Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the 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 the 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

The NIDCR is committed to identifying effective approaches to address dental, oral and craniofacial diseases and disorders. Improving health through the generation of robust data from well-designed and executed clinical trials and clinical studies is a high priority for the NIDCR. To meet this goal, the NIDCR strongly encourages investigators proposing investigator-initiated interventional clinical trials or biomarker clinical validation studies to utilize a two-part grant process:

Part 1: The NIDCR Clinical Trial or Biomarker Clinical Validation Study Planning Grant (R34). The NIDCR will support clinical trial or biomarker clinical validation study planning grants (R34) for comprehensive planning, design and documentation of investigator-initiated Phase I, II, III, or IV clinical trials, or biomarker clinical validation studies that involve prospective collection of specimens and clinical outcomes. Interventional behavioral studies, sometimes referred to as Stage I, II, III or IV studies, should be planned using a different funding opportunity announcement (PAR-14-342). The goal of the R34 grant program is to provide investigators the time and funds necessary to complete the detailed planning and the necessary written supporting documentation for full implementation of a clinical trial or validation study. The NIDCR believes this formal planning process will help grantees meet the rigorous standards required for the implementation of the subsequent study and improve the reproducibility of study results.

Part 2: The NIDCR Clinical Trial or Biomarker Clinical Validation Cooperative Agreement (U01). The NIDCR will accept, peer review, and consider for funding applications for Clinical Trial Implementation or Biomarker Clinical Validation Study Cooperative Agreements (U01) submitted to PAR-11-339. The material in the implementation or validation grant application must be sufficient to demonstrate adequate preparation for launching a study, i.e., that initiation of study staff training, followed by subject recruitment can begin upon award of the cooperative agreement and approval of the study protocol by the oversight committee. The NIDCR will only support clinical trials or prospective biomarker clinical validation studies that are developed using rigorous designs, with full written documentation of all procedures necessary for study implementation. The quality of the planning, design, and documentation products for such studies are given key consideration when the NIDCR considers supporting a clinical trial or biomarker clinical validation study.

This FOA, the NIDCR Clinical Trial or Biomarker Clinical Validation Study Planning Grant (R34), addresses the R34 grant.

A clinical trial is defined by NIH as a prospective biomedical or behavioral research study of human subjects that is designed to answer specific questions about biomedical or behavioral interventions (drugs, treatments, devices, or new ways of using known drugs, treatments, or devices). The purpose of randomized controlled trials (RCTs) is to determine whether a particular intervention is efficacious or effective in changing disease incidence or severity. In addition, clinical trials determine whether interventions are safe, feasible, and acceptable to patients. Clinical research involving an intervention to modify individual, family or group behavior to change a health outcome also fits the definition of a clinical trial. Clinical studies to evaluate clinical laboratory tests or devices (e.g., new imaging techniques, diagnostic tests or surgical planning tools) would meet the definition of a clinical trial if the test or tool was used for making a medical decision about a participant enrolled in the trial, and that decision could possibly affect a health outcome.

Most clinical trials supported by the NIDCR are investigator-initiated Phase I, II, III or IV interventional clinical trials, conducted at single or multiple sites. The trial is usually supported by a coordinating center, statistical units, central laboratories or other specialized services. To adequately plan and design the future clinical trial, investigators often need planning grant support to establish the group of collaborating specialists and prepare all of the documentation necessary for the subsequent U01 application and implementation of the trial.

A biomarker clinical validation study is designed to validate candidate biomarker(s) for prognostic or diagnostic purposes for their specificity, sensitivity, robustness and utility in an independent prospectively recruited cohort. A biomarker is a biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to evaluate response to a treatment for a disease or condition. Biomarker clinical validation studies are an integral part of the biomarker and diagnostics development pathway and, similar to clinical trials, they are time-consuming, labor-intensive, complex, and costly. As such, NIDCR considers these studies logistically equivalent to clinical trials and subject to the same peer review and funding policies as investigator-initiated clinical trials submitted for NIDCR funding.

