Department of Health and Human Services

Part 1. Overview Information

Key Dates

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.

Table of Contents

1. Part 1. Overview Information
2. Part 2. Full Text of the Announcement
   1. Section I. Funding Opportunity Description
   2. Section II. Award Information
   3. Section III. Eligibility Information
   4. Section IV. Application and Submission Information
   5. Section V. Application Review Information
   6. Section VI. Award Administration Information
   7. Section VII. Agency Contacts
   8. Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

The NIDCR is committed to identifying effective preventive, diagnostic and treatment approaches for oral and craniofacial diseases and disorders. Improving health through the generation of robust data from well-designed and executed clinical trials and complex clinical studies is a high priority for the NIDCR.

A clinical trial is defined by NIH as "a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes." Clinical trials are used to determine whether biomedical or behavioral interventions are safe, feasible, acceptable, efficacious, and effective. A biomarker clinical validation study is designed to validate a candidate biomarker(s) for its prognostic or diagnostic utility.

Clinical studies conducting basic behavioral or social sciences research are not considered clinical trials. For the purposes of this announcement, the NIDCR uses the definition of basic behavioral and social sciences research developed by the Office of Behavioral and Social Sciences Research (OBSSR), National Institutes of Health: "Basic research in the behavioral and social sciences is designed to further our understanding of fundamental mechanisms and patterns of behavioral and social functioning, relevant to the Nation’s health and well-being, and as they interact with each other, with biology and the environment. As is the case with basic biomedical research, basic behavioral and social sciences research does not address disease outcomes per se. Rather, it is designed to elucidate knowledge about underlying mechanisms and processes…" Examples of such studies include laboratory-based studies in which behavioral or social probes are used to evoke participants’ responses (e.g., emotional regulation, dental fear, social norms) under varied conditions, and for which proximal behavioral or social outcomes — but not disease outcomes — are assessed. Such studies are sometimes referred to as Type 1 translation studies, or studies that seek to ensure that a particular manipulation actually engages the behavioral or social target it intends to engage. Applications that propose a basic behavioral or social clinical study should apply for support via the parent R21 or R01 FOAs. Applicants are encouraged to contact the NIDCR to discuss which FOA is appropriate for any particular study.

Because clinical trials and biomarker clinical validation studies are resource intensive, NIDCR anticipates funding only those trials or studies of highest priority and mission relevance. Investigators considering preparing and submitting an application are strongly encouraged to consult with NIDCR staff prior to beginning the application process to determine NIDCR interest in the concept that would be proposed in the application.

As announced in NOT-DE-15-008 and NOT-DE-14-009 , the NIDCR provides two types of funding opportunities for support of investigator-initiated interventional clinical trials or biomarker clinical validation studies: (1) clinical trial or biomarker clinical validation study planning grants (R34) and (2) a clinical trial or biomarker clinical validation study cooperative agreement (U01) award. This FOA addresses the NIDCR Clinical Trial or Biomarker Clinical Validation Study Cooperative Agreement (U01); two companion FOAs, NIDCR Clinical Trial or Biomarker Clinical Validation Study Planning Grant (R34), PAR-14-346 and NIDCR Behavioral or Social Intervention Clinical Trial Planning Grant (R34), PAR-14-342 address the R34 planning grant.

Part 1: Both the NIDCR Clinical Trial or Biomarker Validation Study Planning Grant (R34) PAR-14-346 and the NIDCR Behavioral or Social Intervention Clinical Trial Planning Grant (R34) PAR-14-342 supports the complete planning, design and documentation needed for an investigator-initiated Phase I, II, III or IV clinical trial, stage 1-4 behavioral or social intervention study, or biomarker clinical validation study. The R34 grant will provide up to one year of support for clinical trial or biomarker clinical validation study planning.

