[Federal Register Volume 61, Number 119 (Wednesday, June 19, 1996)]
[Notices]
[Pages 31121-31124]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-15558]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Centers for Disease Control and Prevention
[Announcement Number 663]
Applied Research in Emerging Infections--Genetics of
Antimicrobial Resistance and Novel Methods for Detection of Antiviral
Resistance
Introduction
The Centers for Disease Control and Prevention (CDC) is
implementing a program for competitive cooperative agreement and/or
research project grant applications to support applied research on
emerging infections. CDC announces the availability of fiscal year (FY)
1996 funds to provide assistance for a grant/cooperative agreement
program to conduct research on the genetic analysis of antimicrobial
resistance determinants.
The CDC is committed to achieving the health promotion and disease
prevention objectives of Healthy People 2000, a national activity to
reduce morbidity and mortality and improve the quality of life. This
announcement is related to the priority area of Immunization and
Infectious Diseases. (For ordering a copy of Healthy People 2000, see
the section WHERE TO OBTAIN ADDITIONAL INFORMATION.)
Authority
This program is authorized under sections 301 and 317 of the Public
Health Service Act, as amended (42 U.S.C. 241 and 247b).
Smoke-Free Workplace
The CDC strongly encourages all grant recipients to provide a
smoke-free workplace and to promote the nonuse of all tobacco products,
and Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking
in certain facilities that receive Federal funds in which education,
library, day care, health care, and early childhood development
services are provided to children.
Eligible Applicants
Applications may be submitted by public and private, nonprofit and
for-profit organizations and governments and their agencies. Thus,
universities, colleges, research institutions, hospitals, other public
and private organizations, including State and local governments or
their bona fide agents, federally recognized Indian tribal governments,
Indian tribes or Indian tribal organizations, and small, minority- and/
or women-owned businesses are eligible to apply.
Availability of Funds
Approximately $250,000 is available in FY 1996 to fund up to three
awards. It is expected that the average award will be $125,000, ranging
from $80,000 to $250,000.
It is expected that the awards will begin on or about September 30,
1996, and will be made for a 12-month budget period within a project
period of up to two years. Funding estimates may vary and are subject
to change. Continuation awards within an approved project period will
be made on the basis of satisfactory progress and availability of
funds.
Purpose
The purpose of the emerging infections extramural research program
is to provide financial and technical assistance for applied research
projects on emerging infections in the United States. As a component of
the emerging infections extramural research program, the purpose of
this grant/cooperative agreement announcement is to provide assistance
for projects addressing the following two focus areas:
1. Mechanisms of Dissemination of Antimicrobial Resistance Genes
The focus of the investigations should be the examination of the
role of plasmids, transposons, and integrons in antimicrobial
resistance gene dissemination, the natural variation of the nucleotide
sequences of resistance genes, and the impact of those changes on the
resistance phenotype mediated by the genes. This should include
examination of the role of antimicrobial use in institutions and its
effect on gene dissemination. Assistance under this focus area will be
provided for projects specifically addressing either of the following:
a. Improving understanding of the mechanisms by which vancomycin
resistance genes in enterococci or genes encoding extended-spectrum
- lactamases in Klebsiella pneumoniae are spread in hospitals
or other healthcare institutions (including nursing homes and clinics)
and become part of the endemic flora of the institution.
b. Improving understanding of the mechanisms by which macrolide
resistance genes (such as those encoding erythromycin resistance) are
acquired and disseminated in Streptococcus pneumoniae in communities.
2. Antiviral Susceptibility Determination Methods: Development of
improved methods for measuring the susceptibility of herpes simplex
virus (HSV) isolates to acyclovir. Current methods for measuring drug
[[Page 31122]]
susceptibility of HSV isolates are labor-intensive, expensive, and have
not been standardized. These shortcomings stand as impediments to
surveillance for acyclovir-resistant HSV or resistance in other viral
pathogens. Specifically, assistance will be provided for projects
focusing on development of assays based on novel methods or approaches
for measuring the susceptibility of HSV to acyclovir. Such assays
should be capable of providing results comparable to current plaque
reduction and dye-uptake assays.
