Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Dental and Craniofacial Research (NIDCR)

Funding Opportunity Title

NIDCR Clinical Trial Implementation or Biomarker Clinical Evaluation Study Cooperative Agreement (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

Reissue of PAR-08-196

Related Notices

  • June 3, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same.
  • May 30, 2013 (NOT-OD-13-074) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.

Funding Opportunity Announcement (FOA) Number

PAR-11-339

Companion FOA

PAR-11-338, R34 Clinical Trial Planning Grant Program

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.121

FOA Purpose

This FOA issued by the National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health, will support investigator-initiated Phase I, II, III or IV clinical trial cooperative agreement applications or biomarker evaluation studies that require prospective collection of clinical outcomes and clinical specimens.  All applicants must have received an NIDCR Clinical Trial Planning (R34) award to plan the proposed cooperative agreement study (see PAR-11-338 for information about NIDCR Clinical Trial or Biomarker Clinical Evaluation Study Planning Grants).  NIDCR may consider an exception. A unique application is required for each proposed study, and must include a final draft of the study protocol, a Manual of Procedures and other supporting materials such as the Investigator’s Brochure. These documents must meet all National Institutes of Health (NIH), Food and Drug Administration (FDA), and Office of Human Research Protections (OHRP) requirements. All awards will be made as cooperative agreements.

Key Dates
Posted Date

September 16, 2011

Open Date (Earliest Submission Date)
Letter of Intent Due Date

30 days prior to receipt date

Application Due Date(s)

First Receipt Date November 18, 2011, then Standard dates , by 5:00 PM local time of applicant organization.

AIDS Application Due Date(s)

Standard dates by 5:00 PM local time of applicant organization.

Scientific Merit Review

Standard dates

Advisory Council Review

Standard dates

Earliest Start Date(s)

Standard dates

Expiration Date

January 8, 2015

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (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.


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Table of Contents

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

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 associated 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.

As announced in NOT-DE-11-002, the NIDCR will support investigator-initiated interventional clinical trials or biomarker clinical evaluation studies through a two-part grant process: (1) a clinical trial or biomarker clinical evaluation study planning grant (R34) followed by (2) a clinical trial or biomarker clinical evaluation study implementation cooperative agreement (U01) award. This FOA, NIDCR Clinical Trial or Biomarker Clinical Evaluation Study Implementation Cooperative Agreement (U01), addresses the clinical trial or study implementation cooperative agreement; a companion FOA

NIDCR Clinical Trial or Biomarker Clinical Evaluation Study Planning Grant (R34), (PAR-11-338) addresses the R34 grant.

Because clinical trials and biomarker clinical evaluation studies are costly and time-intensive, NIDCR anticipates funding only those trials or studies of the 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.

A clinical trial is defined by NIH as a prospective biomedical or behavioral research study of human subjects that is designed to answer specific questions about biomedical or behavioral interventions (drugs, treatments, devices, biologicals, or new ways of using known drugs, treatments, biologicals or devices). Clinical trials are used to determine whether biomedical or behavioral interventions are safe, feasible, acceptable, efficacious, and effective. A biomarker clinical evaluation study is designed to validate candidate biomarker(s) for their specificity, sensitivity, robustness and utility in an independent prospectively recruited cohort for prognostic or diagnostic purposes.

Examples of studies that might be supported by this FOA include but are not limited to:

1. 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);

2. Clinical trials focusing on the prevention or treatment of oral manifestations or complications of infections caused by herpes viruses, and other pathogens with oral targets or manifestations;

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

4. Clinical trials testing new therapeutics or management strategies for oral candidiasis and other fungal infections;

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

6. Clinical trials to prevent or manage salivary dysfunction;

7. Clinical trials testing treatments for temporomandibular dysfunction;

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

9. Clinical trials testing methods to increase preventive health behaviors or change oral health outcomes through behavioral modification;

10. Clinical evaluation of biomarker(s) of oral or dental diseases, e.g. periodontal diseases, head and neck cancers, salivary dysfunctions, through prospective collection of biospecimens and clinical outcomes; or

11. Clinical evaluation of biomarker(s) of systemic diseases through prospective collection of oral biospecimens and clinical outcomes.

