Part I Overview Information


Department of Health and Human Services

Participating Organizations
Food and Drug Administration (FDA) http://www.fda.gov

Components of Participating Organizations     
Office of Orphan Products Development (OPD) ( http://www.fda.gov/orphan/)

Title:  Clinical Studies of Safety and Effectiveness of Orphan Products; Research Project Grant (R01)

Note: The policies, guidelines, terms, and conditions stated in this announcement may differ from those used by the NIH.

Announcement Type
New

Update: The following update relating to this announcement has been issued:

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide. 

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process with Grants.gov and eRA Commons is necessary before submission and applicants are highly encouraged to start the process at least four weeks prior to the grant submission date. See Section IV.

Request for Application (RFA) Number: RFA-FD-08-001

Catalog of Federal Domestic Assistance Number(s)
93.103

Key Dates
Release/Posted Date: November 29, 2007
Opening Date:  January 6, 2008 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): Not Applicable
NOTE: On time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization). 
Application Submission/Receipt Date(s): February 6, 2008; February 4, 2009
Expiration Date: December 29, 2008 (per re-issuance as RFA-FD-09-001) – Previously: February 5, 2009

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

This Funding Opportunity Announcement (FOA) will use the Research Project Grant (R01) award mechanism.

Note: Special instructions for foreign organizations are denoted by (FOREIGN*).

Table of Contents


Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives


Section II. Award Information
1. Mechanism of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants

    A. Eligible Institutions
    B. Eligible Individuals
2. Cost Sharing or Matching
3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
1. Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
    A. Submission, Review, and Anticipated Start Dates
          1. Letter of Intent
    B. Submitting an Application Electronically to the FDA
    C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
    A. Additional Review Criteria
    B. Additional Review Considerations
    C.  Sharing Research Data
    D.  Sharing Research Resources
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices

2. Administrative and National Policy Requirements
3. Reporting

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)

2. Peer Review Contact(s)
3. Financial/Grants Management Contacts(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement


Section I. Funding Opportunity Description


NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide. 

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process with Grants.gov and eRA Commons is necessary before submission and applicants are highly encouraged to start the process at least four weeks prior to the grant submission date. See Section IV.

1. Research Objectives

The Research Project Grant (R01) is an award to support a discrete, specified, circumscribed project to be performed by named Project Directors/Principal Investigators (PDs/PIs) in areas representing the investigators’ specific interests and competencies based on the mission of FDA.

FDA awards R01 grants to institutions/organizations of all types. This mechanism allows the PDs/PIs to define the scientific focus or objective of the research based on particular areas of interest and competence. Although the PDs/PIs write the grant application and are responsible for conducting and supervising the research, the actual applicant is the research institution/organization.

OPD was created to identify and promote the development of orphan products. Orphan products are drugs, biologics, medical devices, and foods for medical purposes that are indicated for a rare disease or condition (that is, one with a prevalence, not incidence, of fewer than 200,000 people in the United States). Diagnostic tests and vaccines will qualify only if the U.S. population of intended use is fewer than 200,000 people a year. Additional information regarding OPD and the FOA tips page are available on FDA's Web site at www.fda.gov/orphan.

The goal of FDA's OPD grant program is to support the clinical development of products for use in rare diseases or conditions where no current therapy exists or where the product will improve the existing therapy. FDA provides grants for clinical studies on safety and/or effectiveness that will either result in, or substantially contribute to, market approval of these products. Applicants must include in the application's “Background and Significance” section documentation to support the estimated prevalence of the orphan disease or condition and an explanation of how the proposed study will either help gain product approval or provide essential data needed for product development. All funded studies are subject to the requirements of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 331 et seq.), regulations issued under it, and applicable Department of Health and Human Services (HHS) statutes and regulations.

For specific information about the mission of each FDA Center, see About FDA.

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

Section II. Award Information


Except for applications for studies of medical foods that do not need premarket approval, FDA will only award grants to support premarket clinical studies to determine safety and effectiveness for approval under section 505 or 515 of the act (21 U.S.C. 355 or 360e) or safety, purity, and potency for licensing under section 351 of the Public Health Service Act (the PHS Act) (42 U.S.C. 262). FDA will support the clinical studies covered by this notice under the authority of section 301 of the PHS Act (42 U.S.C. 241). FDA's research program is described in the Catalog of Federal Domestic Assistance (CFDA), No. 93.103.