Applicants may submit separate applications for projects under one
or both focus areas.
Program Requirements
Recipients may separately apply and receive support for projects
under one or both of the two focus areas. In conducting activities to
achieve the purpose of this program, the recipient shall be responsible
for the activities under A.1. or A.2. (depending upon which focus areas
the recipient applies and receives support for) and CDC shall be
responsible for conducting activities under B., below:
A. Recipient Activities
1. Mechanisms of Dissemination of Antimicrobial Resistance Genes
a. Select study sites: Study sites may include (a) one or more
hospitals or related health care institutions known to have endemic or
emerging problems with antimicrobial-resistant organisms in which
extensive monitoring of antimicrobial-resistant strains has been
conducted or (b) communities with extensive active surveillance.
b. Collect isolates with corresponding epidemiologic and clinical
data: Assure that the isolates are well characterized with respect to
phenotype, genotype, and mode of transmission from patient to patient.
Collect bacterial strain typing information such as that derived by
pulsed-field gel electrophoresis (PFGE), arbitrary primed polymerase
chain reaction (PCR), restriction fragment length polymorphism (RFLP),
plasmid fingerprinting, serotyping, or other highly discriminatory
strain typing methods. Obtain antibiograms expressed as minimal
inhibitory concentrations (MICs) of common antibiotics. One example of
an appropriate approach to collection of isolates and data would be to
assemble a series of isolates of vancomycin-resistant enterococci (VRE)
from a single hospital with the corresponding PFGE data documenting the
routes of transmission of the isolates among patients in the
institution. The overall rates of infections over several years and the
diversity of strains present in the institutions or communities would
be determined. This would presumably involve microbiology laboratories,
infection control practitioners (for health care institutions), public
health officials, and epidemiologists. Additionally, collection of data
regarding antimicrobial use (expressed as Defined Daily Doses per 1000
patient-days) by area of the institution (e.g., intensive care unit or
other inpatient ward) or in communities would be useful.
c. Characterize the resistance determinants present by phenotypic
and molecular methods: Obtain MICs to an extended array of
antimicrobial agents to classify the phenotype (e.g., teicoplanin to
distinguish VanA from VanB). Determine strain types (when appropriate),
the presence of plasmids or other genetic elements, and the presence of
resistance genes in the strains as identified by using DNA probes or
specific PCR, LCR, or other genetic assays.
d. Monitor transmission and evaluate data: Characterize the
resistance genes present in the isolates, the modes of genetic exchange
of the resistance determinants among isolates in the institutions or
communities, and determine whether changes in the DNA or amino acid
sequences of the genes are associated with broadening of the phenotype
of the isolates carrying the genes. Consider the influence of
antimicrobial use on frequency and mode of gene transmission and on
changes in the phenotype of the isolates. Depending on the studies
conducted, questions that could be addressed include: (1) Is an initial
period of plasmid transfer among organisms followed by dissemination of
a transposable element to multiple plasmids in strains of enterococci
resulting in the vancomycin resistance phenotype being present in
multiple strains of enterococci (as evidenced by widely divergent
pulsed-field gel electrophoresis types)? (2) Do changes in the sequence
of vanB correlate with increased resistance to teicoplanin? (3) Do the
mode of transfer and the phenotype vary by antimicrobial use patterns
in the institution or in certain wards of the institution?
e. Disseminate research findings: Disseminate research results by
appropriate methods such as publication in journals, presentation at
meetings and conferences, etc.
2. Antiviral Susceptibility Determination Methods
a. Study isolates: Identify a source of HSV isolates for study.