Overview of the NIDCR policy for investigator-initiated clinical trials or biomarker clinical evaluation studies:

The first step (Part 1) of the NIDCR clinical trials or biomarker evaluation studies grant process is the Clinical Trial or Biomarker Evaluation Study Planning Grant (R34). The NIDCR Clinical Trial or Biomarker Evaluation Study Planning Grant (R34) supports the complete planning, design and documentation needed for investigator-initiated Phase I, II, III or IV clinical trials or biomarker clinical evaluation study. The R34 grant will provide up to one year of support for clinical trial or biomarker clinical evaluation study planning. R34 awardees who complete their planning activities and have compelling justification to proceed to a clinical trial or biomarker clinical evaluation study will submit a cooperative agreement application (U01) for clinical trial or biomarker clinical evaluation study implementation (details are presented in this FOA). If the investigators conclude that a clinical trial or biomarker clinical evaluation study is not warranted, the reasons for not proceeding with the U01 implementation application must be documented in the final progress report to the NIDCR that summarizes the R34 award activity.

Following the completion of Part 1, the clinical trial or biomarker clinical evaluation study planning process, investigators may apply for Part 2, the Clinical Trial or Biomarker Clinical Evaluation Study Implementation Cooperative Agreement (U01). The NIDCR will accept, peer review, and consider funding applications for implementation of investigator-initiated clinical trials or biomarker clinical evaluation studies only from R34 awardees except on rare occasions. An applicant who can demonstrate that all activities needed for submission of a Clinical Trial Implementation or Biomarker Clinical Evaluation Study Cooperative Agreement (U01) application were completed with other funding may request from the NIDCR an exception for the R34 award prerequisite. Each clinical trial or biomarker clinical evaluation study implementation application will include the clinical protocol, Clinical Investigator's Brochure where appropriate or other equivalent document(s) that contains relevant non-clinical and preclinical data on study products, and the Manual of Procedures. The clinical study must meet all applicable NIDCR, NIH, Food and Drug Administration (FDA), and Office of Human Research Protections (OHRP) policy requirements. Good Clinical Practice guidelines can be found at http://www.fda.gov/oc/gcp/default.htm.  If the application proposes a clinical trial with a drug or device, the investigators must have submitted the appropriate investigational application to the Food and Drug Administration. Consolidated guidance for clinical trials is presented at http://www.fda.gov/RegulatoryInformation/Guidances/ucm122046.htm.

Planning grant awardees must prepare their protocols, Clinical Investigators' Brochures, and Manuals of Procedures to meet NIDCR standards (see http://www.nidcr.nih.gov/GrantsAndFunding/PoliciesandGuidance/ClinicalResearch/ for the NIDCR Clinical Protocol template).

A clinical trial or biomarker clinical evaluation study implementation cooperative agreement application should describe all necessary components to successfully conduct a clinical trial or biomarker clinical evaluation study. This would include a description of the administrative structure, the identification and qualifications of the study chair, the data coordinating center, appropriate clinical site(s) and specialized core facilities (if applicable). Multidisciplinary work should incorporate specific relevant expertise from relevant subject areas to encourage high impact contributions. The materials developed in the R34 phase will allow the U01 applicant to initiate study staff training followed by study subject recruitment soon after peer review and final NIDCR approval of the clinical protocol.

Awardees are required to comply with NIDCR Clinical Terms of Award.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information
Funding Instrument

Cooperative Agreement

Application Types Allowed

New
Renewal
Resubmission
Revisions

The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications. The total amount awarded and the number of awards will depend upon the relevance of the proposed trial to the NIDCR mission and strategic plan, trial or study complexity, anticipated duration, and associated operational trial or study proposed costs.

Award Budget

Application budgets are not limited, but need to reflect actual needs of the proposed project. Because the nature and scope of the proposed research will vary between applications, it is anticipated that the size and duration of each award will also vary.

Award Project Period

The maximum amount of time requested for clinical trial or biomarker clinical evaluation study implementation cooperative agreements may not exceed five years.

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:

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

Nonprofits Other Than Institutions of Higher Education

For profit Organizations

Governments

Other

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 must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal Investigator(s))

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 PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (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.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

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, 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.

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 research
Name, address, and telephone number of the PD(s)/PI(s)
Names of other key personnel
Participating institutions including planned clinical sites
Number and title of this funding opportunity

The letter of intent should be sent to:

Yasaman Shirazi, PhD
Chief, Scientific Review Branch
National Institute of Dental and Craniofacial Research
1DEM, Room 662, MSC 4878
6701 Democracy Boulevard
Bethesda, Maryland 20892
(Courier 20817)
Telephone: 301-594-5593
Fax: 301-480-8303
Email: yasaman.shirazi@nih.gov

Required and Optional Components

The forms package associated with this FOA includes all applicable components, mandatory and optional.  Please note that some components marked optional in the application package are required for application submission. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

Page Limitations

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

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

Other Project Information Component of the SF 424 (R&R)

Item 10. Facilities and Other Resources.