1. Mechanism of Support

Support will be in the form of a research project (R01) grant. All awards will be subject to all policies and requirements that govern the research grant programs of the PHS Act as incorporated in the HHS Grants Policy Statement, dated October 1, 2006, (http://www.hhs.gov/grantsnet/adminis/gpd/index.htm), including the provisions of 42 CFR part 52 and 45 CFR parts 74 and 92. The regulations issued under Executive Order 12372 do not apply to this program. The National Institutes of Health (NIH) modular grant program does not apply to this FDA grant program. All grant awards are subject to applicable requirements for clinical investigations imposed by sections 505, 512, and 515 of the act (21 U.S.C. 360b), section 351 of the PHS Act, regulations issued under any of these sections, and other applicable HHS statutes and regulations regarding human subject protection.

2. Funds Available

Award Amount

Of the estimated FY 2009 funding ($14.2 million), approximately $10 million will fund noncompeting continuation awards, and approximately $4.2 million will fund 10 to 12 new awards, subject to availability of funds. It is anticipated that funding for the number of noncompeting continuation awards and new awards in FY 2010 will be similar to FY 2009. Grants will be awarded up to $200,000 or up to $400,000 in total (direct plus indirect) costs per year for up to 4 years. Please note that the dollar limitation will apply to total costs, not direct costs, as in previous years. A fourth year of funding is available only for phase 2 or 3 clinical studies. Applications for the smaller grants ($200,000) may be for phase 1, 2, or 3 studies. Study proposals for the larger grants ($400,000) must be for studies continuing in phase 2 or 3 of investigation.

Phase 1 studies include the initial introduction of an investigational new drug (IND) or device into humans, are usually conducted in healthy volunteer subjects, and are designed to determine the metabolic and pharmacological actions of the product in humans, the side effects including those associated with increasing drug doses. In some Phase 1 studies that include subjects with the rare disorder, it may also be possible to gain early evidence on effectiveness.

Phase 2 studies include early controlled clinical studies conducted to: (1) Evaluate the effectiveness of the product for a particular indication in patients with the disease or condition and (2) determine the common short-term side effects and risks associated with it.

Phase 3 studies gather more information about effectiveness and safety that is necessary to evaluate the overall risk-benefit ratio of the product and to provide an acceptable basis for product labeling. Budgets for each year of requested support may not exceed the $200,000 or $400,000 total cost limit, whichever is applicable.

Length of Support

The length of support will depend on the nature of the study. For those studies with an expected duration of more than 1 year, a second, third, or fourth year of noncompetitive continuation of support will depend on the following factors: (1) Performance during the preceding year; (2) compliance with regulatory requirements of IND/investigational device exemption (IDE); and (3) availability of Federal funds. A fourth year of funding is available only for phase 2 or 3 clinical studies.

Section III. Eligibility Information


1. Eligible Applicants

1.A. Eligible Institutions

The grants are available to any foreign or domestic, public or private, for-profit or nonprofit entity (including State and local units of government). Federal agencies that are not part of HHS may apply. Agencies that are part of HHS may not apply. For-profit entities must commit to excluding fees or profit in their request for support to receive grant awards. Organizations that engage in lobbying activities, as described in section 501(c)(4) of the Internal Revenue Code of 1968, are not eligible to receive grant awards.

1.B. Eligible Individuals

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI 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 FDA support.

More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a “team science” approach that clearly does not fit the single-PD/PI model.  All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions). 

When multiple PDs/PIs are proposed, FDA requires one PD/PI to be designated as the "Contact” PI, who will be responsible for all communication between the PDs/PIs and the FDA, for assembling the application materials outlined below, and for coordinating progress reports for the project. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above.

The decision of whether to apply for a single PD/PI or multiple PD/PI grant is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for multiple PD/PI grants will require additional information, as outlined in the instructions below, and the FDA review criteria for approach, investigator, and environment has been modified to accommodate applications involving either a single PD/PI or multiple PDs/PIs as indicated below. A weak or inappropriate PD/PI can have a negative effect on the review. Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of all required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

This grant program does not require the applicant to match or share in the project costs if an award is made.

