to the research and its application.

Engagement of the public, communities, a broad range of researchers, companies, and governments may be needed to inform research direction and choices. While many ethical issues are common across biomedical research, development and application of novel discoveries, methods, or technologies to improve health can raise unique ethical issues.

The ethical issues in translational science research may also encompass and cross multiple science domains. Translational researchers and bioethics researchers may not have interacted as they often work in distinct institutional and professional settings. Significant effort may be required to form research teams that communicate effectively and work collaboratively to address ethics research to advance translational projects.

Additional expertise may also be required adding to challenges of this type of research. To address ethical issues in translation, this Funding Opportunity (FOA) will support Research Project Grant (R01) applications that propose to study the ethical issues in translational science research, including the legal and societal implications of such issues.

Applications can propose empiric data generating quantitative and qualitative approaches, legal, economic, and normative analyses, and other types of analytic and conceptual research methodologies, including those that involve direct engagement of diverse stakeholders.

Applications may address research on ethical issues at any stage of the translational research spectrum, including basic to pre-clinical, pre-clinical to clinical research, clinical implementation, and public health. This FOA also seeks opportunities to consider the integration of research on ethical issues with research in broad areas of translational research.

Specific Areas of Research Interest Examples of areas where ethics research could inform translational research include, but are not limited to: Ethical issues associated with general and personalized synthetic biology; integrated and complex organoids; tissue chip platforms; iPS cells; and human-animal chimeras Studies that explore the ethical and societal challenges of medical use of machine learning, artificial intelligence, machine intelligence, and algorithmic medicine Ethical issues associated with data collection, de-identification, ownership, licensing, data sharing, data access, data integration, data mining, data repurposing from perspective of data providers, data users, and society Ethical implications of development and use of gene editing, genomic editing, gene drive for discovery, therapeutic, preventive, enhancement, and societal purposes Individual, community, and societal impact of development, implementation, and use of personalized and precision research and medicine, including but not limited to, issues of access, equity, autonomy, or justice Ethical challenges of innovative research project designs, collaborations, business models for conduct and implementation of translational research among diverse stakeholders Ethical issues in translational research across privacy/confidentiality/transparency/security spectrum impacting individuals, communities, entrepreneurs, industry, society; gaps and needs related to current regulatory models Ethical issues in translational research in development and implementation of behavior change/modification at individual, community, and society level IMPORTANT NOTICE: All applicants are strongly encouraged to contact the Scientific/Research Staff listed in Section VI to discuss potential research projects for alignment with the FOA goals prior to submission of an application.

Non-Responsive and Incomplete Projects Applications considered non-responsive to this FOA will not proceed to peer review. Applications that do not follow the Submission Requirements or include required materials will be considered incomplete and will not be reviewed.

The following types of applications will not be considered responsive to this FOA: Projects that do not address ethical issues in translational science research Projects that do not propose to develop data or knowledge to inform the ethical development, modification, or application of novel findings, technologies, and approaches to improve human health Projects that do not include expertise in bioethics and translational science See Section VIII.

Other Information for award authorities and regulations. Section II. Award Information Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA. Optional: Accepting applications that either propose or do not propose clinical trial(s) Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards NCATS intends to commit total costs of $500,000 in FY 2020, $1,000,000 in FY 2021, and $1,500,000 in FY2022. NCATS expects to fund up to 2 new awards in FY2020, 2 new awards in FY2021, and up to 2 new awards in FY2022 for a total of up to 6 new awards. The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Funds may not directly support any clinical trials beyond phase IIB with exception of Phase III clinical trials for treatment of rare diseases. See NOT-TR-18-025 . Application budgets are limited to $300,000 direct costs in any fiscal year and need to reflect the actual needs of the proposed project.

The scope of the proposed project should determine the project period. The maximum project period is 4 years. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Section III.

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education: Hispanic-serving Institutions Historically Black Colleges and Universities (HBCUs) Tribally Controlled Colleges and Universities (TCCUs) Alaska Native and Native Hawaiian Serving Institutions Asian American Native American Pacific Islander Serving Institutions (AANAPISIs) Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education) For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized) Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Institutions) Non-domestic (non-U.S.) Entities (Foreign Institutions) are 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. Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award.

All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.

System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.

gov registration , but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants.

gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants. gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account.

PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement. 3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.

A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application. An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101 ) Section IV. Application and Submission Information 1.

Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants. gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.

gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution. 2.

Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review. By the date listed in Part 1.

