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

PURPOSE

The National Institute of Dental and Craniofacial Research (NIDCR) intends to continue support for research conducted within a national Dental Practice-Based Research Network (DPBRN). The NIDCR will fund one national DPBRN Administrative and Resource Center (RFA-DE-19-001) and one national DPBRN Coordinating Center (RFA-DE-19-002) as companion awards to support the infrastructure for and implementation of multiple observational studies and clinical trials. This Funding Opportunity Announcement (FOA) is soliciting applications for clinical observational studies and clinical trials to be conducted in the DPBRN through a milestone-driven UG3/UH3 cooperative agreement mechanism. Each UG3/UH3 award will support an individual project which will utilize the DPBRN infrastructure and resources for study planning and implementation. This FOA supports a UG3 clinical study planning phase and potential transition to a UH3 implementation phase, with a combined total funding period of up to six years. Progression to the UH3 phase is based on an administrative review and is dependent on success in meeting UG3 milestones, consideration of the DPBRN as an appropriate venue for conduct of the research, NIDCR program priorities, and availability of funds.

The main goals of the national DPBRN are to streamline the implementation of national oral health research studies in dental practices on topics of importance to practitioners and their patients, to provide evidence useful in daily patient care, and to facilitate the translation of research findings into clinical practice.

This FOA cannot be used to test an FDA-regulated drug, biologic or device. Applications proposing such trials will be deemed non-responsive and will not proceed to review. Applicants interested in conducting such efficacy trials are directed to the NIDCR Clinical Trial Planning and Implementation Cooperative Agreement (UG3/UH3).

BACKGROUND

Practice-based research networks can generate important and timely information to guide the delivery of health care and improve patient outcomes. A DPBRN is a unique venue in which to conduct clinical research. It provides practitioners with an opportunity to propose or participate in research studies, conducted in participating dental offices with consenting patients. DPBRN studies draw on the experience and insight of practicing clinicians to help identify and frame research questions, which typically address issues faced by dental practitioners in the daily care of their patients. Because research is conducted in the real-world environment of dental practice, results have the potential to be readily accepted and adopted by practitioners and translated into daily practice. DPBRNs can support a variety of clinical studies to help expand and strengthen the profession’s evidence base and further refine care.

One benefit of practice-based research is the ability to collect data from practitioners about factors contributing to decision-making and procedures performed, and separately, to collect data from a patient's perspective, either during a patient's visit with the practitioner or outside of the office visit. Another benefit is the ability to efficiently enroll large numbers of patients with a wide geographic distribution and from a variety of practice settings/types; many practitioners can be engaged in DPBRN studies, with each contributing a relatively small number of patients. An important characteristic of the DPBRN is the ability to address emerging topics of public health interest, taking advantage of the existing infrastructure and capacity for launching studies in a timely manner.

In 2005, the NIDCR launched the first phase of the DPBRNs by supporting three regional DPBRNs, which conducted multiple clinical studies over seven years. To build upon the strengths of the regional DPBRNs and coordinate their efforts, NIDCR launched the second phase of the DPBRNs in 2012 by funding one national, geographically diverse network. In the next phase, NIDCR intends to support a similar national infrastructure, to facilitate the conduct of research within a DPBRN setting. It is envisioned that the future DPBRN will continue the work of the previous DPBRNs funded by NIDCR and will build on the knowledge gained from the previous two phases.

OVERVIEW OF NATIONAL DPBRN INFRASTRUCTURE

The national DPBRN infrastructure will comprise one national DPBRN Administrative and Resource Center and one national DPBRN Coordinating Center, funded as companion awards.

A national DPBRN Administrative and Resource Center (described in RFA-DE-19-001) will coordinate the efforts of dental practitioners representing general dentistry/specialty affiliation and a variety of practice settings/types. The national DPBRN will be organized into regional Nodes or administrative hubs focused on general dentistry research, plus a dental specialty Node, with wide geographic distribution that, combined, are capable of reaching all interested participants within all states in the US. Practitioners and office/clinic staff will receive responsible research conduct training required by NIH and IRBs and study-specific training to perform research in their offices/clinics, including recruiting, enrolling, and collecting data on their patients.