3. Other-Special Eligibility Criteria

Applicants may submit more than one application, provided each application is scientifically distinct.

Section IV. Application and Submission Information


FDA is accepting new applications for this program electronically via www.grants.gov.  Applicants should apply electronically by visiting the Web site www.grants.gov and following instructions under “Apply for Grants.”  We strongly encourage using the “Tips” posted on www.grants.gov under the announcement number when preparing your submission.

To download a SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

PDs/PIs should work with their institutions/organizations to make sure they are registered in the eRA Commons.

Several additional separate actions are required before an applicant institution/organization can submit an electronic application, as follows:

1) Organizational/Institutional Registration in Grants.gov/Get Registered  

2) Organizational/Institutional Registration in the eRA Commons

3) Project Director/Principal Investigator (PD/PI) Registration in the eRA Commons: Refer to the  eRA Commons System (COM) Users Guide.

Both the PD/PI(s) and AOR/SO need separate accounts in the eRA Commons since both are authorized to view the application image.  Note that if a PD/PI is already registered in the eRA Commons, another registration to apply for an FDA opportunity is not necessary.

Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.

Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered in both Grants.gov and the Commons. The FDA will accept electronic applications only from organizations that have completed all necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the “Attachment” files may be useable for more than one FOA.

For further assistance, contact: Marc Pitts at 301-827-7162.

Telecommunications for the hearing impaired: 301-480-0434.

2. Content and Form of Application Submission

Special instructions for applicants who are submitting a renewal or revision: Applicants submitting a renewal or resubmission are required to enter the previous grant number into the Federal Identifier field in the SF424 (R&R) Cover Component form (box #8).  Renewal and resubmission applications that do not include this number will receive an error.  Applicants should log on to the eRA Commons to obtain the previous grant number.  If the number is not available in Commons, contact Marc Pitts, 301- 827-7162 at FDA to get the previous grant number in order to submit the application. Visit http://era.nih.gov/ElectronicReceipt/resubmission_FAQ.htm for additional information.

Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to FDA. There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by FDA (e.g., the “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component must contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”

The SF424 (R&R) application has several components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY includes all applicable components, required and optional. A completed application in response to this FOA includes the data in the following components:

Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398 Research & Related Budget
Research & Related Subaward Budget Attachment(s) Form

Optional Components:
PHS398 Cover Letter File

Foreign Organizations (Non-domestic (non-U.S.) Entity)

Applications from foreign organizations must:

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.

SPECIAL INSTRUCTIONS  

Applications with Multiple PDs/PIs

When multiple PDs/PIs are proposed, FDA requires one PD/PI to be designated as the "Contact” PI, who will be responsible for all communication between the PDs/PIs and the FDA, for assembling the application materials outlined below, and for coordinating progress reports for the project. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above.

Information for the Contact PD/PI should be entered in item 15 of the SF424(R&R) Cover component. All other PDs/PIs should be listed in the Research & Related Senior/Key Person component and assigned the project role of “PD/PI.” Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included in the “Credential” field of the Research & Related Senior/Key Person component. Failure to include this data field will cause the application to be rejected.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership of the project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled “Multiple PD/PI Leadership Plan” (section 14 of the PHS398 Research Plan component), must be included. The governance and organizational structure of the research project should be described, including communication plans, process for making decisions on scientific direction, allocation of resources, publications, intellectual property issues, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs, including responsibilities for human subjects or animal studies as appropriate.

Applications Involving a Single Institution

When all PDs/PIs are within a single institution, follow the instructions contained in the SF424 (R&R) Application Guide.

Applications Involving Multiple Institutions 

When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget using the Research & Related Budget component. All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form. See Section 4.8 of the SF424 (R&R) Application Guide for further instruction regarding the use of the subaward budget form. 

3. Submission Dates and Times

See Section IV.3.A for details.

3.A. Submission, Review, and Anticipated Start Dates
Release/Posted Date: November 28, 2007
Opening Date:  January 6, 2008 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): Not Applicable
NOTE: On time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization). 
Application Submission/Receipt Date(s): February 6, 2008; February 4, 2009
Expiration Date: February 5, 2009

3.A.1. Letter of Intent

A letter of intent is not required for the funding opportunity.

3.B. Submitting an Application Electronically to FDA

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/Apply and follow steps 1-4. Note:  Applications must only be submitted electronically.