Ideally, this should include isolates from fresh clinical specimens
that can be tested in parallel with the plaque reduction or dye uptake
methods and for which acyclovir resistance has previously been
documented.
b. Devise a novel assay for determining the level of acyclovir
susceptibility of clinical HSV isolates: Establish a quality control
system to insure the reproducibility of the assay. A quality control
strain of HSV should be designated as part of the testing method and
data showing its effectiveness should be established. A useful novel
assay should be at least equivalent in performance and (ideally)
substantially less expensive than current assays. The new method should
be adaptable to a high-throughput, semi- automated format. Establish
criteria for designating HSV isolates as ``susceptible'' or
``resistant'' to acyclovir.
c. Evaluate the performance of the new assay in comparison with the
plaque reduction assay. To be useful for surveillance of resistance,
any new assay should be substantially equivalent to those in current
use (Am. J. Med. 73:380-382,1982).
B. CDC Activities
1. Research Project Grants
A research project grant is one in which substantial programmatic
involvement by CDC is not anticipated by the recipient during the
project period. Applicants for grants must demonstrate an ability to
conduct the proposed research with minimal assistance, other than
financial support, from CDC. This would include possessing sufficient
resources for clinical, laboratory, and data management services and a
level of scientific expertise to achieve the objectives described in
their research proposal without substantial technical assistance from
CDC.
2. Cooperative Agreements
In a cooperative agreement, CDC will assist recipients in
conducting the proposed research. The application should be presented
in a manner that demonstrates the applicant's ability to address the
research problem in a collaborative manner with CDC. In addition to the
financial support provided, CDC will collaborate by (1) providing
technical assistance in the design and conduct of the research; (2)
performing selected laboratory tests as appropriate; (3) participate in
data management, the analysis of research data, and the interpretation
and presentation of research findings; and
[[Page 31123]]
(4) providing biological materials (e.g., strains) as necessary for
studies, etc.
C. Determination of Which Instrument to Use
Applicants must specify the type of award for which they are
applying, either grant or cooperative agreement. CDC will review the
applications in accordance with the Evaluation Criteria. Before issuing
awards, CDC will inform the proposed grantee whether a grant or
cooperative agreement is the appropriate instrument based upon the need
for substantial CDC involvement in the project.
Notice of Intent To Apply
In order to assist CDC in planning for and executing the evaluation
of applications submitted under this Program Announcement, all parties
intending to submit an application are requested to inform CDC of their
intention to do so at their earliest convenience prior to the
application due date. Notification should include 1) name and address
of institution, 2) name, address, and phone number of contact person,
and 3) under which focus area(s) application(s) will be submitted.
Notification should be provided to Greg Jones, M.P.A., by facsimile
(404) 639-4195, E-mail gjj1@cidod1.em.cdc.gov or postal mail at
National Center for Infectious Diseases, Centers for Disease Control
and Prevention, 1600 Clifton Road, NE., Mailstop C-19, Atlanta, Georgia
30333.
Application Process
Applicants may apply for assistance for projects in one or both of
the specific programmatic focus areas identified under Purpose and
Program Requirements above. If applying for assistance for more than
one of the two focus areas, a separate and complete application must be
submitted for each project/focus area.
Evaluation Criteria
The applications will be reviewed and evaluated according to the
following criteria:
1. Background and Need (20 points): Extent to which applicant's
discussion of the background for the proposed project demonstrates a
clear understanding of the purpose and objectives of this grant/
cooperative agreement program. Extent to which applicant illustrates
and justifies the need for the proposed project that is consistent with
the purpose and objectives of this grant/cooperative agreement program.
