[Federal Register Volume 77, Number 138 (Wednesday, July 18, 2012)]
[Notices]
[Pages 42317-42318]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-17454]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-N-0011]


Establish a Patient-Based Registry To Evaluate the Association of 
Gadolinium Based Contrast Agents Exposure and Nephrogenic Systemic 
Fibrosis

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of grant funds for the support of the development of a 
patient-based registry to evaluate the association of gadolinium based 
contrast agents (GBCAs) exposure and nephrogenic systemic fibrosis 
(NSF). The goal of the GBCA project is to study the safety of the GBCAs 
when used as indicated.

DATES: Important dates are as follows:
    1. The application due date is August 1, 2012.
    2. The anticipated start date is September 13, 2012.
    3. The opening date is July 2, 2012.
    4. The expiration date is August, 2, 2012.

ADDRESSES: Submit the paper application to: Vieda Hubbard, Grants 
Management (HFA-500), 5630 Fishers Lane, Rockville, MD 20857, and a 
copy to Ira Krefting, Center for Drug Evaluation and Research, Division 
of Medical Imaging Products, 10903 New Hampshire Ave., Bldg. 22, rm. 
2100, Silver Spring, MD 20993. For more information, see section III of 
the SUPPLEMENTARY INFORMATION section of this notice.

FOR FURTHER INFORMATION AND ADDITIONAL REQUIREMENTS CONTACT: Ira 
Krefting, Center for Drug Evaluation and Research (CDER), Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 2100, Silver 
Spring, MD 20993, 301-796-1135, Email: [email protected]; or
Vieda Hubbard, Office of Acquisitions and Grants Services (HFA-500), 
Food and Drug Administration, 5630 Fishers Lane, rm. 2034, Rockville, 
MD 20857, 301-827-7177, Email: [email protected].

    For more information on this funding opportunity announcement (FOA) 
and to obtain detailed requirements, please refer to the full FOA 
located at: http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/UCM311309.pdf.

SUPPLEMENTARY INFORMATION:

I. Funding Opportunity Description

    RFA-FD-12-029
    93.103

A. Background

    Annually, millions of patients undergo magnetic resonance imaging 
(MRI) and magnetic resonance angiography (MRA) procedures employing 
GBCAs. Postmarketing data indicate that six of the eight GBCAs approved 
for use in the United States have been directly implicated in the 
development of NSF, a newly characterized, potentially fatal systemic 
fibrotic skin and internal organ condition. Among the factors that may 
increase the risk for NSF are repeated or higher than recommended doses 
of GBCA and degree of renal impairment at the time of exposure; imaging 
patients with severe renal failure appear to be at highest risk. In 
one, early retrospective study of 370 patients with severe renal 
failure who received gadodiamide the estimated risk for development of 
NSF was 4 percent (Ref. 1). In a recent retrospective chart review 
study by Wang of 52,954 contrast MR examinations with restrictive 
guidelines for GBCA in patients with renal failure no new cases of NSF 
were found (Ref. 2).

[[Page 42318]]

    In addition, the NSF risk appears to vary among the GBCAs. 
Postmarketing data and corroborating preclinical data that demonstrated 
a significant, unacceptable NSF risk has led FDA to recently 
contraindicate Omniscan, Magnevist, and Optimark for patients with 
acute kidney injury and severe chronic renal failure. The risk of NSF 
associated with the remaining marketed GBCAs for patients with these 
kidney conditions is expected to be lower, but is not fully understood. 
Therefore, there is a public health need to study the risk of NSF 
associated with the exposure of those remaining marketed GBCAs and to 
inform the development of reliable knowledge, practice guidelines, and 
regulatory processes in relationship to the safety of these agents.