Part 2: The goal of The Clinical Trial or Biomarker Clinical Validation Study Cooperative Agreement (U01) is to support highly meritorious investigator-initiated clinical trials or biomarker clinical validation studies. The NIDCR will accept, peer review, and consider funding applications from R34 awardees and other applicants who can demonstrate that all documentation needed for submission of a Clinical Trial or Biomarker Clinical Validation Study Cooperative Agreement (U01) application is complete.

Examples of studies that might be supported by this FOA 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;
• Clinical validation of biomarker(s) of oral or dental diseases, e.g. periodontal diseases, head and neck cancers, salivary gland cancers, salivary dysfunctions, or systemic diseases significantly impacting the oral cavity through prospective collection of biospecimens and data on clinical outcomes;
• Clinical trials testing the efficacy/effectiveness and mechanisms of action of behavioral or social interventions to improve dental, oral or craniofacial health;
• Clinical trials adapting behavioral or social principles, methods or interventions from other areas of health to be applied and tested in dental, oral or craniofacial health, or in the dental setting;
• Clinical trials developing and testing algorithms for tailoring or targeting behavioral or social interventions for individuals, groups, communities, or settings in which further testing is justified.

The materials contained in the U01 application should be sufficient to initiate study staff training followed by study subject recruitment soon after peer review and final NIDCR approval of the clinical protocol and associated documents. Awardees are required to comply with NIDCR Clinical Terms of Award . The clinical study must meet all applicable NIH, Food and Drug Administration (FDA), and Office of Human Research Protections (OHRP) policy requirements. If the application proposes a clinical trial with an investigational drug or device, the investigators must have submitted the appropriate investigational application to the FDA. Guidance documents can be found at http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/GuidancesInformationSheetsandNotices/ucm219433.htm#

Section II. Award Information

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.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

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)

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.

Required Registrations

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.

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.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

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.

Section IV. Application and Submission Information

1. Requesting an Application Package

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.

2. Content and Form of Application Submission

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.

Letter of Intent

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
Telephone: 301-594-5593
Fax: 301-480-8303
Email: yasaman.shirazi@nih.gov

Page Limitations

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.

SF424(R&R) Cover

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.

Facilities and Other Resources: As per the instructions, this information is used to assess the capability of the organizational resources available to perform the effort proposed. In addition to the SF 424 (R&R) application instructions, the application must include relevant information that addresses the feasibility of recruiting subjects who are eligible for the clinical trial or biomarker clinical validation study. Specifically, applicants must provide evidence that each recruiting center has access to a sufficient number of study participants who meet the eligibility criteria as defined in the submitted protocol. For multi-site applications, information must be provided for each site participating in the trial or study.

Other Attachments:

Each clinical trial or biomarker clinical validation study cooperative agreement application must include the draft Manual of Procedures, a Quality Management Plan and a Data Management Plan. For behavioral or social intervention trials, the U01 application should include the intervention monitoring manuals, a draft Manual of Procedures, a Quality Management Plan, and a Data Management Plan. The application must include the following study documents titled:

• Quality Management Plan: This plan should include the plans to standardize and monitor adherence to the clinical protocol and train study staff.
• Data Management Plan: This plan should include how the data coordination center will develop processes to support data capture and monitor data in a timely manner.
• Manual of Procedures (MOP): A draft MOP should be included with a synopsis of the protocol.
• Investigator's Brochure: For drug and device studies, the Investigator's Brochure (or equivalent risk information) if applicable should be attached.
• The Intervention Manual: For behavioral or social intervention studies only, the intervention manual and fidelity monitoring procedures should be attached.

NIDCR templates are available as a tool to assist investigators in formatting these documents. Investigators are referred to the NIDCR Toolkit website for clinical research guidance and templates http://www.nidcr.nih.gov/Research/toolkit/

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

The budget should include funding needs for the entire trial or study and data analysis period.

Investigators must submit a justified, individual budget for each year of support requested. Separate budgets must be prepared for each subcontract and/or for each collaborating center or core, if multiple centers or cores are proposed.