Examples of studies that might be planned with the R34 award include but are not limited to:

• Clinical trials involving chemotherapeutic, pharmacologic, or other interventions to prevent and/or treat periodontal diseases and various types of dental caries (e.g., Early Childhood Caries (ECC), root caries, and caries related to head and neck radiation);

• Clinical trials testing new dental materials for restoration of carious lesions;

• Clinical trials testing non-opiate methods of reducing post-operative pain and swelling after dental surgery;

• Clinical trials focusing on the prevention or treatment of HIV/AIDS, its associated oral complications, co-infections or malignancies, and dental diseases caused by bacteria, fungi or viruses;

• Clinical trials testing therapies to prevent or treat oral candidiasis, oral herpes virus infections and other pathogens with oral targets that commonly occur in those with congenital or acquired immune dysfunction;

• Clinical trials testing treatments for oral mucositis and other oral manifestations of systemic diseases;

• Clinical trials comparing therapies for oral diseases in medically complex patients, including those with cleft lip / cleft palate;

• Clinical trials to prevent or manage salivary dysfunction;

• Clinical trials testing treatments for temporomandibular dysfunction and other orofacial pain conditions; and

• Clinical validation of biomarker(s) of oral or dental diseases, e.g. periodontal diseases, head and neck cancers, salivary dysfunctions, or systemic diseases significantly impacting the oral cavity through prospective collection of biospecimens and data on clinical outcomes.

The R34 grant award will provide one year of support for activities directed towards the planning and design of a clinical trial or biomarker clinical validation study. The Clinical Trial or Biomarker Clinical Validation Study Planning Grant is not designed for the collection of preliminary data (clinical or pre-clinical) about the efficacy of an intervention, or the collection of prospective data to support the rationale for a clinical trial or study. Planning activities such as evaluating the potential study population to determine the number of subjects at a site that would fulfill eligibility criteria for the future trial is encouraged. Applicants and recipients of R34 funding should note that funding of an R34 Planning Grant does not guarantee or imply funding for a subsequent clinical trial implementation or biomarker clinical validation study application.

The R34 planning grant process is designed to:

• permit early peer review of the rationale for the proposed clinical trial or biomarker clinical validation study;

• permit early assessment of the design of the proposed trial or study; and

• provide support for the development of a complete study protocol and associated documents and support the development of other essential elements of a clinical trial or biomarker clinical validation study.

Examples of activities supported by the R34 include, but are not limited to, developing the following:

• A clinical protocol following International Conference on Harmonisation (ICH) E6 Good Clinical Practice Consolidated Guidance, prepared using the standard NIDCR interventional or observational protocol template (see NIDCR Toolkit for Clinical Researchers).

• The Manual of Procedures (MOP) including a detailed description of study procedures and process details, validation, and quality control for any non-standard clinical or laboratory/mechanistic testing which will be performed;

• The statistical analysis plan;

• The consent form(s) and, if applicable, assent form(s);

• The Clinical Investigators Brochure (CIB) or equivalent, if applicable;

• A plan for the acquisition and administration of study agent(s), if applicable;

• Detailed description of Roles and Responsibilities of study personnel;

• Detailed timeline or Gantt Chart;

• Quality and data management plan;

• Recruitment and retention plan, including strategies to put in place should enrollment or retention for follow up not meet specified metrics;

• A complete set of suitable documents for submission to the appropriate regulatory authorities with a product development plan if the study product will be under Investigational New Drug Application (IND) or Investigational Device Exemption (IDE).

Investigators planning a biomarker clinical validation study are expected to undertake most of these activities during the planning phase, including the development of a clinical protocol using the standard NIDCR protocol template, a Manual of Procedures, consent/assent forms, a complete statistical analysis plan, recruitment and retention plans, a detailed study timeline, and a quality management plan. NIDCR clinical research policy and guidance information as well as NIDCR templates are available at the NIDCR Toolkit for Clinical Researchers.