PAPER APPLICATIONS WILL NOT BE ACCEPTED. 
 
3.C. Application Processing

Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the application submission/receipt date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the receipt date(s) and time, the application may be delayed in the review process or not reviewed.

Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two business days to view the application image.

Upon receipt, applications will be evaluated for completeness.  Incomplete applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. The submitting AOR receives the Grants.gov acknowledgments. The AOR and the PI receive Commons acknowledgments. Information related to the assignment of an application to a Scientific Review Group is also in the Commons.

Note: Since email can be unreliable, it is the responsibility of the applicant to check periodically on their application status in the Commons. 

FDA will not accept any application in response to this FOA that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application. FDA will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of an application already reviewed with substantial changes, but such application must include an “Introduction” (3 pages maximum) addressing the previous critique. Note such an application is considered a "resubmission" for the SF424 (R&R).

4. Intergovernmental Review

This initiative is not subject to Intergovernmental Review under the terms of Executive Order 12372.

5. Funding Restrictions

Protection of Human Research Subjects

All institutions engaged in human subject research financially supported by HHS must file an assurance of protection for human subjects with the OHRP (45 CFR part 46). Applicants are advised to visit the OHRP Web site at http://www.hhs.gov/ohrp for guidance on human subject protection issues.

The requirement to file an assurance applies to both “awardee” and collaborating “performance site” institutions. Awardee institutions are automatically considered to be “engaged” in human subject research whenever they receive a direct HHS award to support such research, even where all activities involving human subjects are carried out by a subcontractor or collaborator. In such cases, the awardee institution bears the responsibility for protecting human subjects under the award.

The awardee institution is also responsible for, among other things, ensuring that all collaborating performance site institutions engaged in the research hold an approved assurance prior to their initiation of the research. No awardee or performance site institution may spend funds on human subject research or enroll subjects without the approved and applicable assurance(s) on file with OHRP. An awardee institution must, therefore, have its own IRB of record and assurance. The IRB of record may be an IRB already being used by one of the “performance sites,” but it must specifically be registered as the IRB of record with OHRP.

For further information, applicants should review the section on human subjects in the application instructions as posted on the Grants.gov application Web site. The clinical protocol should comply with ICHE6 “Good Clinical Practice Consolidated Guidance” which sets an international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects. All human subject research regulated by FDA is also subject to FDA's regulations regarding the protection of human subjects (21 CFR parts 50 and 56). Applicants are encouraged to review the regulations, guidance, and information sheets on human subject protection and good clinical practice available on the Internet at http://www.fda.gov/oc/gcp/.

Key Personnel and Human Subject Protection Education

The awardee institution is responsible for ensuring that all key personnel receive appropriate training in their human subject protection responsibilities. Key personnel include all principal investigators, co-investigators, and performance site investigators responsible for the design and conduct of the study. HHS, FDA, and OPD do not prescribe or endorse any specific education programs. Many institutions have already developed educational programs on the protection of research subjects and have made participation in such programs a requirement for their investigators. Other sources of appropriate instruction might include the online tutorials offered by the Office of Human Subjects Research, NIH at http://ohsr.od.nih.gov/ and by OHRP at use http://www.hhs.gov/ohrp/education/.

Within 30 days of the award, the principal investigator should provide a letter to FDA's grants management office that includes the names of the key personnel, the title of the human subjects protection education program completed for each key personnel, and a one-sentence description of the program. This letter should be signed by the principal investigator and cosigned by an institution official and sent to the Grants Management Specialist whose name appears on the official Notice of Grant Award (NGA).

6. Other Submission Requirements

Informed Consent

Consent forms, assent forms, and any other information given to a subject are part of the grant application and must be provided, even if in a draft form. The consent forms should be attached in an appendix section. The applicant is referred to HHS regulations at 45 CFR 46.116 and 21 CFR 50.25 for details regarding the required elements of informed consent.  

PD/PI Credential (e.g., Agency Login)

FDA requires the PD/PI(s) to fill in his/her Commons User ID in the “PROFILE – Project Director/Principal Investigator” section, “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component.

Organizational DUNS

The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”

PHS398 Research Plan Component Sections

Items 2-5 of the PHS398 Research Plan component are limited to 25-pages. While each section of the Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to FDA in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.   