The national DPBRN will provide direction, oversight, and coordination of DPBRN studies and utilization of DPBRN resources. A practitioner Executive Committee will evaluate the feasibility and clinical interest of research topics. The Node personnel (Node Director and Node Coordinators), who serve as liaisons to practitioners and their patients, will participate on study teams of projects selected for UG3/UH3 funding during the planning and implementation phases to provide input about DPBRN operations and activities. Node personnel functions may include: providing oversight of network resources and operations; advising study teams as teams develop clinical research documents, study procedures/processes, materials for practitioners, and training materials for DPBRN personnel; assuring that practitioners are appropriately trained per NIH, IRB and study-specific requirements; and monitoring study execution by practitioners and office/clinic staff. Further, the national DPBRN infrastructure will include the following resources that will be equitably available to the research teams: a) Practitioner Recruitment and Engagement Component, b) Practitioner Training Component, c) Practitioner and Patient Compensation System, and d) Communication and Dissemination Component.

A national DPBRN Coordinating Center (described in RFA-DE-19-002) will serve as the central locus for data coordination/management of studies conducted within the national DPBRN. Coordinating Center personnel will also serve on study teams of projects selected for UG3/UH3 funding. The Coordinating Center’s data coordination/management functions for studies may include: providing scientific input and biostatistics support; assisting study teams in the preparation of study protocols, case report forms, and other study-related documents; developing and maintaining a data management system for study data collection and storage and adverse event reporting; providing randomization support; overseeing data quality management and study monitoring procedures; maintaining primary responsibility for reporting to study teams, the DPBRN Administrative and Resource Center, NIDCR and Data and Safety Monitoring Boards (DSMBs); and providing final datasets ready for analysis by individual study teams.

OVERALL PROGRAM STRUCTURE AND RESEARCH SCOPE

This FOA is soliciting applications for clinical research studies to be conducted in the national DPBRN. UG3/UH3 awards will provide project-specific funds to support the development and implementation of clinical trials or observational clinical studies involving prospective and/or retrospective data collection from DPBRN-participating practitioners and their patients. The UG3/UH3 funding mechanism supports individual projects in two phases, for a total funding period of up to six years. The study development activities and study implementation plans should be well-developed, and the final design of the UH3 clinical study should be defined in the UG3/UH3 grant application. The NIDCR will be substantially involved with the UG3/UH3 awardees as a partner in providing overall scientific and operational guidance, consistent with the Cooperative Agreement mechanism.

Potential applicants are strongly encouraged to contact NIDCR Scientific/Research staff well in advance of the application due date and no later than ten weeks before that date to discuss the suitability of conducting the proposed study within the DPBRN infrastructure. Pre-application consultation may include an introductory conference call with NIDCR Scientific/Research staff. Potential applicants are also strongly encouraged to read the FOAs for the national DPBRN Administrative and Resource Center (RFA-DE-19-001) and national DPBRN Coordinating Center (RFA-DE-19-002).

UG3 Clinical Study Planning Phase

The UG3 planning phase will provide up to two years of support for development of study documents (e.g., study protocol, data collection instruments, Manual of Procedures, study procedure/training documents for practitioners) and finalization of study procedures and operations necessary to implement a clinical study in the DPBRN setting. Additional planning activities such as piloting study procedures to streamline data collection and flow within a busy dental office/clinic setting are allowable. The UG3 phase cannot be used to collect data to support the rationale for a clinical study or pilot test an intervention to develop the final clinical trial design.

Activities supported during the UG3 phase may include, but are not limited to, development of the following:

• A final clinical protocol, prepared using the standard NIDCR observational or interventional protocol template (see NIDCR Toolkit for Clinical Researchers), that is ready for submission to the central IRB;
• Final data collection instruments (case report forms) that are ready to be programmed into an electronic data management system;
• The consent form(s) for practitioners and/or patients and assent form(s), if applicable;
• The final statistical analysis plan;
• A plan for the administration of study intervention, for clinical trials;
• A project work scope to detail study pre-launch and implementation activities during the UH3 phase and the roles/responsibilities of study team personnel and DPBRN infrastructure personnel (e.g., biostatistician, Study Manager, Node Coordinators) in accomplishing these activities;
• The Manual of Procedures (MOP) to be used by Node personnel, who will train practitioners and office/clinic staff on study procedures, including the consent process. The MOP should include a detailed description of study procedures and quality management processes to ensure consistency, completeness and accuracy of data collection across offices/clinics.
• Study procedure training or study-at-a-glance documents for participating practitioners and office/clinic staff, to ensure consistency of data collection procedures across offices/clinics.
• The study-specific data management plan; and
• A recruitment/enrollment and retention plan for the clinical study.