If parts of the costs of the trial or study are to be borne by sources other than NIH, these contributions must be presented in detail in the budget justification. These outsource costs do not constitute cost sharing as defined in the current NIH Grants Policy Statement and should not be presented as part of the requested budget.

R&R Subaward Budget

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.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy:

Significance: The significance and biological relevance of the proposed trial or biomarker clinical validation study must be stated clearly. It should be supported by the following:

• A clear statement of the question(s) that the trial or study will address and its importance;
• The potential of the trial or study results to impact knowledge or change clinical practice, individual or community oral health behaviors or health care policy;
• The generalizability of potential findings to US populations if this is a Phase III trial or multi-center biomarker clinical validation study.
• Information adequate to determine the significance and timeliness of, as well as the need to perform, the trial or study;
• The biological, behavioral or social mechanisms, and clinical data that support conducting the trial or study;
• For behavioral or social intervention trials , the rationale for the selected intervention, including the behavioral or social target(s) the intervention is meant to engage,
• For behavioral or social intervention trials, how results will contribute to a broader understanding of behavior or social change, beyond those experienced by study participants (e.g., identification of how and/or for whom a behavioral or social intervention produces its effects, identification of an algorithm for tailoring or targeting an intervention for different individuals or communities);
• Rigorous preliminary data obtained from applicant’s pre-clinical or clinical studies or the literature supporting the need for a clinical trial or biomarker clinical validation study to test the proposed hypothesis or intervention and the choice of the particular intervention;
• For biomarker clinical validation studies, relevant data about the analytical performance of the biomarker assay (e.g., laboratory validation studies, limits of detection, and preliminary data from discovery cohort studies) that demonstrate their suitability for further pilot testing; the known associations of the biomarker and disease states, and the proposed future use of the biomarker.

Innovation: A compelling argument of how the proposed study will shift clinical practice or inform health care policy should be presented. The application should describe any novel theoretical concepts, approaches or methodologies, instrumentation or interventions that will be used in the proposed clinical trial or biomarker clinical validation study. For behavioral or social intervention trials, application of principles, concepts, or methods that produce results that contribute to the understanding of behavior or social change, beyond the development of an intervention for a specific community or population.

Approach: The approach should be presented briefly. The following should be covered:

• The translation of the clinical question into a statistical hypothesis;
• Data from well conducted pre-clinical and pilot studies or other sources, including a discussion of the adequacy of the populations used in the pilot studies or the justification for the animals used in pre-clinical studies, demonstrating the feasibility of the trial or study;
• For biomarker validation studies, describe the characteristics of the candidate biomarkers (e.g., laboratory validation studies demonstrating the accuracy, precision, reproducibility, limits of detection, and preliminary estimates of sensitivity and specificity from discovery cohort studies) that demonstrate their suitability for further testing;
• A description of the conceptual framework and rationale for the proposed study design, including the phase of a clinical trial;
• For behavioral or social intervention trials, a clear statement of the rationale for the selected intervention, including the behavioral or social target(s) the intervention is meant to engage, how the study will measure whether the intervention has engaged the intended target, and how engaging the intended target is hypothesized to cause change in dental, oral or craniofacial behaviors or conditions;
• Primary and secondary outcome variable(s) and other data to be collected, including an explanation of the relevance to the clinical and statistical hypothesis being tested;
• For behavioral or social intervention studies, a strong rationale for the selection of behavioral, social or clinical outcomes; where clinical outcomes are not included, a strong rationale for the known or hypothesized relationship between behavioral or social outcomes and clinical outcomes relevant to dental, oral or craniofacial health;
• For behavioral or social intervention studies how engaging the intended target is hypothesized to cause change in dental, oral or craniofacial behaviors or conditions.
• Appropriateness of a composite outcome if multiple outcome variables are combined;
• Criteria for evaluating and validating outcome variables;
• The plan for the acquisition, route, timing and administration of study agent(s) if appropriate;
• A discussion of the risk information contained in the Investigator’s Brochure or equivalent literature as applicable;
• Allowable ancillary therapies;
• Control selection, if a control group is included;
• Inclusion/exclusion criteria;
• Statistical analysis plan, including sample size and power calculation;
• Plan for handling missing data such as due to attrition or exclusion;
• A discussion of potential biases or challenges in the protocol and how they will be addressed and minimized;
• A time line for implementing and completing the trial or study including plans to add or drop enrollment centers;
• Randomization and allocation methods if needed, masking methods (if appropriate), plans for coordinating randomization procedures and assignments, data transmittal, patient assignment, and for transmitting policy and procedural advice to the investigators at the participating centers;
• The proposed organizational structure, administration and management of the trial or study, including the relationships among the administrative center, data coordinating center (if included), participating enrollment centers, and the laboratory/ testing center; and