All application instructions outlined in the SF424 (R&R) Application Guide are to be followed along with the following additional requirements:

Appendix Materials

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process.

Note: While each section of the PHS398 Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to monitor better formatting requirements such as page limits. All attachments must be provided to FDA in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.

Foreign Applications  (Non-domestic (non-U.S.) Entity)

Section V. Application Review Information


1. Criteria (Update: Enhanced review criteria have been issued for the evaluation of research applications received for potential FY2010 funding and thereafter - see NOT-OD-09-025).  

A. General Information

FDA grants management and program staff will review all applications sent in response to this notice. To be responsive, an application must be submitted in accordance with the requirements of this notice. Applications found to be nonresponsive will be returned to the applicant without further consideration.

Applicants are strongly encouraged to contact FDA to resolve any unanswered questions about criteria before submitting their application. Please direct all questions of a technical or scientific nature to the OPD program staff and all questions of an administrative or financial nature to the grants management staff (see Agency Contacts in section VII of this document).

B. Program Review Criteria

1. Applications must propose clinical trials intended to provide safety and/or efficacy data.

2. There must be an explanation in the ``Background and Significance' section of how the proposed study will either contribute to product approval or provide essential data needed for product development.

3. The ``Background and Significance' section of the application must contain information documenting the prevalence, not incidence, of the population to be served by the product is fewer than 200,000 individuals in the United States. The applicant should include a detailed explanation supplemented by authoritative references in support of the prevalence figure. Diagnostic tests and vaccines will qualify only if the population of intended use is fewer than 200,000 individuals in the United States per year.

4. The study protocol proposed in the grant application must be under an active IND or IDE (not on clinical hold) to qualify the application for scientific and technical review. Additional IND/IDE information is described as follows:

5. The requested budget must be within the limits, either $200,000 in total costs per year for up to 3 years for any phase 1 study, or $400,000 in total costs per year for up to 4 years for phase 2 or 3 studies. Any application received that requests support over the maximum amount allowable for that particular study will be considered non-responsive.

6. In an appendix to the application, there must be evidence that the product to be studied is available to the applicant in the form and quantity needed for the clinical trial proposed. A current letter from the supplier as an appendix will be acceptable. If negotiations regarding the supply of the study product are underway but have not been finalized at the time of application, please provide a letter indicating such in the application. Verification of adequate supply of study product will be necessary before an award is made.

7. The protocol should be submitted in the application. Page limits, font size and margins should comply with the Application Guide, Electronic Submission of Grant Applications.

C. Scientific/Technical Review Criteria

The ad hoc expert panel will review the application based on the following scientific and technical merit criteria:

1. The soundness of the rationale for the proposed study;

2. The quality and appropriateness of the study design, including the design of the monitoring plans;

3. The statistical justification for the number of patients chosen for the study, based on the proposed outcome measures, and the appropriateness of the statistical procedures for analysis of the results;

4. The adequacy of the evidence that the proposed number of eligible subjects can be recruited in the requested timeframe;

5. The qualifications of the investigator and support staff, and the resources available to them;

6. The adequacy of the justification for the request for financial support;

7. The adequacy of plans for complying with regulations for protection of human subjects and monitoring; and

8. The ability of the applicant to complete the proposed study within its budget and within time limits stated in this RFA.

2. Review and Selection Process

Responsive applications will be reviewed and evaluated for scientific and technical merit by an ad hoc panel of experts in the subject field of the specific application. Consultation with the proper FDA review division may also occur during this phase of the review to determine whether the proposed study will provide acceptable data that could contribute to product approval. Responsive applications will be subject to a second review by the National Cancer Institute, National Cancer Advisory Board (NCAB) for concurrence with the recommendations made by the first-level reviewers, and funding decisions will be made by the Commissioner of Food and Drugs or his designee.

A score will be assigned based on the scientific/technical review criteria. The review panel may advise the program staff about the appropriateness of the proposal to the goals of the OPD grant program.

2.A. Additional Review Criteria

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed.

Inclusion of Women, Minorities and Children in Research:
The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated.

Care and Use of Vertebrate Animals in Research: The adequacy of the plans for care and use of vertebrate animals to be used in the project will be assessed.