2. Capacity (40 points total):
a. Extent to which applicant describes adequate resources and
facilities (both technical and administrative) for conducting the
project. (10 points)
b. Extent to which applicant documents that professional personnel
involved in the project are qualified and have past experience and
achievements in research related to that proposed as evidenced by
curriculum vitae, publications, etc. (20 points)
c. Extent to which applicant includes letters of support from non-
applicant organizations, individuals, etc. Extent to which the letters
clearly indicate the author's commitment to participate as described in
the operational plan. (10 points)
3. Objectives and Technical Approach (40 points total):
a. Extent to which applicant describes specific objectives of the
proposed project which are consistent with the purpose and goals of
this grant/cooperative agreement program and which are measurable and
time-phased. (10 points)
b. Extent to which applicant presents a detailed operational plan
for initiating and conducting the project, which clearly and
appropriately addresses all Recipient Activities. Extent to which
applicant clearly identifies and describes appropriate study sites (per
Recipient Activities 1.a.) or HSV isolates (per Recipient Activities
2.a.). Extent to which applicant clearly identifies specific assigned
responsibilities for all key professional personnel. Extent to which
the plan clearly describes applicant's technical approach/methods for
conducting the proposed studies and extent to which the plan is
adequate to accomplish the objectives. Extent to which applicant
describes specific study protocols or plans for the development of
study protocols that are appropriate for achieving project objectives.
If the proposed project involves human subjects, the degree to
which the applicant has met the CDC policy requirements regarding the
inclusion of women, ethnic, and racial groups in the proposed research.
This includes:
(1) The proposed plan for the inclusion of both sexes and racial
and ethnic minority populations for appropriate representation.
(2) The proposed justification when representation is limited or
absent.
(3) A statement as to whether the design of the study is adequate
to measure differences when warranted.
(4) A statement as to whether the plans for recruitment and
outreach for study participants include the process of establishing
partnerships with community(ies) and recognition of mutual benefits
will be documented. (see Other Requirements for additional information
regarding this requirement for research projects). (15 points)
c. Extent to which applicant describes adequate and appropriate
collaboration with CDC and/or others during various phases of the
project. (10 points)
d. Extent to which applicant provides a detailed and adequate plan
for evaluating study results and for evaluating progress toward
achieving project objectives. (5 points)
4. Budget (not scored):
Extent to which the proposed budget is reasonable, clearly
justifiable, and consistent with the intended use of grant/cooperative
agreement funds.
5. Human Subjects (not scored):
If the proposed project involves human subjects, whether or not
exempt from the DHHS regulations, the extent to which adequate
procedures are described for the protection of human subjects. Note:
Objective Review Group (ORG) recommendations on the adequacy of
protections include: (1) Protections appear adequate and there are no
comments to make or concerns to raise, or (2) protections appear
adequate, but there are comments regarding the protocol, or (3)
protections appear inadequate and the ORG has concerns related to human
subjects, or (4) disapproval of the application is recommended because
the research risks are sufficiently serious.
Executive Order 12372 Review
This program is not subject to Executive Order 12372,
Intergovernmental Review of Federal Programs.
Public Health System Reporting Requirements
This program is not subject to the Public Health System Reporting
Requirements.
Catalog of Federal Domestic Assistance Number
The Catalog of Federal Domestic Assistance Number is 93.283.
Other Requirements
Paperwork Reduction Act
Projects that involve the collection of information from ten or
more individuals and funded by the grant/cooperative agreement will be
subject to review by the Office of Management and Budget (OMB) under
the Paperwork Reduction Act.
Human Subjects
If the proposed project involves research on human subjects, the
applicant must comply with the
[[Page 31124]]
Department of Health and Human Services Regulations (45 CFR Part 46)
regarding the protection of human subjects. Assurance must be provided
to demonstrate that the project will be subject to initial and
continuing review by an appropriate institutional review committee. In
addition to other applicable committees, Indian Health Service (IHS)
institutional review committees also must review the project if any
component of IHS will be involved or will support the research. If any
American Indian community is involved, its tribal government must also
approve that portion of the project applicable to it. The applicant
will be responsible for providing evidence of this assurance in
accordance with the appropriate guidelines and form provided in the
application kit.