Milestones and UG3/UH3 Transition

All projects must be driven by well-defined milestones for the UG3 planning phase and annual milestones for the UH3 implementation phase. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity. All UG3 grants will need to meet milestones to have an opportunity to move to the UH3 implementation phase. At the completion of the UG3 planning phase, the applicant will be required to submit a detailed transition request package, which will undergo an administrative review to determine whether the study will be awarded funding for the UH3 implementation phase. The UH3 funding period will provide up to four or five years of support, depending on the duration of the UG3 phase (total UG3/UH3 funding of up to six years), to implement the clinical study in the DPBRN. Continued funding during the UH3 phase will be dependent upon meeting annual UH3 milestones, and it is expected that the study will be completed within the UH3 grant period.

Prospective applicants should note that initial funding of the UG3/UH3 cooperative agreement does not guarantee funding of the UH3 phase. Transition to the UH3 phase is dependent on having successfully met the UG3 planning milestones, with consideration of the DPBRN as an appropriate venue in which to conduct the proposed research, NIDCR program priorities, and availability of funds. The quality of the study planning, design, and documentation products for the clinical study are given key consideration when the NIDCR considers the transition to the UH3 phase. The documents and processes developed during the UG3 phase should be sufficient to demonstrate readiness to complete study activation requirements and launch the study within the DPBRN in a timely manner, if awarded the UH3 phase funding.

Research Objectives

The national DPBRN will conduct multiple national oral health clinical studies with a focus on general dental practice and will also incorporate projects of interest to dental specialists and other dental professional groups, specific dental practice settings/types (e.g., federal services, public dental health clinics), and patient advocacy groups. Public-private partnerships may be proposed as part of the recruitment or research plan (e.g. private partner contributing to recruitment strategy to promote practitioner participation in national DPBRN studies). If so, the rationale for this approach should be provided.

Research studies will address oral health issues of importance to dental practitioners and their patients. Numerous study designs may be appropriate for clinical research conducted in the DPBRN. Applicants should propose the strongest research design that is appropriate, acceptable and feasible to answer the research questions. Potential applicants are strongly encouraged to review NIH s Definition of a Clinical Trial. Clinical trial designs may be used where appropriate to establish efficacy or effectiveness of strategies for the prevention, diagnosis, management and/or treatment of oral diseases and conditions. Applicants may also propose other types of clinical studies such as retrospective or prospective observational studies with clearly defined and measurable outcomes. Examples of study designs include cohort studies prospectively ascertaining risk factors for oral disease development, studies that provide longitudinal follow-up of prevention or treatment practices, case-control studies with longitudinal follow-up, cost-effectiveness or efficiency assessments of prevention or treatment practices, and retrospective database analyses proposing extraction of oral health data from individual electronic health records with adjudication of findings. While good evidence exists for many treatments used by dental practitioners to prevent and manage dental, oral, and craniofacial diseases, dissemination and implementation of this knowledge remains a challenge. Therefore, a goal of each study carried out by the national DPBRN is to strengthen the knowledge base for clinical decision-making, and to enhance translation of research findings into practice.

Examples of clinical research studies that might be conducted in the national DPBRN include but are not limited to:

• Research to determine factors that contribute to practitioners decision making regarding oral disease prevention or treatment, such as sealant placement;
• Research to determine the prevalence or incidence of occupational risks in dentistry or interventions to minimize these occupational risks;
• Studies to develop and implement medical condition and risk behavior screening approaches in dental care settings, and to facilitate referral to treatment;
• Research to understand dental provider and patient expectations of acute post-procedure pain to better manage the post-procedure pain experience;
• Research to assess timing of implant placement and treatment outcomes relative to craniofacial growth patterns;
• Observational cohort studies assessing treatment outcomes for oral diseases or conditions (e.g. periodontal disease, Sj gren's syndrome, orofacial pain conditions);
• Research to assess temporomandibular joint function and pain outcomes following orthodontic treatment in patients with and without chronic temporomandibular disorders;
• Research to optimize opioid risk mitigation clinical tools, such as those encouraging the use of prescription drug monitoring programs (PDMPs) and counseling prior to prescribing opioids for acute pain management;
• Clinical trials of interventions to prevent or manage salivary dysfunction.