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

Applications from Foreign Organizations: Applications from foreign institutions or international organizations will be evaluated and scored during the initial review process using the standard review criteria. In addition, the following will be assessed as part of the review process and award decision

2.B. Additional Review Considerations

Budget and Period of Support: The reasonableness of the proposed budget and the appropriateness of the requested period of support in relation to the proposed research may be assessed by the reviewers. Is the number of person months listed for the effort of the PD/PI(s) appropriate for the work proposed? Is each budget category realistic and justified in terms of the aims and methods?

2.C. Sharing Research Data

Not Applicable

2.D. Sharing Research Resources

Not Applicable

3. Anticipated Announcement and Award Dates

Earliest Anticipated Start/Award Date(s):  November 1, 2008 and November 1, 2009

Section VI. Award Administration Information


1. Award Notices

After the 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

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

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. See Section IV.5., “Funding Restrictions.”       

2. Administrative and National Policy Requirements

All FDA grant awardees must adhere to the requirements stated in the RFA, the NGA, associated Terms and Conditions, as well as any relevant FDA or HHS statutory or regulatory requirements.

DHHS Grants Policy Statement Link: http://www.hhs.gov/grantsnet/adminis/gpd/index.htm

3. Reporting

Monitoring Activities

1.  OPD Monitoring of Clinical Trials language:

These guidelines are intended to provide information for principal investigators who are conducting clinical trials. The procedures outlined herein are in addition to (and not in lieu of) Institutional Review Board (IRB), Office for Human Research Protections (OHRP) and other Food and Drug Administration (FDA) requirements.

It is an OPD policy that data and safety monitoring of a clinical trial is to be commensurate with the risks posed to study participants and with the size and complexity of the study. In addition, the OPD requires that a Grantee's and any third party engaged in supporting the clinical research be responsible for oversight of data and safety monitoring, ensuring that monitoring systems are in place, that the quality of the monitoring activity is appropriate, and that the OPD Project Officer is informed of recommendations emanating from monitoring activities.

FDA Requirements for Monitoring:

The  OPD requires that each clinical trial it supports, regardless of phase, have data and safety monitoring procedures in place to safeguard the well-being of study participants and to ensure scientific integrity. Monitoring must be performed on a regular basis throughout the subject accrual, treatment, and follow-up periods.

The specific approach to monitoring will depend on features of the clinical trial to be conducted. e.g. several levels of monitoring: Data and Safety Monitoring Board (DSMB), Study Monitoring Committee (SMC) and Independent Medical Monitor (IMM).

Monitoring activities should be appropriate to the study, study phase, population, research environment, and degree of risk involved.

In small, single-site studies, safety monitoring is often performed by the independent medical monitor or a safety monitoring committee in conjunction with the study statistician. All Phase III studies and any high risk Phase I or II clinical trial will also require a DSMB. It may be desirable to utilize a DSMB for:

Study Monitoring Plan:

The OPD requires that the protocol document include a section describing the proposed plan for interim data monitoring. This section will detail who is to be responsible for interim monitoring (i.e., a DSMB, an SMC, or the study investigator), what data will be monitored (i.e., performance and safety data only vs. efficacy data as well), the timing of the first data review (e.g., "the first interim look will occur when the initial 20 participants have completed the 6 month follow-up visit"), and the frequency of interim reviews (which will depend on such factors as the study design, interventions and anticipated recruitment rate). The plan will specify "stopping guidelines" and other criteria for the monitors to follow in their review of the interim data.

A preliminary monitoring plan must be submitted as part of the Research Plan portion of the grant application for a clinical trial. The plan will be examined as part of the peer review process, and any comments and concerns will be included in an administrative note in the summary statement. OPD staff will ensure that all concerns are resolved before the grant award is made.

