Source: http://grants.nih.gov/grants/guide/rfa-files/RFA-FD-11-001.html
Timestamp: 2016-08-29 05:47:44
Document Index: 180214351

Matched Legal Cases: ['art9', 'art 46', 'arts 50', 'art 5', 'art 20', 'art 50', 'art 46', 'art 52', 'arts 74']

Administration (FDA), (http://www.fda.gov)
of Participating Organizations Office of Orphan Products Development (OPD), (http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/default.htm)
Title: Clinical Studies of Safety and Effectiveness of Orphan
and conditions stated in this announcement may differ from those used by the National
reissue of RFA-FD-09-001.
Update: The following update relating to this announcement has been issued: August 1, 2012 - This RFA has been reissued as RFA-FD-13-001.
for Applications (RFA) Number: RFA-FD-11-001
electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms
and the SF424 (R&R) Application Guide.
Opening Date: December 2, 2010 (Earliest date an application may be
Applicable Application Due Date(s): February 2, 2011;
2011 and 2012 and November 2011 and 2012
Council Review Date(s): September 2011 and 2012
and February 2012 and 2013
Earliest Anticipated Start Date(s): November 2011
Expiration Dates: February 2, 2012, October 16, 2012 resubmission Due Dates for E.O. 12372 Not Applicable (See: http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part9.htm#_Toc54600164) Additional Overview Content Executive
Summary Purpose. 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 being developed will be superior to the existing therapy. FDA
products. Applicants must include in the application's Background and
Significance section documentation to support the estimated prevalence of the
either help support product approval or provide essential data needed for
product development. Mechanism of Support. This FOA will
utilize the research project (R01) grant. All awards will be subject to all
incorporated in the HHS Grants Policy Statement, dated January 1, 2007 (http://www.hhs.gov/grantsnet/adminis/gpd/index.htm),
The NIH modular grant program does not apply to this FDA grant program. 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.) and regulations issued under it
and to applicable Department of Health and Human Services (HHS) statutes and
regulations. All grant awards are subject to applicable requirements for
clinical investigations imposed by sections 505, 512, and 515 of the act,
section 351 of the PHS Act, and regulations issued under any of these sections.
Funds Available and Anticipated Number of Awards. Of the estimated FY 2012 funding ($14.1 million), approximately $10 million
will fund non-competing continuation awards, and approximately $4.1 million
will fund 5 to 12 new awards, subject to availability of funds. It is
anticipated that funding for the number of non-competing continuation awards
and new awards in FY 2013 will be similar to FY 2012.
Budget and Project Period. Phase
1 studies are eligible for grants of up to $200,000 per year for up to 3
years. Phase 2 and 3 studies are eligible for grants of up to $400,000 per
year for up to 4 years. Please note that the dollar limitation will apply to
total costs (direct plus indirect). Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
Number of PDs/PIs. More than one PD/PI may
Introduction addressing the most recent peer review critique (Summary
application. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-09-003.html and NOT-OD-09-016 Renewals. Renewal applications
the hearing impaired are available at: TTY: 301-480-0434. Table
Description 1. Research Objectives Section II. Award Information 1. Mechanism of Support 2. Funds Available Section
III. Eligibility Information 1. Eligible Applicants 2. Cost Sharing or Matching
V. Application Review Information 1. General Information
4. Additional Review Criteria 5. Additional Review Considerations
VII. Agency Contacts 1. Scientific/Research Contact(s) 2. Financial/Grants Management Contact(s) 3. Technical Contact(s)
1. Required Federal Citations Part II - Full Text of Announcement
was created to identify and promote the development of orphan products. Orphan
products are drugs, biologics, medical devices, and medical foods that are
indicated for a rare disease or condition (that is, one with prevalence, not
incidence, of fewer than 200,000 people in the United States). Diagnostics and
vaccines will qualify for orphan status only if the U.S. population to whom
they will be administered is fewer than 200,000 people per year. 1.B. Research Objectives 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 proposed product will be superior to the existing therapy. FDA
orphan disease or condition (or in the case of a vaccine or diagnostic,
study will either help support product approval or provide essential data
needed for product development. See Section VIII, Other Information
- Required Federal Citations, for
Project (R01) grant is an award made to support a discrete, specified,
representing the investigator's specific interest and competencies, based on
See Section III.1.1.B for multiple PD/PIs. All
awards will be subject to all policies and requirements that govern the research
grant programs of the PHS as incorporated in the HHS Grants Policy Statement,
dated January 1, 2007 (http://www.hhs.gov/grantsnet/adminis/gpd/index.htm),
grant awards are subject to applicable requirements for clinical investigations
imposed by sections 505, 512, and 515 of the act, section 351 of the PHS Act,
regulations issued under any of these sections, and other applicable HHS
statutes and regulations regarding human subject protection.