Additional Information

(1) Applicants to this FOA will be required to incorporate the DPBRN infrastructure into their proposed study plans, including central coordination through the DPBRN Administrative and Resource Center and data management through the DPBRN Coordinating Center. Applicants will be required to use the single IRB that will be established for the DPBRN and is consistent with NIH’s Single IRB Policy as described in NOT-OD-16-094.

(2) Applications to this FOA should include biostatistical expertise to provide study-specific leadership in statistical design and data analysis.

(3) The DPBRN infrastructure personnel and NIDCR Program staff will work with awardees and their study teams to develop the proposed study in the UG3 phase and implement the study during the UH3 phase.

(4) A Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) for an application in response to this FOA may not be a PD(s)/PI(s) or Key Personnel (i.e., Node PD(s)/PI(s)) for an application submitted in response to RFA-DE-19-001 or RFA-DE-19-002.

(5) Priority of funding for DPBRN studies deemed to be highly meritorious by peer review will be based on factors including infrastructure capacity and availability of the patient population within the DPBRN. Further, timing of funding will be determined by the NIDCR to assure that studies can be developed and conducted within the proposed study timeline for the UG3/UH3 grant period included in the Study Record: PHS Human Subjects and Clinical Trials Information of the grant application. It is understood that the proposed timeline for study implementation activities in the UH3 phase may be revised as activities in the UG3 phase progress.

(6) At the time of an award, the PD(s)/PI(s), DPBRN personnel, and NIDCR will negotiate a project work scope and study development activity timeline (for UG3 award) and implementation activity timeline (for UH3 award). The project work scope and timeline will include identifying the primary individual or entity and other contributors responsible for study development, start-up and implementation activities, and the timeline for completion of these activities.

(7) The proposed clinical study must meet all applicable NIH and Office for Human Research Protections (OHRP) policy requirements. Awardees are required to comply with the NIDCR Clinical Terms of Award and the NIDCR Policy on Data and Safety Monitoring for any planning phase activities that involve human subjects and all UH3 studies. It is recommended that applicants use the NIDCR tools and templates for development of the clinical study documents, located in the NIDCR Toolkit for Clinical Researchers.

See Section VIII. Other Information for award authorities and regulations.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from 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) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not 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).

Additional Eligibility Guidance

A Program Director(s)/Principal Investigator(s) for an application in response to this FOA may not be a PD(s)/PI(s) or Key Personnel (i.e., Node PD(s)/PI(s)) for an application submitted in response to RFA-DE-19-001 or RFA-DE-19-002.

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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
Telephone: 301-594-5593
Fax: 301-480-8303
Email: [email protected]

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.

Other Attachments: The application must contain the following information, according to the instructions below. The information provided here will be considered by reviewers and is meant to supplement, not duplicate, information provided in the Research Plan. The following documents must be uploaded as separate pdf files with the names indicated below.

1. Schedule of Events. The filename "Schedule of Events" should be used to name this attachment.

Provide a schematic, table, or text description of the protocol-specified schedule of events for an individual study participant. It should capture each study visit/assessment time point and planned activity(ies) for each time point.

2. Milestone Plan. The filename "Milestone Plan" should be used to name this attachment. A milestone is defined as: a scheduled event in the project timeline that signifies the completion of a major project stage or activity. The Milestone Plan must describe objective, measurable milestones with separate milestones for the UG3 and UH3 phases. The milestone plan must include clearly stated milestones that will be reached at the end of the UG3 planning phase and annual milestones that will be completed during the UH3 implementation phase. The milestone plan should address anticipated challenges to meeting milestones and propose potential mitigation or corrective action strategies.

Milestones may be refined and finalized in consultation with NIDCR Program Staff at the time of the UG3 phase award and the UH3 phase award, if granted.