2.  Oversight Activities

The program project officer will monitor grantees periodically. The monitoring may be in the form of telephone conversations, e-mails, or written correspondence between the project officer/grants management officer or specialist and the principal investigator. Information including, but not limited to, information regarding study progress, enrollment, problems, adverse events, changes in protocol, and study monitoring activities will be requested. Periodic site visits with officials of the grantee organization may also occur. The results of these monitoring activities will be recorded in the official grant file and will be available to the grantee upon request consistent with applicable disclosure statutes and with FDA disclosure regulations. Also, the grantee organization must comply with all special terms and conditions of the grant, including those which state that future funding of the study will depend on The program project officer will monitor grantees periodically. The monitoring may be in the form of telephone conversations, e-mails, or written correspondence between the project officer/grants management officer or specialist and the principal investigator. Information including, but not limited to, information regarding study progress, enrollment, problems, adverse events, changes in protocol, and study monitoring activities will be requested. Periodic site visits with officials of the grantee organization may also occur. The results of these monitoring activities will be recorded in the official grant file and will be available to the grantee upon request consistent with applicable disclosure statutes and with FDA disclosure regulations. Also, the grantee organization must comply with all special terms and conditions of the grant, including those which state that future funding of the study will depend on recommendations from the OPD project officer. The scope of the recommendations will confirm the following: (1) There has been acceptable progress toward enrollment, based on specific circumstances of the study; (2) there is an adequate supply of the product/device; and (3) there is continued compliance with all applicable FDA and HHS regulatory requirements for the trial.

In addition to the requirement for an active IND/IDE discussed in section V.B.4 of this document, documentation of assurances with the Office of Human Research Protection (OHRP) (see section IV.5.A of this document) must be on file with the FDA grants management office before an award is made. Any institution receiving Federal funds must have an institutional review board (IRB) of record even if that institution is overseeing research conducted at other performance sites. To avoid funding studies that may not receive or may experience a delay in receiving IRB approval, documentation of IRB approval and Federal Wide Assurance (FWA or assurance) for the IRB of record for all performance sites must be on file with the FDA grants management office before an award to fund the study will be made. In addition, if a grant is awarded,

3. Reporting Requirement

The grantee must file a final program progress report, financial status report, and invention statement within 90 days after the end date of the project period as noted on the notice of grant award.

When multiple years are involved, awardees will be required to submit the Non-Competing Grant Progress Report (PHS 2590) annually and financial statements as required in the HHS Grants Policy Statement, dated October 1, 2006, (http://www.hhs.gov/grantsnet/adminis/gpd/). Also, all new and continuing grants must comply with all regulatory requirements necessary to keep the status of their IND/IDE “active” and “in effect,” that is, not on “clinical hold.” Failure to meet regulatory requirements will be grounds for suspension or termination of the grant.

Section VII. Agency Contacts


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

1. Scientific/Research Contacts:

FDA encourages your inquiries concerning this funding opportunity and welcomes the opportunity to answer questions from potential applicants.

Scientific/Research Contact: Katherine Needleman, Acting Director, Orphan Products Grants Program, Office of Orphan Products Development (HF-35), Food and Drug Administration 5600 Fishers Lane, Rm. 6A-55, Rockville, MD 20857, 301-827-3666, e-mail: katherine.needleman@fda.hhs.gov.

IND/IDE Contact Information:   http://www.fda.gov/oc/gcp/othercontact.html

For Questions about whether a product is subject to IDE regulations: Call 301-594-1190.

For assistance with identifying the appropriate office for IND/IDE submission please contact the Orphan Product Development Office Main line on 301-827-3666.

2. Peer Review Contacts:
Not applicable.

3. Financial/Grants Management Contacts:

Administrative/Financial Management Contact: Marc Pitts, Grants Management Specialist, Division of Acquisition Support and Grants, Office of Acquisitions & Grant Services (HFA-500), Food and Drug Administration, 5630 Fishers Lane, Rm. 2104 Rockville, MD 20857, 301-827-7162, email:marc.pitts@fda.hhs.gov.

Section VIII. Other Information


Required Federal Citations

Clinical Trials Data Bank

The Food and Drug Administration Modernization Act of 1997 established a requirement that certain information be entered into the Clinical Trials Data Bank (CTDB) for federally and privately funded clinical effectiveness trials conducted under an IND for drugs (including trials for biological products) to treat serious or life-threatening diseases or conditions (42 U.S.C. 282(j)). Information on noneffectiveness trials, or for drugs to treat diseases or conditions not considered serious or life-threatening, may also be entered into this database but such information is not required. This CTDB provides patients, family members, healthcare providers, researchers, and members of the public easy access to information on clinical trials for a wide range of diseases and conditions. The U.S. National Library of Medicine has developed this site in collaboration with NIH and FDA. The CTDB is available to the public through the Internet at http://clinicaltrials.gov.