Overview Information , prospective applicants are asked to submit a letter of intent that includes the following information: Descriptive title of proposed activity Name(s), address(es), and telephone number(s) of the PD(s)/PI(s) Names of other key personnel Participating institution(s) Number and title of this funding opportunity The letter of intent should be sent to: All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed Instructions for Application Submission The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide must be followed. Applicants must provide clear evidence that the proposed team is comprised of skilled investigators in all areas of interdisciplinary science needed to accomplish the proposed research, including bioethics and translational science. The role and expertise of collaborators and team members must be well described.

All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed. PHS 398 Cover Page Supplement All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: Research Strategy : Research under this FOA should focus on approaches that thoughtfully address ethical considerations in translational science research. Applicants should make a convincing case for why the specific ethical topic chosen is particularly important at this time for advancing translational research.

Applicants should describe how the proposed research will inform the ethical development, modification, or application of a novel discovery, technology, or approach to improve human health. Sufficient detail should be provided regarding the methodological approach. A discussion of the influence of the research results on the ethical issue in the targeted translational research area should be included.

Consideration regarding additional research that might stem from the proposed project should be described. High risk projects with limited preliminary results are welcome if impact is suitably high. Project Timelines and Milestones: A Timeline that incorporates identifiable Milestones must be included as part of the Research Strategy.

Milestones are clearly defined indicators of progress at critical periods in the project written concretely enough to evaluate what will be achieved at each stage of project. Applicants should describe how results will inform and extend current ethical standards or approaches in translational science research.

Resource Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide. The following modifications also apply: Generally, Resource Sharing Plans are expected, but they are not applicable for this FOA. Only limited Appendix materials are allowed.

Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions: If you answered Yes to the question Are Human Subjects Involved?

on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record. Study Record: PHS Human Subjects and Clinical Trials Information All instructions in the SF424 (R&R) Application Guide must be followed.

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed. PHS Assignment Request Form All instructions in the SF424 (R&R) Application Guide must be followed.

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement , and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide. 3. Unique Entity Identifier and System for Award Management (SAM) See Part 1.

Section III. 1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants. gov 4.

Submission Dates and Times Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next business day. Organizations must submit applications to Grants. gov (the online portal to find and apply for grants across all Federal agencies).

Applicants must then complete the submission process by tracking the status of the application in the eRA Commons , NIH’s electronic system for grants administration. NIH and Grants. gov systems check the application against many of the application instructions upon submission.

Errors must be corrected and a changed/corrected application must be submitted to Grants. gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission. Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission. Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E. O.

12372) This initiative is not subject to intergovernmental review. All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement . Pre-award costs are allowable only as described in the NIH Grants Policy Statement .

7. Other Submission Requirements and Information Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide . If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance . For assistance with application submission, contact the Application Submission Contacts in Section VII .

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide. See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations , NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Post Submission Materials Applicants are required to follow the instructions for post-submission materials, as described in the policy . Any instructions provided here are in addition to the instructions in the policy. Section V.

Application Review Information Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

In addition, for applications involving clinical trials: A proposed Clinical Trial application may include study design, methods, and interventions that are not by themselves innovative but address an ethical issue in clinical translational research and will produce data or results that could inform ethical development, modification, or application of novel findings, technologies, and approaches to improve human health, including their impact on individuals, families, communities, and society.

Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues to scientific investigation.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved?

How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field ? Further criteria specific to this opportunity: Have the ethical issue being addressed and its impact been clearly described? Are there sufficient details on how this ethics research will be beneficial to advance translational science research?

Has a convincing case been made as to why the ethical topic is particularly important at this time for advancing translational science research? Will the proposed research inform the ethical development, modification, or application of a novel discovery, technology, or approach to improve human health? Will the results from this project inform the ethical issues in targeted translational research area?

Will the results of this project inform and extend current ethical standards or approaches in translational science research? In addition, for applications involving clinical trials Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge or biological mechanisms?

For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing safety, efficacy, or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors, or health care policy? For trials focusing on mechanistic, behavioral, psychological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)?

If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Further criteria specific to this opportunity: Does the application have highly skilled investigators in all required interdisciplinary areas, including bioethics and translational science?

Are the role and expertise of collaborators and team well described? In addition, for applications involving clinical trials With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines?

Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense?

Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? In addition, for applications involving clinical trials Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project ? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed?

Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

Further criteria specific to this opportunity: If the project is high risk with limited preliminary results, has a sound rationale been provided as to why the approach proposed is the most appropriate and likely to generate an exceptionally high impact if successful? Is a proposed Timeline with identifiable Milestones included? Are the Milestones clearly defined indicators of progress at critical periods in the project?

Are Milestones written concretely enough to evaluate what will be achieved at each stage of the project? Does the applicant clearly describe how the results of the project will inform and extend current ethical standards or approaches in translational science research?

In addition, for applications involving clinical trials Does the application adequately address the following, if applicable: Is the study design justified and appropriate to address primary and secondary outcome