• Milestones that may be completed during the UG3 phase include, but are not limited to:
• Demonstration that the necessary study population is available within the DPBRN
• Collection of any data to determine feasibility of study procedures and establish a timeline for accrual of study participants
• Finalization of clinical protocol
• Acceptance of the protocol by NIDCR
• Finalization of data collection instruments that are ready to be programmed into an electronic data management system
• Finalization of study-related documents, including consent/assent documents, that are ready for submission to IRB and/or applicable oversight committees
• Finalization of the statistical analysis plan
• Near-final drafts of all documents necessary to implement the study (e.g., Manual of Procedures, study procedure documents for practitioners, study-specific data management plan)

• Milestones that may be completed during the UH3 phase include, but are not limited to:
• Finalization of the data management system
• Practitioner training
• Study activation
• Enrollment of the first patient participant
• Enrollment and randomization, if applicable, of 25%, 50%, 75% and 100% of the projected study population
• Retention target for the study population
• Completion of data collection time period
• Completion of primary outcome data analyses
• Reporting of results in ClinicalTrials.gov, if applicable

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

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

A detailed budget should be provided in the UG3/UH3 application. Budget justifications must be included.

The UG3 budget should include travel funds for the PD(s)/PI(s) to attend an annual face-to-face administrative meeting of DPBRN infrastructure personnel, up to $1500 per person per trip.

The UG3/UH3 budget may include:

• Up to 3.6 person months combined for all PD(s)/PI(s)
• Up to 1.8 person months for each co-Investigator
• Support for a study-specific Study Manager, unless the PD(s)/PI(s) intends to work with a Study Manager from the DPBRN Coordinating Center
• Biostatistical support to provide study-specific leadership in statistical design and data analysis.
• Practicing dental practitioner(s), who may serve a consultant role to provide input about the clinical interest of the study topic and feasibility of performing study procedures within a dental office/clinic setting
• Practitioner and patient remuneration
• Study-specific equipment and supplies
• Study-specific publication costs
• Study-specific costs required for DPBRN resources, operations and/or data systems (i.e., image collection) not otherwise specified in RFA-DE-19-001 or RFA-DE-19-002.
• Study-specific DPBRN infrastructure personnel effort for roles/responsibilities not otherwise specified in RFA-DE-19-001 or RFA-DE-19-002.

The budget will not include costs that are already covered by the DPBRN infrastructure, described in RFA-DE-19-001 and RFA-DE-19-002. Funds to travel to a DPBRN-supported research meeting for practitioners should not be requested, as these travel funds should be paid through DPBRN infrastructure funds.

If parts of the costs of the 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.

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

Provide the overall goals for the entire application and indicate separately Specific Aims to be accomplished in the UG3 phase and in the UH3 phase. Clearly label them as UG3 Specific Aims and UH3 Specific Aims.

Research Strategy

Significance:

The significance, biological and clinical relevance of the proposed study must be stated clearly. It should be supported by the following:

• A clear statement of the question(s) the study will address and its importance.
• The scientific rationale and clinical need for the study, including an assessment of previous preclinical and/or clinical studies and their quality (if applicable).
• The potential for the study results to impact knowledge or clinical practice.
• If the proposed study is a Phase III clinical trial, information about the generalizability of potential findings to US populations.

Investigator(s):

• Describe the expertise of the study team and the team’s ability to plan and implement the planned study and perform appropriate analyses of data collected.

Approach:

The Approach section should have a clear demarcation of the UG3 and UH3 portions of the application.

For the UG3 phase:

• Describe the study development activities planned for the UG3 phase.

For the UH3 phase, if the proposed study design is not a clinical trial:

• Address the feasibility of recruiting participants who are eligible for the proposed research.
• Provide a concise snapshot of the planned clinical study. It is expected to:
• Clearly state the study objectives.
• Describe and provide rationale for the study design, including study groups.
• Specify the primary and important secondary outcome measures that align with each objective and provide justification for selection of the study outcomes.
• Describe how the primary and important secondary outcome variables will be collected and the criteria for measuring the outcomes.
• Describe the study population, including the sample size, pertinent demographic information, required health status or disease condition, and geographic location. Explain why the study population is an appropriate group to address the study objectives. Do not duplicate information described in Section 2 (Study Population Characteristics) of the Study Record: PHS Human Subjects and Clinical Trials Information form.
• Provide a statistical analysis plan, including power calculations, data analysis approaches, and plans for handling missing data.
• Discuss potential biases or challenges in the proposed study and how they will be minimized and/or addressed.