Awardees are required to comply with the NIDCR Clinical Terms of Award for any planning phase activities that involve human subjects, and will be required to comply with the Clinical Terms of Award for studies implemented under a future U01 award. It is recommended that R34 awardees use the NIDCR tools and templates for development of the clinical trial or clinical study documents. The details can be found at the following websites: NIDCR Clinical Terms of Award and NIDCR Toolkit for Clinical Researchers. The implementation of the Clinical Terms of Award ensures that the conduct of the clinical trial or clinical study meets widely-accepted standards.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

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

• Small Businesses

• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments

• County Governments

• 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

Other

• 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

• Regional 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

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) (formerly CCR) 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 and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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.

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.

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).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;

• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or

• Of an application with a changed grant activity code.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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:

Yasaman Shirazi, PhD
Chief, Scientific Review Branch
National Institute of Dental and Craniofacial Research
Telephone: 301-594-5593
Fax: 301-480-8303
Email: yasaman.shirazi@nih.gov

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed,

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.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

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:

Specific Aims: The goals of the future clinical trial or biomarker clinical validation study, and the clinical outcome(s) to be assessed in the future study should be stated concisely. The specific objectives to be accomplished during the R34 planning period and how they relate to the goals of the proposed future trial or study must be clearly and concisely presented.

Research Strategy:

Significance

• The significance, timeliness and biological relevance of the proposed clinical trial or biomarker clinical validation study must be stated clearly, with a clear explanation of the importance of the proposed clinical endpoints. There should be a discussion of the need for the trial or study.

• The application should include a description of how the trial or study will test the proposed hypothesis(es).

• The rationale for selection of the intervention or biomarker should be presented.

• For biomarker clinical validation studies, analyses of available evidence on the analytical performance of the biomarker assay, the known associations of the biomarker and disease states, and the proposed future use of the biomarker should be included.

• The potential of future study results to change clinical practice, improve our knowledge of the clinical condition, improve clinical outcomes or change health care policy should be discussed.

• If the application proposes a future Phase III trial or multi-center biomarker clinical validation study, the generalizability of potential findings should be discussed. This includes describing how findings from studies conducted at foreign sites will impact health care delivery or policy in the US, if that is the intent of the trial or study.

Innovation

• A compelling argument of how the proposed clinical trial or biomarker clinical validation study will shift clinical practice paradigms or inform health care policy should be presented.

• The application should describe any novel theoretical concepts, approaches or methodologies, instrumentation or interventions that are anticipated to be used in the proposed clinical trial or biomarker clinical validation study.

Approach

The approach for the future clinical trial or biomarker clinical validation study and the planning activities that will be accomplished during the R34 period should be presented briefly. The preliminary approach for the U01 and specific R34 activities should be identified and described within the application. The following should be covered:

• A description of and justification for the design of the proposed future study;

• Translation of the clinical question into a statistical hypothesis;

• Preliminary primary and secondary outcome variable(s) and data to be collected, including relevance to the clinical and statistical hypothesis being tested;

• Preliminary statistical plan and sample size estimate;

• The plan for the acquisition and administration of study agent(s) with the rationale for the chosen route of administration, if appropriate;

• Rationale for the dose of an interventional agent, if appropriate;

• Preliminary organizational structure for the administration and management of the trial or study, including the administrative center, data coordinating center, participating enrollment centers / sites, and the laboratory/ testing center; and

• Justification that conducting a study at foreign sites will change health care practices or policy in the US, if that is the intent.

For the R34 phase

• Plans to develop the committee structure appropriate to the complexity of the clinical trial or biomarker study;

• A discussion of activities and outcomes that will be achieved during the planning phase such as developing the protocol and associated documents, the draft Manual of Procedures and, if applicable, documents required for Investigational New Drug Application (IND) or Investigational Device Exemption (IDE);

• A plan for the selection of potential clinical sites, including how they will be evaluated for inclusion in the future study;

• A discussion of potential challenges that are anticipated during planning and study implementation, and how they will be addressed; and

• A projection of the initial time line for implementing and completing the trial or study. .