Women, Racial and Ethnic Minorities
It is the policy of the Centers for Disease Control and Prevention
(CDC) and Agency for Toxic Substances and Disease Registry (ATSDR) to
ensure that individuals of both sexes and the various racial and ethnic
groups will be included in CDC/ATSDR-supported research projects
involving human subjects, whenever feasible and appropriate. Racial and
ethnic groups are those defined in OMB Directive No. 15 and include
American Indian, Alaskan Native, Asian, Pacific Islander, Black, and
Hispanic. Applicants shall ensure that women, racial and ethnic
minority populations are appropriately represented in applications for
research involving human subjects. Where clear and compelling rationale
exists that inclusion is inappropriate or not feasible, this situation
must be explained as part of the application. This policy does not
apply to research studies when the investigator cannot control the
race, ethnicity and/or sex subjects. Further guidance to this policy is
contained in the Federal Register, Vol. 60, No. 179, pages 47947-47951,
dated Friday, September 15, 1995.
Application Submission and Deadline
The original and two copies of each application Form PHS-5161-1
(revised 7/92, OMB Control Number 0937-0189) must be submitted to
Sharron P. Orum, Grants Management Officer, Grants Management Branch,
Procurement and Grants Office, Centers for Disease Control and
Prevention (CDC), 255 East Paces Ferry Road, NE., Room 300, Mailstop E-
18, Atlanta, Georgia 30305, Attention: Marsha Driggans, on or before
August 5, 1996:
1. Deadline: Applications shall be considered as meeting the
deadline if they are either:
a. Received on or before the deadline date; or
b. Sent on or before the deadline date and received in time for
submission to the objective review group. (Applicants must request a
legibly dated U.S. Postal Service postmark or obtain a legibly dated
receipt from a commercial carrier or U.S. Postal Service. Private
metered postmarks shall not be acceptable as proof of timely mailing.)
2. Late Applications: Applications which do not meet the criteria
in 1.a. or 1.b. above are considered late applications. Late
applications will not be considered in the current competition and will
be returned to the applicant.
Where To Obtain Additional Information
A complete program description and information on application
procedures are contained in the application package. An application
package and business management and technical assistance may be
obtained from Marsha Driggans, Grants Management Specialist, Grants
Management Branch, Procurement and Grants Office, Centers for Disease
Control and Prevention (CDC), 255 East Paces Ferry Road, NE., Mailstop
E-18, Room 300, Atlanta, Georgia 30305, telephone (404) 842-6523, E-
mail mdd2@opspgo1.em.cdc.gov, facsimile (404) 842-6513.
Programmatic technical assistance may be obtained from Dr. Fred C.
Tenover, Hospital Infections Program, National Center for Infectious
Diseases, Centers for Disease Control and Prevention (CDC), 1600
Clifton Road, NE., Mailstop G-08, Atlanta, Georgia 30333, E-mail
fnt1@cidhip1.em.cdc.gov, telephone (404) 639-3246.
Please refer to Announcement Number 663 when requesting information
regarding this program.
Important Notice: Atlanta, Georgia, will be the host of the 1996
Summer Olympics Games, July 19 through August 4, 1996. As a result of
this event, it is likely that the Procurement and Grants Office (PGO),
CDC, may experience delays in the receipt of both regular and overnight
mail deliveries. Contacting PGO employees during this time frame may
also be hindered due to the possible telephone disruptions. To the
extent authorized, please consider the use of voice mail, E-mail, and
facsimile transmission to the maximum extent practicable. However, do
not fax lengthy documents or grant applications.
You may obtain this announcement from one of two Internet sites on
the actual publication date: CDC's homepage at http://www.cdc.gov or at
the Government Printing Office homepage (including free on-line access
to the Federal Register at http://www.access.gpo.gov).
Potential applicants may obtain a copy of Healthy People 2000 (Full
Report, Stock No. 017-001-00474-0) or Healthy People 2000 (Summary
Report, Stock No. 017-001-00473-1) referenced in the Introduction
through the Superintendent of Documents, Government Printing Office,
Washington, DC 20402-9325, telephone (202) 512-1800.
Dated: June 11, 1996.
Joseph R. Carter,
Acting Associate Director for Management And Operations, Centers for
Disease Control and Prevention (CDC).
[FR Doc. 96-15558 Filed 6-18-96; 8:45 am]
BILLING CODE 4163-18-P