For the UH3 phase, if the proposed study design is a clinical trial:

• Address the feasibility of recruiting participants who are eligible for the proposed research.
• Provide an overview of the proposed study design that must justify the selected trial elements provided in the Protocol Synopsis, including:
• Rationale for the selected trial design/interventional model (e.g., single-group, parallel, cross-over, factorial) and allocation method.
• Rationale for selection of the intervention to be tested and a description of how and at what frequency the intervention will be administered.
• For behavioral interventions, demonstration that an intervention engages the mechanism of action target(s) it intends to, and that target engagement can be measured.
• Justification for selection of the primary and secondary outcome measures and a description of how the outcome variables will be collected and the criteria for measuring the outcomes.
• Description of the study population, including the sample size, pertinent demographic information, required health status or disease condition, and geographic location. Explain why the study population is an appropriate group to address the study objectives. Do not duplicate information described in Section 2 (Study Population Characteristics) of the Study Record: PHS Human Subjects and Clinical Trials Information form.
• Discuss potential biases or challenges in the proposed trial and how they will be minimized and/or addressed.

Environment:

• Provide rationale for why the DPBRN is an appropriate venue for the proposed study.
• Provide a proposal of DPBRN resources to be used to ensure successful development and implementation of the proposed study to be conducted in the DPBRN.

Letters of Support: Letters of support from research collaborators, patient organizations, or other groups the investigators propose to work with should be included.

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, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan and a plan to share research resources (data collection instruments, study protocols), managed by the DPBRN infrastructure, as appropriate and consistent with achieving the goals of the DPBRN program.

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

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

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Section 2 - Study Population Characteristics

2.5 Recruitment and Retention Plan

The DPBRN infrastructure personnel will contribute towards recruiting practitioners for participation in studies conducted within the DPBRN and developing systems to assist practitioners in maintaining high rates of patient recruitment and retention. DPBRN infrastructure personnel may also assist with DPBRN study retention efforts.

Describe the plan to recruit/enroll the practitioner population of interest for the clinical study and the plan for patient recruitment with DPBRN-participating offices/clinics, including outreach activities and pre-study assessments of the ability of participating practices to recruit the proposed target number of participants. Include a discussion of any study design strategies and/or methods to minimize selection bias and maximize flexibility for practitioner and patient recruitment. Describe the plan to meet the study’s retention targets. Include a discussion of strategies for retention of practitioners and their patients, including any methods to maximize flexibility for data collection after baseline (e.g., data collection independent of office visits).

2.7 Study Timeline

Applicants should provide separate project performance timelines for the UG3 planning phase and the UH3 implementation phase of grant period. The UH3 timeline should include the estimated time for completion of each of the UG3 milestones (see "Other Attachments"). UH3 timeline should include the estimated time to: a) open study to enrollment; b) complete data collection; and c) complete final data analysis. Project performance timelines will be refined and finalized in consultation with NIDCR Program Staff and DPBRN personnel at the time of the UG3 phase award and the UH3 phase award, if granted.

Section 3 - Protection and Monitoring Plans

3.2 Is this a multi-site study that will use the same protocol to conduct non-exempt human subjects research at more than none domestic site?

In the associated single IRB plan attachment, indicate that the study will be submitted to the single IRB that will be established for the DPBRN.

3.3 Data and Safety Monitoring Plan

Section 3.3 must be completed for all applications, including those that do not propose a clinical trial. Data and safety monitoring will be the joint responsibility of the study team, the DPBRN Administrative and Resource Center, and the DPBRN Coordinating Center. The DPBRN Coordinating Center will develop a data management system for study data collection and adverse event reporting and will maintain primary responsibility for reporting of adverse events, unanticipated study events and protocol deviations to ensure participant safety.

Describe the study-specific plan to ensure data and safety monitoring, including plans to assure the integrity of the clinical study data being collected, proposed methods and systems for data collection (e.g., paper or electronic data collection systems) and data entry, and procedures for data quality management and study monitoring. Do not name members of any oversight board in the application. The NIDCR will appoint members of any oversight committees after consultation with the investigators.

3.5 Overall Structure of the Study Team

Section 3.5 must be completed for all applications, including those that do not propose a clinical trial. Indicate that DPBRN Administrative and Resource Center personnel will participate on study teams to provide input about DPBRN operations, activities, and resources, and DPBRN Coordinating Center personnel will serve on study teams to provide data coordination/management functions.

Biostatistician and Study Manager: If the study team intends to work with a biostatistician not affiliated with the DPBRN Coordinating Center, describe the roles and responsibilities of the biostatistician for the proposed project. If the study team intends to work with a Study Manager not affiliated with the DPBRN Coordinating Center, describe the roles and responsibilities of the Study Manager.