for applications for studies of medical foods that do not need pre-market
approval, FDA will only award grants to support pre-market 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. 2. Funds Available 2.A. Award Amount
estimated FY 2012 funding ($14.1 million), approximately $10 million will fund
noncompeting continuation awards, and approximately $4.1 million will fund 5 to
10 new awards, subject to availability of funds. It is anticipated that funding
for the number of noncompeting continuation awards and new awards in FY 2013 will
be similar to FY 2012. Phase 1 studies are eligible for grants of up to
$200,000 per year for up to 3 years. Phase 2 and 3 studies are eligible for grants
of up to $400,000 per year for up to 4 years. Please note that the dollar
limitation will apply to total costs (direct plus indirect). Budgets for each
year of requested support may not exceed the $200,000 or $400,000 total cost
limit, whichever is applicable.
following definitions are provided to illustrate drug and biologic products study
phases. Devices and medical foods may have alternative considerations.
studies include the initial introduction of an investigational new drug (IND) into humans, are usually conducted in healthy volunteer subjects, and are designed to
determine the metabolic and pharmacological actions of the product in humans,
and 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.
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. 2.B. 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. 2.C.
addition to the requirement for an active IND/IDE discussed in Section V.3 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, grantees will be
informed of any additional documentation that should be submitted to FDA's IRB. Because
grants policies as described in the HHS Grants Policy Statement http://www.hhs.gov/grantsnet/adminis/gpd/index.htm will apply to the applications submitted and awards made in response to this
FOA. Section III. Eligibility Information 1. Eligible Applicants 1.A. Eligible Institutions
The following organizations/institutions are eligible to
apply: Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education Hispanic-serving Institutions
Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of
Higher Education) Small Businesses For-Profit Organizations (Other than Small Businesses) State Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribally Designated Organizations
Regional Organizations Non-domestic (non-U.S.) Entities (Foreign Organizations) Other(s): Eligible Agencies of the Federal Government
grants are available to any foreign or domestic, public or private, for-profit
or nonprofit entity (including State and local units of government). Federal
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
individuals with disabilities are always encouraged to apply for support. Multiple
PDs/PIs The decision of whether to apply for a grant with a
will require additional information, as outlined in the instructions below. More
research projects is available at http://grants.nih.gov/grants/multi_pi. When
multiple PDs/PIs are proposed, FDA requires one PD/PI to be designated as the
PDs/PIs and the FDA, for assembling the application materials outlined below,
team beyond those mentioned above. Information for the Contact PD/PI should be entered in
Commons ID of each PD/PI must be included in the Credential field of the Research
field will cause the application to be rejected. All
approach for the proposed project. Multiple PD/PI Leadership Plan: For
instruction regarding the use of the subaward budget form. 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.