Human Subjects Protection:

• Plans and strategies for patient recruitment and retention, plans for recruitment outreach and, as appropriate, follow-up procedures to ensure collection of data at stated intervals;
• Justification for inclusion or exclusion of children or by gender or minority status;
• As related to human subjects protection, describe and justify the selection of an intervention’s dose, frequency and administration;
• If the proposed research includes an NIH-defined Phase III Clinical Trial, a discussion of expected sex/gender, racial, and ethnic differences in intervention effect and a discussion of valid analysis plans (see Part III, 4.2.1 of the SF 424 instructions).

Data and Safety Monitoring Plan:

Do not name members of any oversight board in the application. The NIDCR will appoint members of any oversight committees after consultation with the clinical trial or study investigator team.

Letters of Support: Letters of support signed by individuals who have the authority to commit the institution should be attached.

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, with the following modification:

• All applications submitted for the January 25, 2015, due date or after are expected to comply with the NIH Genomic Data Sharing Policy as detailed in NOT-OD-14-111, as applicable.
• Investigators seeking $500,000 or more in direct costs in any year are expected to address a Data Sharing Plan, or explain why data-sharing is not possible.

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.

The application must include the following required materials in the Appendix (Note: A maximum of 10 PDF attachments is allowed in the Appendix.):

• Clinical Protocol: A final draft of the Clinical Protocol. The NIDCR template is available as a sample format;
• Consent form and, if applicable, assent form.
• Other materials essential for the implementation of the clinical trial or biomarker clinical validation study, such as pivotal data collection instruments or document(s) that contain relevant non-clinical and preclinical data on study products can be attached but are not required.

Planned Enrollment Report

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

PHS 398 Cumulative Inclusion Enrollment Report

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

Foreign Institutions

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. Submission Dates and Times

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.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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.

6. 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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

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 and compliance with application instructions by the Center for Scientific Review and responsiveness by the National Institute of Dental and Craniofacial Research, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH program staff at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

Post Submission Materials

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

Section V. Application Review Information

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.

1. Criteria

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.

Overall Impact

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).

Scored Review Criteria

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?

Does the proposed clinical trial or biomarker clinical validation study have a clear statement of the question(s) that the trial or study will address, its importance and the potential of the trial or study results to impact knowledge or change clinical practice, community behaviors or health care policy?

Is the proposed trial timely and is there a need to perform the trial or study? Is there sufficient preliminary data from pre-clinical or clinical studies or the literature supporting the need for a clinical trial or biomarker clinical validation study to test the proposed hypothesis or intervention and the choice of the particular intervention?

For behavioral or social intervention trials, will the results contribute to a broader understanding of behavior or social change, beyond those experienced by study participants (e.g., identification of how and/or for whom a behavioral or social intervention produces its effects, identification of an algorithm for tailoring or targeting an intervention for different individuals or communities)?

For biomarker clinical validation studies, are analyses of available evidence on the analytical performance of the biomarker assay, the known associations of the biomarker and disease states, its preliminary specificity and sensitivity, and the proposed future use of the biomarker presented?

Could potential findings be generalized to US populations if this is a Phase III trial or multi-center biomarker clinical validation study?