Section 4 - Protocol Synopsis

4.7 Dissemination Plan

UG3/UH3 applicants must submit a plan for the dissemination of NIH-funded clinical trial information that will address how the expectations of the NIH Policy on the Dissemination of NIH-funded Clinical Trial Information will be met. Responsibility for adhering to this policy lies with the UG3/UH3 grantee institution, not with the DPBRN Administrative and Resource Center or DPBRN Coordinating Center awardees.

Delayed Onset Study

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

Do not enter a delayed onset study. The UH3 study should not be considered a delayed onset study, as it is expected that the proposed study can be described even though it will not start immediately (i.e., the UH3 study will have a delayed start).

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

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

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

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. 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. For assistance with application submission, contact the Application Submission Contacts in Section VII.

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 NIDCR, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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

Only the review criteria described below will be considered in the review process.

Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this specific announcement, note the following:

(1) Successful UG3/UH3 applications will utilize the DPBRN infrastructure and resources for study planning during the UG3 phase and, if criteria are met to transition to the UH3 phase, study implementation during the UH3 phase. DPBRN infrastructure and resources are available through the DPBRN Administrative and Resource Center (described in RFA-DE-19-001) and DPBRN Coordinating Center (described in RFA-DE-19-002).

(2) The DPBRN is a unique venue in which to conduct clinical studies. The DPBRN infrastructure will provide centralized study operations, data management, and coordination. The DPBRN includes a strong, flexible network of practitioners and offices/clinics (sites) with capacity to implement large, national clinical studies. Study enrollment and retention will be overseen by the DPBRN.

In addition, for applications involving clinical trials:

A proposed Clinical Trial application may include study design, methods, and interventions that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or may lead to new avenues of scientific investigation.

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

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

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Does the proposed study have a clear statement of the question(s) that the study will address and its importance? Does the application provide sufficient scientific rationale and clinical need for the study? How compelling is the potential for the proposed study to increase knowledge or inform clinical practice?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well-supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding? For Phase III trials, is there potential for generalizability of study findings to US populations?

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 sufficient expertise to develop and implement the planned study and perform appropriate analyses of data collected?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to plan and implement the proposed clinical trial and meet milestones and timelines? Is the organizational structure appropriate? Do they have appropriate expertise in study coordination and statistics?

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

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

Does the application address the feasibility of recruiting participants who are eligible for the proposed research? Are the study objectives stated clearly? Is there a description of the proposed study design, and is it appropriate to address the study objectives? Are the primary and secondary outcome variables described, justified, and is there a description of how they will be collected and measured? Is the study population appropriate and justified? Is the statistical analysis plan appropriate? Does the application address potential biases or challenges, and are plans to minimize these biases appropriate? Is there an adequate discussion of potential challenges that are anticipated during planning and study implementation, and how they will be addressed? Is the timeline for developing, implementing, and completing the study appropriate?

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 individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

For the UG3 planning phase: Are there clear plans for developing a final study protocol, final data collection instruments (e.g. case report forms) and other study-related documents?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable:

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well-justified? Is there justification for selection of the intervention, and is there adequate discussion of how and at what frequency the intervention will be administered? For behavioral interventions, does the application demonstrate that the intervention engages the mechanism of action target(s) it intends to, and that target engagement can be measured?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approaches appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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? Is the DPBRN an appropriate venue in which to conduct the research? How well does the project leverage resources of and ensure collaboration with the DPBRN?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers?

If multi-sites/centers, is there evidence of the ability of the sites or centers to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

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.

Study Timeline

Is the project performance timeline for the UG3 phase feasible to accomplish the proposed study development activities within the proposed timeframe? Is the project performance timeline for the UH3 phase feasible to implement and complete the study within the proposed timeframe? Does the UH3 timeline include the estimated time to: a) open study to enrollment; b) complete data collection; and c) complete final data analysis?

Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Other Attachments

Regarding the additional documents included as "Other Attachments":

Schedule of Events

Is the Schedule of Events for an individual study participant described and appropriate for the study design and data to be collected? Are the procedures and frequency of visits in the proposed schedule of events for the study reasonable and feasible?

Milestone Plan

Are the milestones and activities clearly stated? Are appropriate, measurable milestones clearly defined for the UG3 phase? Is it likely that the investigator team will meet these milestones within the proposed UG3 project period? Are appropriate, measurable annual milestones clearly defined for the UH3 phase? Are the annual milestones feasible to be accomplished during the proposed UH3 project period? Does the application address contingency plans in the event the UG3 and/or UH3 milestones are not achieved?