B. Research Objectives

    The primary goal of this project is to employ an existing Quality 
Assurance (QA) registry of patients with renal failure who received 
GBCAs as the basis for a prospective registry study of the risk of NSF 
associated with GBCAs among renal patients. Patients already enrolled 
in this QA registry will be invited to enroll in an outpatient registry 
to study their risk of NSF. Data from this project will help understand 
the effect of cumulative dosing of the GBCAs in patients with slow 
deterioration of renal function as occurs with aging, and the data 
might also provide further reassurance as to the safety of the GBCAs 
identified as having minimal association with the risk of NSF by 
prospectively following patients who have received GBCAs. In addition, 
the project will also provide data on the occurrence of allergic 
reactions associated with the GBCA administration. A recent report by 
Prince suggests an increased risk of allergic reactions with MultiHance 
(Ref. 3).
    The prospective design of this project is important since most 
previous clinical investigations have been based on chart review or 
other retrospective data. Implementation of this project may also 
provide the structure for future prospective investigations of other 
diseases with an acute phase of hospitalization superimposed on a 
chronic course.

C. Eligibility Information

    This is a sole source cooperative agreement to: University of 
Pittsburg Medical Center.

II. Award Information/Funds Available

A. Award Amount

    CDER anticipates providing in FY2012 $250,000 (total costs include 
direct and indirect costs), for one award subject to availability of 
funds in support of this project.

B. Length of Support

    Support will be 1 year with the possibility of an additional year 
of noncompetitive support. Continuation beyond the first year will be 
based on satisfactory performance during the preceding year, receipt of 
a noncompeting continuation application and subject to the availability 
of Fiscal Year appropriations.

III. Paper Application, Registration, and Submission Information

    To submit a paper application in response to this FOA, applicants 
should first review the full announcement located at: http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/UCM311309.pdf. (FDA has verified 
the Web site addresses throughout this document, but FDA is not 
responsible for any subsequent changes to the Web sites after this 
document publishes in the Federal Register.) Persons interested in 
applying for a grant may obtain an application at: http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/UCM311309.pdf. For all paper application submissions, the 
following steps are required:
     Step 1: Obtain a Dun and Bradstreet (DUNS) Number.
     Step 2: Register With Central Contractor Registration.
     Step 3: Register With Electronic Research Administration 
(eRA) Commons Steps 1 and 2, in detail, can be found at: http://www07.grants.gov/applicants/organization_registration.jsp. Step 3, in 
detail, can be found at: https://commons.era.nih.gov/commons/registration/registrationInstructions.jsp. After you have followed 
these steps, submit one paper application to: Vieda Hubbard, Grants 
Management, Food and Drug Administration, Division of Support and 
Grants, 5630 Fishers Lane, rm. 1079, HFA 500, Rockville, MD 20857 and a 
copy to Ira Krefting, Center for Drug Evaluation and Research, Division 
of Medical Imaging Products, 10903 New Hampshire Ave. Bldg. 22, Rm. 
2100, Silver Spring, MD 20993.

IV. References

    The following references have been placed on display in the 
Division of Dockets Management, 5630 Fishers Lane, rm. 1061, Rockville, 
MD 20852, and may be seen by interested persons between 9 a.m. and 4 
p.m., Monday through Friday.

    1. Marckmann, Peter; Skov, Lone; Rossen, Kristian; Dupont, 
Anders; Damholt, Mette Brimnes; Heaf, James Goya; and Thomsen, 
Henrik, Journal of the American Society of Nephrology, 17:2359, 
2006.
    2. Wang, Yingbing; Alkasab, Tarik; Narin, Ozden; Nazarian, 
Rosalynn; Kaewali, Rathachai, Kaewlai; Kay, Jonathan; and Abujudeh, 
Hani, Radiology, 260:105, 2011.
    3. Prince, Martin; Zhang, Honglei; Zou, Zhitong; Staron, Ronald; 
and Brill, Paula, American Journal of Radiology, 196(2):W138, 2011.

    Dated: July 13, 2012.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2012-17454 Filed 7-17-12; 8:45 am]
BILLING CODE 4160-01-P