Human Subjects Section

All R34 applications (regardless of whether they involve HS in the planning phase or not) should provide a plan and documentation for HS protection in a subsequent U01 for all interventional clinical trials or the biomarker validation studies. Applicants should include a description of the requisite study population with preliminary estimates of its availability, and describe plans to develop recruitment, outreach, follow-up and retention strategies. In addition, plans for addressing any ethical and safety issues, and challenges anticipated regarding the proposed intervention should be included. This could include justification of a placebo arm in a future RCT or a design that simply monitors disease progression in a biomarker validation study.

Human Subjects Protections: R34 applications that involve human subjects to evaluate and determine the eligibility of the potential subject population for participation in the future trial or biomarker validation should fully address the HS protection in the Human Subject Section. Applicants are encouraged to distinguish clearly between HS involvement during the R34 phase, and HS involvement proposed for the subsequent U01 clinical trial implementation or biomarker validation application.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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.

Part I. Overview Information contains information about Key Dates. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

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.

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 Applying Electronically.

Important reminders:
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 by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

Applicants are required to follow our Post Submission Application Materials policy.

Important Update: See NOT-OD-16-006 and NOT-OD-16-011 for updated review language for applications for due dates on or after January 25, 2016.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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.

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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?

• Is there a clear statement of the importance of the question(s) and its timeliness?

• Is there enough preliminary data or literature supporting the future clinical trial or biomarker clinical validation study?

• Is there enough evidence to justify a future biomarker clinical validation study, including analyses of available evidence on the analytical performance of the biomarker assay and its association with disease states?

• Does the proposed future clinical trial or biomarker validation study have the potential to change clinical practice, improve our knowledge of the clinical condition, or improve clinical outcomes or change health care policy?

• If this is an application for a future Phase III clinical trial, would potential findings be generalizable to US populations?

Investigator(s)

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?

For multidisciplinary projects, does the investigator team have sufficient range and depth of expertise to design, conduct and complete the proposed study? Is there appropriate professional experience in administration of complex projects, development of an appropriate study design, study team, and committee structure appropriate to the complexity of the trial or study?

Innovation

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?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?;

• Is the description of, and rationale for, the proposed future study design appropriate to the research question(s) posed?

• Is the preliminary statistical plan and sample size estimate appropriate to the research question(s) and study design?

• Are the proposed primary and secondary outcome variable(s) and data to be collected, including relevance to the clinical and statistical hypothesis being tested appropriate?

• Are there clear plans to obtain any study agents?

• Are there clear plans for developing a clinical protocol and associated documents, and if applicable, documents required for Investigational New Drug (IND) Application or Investigational Device Exemption (IDE)?

• Are there appropriate plans for the selection and evaluation of potential clinical sites and necessary populations for the future study?

• Are there plans to address any ethical and safety issues?

• Is there an adequate discussion of potential challenges that are anticipated during planning and study implementation, and how they will be addressed?

• Are the plans to organize a research team and develop a leadership structure appropriate to the complexity of the clinical trial?

• Is the projected time line for implementing and completing the trial or study feasible?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? Are adequate facilities in place to conduct clinical trials or biomarker clinical validation studies? Is there a plan to determine if study populations required for the proposed study are available at the proposed clinical site(s)?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable

Revisions

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Institute of Dental and Craniofacial Research in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

• Will receive a written critique.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications . Following initial peer review, recommended applications will receive a second level of review by the National Advisory Dental and Craniofacial Research Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.

• Availability of funds.

• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: https://grants.nih.gov/support/index.html
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-945-7573
Email: GrantsInfo@nih.gov

Jane C. Atkinson, DDS
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-435-7908
Email: jatkinso@mail.nih.gov

Yasaman Shirazi, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-5593
Email: yasaman.shirazi@nih.gov

Diana Rutberg, MBA
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
Email: rutbergd@mail.nih.gov

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.