For research that involves human subjects but does not involve one of the 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 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.

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 individuals of all ages (including children and older adults) 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.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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.

Not Applicable

Not Applicable

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.

Not Applicable

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).

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 Data Sharing Plan (GDS).

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

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 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.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. 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. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials, by law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE). No IND/IDE studies can be conducted under this FOA.

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.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 Part 75, 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 primary responsibility for:

• Providing scientific leadership for all aspects of the study, including planning, 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 the DPBRN and other investigators. The PD(s)/PI(s) 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;
• While developing the study during the UG3 planning phase and implementing the study during the UH3 phase, convening or participating on teleconferences to facilitate collaboration and communication with the DPBRN Administrative and Resource Center and DPBRN Coordinating Center personnel, NIDCR Program staff, and steering committees;
• Adhering to the NIDCR Clinical Terms of Award and the NIDCR Policy on Data and Safety Monitoring requiring that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study;
• Upon implementation of the study, following the procedures required by the protocol and DPBRN regarding study conduct and monitoring, participant management, data collection, and quality control;
• Retaining custody of and having primary rights to the data developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies;
• Managing 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;
• Making all study materials and procedure manuals and final datasets available in the public domain, managed by the DPBRN infrastructure. Awardees are expected to publish and publicly disseminate results, data, and other products of the study, concordant with DPBRN and NIH governance policies and protocols. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of support by the NIDCR/NIH and DPBRN infrastructure awards;
• Obtaining 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 have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

An NIDCR Project Scientist will be assigned. The NIDCR Project Scientist will:

• Consult with the PD(s)/PI(s) regarding UG3 milestones for the planning phase of the study and annual milestones for the UH3 implementation phase;
• Serve as a resource to provide scientific/programmatic support during research study planning and implementation by providing input on experimental and clinical approaches and study protocols, and advising in the management and operational aspects of study development and implementation;
• Work closely with the study PD(s)/PI(s), DPBRN Administrative and Resource Center personnel, and DPBRN Coordinating Center personnel to facilitate collaboration during the study planning and implementation phases;
• Participate on teleconferences with PDs/PIs and DPBRN personnel to monitor study development and implementation progress, adherence to the study protocol, conduct of the study, and recruitment and retention of study participants;
• Review the progress of the study through consideration of routine reporting, site visits, oversight committee recommendations, etc. This review may include, but not be limited to, compliance with the study protocol, meeting participant enrollment targets, adherence to uniform data collection procedures, and the timeliness and quality of data reporting;
• Have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. NIDCR staff may use information obtained from the data for the preparation of internal reports on the activities of the study. However, awardees and the DPBRN will retain custody of and have primary rights to all data developed under these awards, subject to Government right of access consistent with HHS, PHS and NIH policies.

An NIDCR Program Official will be assigned. The NIDCR Program Official will:

• Carry out continuous review of all activities to ensure that the objectives are being met and that all regulatory, fiscal, and administrative matters are handled according to NIH guidelines;
• Have the option to withhold support to a participating institution if technical performance requirements are not met;
• Perform other duties required for normal program stewardship of grants.

An NIDCR Medical Officer will monitor the studies and serve as the Medical Monitor.

The NIDCR reserves the right to terminate or curtail 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 and retention, 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:

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

• Awardees will work collaboratively with the DPBRN Administrative and Resource Center and the DPBRN Coordinating Center and may be required to accept common development and implementation procedures, methodologies, training, clinical research data collection systems, and quality management processes necessary to develop and deploy studies in the DPBRN.
• Study Teams: DPBRN Administrative and Resource Center and Coordinating Center personnel will be active participants on study teams, and a designated NIDCR staff person will participate on study team teleconferences periodically to monitor progress with study development and implementation activities.

Dispute Resolution:

With the exception of the decision about transitioning to the UH3 phase, 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 chosen by the PD/PI, 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.

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 RPPR, 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.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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, application errors and warnings, documenting system problems that threaten on-time submission, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application processes and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Dena Fischer, DDS, MSD, MS
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4876
Email: [email protected]

Yasaman Shirazi, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-5593
Email: [email protected]

Diana Rutberg, MBA
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
Email: [email protected]

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 Part 75.