addressing the previous peer review critique (Summary Statement). The
Summary Statement must be included as an Appendix in the application. Resubmissions
are intended for those applications that were previously submitted to OPD,
reviewed and received a score on the application. Renewals. Renewal
Revisions. Active grants in regulatory
compliance may be eligible to submit a competing supplement application. A
competing supplement (also called Revision) is a request for additional funds
for a current award to expand the scope of work. Competing supplements may be
submitted throughout the fiscal year and will be permitted for this FOA to
compete for funding. Please contact the OPD program contact for further
comply with the President’s Management Agenda, HHS is participating as a
partner in the new government-wide grants.gov application site. Applicants should apply electronically by visiting the web site www.grants.gov and following instructions under Apply for Grants. Users of grants.gov
site. We strongly encourage using the Tips posted on www.grants.gov under the announcement number when preparing your submission. This process is
similar to the R01 Grant Application process currently used at the National
Institutes of Health (NIH). You can visit the following website for
helpful background on preparing to apply, preparing an application, and
submitting an application to Grants.gov: http://era.nih.gov/ElectronicReceipt/. In order to apply electronically, the applicant must have a Data Universal
Number System (DUNS) number, and register in the Central Contractor
Registration (CCR) database, in eRA Commons (http://era.nih.gov/ElectronicReceipt/preparing.htm),
and in grants.gov (further information below). To
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: Grants.gov (http://www.grants.gov/GetStarted) and eRA Commons (http://era.nih.gov/ElectronicReceipt/preparing.htm) A
institutions/organizations to make sure they are registered in the eRA Commons. Several
can submit an electronic application, as follows: 1) Organizational/Institutional
Registration in Grants.gov/Get Registered Your organization will need to obtain a DUNS number (https://eupdate.dnb.com/requestoptions/government/ccrreg/)
Grants.gov registration process. The DUNS number is a 9-digit identification number that
uniquely identifies business entities.
The CCR database is a government-wide warehouse of commercial
and financial information for all organizations conducting business with the
Service records, a step that will take an additional one to two business days. Tips for foreign organization registration are available
at: http://era.nih.gov/ElectronicReceipt/preparing.htm#4 Direct questions regarding Grants.gov registration can be
Customer Support (http://www.grants.gov/help/help.jsp) Contact Center Phone: 800-518-4726 Business Hours: M-F 7:00 a.m. - 9:00 p.m. Eastern Time
Email support@grants.gov 2) Organizational/Institutional Registration in the eRA Commons (https://commons.era.nih.gov/commons/registration/registrationInstructions.jsp) To find out if an organization is already
Commons-registered, see the "List of Grantee Organizations Registered in eRA Commons. (http://era.nih.gov/commons/quick_queries/index.cfm#commons) Direct questions regarding the Commons registration can
be directed to: eRA Commons Help Desk
Investigator (PD/PI) Registration in the eRA Commons: Refer to the eRA
application must also be registered in the eRA Commons. In the case of
multiple PDs/PIs, all PDs/PIs must be registered in the eRA Commons prior to
role, both roles should exist under one Commons account. When multiple PDs/PIs
own organization to be able to access the Commons. This registration/affiliation must be done by the AOR/SO
or their designee who is already registered in the Commons. Both the PD/PI(s) and AOR/SO need separate accounts in
the eRA Commons since both are authorized to view the application image.
determine whether their organization/institution is already registered in both Grants.gov and the Commons (https://commons.era.nih.gov/commons/).
experience technical difficulties with your online submission, you
should contact the grants.gov Customer Response Center http://www.grants.gov/web/grants/support.html. If the Customer Response Center is unable to resolve your problem, please contact Vieda Hubbard,
Grants Management Specialist, Division of Acquisition Support and Grants
(DASG), Office of Acquisition and Grant Services (OAGS), Food and Drug
Administration, at 301-827-7177, or by e-mail at vieda.hubbard@fda.hhs.gov. 1. Request Application
Information In FY 2012 and 2013, all applications must be submitted electronically through
Grants.gov. Applicants must download the SF424 (R&R) application forms and
the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply. Note:
For further assistance, contact: Marc Pitts at 301-827-7162. Telecommunications
Guide. For additional information, see Frequently Asked Questions“ Application
Guide, Electronic Submission of Grant Applications (http://grants.nih.gov/grants/ElectronicReceipt/faq_full.htm#application).
receive an error message. 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. If an application for the same study was
the previous review and include a copy of the summary statement itself as part
of the resubmitted application. An application that has received two
prior disapprovals is not eligible for resubmission. Prepare
with the SF424 (R&R) Application Guide for this FOA through
Grants.gov/Apply. Note
that the move to electronic applications has brought a change in terminology.