It is suggested that these documents  be prepared using the NIDCR templates. Investigators are referred to the NIDCR Toolkit website for clinical research guidance and templates http://www.nidcr.nih.gov/ClinicalTrials/ToolkitClinicalResearchers/PoliciesGuidance/.

Budget

PHS 398 Components

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

PHS Cover Letter Component

the budget request is greater than $500,000 in direct costs in any one year. The cover letter must identify the IC and the staff member who agreed to accept assignment of the application.

PHS 398 Research Plan Component

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

Specific Aims: The goals of the trial or study and the expected outcome(s) should be concisely stated. The specific objectives of the trial or study must be clearly and concisely presented, including a specification of the primary and major secondary endpoints to be measured. There should be a clear explanation of the importance of the various endpoints, and  how the results of the trial or study will l impact our knowledge or clinical management of the disease. If this is a Phase III trial or multi-center biomarker clinical evaluation study, the generalizability of potential findings should be discussed.

Research Strategy:

The Research Strategy section should be focused and should reference the appropriate sections of the clinical trial or biomarker clinical evaluation study application, such as documents included in Item 12. Other Attachments (e.g., Clinical Protocol, Manual of Procedures) and the Human Subjects Section.

Significance

Innovation

Approach

The approach should be presented briefly and reference appropriate sections of the appended Clinical Protocol and/or Manual of Procedures.  The following should be covered:

The organizational structure, administration and management of the trial, especially the relationships among the administrative center, data coordinating center, participating enrollment centers, and the laboratory/ testing center; and scientific composition and responsibilities of the administrative and scientific committees such as the steering committee, executive committee, and publication committee. 

Requirements for preparing the Human Subjects Section.

Instructions in the Application Guide SF424 (R&) “Part II Supplemental Instructions for Preparing the Protection of Human Subjects Section of the Research Plan” should be closely followed, and as required, include:

Data and Safety Monitoring (DSM) Plan

A Data and Safety Monitoring (DSM) Plan that is commensurate with the risk level of the proposed clinical research must be included for all NIDCR clinical trials and studies

 (see http://grants.nih.gov/grants/guide/notice-files/not98-084.html and http://www.nidcr.nih.gov/ClinicalTrials/ToolkitClinicalResearchers/PoliciesGuidance/DataandSafetyMonitoring.htm). All clinical trial or biomarker clinical evaluation study applications must include a general description of the monitoring plan, policies, procedures, responsible entities, and approaches to identifying, managing and reporting reportable events (adverse events and unanticipated problems), to the applicable regulatory agencies (e.g., Institutional Review Board (IRB), the NIDCR/NIH, the Office of Biotechnology Activities (as appropriate), the Office of Human Research Protections, the Food and Drug Administration, and the Data and Safety Monitoring Board (if one is used). The DSM Plan must address the following areas:

Awardees under this FOA must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI "Award Administration Information." NIDCR reserves the right to review the complete set of documents submitted to the appropriate regulatory authorities, the product development plan, and communications with the regulatory authorities if study product will be under Investigational New Drug Application (IND) or Investigational Device Exemption (IDE).

Resource Sharing Plan

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

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, with the following modifications: 

The following required materials should be submitted in the Appendix (note: A maximum of 10 PDF attachments is allowed in the Appendix.)

Foreign Organizations

Foreign (non-US) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations 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 in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via 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.

Applicants are responsible for viewing their application 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 SF 424 (R&R) Application Guide.  Paper applications will not be accepted.

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD(s)/PI(S) Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

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 Central Contractor Registration (CCR). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review NIH. Applications that are incomplete will not be reviewed.

In order to expedite review, applicants are requested to notify the NIDCR Referral Office by email at adombroski@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD(s)/PI(s) name, and title of the application.

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 SF 424 (R&R) Application Guide.

Applicants must include a cover letter with the application that identifies the staff member and IC who agreed to accept assignment of the application requesting $500,000 or more in direct costs in any year.  This policy applies to all new, revision, or resubmission applications. See NOT-OD-02-004.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Section V. Application Review Information

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/priority 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?

Is the significance of the proposed clinical trial or biomarker clinical evaluation study supported by the following?  

Investigator(s)    

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? 

Are the leadership and organization of the study clearly described and dothey adequately address the following:

Innovation

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

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? 

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

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

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?   Are adequate facilities in place to conduct clinical trials or biomarker clinical evaluation studies? Is the study population required for the proposed study available at the proposed clinical sites?  Does the data coordination 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/priority score, but will not give separate scores for these items.