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?

Does the overall team have the sufficient multidisciplinary clinical and research experience to organize a complex clinical trial or biomarker clinical validation study? Do the data coordinating center investigators and trial statistician have appropriate expertise to implement, monitor and analyze the study results?

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? For behavioral or social intervention trials, will the application of principles, concepts, or methods produce results that contribute to the understanding of behavior or social change, beyond the development of an intervention for a specific community or population?

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?

For all proposed clinical trials or biomarker clinical validation studies, is the experimental design adequate and does it include the following:

Is the clinical question translated into a justified statistical hypothesis(es)?

For behavioral or social intervention trials, is there a clear statement of the rationale for the selected intervention, including the behavioral or social target(s) the intervention is meant to engage, how the study will measure whether the intervention has engaged the intended target, and how engaging the intended target is hypothesized to cause change in dental, oral or craniofacial behaviors or conditions?

Is there adequate robust preliminary data demonstrating the feasibility of the trial or study? Is there a description of and rationale for the proposed study design, including the phase of a clinical trial?

Are the primary and secondary outcome variable(s) described, justified and is there a description of how they will be collected in a validated manner?

For behavioral or social intervention studies, is there a strong rationale for the selection of behavioral, social or clinical outcomes? Where clinical outcomes are not included, is there a strong rationale for the known or hypothesized relationship between behavioral or social outcomes and clinical outcomes relevant to dental, oral or craniofacial health?

If applicable, is the plan for the acquisition and administration of study agent(s) appropriate, including a description of allowable ancillary therapies? Is there an appropriate discussion of known safety information related to the proposed intervention?

Is there justification for the use of the proposed study population, including control selection and the inclusion/exclusion criteria? Is the timeline for completing the study and enrolling the request population feasible?

Is the statistical analysis plan, including sample size and power calculation justified, including a discussion of potential biases or challenges in the protocol and how they will be addressed?

Are the leadership and organization of the study team clearly described?

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?

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 the study? Is the required study population available at the proposed clinical sites? Does the data coordinating center have the technical infrastructure to support data capture and monitor data in a timely fashion?

Additional Review Criteria

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.

Supporting Clinical Documents

With regard to the additional documents included as "Other Attachments"

Are plans for coordinating randomization and allocation procedures and assignments, data transmittal, masking (if appropriate) and for transmitting policy and procedural advice to the investigators at the participating centers appropriate?

Are the management plans adequate, including the Quality management plan, the Data management plan, and the plans to monitor and add or drop enrollment centers?

Does the Manual of Procedures provide assurance of optimal standardization, quality control, scientific integrity, patient safety and consistent protocol implementation across subjects and the clinical site(s), increasing the likelihood that the results of the study will be scientifically credible?

If the study requires an Investigator's Brochure, is the brochure or other equivalent risk information adequate?

If the study requires an Intervention Manual (behavioral or social intervention studies only), does it provide assurance of optimal standardization, quality control, scientific integrity, patient safety and consistent protocol implementation across subjects and the clinical site(s)?

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

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

Additional Review Considerations

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) Genomic Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NIDCR, 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 on the basis of established PHS referral guidelines 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.

3. Anticipated Announcement and Award Dates

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.

Section VI. Award Administration Information

1. Award Notices

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.

2. Administrative and National Policy Requirements

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

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the following primary responsibilities:

• All aspects of the study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators are the PD(s)/PI(s) responsibilities. The awardee agrees to accept close coordination, cooperation, and participation of NIDCR staff in those aspects of scientific and technical management of the study as stated in these terms and conditions.
• The PD(s)/PI(s) will meet NIDCR policy requiring that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study. An NIDCR policy notice was published in the NIH Guide on March 27, 2008, and is available at: http://grants1.nih.gov/grants/guide/notice-files/NOT-DE-08-001.html. The full policy, including terms and conditions of award, is available at the following NIDCR Website: http://www.nidcr.nih.gov/GrantsAndFunding/PoliciesandGuidance/ClinicalResearch/NIDCRClinicalTermsofAward.htm.
• Upon implementation of the protocol, each study, whether a single entity or a consortium of entities, will follow the procedures required by the protocol regarding study conduct and monitoring, participant management, data collection, and quality control.
• The PD(s)/PI(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.
• The PD(s)/PI(s) will manage involvement of industry or any other third party in the study. Except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by the NIDCR.
• The PD(s)/PI(s) will make all study materials and procedure manuals available in the public domain. Awardees are expected to publish and publicly disseminate results, data, and other products of the study, concordant with governance policies and protocols. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of support by the NIDCR/NIH.
• The PD(s)/PI(s) will obtain prior written approval of the NIDCR Grants Management Specialist, in consultation with the NIDCR Program Officer, for changes in any of the key personnel identified in the Notice of Grant Award.

NIH staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

An NIDCR Program staff member(s) acting as a Project Scientist(s) will be assigned to have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. Additional NIDCR staff members may be designated to have substantial involvement. The NIDCR Project Scientist(s) and any other substantially involved staff members will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications. If such participation is deemed essential, these individuals will seek NIDCR waiver according to the NIDCR procedures for management of conflict of interest. Some Program Officials will also have substantial programmatic involvement. In that case, the individual involved will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications or will seek an NIDCR waiver as stated above.

The main activities of the NIDCR substantially involved staff members include but are not limited to the following aspects:

• Providing input on experimental and clinical approaches, assisting in designing protocols, and consulting on updates to project milestones;
• Assisting and advising awardees with regard to various regulatory and compliance issues;
• Participating in monthly teleconferences with PDs/PIs to monitor progress and facilitate cooperation;
• Monitoring progress of the trial towards meeting its primary outcome;
• Tracking monthly accrual of participants;
• Participating in the activities of the Steering Committee and the implementation of its guidelines and procedures; and
• Reviewing the progress of the study, and of each participating component, through consideration of the annual reports, site visits, logs, etc. This review may include, but not be limited to, compliance with the study protocol, meeting subject enrollment targets, adherence to uniform data collection procedures, and the timeliness and quality of data reporting.

An NIDCR Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. An NIDCR Medical or Dental Officer will monitor the studies and serve as the Medical Monitor.

As appropriate to the funded study, the following collaborative responsibilities will be incorporated in the grant award:

As appropriate to the funded clinical trial or biomarker clinical evaluation study, the following collaborative responsibilities will be incorporated in the grant award:

As necessary, a Steering Committee (SC), composed of the principal investigator (or multiple principal investigators), and the heads of the participating clinical centers, Data Coordinating Center and any specialized core facilities, will be constituted. The SC will guide the study funded under this initiative. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

The NIDCR reserves the right to terminate, temporarily suspend, or modify a study or any portion of a study in the event of (a) failure to implement the study protocol, (b) a substantial shortfall in participant recruitment, follow-up, data reporting and dissemination, quality control or other major breach of the protocol, (c) substantive changes in the agreed-upon protocol with which the NIDCR does not concur, (d) reaching a major study objective substantially before schedule with persuasive statistical evidence, or human subject ethical issues that may dictate a premature termination.

Areas of Joint Responsibility include:

None, all responsibilities are divided between awardees and NIH staff as described above.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. Members will be: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually 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.

Section VII. Agency Contacts

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

Application Submission Contacts

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

Scientific/Research Contact(s)

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

For behavioral and social sciences clinical trials

Melissa W. Riddle, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-451-3888
Email: riddleme@nidcr.nih.gov

For HIV/AIDS and associated oral manifestations and malignancies

Isaac Rodriguez-Chavez
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-7985
Email: isaac@mail.nih.gov

Peer Review Contact(s)

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

Financial/Grants Management Contact(s)

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

Section VIII. Other Information

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.

Authority and Regulations

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.