The Grants.gov terminology is as follows: New =
complete the Research & Related Budget component of the SF424). Not seek charge back of customs and import fees. Make every effort to comply with the format
specifications, which are based upon a standard U.S. paper size of 8.5 x 11
within each PDF. Comply with Federal/FDA policies on human subjects, animals,
and biohazards. Comply with Federal/FDA biosafety and biosecurity
regulations. See Section VI.2., Administrative and National Policy
Requirements. Indicate in the 398 Research Plan how the proposed
project has specific relevance to the mission and objectives of FDA and has the
potential for significantly advancing sciences in the United States. Proposed
with Multiple PDs/PIs See Section
III.1.B 3. Submission Dates and Times See Section
Anticipated Start Dates Opening Date: December 2, 2011 (Earliest date an application may be
Letters of Intent Receipt Date(s): Not Applicable Application Due Date(s): February 2, 2011 and February
1, 2012 Resubmission Due Date(s): October 14, 2011 and October 15, 2012
Peer Review Date(s): May 2011 and 2012 and November 2011
Council Review Date(s): September 2011 and 2012 and
February 2012 and 2013
note that there is only one receipt date for FY 2012 and one receipt date for
FY 2013 for new and resubmitted applications. Resubmissions and
14, 2011 and October 15, 2012. Resubmissions will also be accepted in the
February receipt dates in both Fiscal years.
institution/organization). Applications must be received by the close of business on
the established receipt date. Late applications may be accepted under
extreme circumstances beyond the control of the applicant. Applications
not received on time will not be considered for review and will generally be
returned to the applicant. The
protocol in the grant application should be submitted to the IND/IDE no later
than January 3, 2011 for FY 2012 and no later than January 2, 2012 for FY 2013. The current version of
the protocol that is included in the grant application and is intended to be
used if the study is funded is the protocol that MUST be submitted to the
IND/IDE before the application is reviewed. The date that corresponds with the IND/IDE
3.B. Submitting an Application Electronically to the FDA To submit an application in response to this FOA, applicants should access this
order to expedite the review, applicants are requested to notify the FDA Referral Office by email marc.pitts@fda.hhs.gov when the application
IV.3.A. for all dates.) If an application is not
review process or not reviewed. Once an
Representative/Signing Official (AOR/SO) have two weekdays (Monday- Friday,
further action is necessary. If everything is acceptable, no further action is
necessary. The application will automatically move forward for processing after
two business days, excluding Federal holidays. Prior to the submission deadline, the AOR/SO can Reject
two day viewing window. This option should be used if it is determined that
and submit a Changed/Corrected application. In these
cases, please contact the eRA Help Desk to ensure that the issues are addressed
and corrected. Once rejected, applicants should follow the instructions for
correcting errors in Section 2.12 of the SF424 (R&R) Application Guide (http://grants.nih.gov/grants/funding/424/index.htm#),
later in the process. If the two day window falls after the submission
deadline, the AOR/SO will have the option to Reject the application if, due to
AOR/SO should first contact the eRA Commons Helpdesk (http://ithelpdesk.nih.gov/eRA/)
of action. FDA will not penalize the applicant for an eRA Commons or Grants.gov
system issue. If the AOR/SO chooses to Reject the image after the
subject to the NIH/FDA late policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-05-030.html)
explained in the cover letter attachment. Late applications
may be accepted under extreme circumstances beyond the control of the
applicant. In the absence of such extreme circumstances beyond the applicant's
control, applications not received on time will not be considered for review
and will generally be returned to the applicant. Both the AOR/SO and PD/PI will receive e-mail
moves forward in the process after two days. In unusual circumstances, additional information may be
considered, on a case by case basis, for inclusion in the ad hoc expert panel
review, however, the FDA cannot assure inclusion of any information after the
receipt date other than evidence of final IRB approval, FWA or assurance, and
certification of adequate supply of study product. Upon
applications will not be reviewed.. There will be an acknowledgement of receipt of applications from Grants.gov
essentially the same as one already reviewed. However,
include an Introduction (3 pages maximum) addressing
Intergovernmental Review This initiative is not subject to Intergovernmental Review under the terms of
5. Funding Restrictions All FDA awards are subject to the terms and
5.A. Protection of Human Research
institutions engaged in human subject research financially supported by HHS
must file an assurance of protection for human subjects with the Office of
Human Research Protections (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. Federal regulations (45 CFR 46) require that
and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm). 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
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.