Clinical Trial or Biomarker Clinical Evaluation Study Plans:

Data and Safety Monitoring

             Risks involved;

             Ethical aspects of risks;

             Risk-benefit balance;

             Informed consent procedures;

             Procedures for assessing, recording and reporting adverse events and unanticipated Problems;       

             Criteria for withdrawal;

             Clinical Monitoring Plan;

             Safety Oversight (Independent Safety Monitor, Safety Monitoring Committee, or Data and Safety Monitoring Board (required for a Phase III trial); and

             Provisions for early trial or study termination.

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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children 

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

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/priority score.

Applications from Foreign Organizations

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

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

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. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

·       Will receive a written critique.

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

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 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 the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants 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 OMB administrative guidelines, HHS 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 terms and conditions of award are representative of the specific terms and conditions that will be negotiated with an applicant prior to award. The terms and conditions will be modified as appropriate to each clinical trial consistent with necessary roles and responsibilities. At a minimum, all awardees must abide by the conditions set forth in the NIDCR Clinical Terms of Award.

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 primary responsibility for:

        1.  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.  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;

         2.   Meeting NIDCR policy requiring that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study. An updated NIDCR policy 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 clinical center, whether a single institution or a consortium of institutions, will follow the procedures required by the protocol regarding study conduct and monitoring, patient management, data collection, and quality control;

         3.   Retaining custody of and having 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;

          4.  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;

          5.  Making 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; and

          6.  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:

             1.  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 will retain custody of and have primary rights to all data developed under these awards, subject to Government rights of access consistent with HHS, PHS, and NIH policies;

            2.  Provide guidance and support in the development, assembly, and submission of all required regulatory documents, e.g., those regarding the use of investigational drugs, to the Food and Drug Administration;

            3.  Serve as a resource to provide scientific/programmatic support during the accomplishment of the research by participating in the design of the activities, advising in the selection of sources or resources (e.g., determining where a particular reagent can be found), provision of research resources and reagents available from the NIDCR grantees and contractors, advising in management and technical performance, or participating in the preparation of publications; and

              4.  Review the progress of the study, and of each participating facility, through consideration of the annual reports, site visits, patient logs, etc. This review may include, but is not limited to, compliance with the study protocol, meeting patient enrollment targets, adherence to uniform data collection procedures, and the timeliness and quality of data reporting.

An NIDCR Medical Officer will monitor the clinical trials or biomarker clinical evaluation studies and serve as the Medical Monitor. Should a pharmaceutical or biotechnology company sponsoring a clinical trial or biomarker clinical evaluation study choose to name its own Medical Monitor, then the NIDCR Medical Officer will work with the company-assigned Medical Monitor.

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

A Steering Committee (SC), composed of the principal investigator, as well as the principal investigators of the clinical center(s) / site(s), the Data Coordinating Center and the specialized core facilities (if any). The NIDCR Project Scientist or Program Official may be non-voting observers on the SC and, as appropriate, its subcommittees. The SC will have primary responsibility for facilitating the conduct and monitoring of studies and reporting study results. Awardees will be required to accept and implement the common protocol and procedures approved by the SC. As the components of the SC may be geographically dispersed, the SC should meet with monthly conference calls, supplemented as deemed necessary by face-to-face meetings.  Each full member will have one vote. 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 or curtail the study (or an individual award) 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 (e) human subject ethical issues that may dictate a premature termination.

Additionally, an agency Program Official or IC Program Director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

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. It will have three members: 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 regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) 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

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Scientific/Research Contact(s)

Jane Atkinson, DDS
Director, Center for Clinical Research
Division of Extramural Research
National Institute of Dental and Craniofacial Research
1DEM, Room 634, MSC 4878
6701 Democracy Boulevard
Bethesda, MD 20892-4878
Telephone: (301) 435-7908
Fax: (301) 480-8319
Email: jatkinso@mail.nih.gov

Peer Review Contact(s)

Yasaman Shirazi, PhD
Chief, Scientific Review Branch
NIDCR, NIH
6701 Democracy Boulevard, Suite #662
Bethesda, Maryland 20892
(Courier 20817)
Tel: (O)301-594-5593, (c)301-335-6233
Fax: 301-480-8303
Email: yasaman.shirazi@nih.gov

Financial/Grants Management Contact(s)

Mary Greenwood
Chief, Grants Management Branch
National Institute of Dental and Craniofacial Research
1DEM, Room 658
6701 Democracy Blvd, MSC 4878
Bethesda, MD 20892-4878
Telephone: (301) 594-4808
Fax: (301) 480-3562
E-mail: md74u@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.


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