The CTDB contains the following information: (1) Information about clinical trials, both federally and privately funded, of experimental treatments (drug and biological products) for patients with serious or life-threatening diseases or conditions; (2) a description of the purpose of each experimental drug; (3) the patient eligibility criteria; (4) a description of the location of clinical trial sites; and (5) a point of contact for those wanting to enroll in the trial. In 2007, the Best Pharmaceuticals for Children Act also required that the CTDB include a description of whether, and through what procedure, the manufacturer or sponsor of an IND will respond to a request for protocol exception, with appropriate safeguards, for single-patient and expanded access use of the investigational drug, particularly in children. The OPD program staff will provide more information to grantees about entering the required information in the CTDB after awards are made.

Freedom of Information Act (FOIA)

The Freedom of Information Act, 5 U.S.C. 552, provides individuals with a right to access certain records in the possession of the Federal government. The government may withhold information pursuant to the exemptions and exclusions contained in the act. The exact language of the exemptions can be found in the act. Additional guidance on the exemptions and how they apply to certain documents can be found in the HHS regulations implementing the FOIA (45 CFR part 5). (Also see the HHS Web site http://www.hhs.gov/foia/

Data included in the application may be considered trade secret or confidential commercial information within the meaning of the Freedom of Information Act (5 U.S.C. 552) and FDA's statute and implementing regulations. FDA will protect trade secret or confidential commercial information to the extent allowed under applicable law.

Use of Animals in Research

Recipients of PHS support for activities involving live vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Inclusion of Women And Minorities in Clinical Research

Applicants for PHS clinical research grants are encouraged to include minorities and women in study populations so research findings can be of benefit to all people at risk of the disease or condition under study. It is recommended that applicants place special emphasis on including minorities and women in studies of diseases, disorders, and conditions that disproportionately affect them. This policy applies to research subjects of all ages. If women or minorities are excluded or poorly represented in clinical research, the applicant should provide a clear and compelling rationale that shows inclusion is inappropriate.

Inclusion of Children as Participants in Clinical Research

FDA regulations at 21 CFR part 50, subpart D contain additional requirements that must be met by IRBs reviewing clinical investigations regulated by FDA and involving children as subjects. FDA is part of HHS; accordingly, the research project grants under this program are supported by HHS, and HHS regulations at 45 CFR part 46, subpart D also apply to research involving children as subjects.

Standards for Privacy of Individually Identifiable Health Information

HHS issued final modification to the ``Standards for Privacy of Individually Identifiable Health Information,' the ``Privacy Rule,' on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the HHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR Web site http://www.hhs.gov/ocr/ provides information on the Privacy Rule, including a complete regulation text and a set of decision tools on ``Am I a covered entity?' Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

Healthy People 2010

PHS is committed to achieving the health promotion and disease prevention objectives of ``Healthy People 2010,' a PHS-led national activity for setting priority areas. This Funding Opportunity Announcement is related to one or more of the priority areas. Potential applicants may obtain a copy of ``Healthy People 2010' at http://www.health.gov/healthypeople.

Smoke-Free Workplace

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Authority and Regulation

This program is described in the CFDA at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of sections 301 and 405 of the PHS Act as amended (42 U.S.C. 241 and 284) and under federal regulations 42 CFR part 52 and 45 CFR parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the HHS Grants Policy Statement, dated October 1, 2006, (http://www.hhs.gov/grantsnet/adminis/gpd/index.htm)

Human Subjects Protection

Federal regulations (45 CFR 46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Human Embryonic Stem Cell Research and Cloning

HHS funds may not be used to support human embryo research under any extramural award instrument. HHS funds may not be used for the creation of a human embryo for research purposes or for research in which a human embryo is destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero under 45 CFR 46.204 and 46.207 and Subsection 498(b) of the PHS Act 42 U.S.C. 289g(b). The term “human embryo” includes any organism not protected as a human subject under 45 CFR part 46, as of the date of enactment of the governing appropriations act, that is derived by fertilization, parthenogenesis, cloning, or any other means from one or more human gametes or human diploid cells.

In addition to the statutory restrictions on human fetal research under Subsection 498((b) of the PHS Act, HHS is prohibited, by a March 4, 1997, Presidential memorandum, from using Federal funds for cloning human beings.


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