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/. 5.B. Key Personnel and Human Subject Protection
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 http://www.hhs.gov/ohrp/education/.
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 and Information 6.A. Informed
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 and FDA regulations at 45 CFR 46.116 and 21 CFR 50.25 for
details regarding the required elements of informed consent. 6.B. PD/PI Credential (e.g., Agency
requires the PD/PI(s) to fill in his/her Commons User ID in the PROFILE Project
Research & Related Senior/Key Person Profile component. 6.C. Organizational DUNS
Questions Application Guide, Electronic Submission of Grant Applications. 6.D. PHS398
must be followed as outlined in the SF424 (R&R) Application Guide. Although each section of the
(R&R) Application Guide must be followed. 6.E. Appendix Materials
component. An
6.F. Foreign Applications
of FDA and has the potential for significantly advancing sciences in the United States. Section V. Application Review Information
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
non-responsive will receive notice that the application will not be reviewed. Applicants
are strongly encouraged to contact FDA to resolve any 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).
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.
will be assigned to each application based on the scientific/technical review
appropriateness of the proposal to the goals of the OPD grant program.
decisions: Scientific merit of the proposed project as determined by
peer review. Availability of funds. Relevance of the proposed project to program priorities. The goal of FDA's OPD
product will be superior to the existing therapy. In their written critiques, reviewers will be asked to
have major scientific impact and thus deserve a meritorious priority score. Investigators: Assessing the competence of the
principal investigator(s) and key personnel to conduct the proposed
research. This includes their academic qualifications, research
experiences, productivity, and any special attributes.
Resources and Environment: Evaluating any special attributes
or deficiencies relevant to the conduct of the proposed studies.
Budget: Evaluating whether all items of
the requested budget are appropriate and justified. Human Subjects and Monitoring: Evaluating
possible physical, psychological, or social injury patients might experience as
subjects in the proposed research. Discussing whether the rights and
welfare of the individuals will be adequately protected. Assessing the
safety-monitoring plan including the reporting of adverse events. Evaluating
the informed consent documents as well as the plan to monitor the integrity of
the data collected and the compliance with the protocol.
hoc expert panel will review the application based on the following scientific
and technical merit criteria:
soundness of the rationale for the proposed study;
quality and appropriateness of the study design, including the design of 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
ability of the applicant to complete the proposed study within its budget and
within time limits stated in this RFA. 3. Program Review Criteria 1.
Applications must propose clinical trials intended to provide safety and/or efficacy
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.
Background and Significance section of the application must contain information
documenting that the prevalence, not incidence, of the disease or condition for
which the product is indicated 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 to whom they will be
administered is fewer than 200,000 individuals in the United States per year.
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:
proposed clinical protocol should be submitted to the applicable FDA IND/IDE
review division a minimum of 30 days before the grant application
deadline. The number assigned to the IND/IDE that includes the proposed
study should appear on the face page of the application with the title of the
project. The date the subject protocol was submitted to FDA for the
IND/IDE review should also be provided. Protocols that would otherwise be
requirements. Only
medical foods that do not need pre-market approval and medical devices that are
classified as non-significant risk (NSR) are free from these IND/IDE
requirements. Applicants studying an NSR device should provide a letter in the
application from the FDA Center for Devices and Radiologic Health indicating
the device is an NSR device.
requested budget must be within the limits, either $200,000 in total costs per
year for up to 3 years for any phase study, or $400,000 in total costs per year
for up to 4 years for Phase 2 or 3 studies. Any application received that
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.
protocol should be submitted in the application. The protocol may be included
as an appendix. Page limits, font size and margins should comply with the
Application Guide, Electronic Submission of Grant Applications
Applications (formerly revised/amended applications): The adequacy of the responses to
comments from the most recent scientific review group will be assessed
including the appropriateness of the improvements in the resubmission
application. Protection
assessed. See the Human Subjects Sections of the
will also be evaluated. See the Human Subjects
Sections of the PHS398 Research Plan component of the SF424 (R&R).
assessed. See the Other Research Plan Sections of the
protection is adequate. 5.
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
not be affected by the evaluation of the budget. Applications
assessed. 6.
7. Anticipated Announcement and Award Dates Earliest Anticipated Start/Award Date(s): November 1, 2011 and November
1. Award Notices After the review of the application is completed, the PD/PI will be able to
FDA may request information from the applicant prior to making the award. For details, applicants may refer to the HHS Grants Policy Statement http://www.hhs.gov/grantsnet/adminis/gpd/index.htm.
allowable pre-award costs. See Section IV.5., Funding
Administrative and National Policy Requirements All FDA grant and cooperative agreement awards include
the HHS Grants Policy Statement as part of the NoA. For these terms of
award, see the HHS Grants Policy Statement. DHHS Grants Policy
Statement Link: http://www.hhs.gov/grantsnet/adminis/gpd/index.htm 3. Reporting 3.A. Monitoring Activities 3.A.1.
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), other Food and Drug Administration (FDA), and Good
Clinical Practices 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 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
requires that each clinical trial it supports, regardless of phase, has 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. Guidance is available at: http://www.fda.gov/RegulatoryInformation/Guidances/ucm126400.htm and http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073122.pdf. 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. Phase 3 studies and high risk Phase 1 or 2 clinical
trials frequently use a DSMB. It may be desirable to utilize a DSMB for: Trials involving highly experimental therapies or
specialized review procedures external to the OPD (e.g., gene therapy or
xenotransplantation); Trials involving substantial risk to study participants
(e.g., studies with irreversible outcomes); or Trials involving particularly vulnerable study
participants (e.g., children or persons with impaired ability to consent). 3.A.3. Study Monitoring Plan
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. Guidance on these topics is available at: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127073.pdf. 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. 3.B. 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
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.
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
informed of any additional documentation that should be submitted to FDA's IRB. 3.C.
Reporting Requirement The
noted on the notice of grant award.
Non-Competing Grant Progress Report (PHS 2590) annually and financial
2007 (http://www.hhs.gov/grantsnet/adminis/gpd/).
Awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the HHS Grants Policy
listing and a justification for any study changes that occurred in the past
year must be included in the Non-Competing Continuation Grant Progress Report
to answer questions from potential applicants. 1. Scientific/Research Contact(s): Katherine
2. Financial/Grants Management Contact(s): Vieda
3. Technical Contact(s): Marc
1. Required Federal Citations 1.A. Clinical Trials Data Bank The
Food and Drug Administration Amendments Act of 2007 (FDAAA) contains provisions
that expand the current database known as ClinicalTrials.gov to include
additional requirements for individuals and entities, including grantees, who
are involved in conducting clinical trials that involve products regulated by
FDA or that are funded by the Department of Health and Human Services (HHS),
including FDA. These additional requirements include mandatory
results for certain trials for inclusion in the ClinicalTrials.gov
database. ClinicalTrials.gov, which was created after the Food and Drug
Administration Modernization Act of 1997, 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 (NLM) has developed this site in
collaboration with NIH and FDA. ClinicalTrials.gov is available to the public
through the Internet at http://clinicaltrials.gov. ClinicalTrials.gov
contains information about certain clinical trials, both federally and
privately funded, of drugs (including biological products) and medical
devices. The types of trials that are required to be registered, and for
which results must be reported, are known as "applicable clinical
trials." FDAAA defines the types of clinical trials that are
"applicable clinical trials" and, therefore, are subject to the
registration and results reporting requirements. The registry listing for
each trial includes information such as descriptive information about the
trial, patient eligibility criteria, recruitment status, location information
on the clinical trial sites, and points of contact for those wanting to enroll
in the trial. The database also contains information on the results of
clinical trials. More detailed information on the definition of
"applicable clinical trial" and the registry and results reporting
requirements can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-014.html and http://prsinfo.clinicaltrials.gov/fdaaa.html. FDAAA
also added new requirements concerning clinical trials supported by grants from
HHS, including FDA. Under these provisions, any grant or progress report
forms required under a grant from any part of HHS, including FDA, must include
a certification that the person responsible for entering information into
ClinicalTrials.gov (the "responsible party") has submitted all
required information to the database. There are also provisions regarding
when agencies within HHS, including FDA, are required to verify compliance with
the database requirements before releasing funding to grantees. OPD
program staff will be providing additional information on these requirements,
including the appropriate means by which to certify that a grantee has complied
with the database requirements. 1.B. Data and Safety Monitoring Plan See Section VI.3.A. for more detail and other FDA
monitoring requirements. The establishment of data and safety monitoring
interventions that entail potential risk to the participants, and generally for
Phase 3 clinical trials. Although Phase 1 and Phase 2 clinical trials may also
use DSMBs, smaller clinical trials may not require this oversight format, and
1.C. Access to Research Data through the Freedom of Information Act (FOIA) The Freedom of Information Act (FOIA), 5 U.S.C. 552, provides individuals with
a right to access certain records in the possession of the Federal government,
subject to certain exemptions. The government may withhold information pursuant
to the exemptions and exclusions contained in the FOIA. The exact language of
the exemptions can be found in the FOIA. 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) and FDA regulations implementing the
FOIA (21 CFR part 20). (Also see the HHS Web site http://www.hhs.gov/foia/ and FDA Web site at http://www.fda.gov/RegulatoryInformation/FOI/default.htm
included in the application may be considered trade secret or confidential
commercial information within the meaning of relevant statutes and implementing
regulations. FDA will protect trade secret or confidential commercial
information to the extent allowed under applicable law.
1.D. Use of Animals in Research Recipients
of PHS support for activities involving live vertebrate animals must comply
1. E. 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.
1.F. 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
1.G. 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
researcher and his/her institution. The OCR Web site http://www.hhs.gov/ocr/
provides information on the Privacy Rule.
1.H. 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.
1.I. Smoke-Free Workplace The PHS
1.J. Authority and Regulation This program is not subject to the intergovernmental
review requirements of Executive Order 12372. FDA's research program is
described in the Catalog of Federal Domestic Assistance (CFDA), No. 93.103 http://www.cfda.gov/. FDA
section 301 of the PHS Act as amended (42 U.S.C. 241) and
under applicable regulations at 42 CFR Part 52 and 45 CFR Parts 74 and 92. All
imposed by sections 505, 512, and 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), section 351 of the PHS Act,
including regulations issued under any of these sections.
at http://www.fda.gov/oc/gcp/. 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. All
awards will be subject to all policies and requirements that govern the
research grant programs of the PHS as incorporated in the HHS Grants Policy
Statement, dated January 1, 2007 (http://www.hhs.gov/grantsnet/adminis/gpd/index.htm). Weekly TOC for this Announcement