[Federal Register Volume 63, Number 175 (Thursday, September 10, 1998)]
[Notices]
[Pages 48510-48513]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-24257]


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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention
[Program Announcement 99013]


Notice of Availability of Funds; Economic and Outcome Analysis of 
Antimicrobial Resistance in Hospital-Acquired Infections Among 
Intensive Care Unit Patients

A. Purpose

    The Centers for Disease Control and Prevention (CDC) announces the 
availability of fiscal year (FY) 1999 funds for a cooperative agreement 
program for economic and outcome analysis of antimicrobial resistance 
in hospital-acquired infections among intensive care unit (ICU) 
patients. This program addresses the ``Healthy People 2000'' priority 
area(s) of Immunization and Infectious Diseases.
    The purpose of the program is to provide assistance to the National 
Nosocomial Infections Surveillance

[[Page 48511]]

(NNIS) system hospitals to quantify the impact of antimicrobial 
resistance on their institution and their patients. Understanding the 
economic costs and patient outcomes associated with such resistant 
infections will aid the infection control community in their efforts to 
justify the allocation of resources to improve efforts at preventing 
the emergence and spread of antimicrobial resistant pathogens. This 
data will originate from several institutions and allow generalizable 
estimates of the economic impact and patient outcomes associated with 
antimicrobial resistance at U.S. hospitals.
    The specific objectives of this cooperative agreement are:
    1. Assess the impact of antimicrobial resistance, specifically 
methicillin resistant S. aureus and vancomycin-resistant enterococci, 
causing nosocomial infections, specifically primary bloodstream 
infections, both in terms of poor patient outcomes (e.g., morbidity and 
mortality) and economic cost, at participating hospitals.
    2. Disseminate information regarding economic costs incurred from 
antimicrobial resistant organisms.

B. Eligible Applicants

Limited Competition

    Assistance will be provided only to U.S. hospitals actively 
participating in the Intensive Care Unit (ICU) component of CDC's NNIS 
System, and have used NNIS definitions and methodology for surveillance 
of nosocomial infections to identify 60 ICU patients with 
nosocomial primary bloodstream infection, 20 of which were 
associated with methicillin resistant Staphylococcus aureus, and 15 of 
which were associated with vancomycin resistant enterococci over the 
past 5 years.
    Competition is limited to hospitals actively participating in the 
NNIS System, currently the only source of national data on risk-
adjusted, nosocomial infection rates in the United States using 
standardized methodology.

    Note: Public Law 104-65 states that an organization described in 
section 501(c)(4) of the Internal Revenue Code of 1986 that engages 
in lobbying activities is not eligible to receive Federal funds 
constituting an award, grant, cooperative agreement, contract, loan, 
or any other form.

C. Availability of Funds

    Approximately $130,000 is available in FY 1999 to fund 
approximately 5 awards. It is expected that the average award will be 
$25,000, ranging from $15,000 to $30,000 depending on the number of 
case- and control-patients included in the applicant's proposal. It is 
expected that the awards will begin on or about December 15, 1998 and 
will be made for a 12-month budget period within a 12-month project 
period. Funding estimates may change.

D. Program Requirements

    In conducting activities to achieve the purpose of this program, 
the recipient shall be responsible for conducting activities under A., 
below, and CDC shall be responsible for conducting activities under B. 
below.

A. Recipient Activities

    1. Design a matched case-control study, where case-patients (i.e., 
those infected with the antimicrobial resistant pathogen) will be 
compared to matched control-patients (i.e., those infected with the 
respective antimicrobial susceptible pathogen). Factors that may 
influence patient outcome, costs of hospitalization, and adaptability 
of criteria to other recipients should be considered. Examples of 
matching criteria may include location of patient, month or year of 
infection, APACHE II score (+/-5 points), comorbid conditions, or a 
combination of these characteristics. A published example includes that 
performed by D. Pittet, et al. when determining extra costs of 
nosocomial bloodstream infection in critically ill patients (JAMA. 
1994;271:1598-1601).
    2. Collect limited existing data from medical records of all 
potential case- and control-patients eligible for matching algorithm.
    3. Collect detailed data on case- and control-patients of two 
types: financial and clinical (i.e., descriptive and patient outcome). 
Determining excess costs may require recording total costs of 
hospitalization per study patient and costs by each day of 
hospitalization. In addition, it would be desirable to record costs by 
category (i.e., laboratory or diagnostic tests, pharmaceuticals, bed 
occupancy, physician, extra nursing, materials). Patient outcome data 
must include, but not limited to, mortality, length of stay, response 
to therapy, and relapse or recurrent infection.
    4. Publish results through collaboration with other recipients of 
this cooperative agreement and CDC.

B. CDC Activities

    1. Provide technical assistance in the design and conduct of a pair 
wise-matched case-control study which may include data collection forms 
and designing innovative approaches to matching controls to cases.
    2. Provide assistance to recipients regarding development of study 
protocols, data collection methods, and analyses, as necessary.
    3. Assist in the development of data management processes, 
materials, and protocols.
    4. Coordinate pooling data from each site and participate in the 
analysis of study information and dissemination of study findings.
    5. The CDC IRB will review and approve the protocol initially and 
on at least an annual basis until the research project is completed.

E. Application Content

    Use the information in the Program Requirements, Other 
Requirements, and Evaluation Criteria sections to develop the 
application content. Your application will be evaluated on the criteria 
listed, so it is important to follow them in laying out your program 
plan. The narrative should be no more than 10 double-spaced pages 
(excluding budget and appendixes), printed on one side, with one inch 
margins, and unreduced font. Unless indicated otherwise, all 
information requested below must appear in the narrative. Materials or 
information that should be part of the narrative will not be accepted 
if placed in the appendixes. The application narrative must contain the 
following sections in the order presented below:
    1. Abstract: Provide a brief (two pages maximum) abstract of the 
project. State the length of the project period (maximum is 1 year) for 
which assistance is being requested (see ``Availability of Funds'' for 
additional information).
    2. Background and Need: Discuss the background and need for the 
proposed project. Illustrate and justify the need for the proposed 
project that is consistent with the purpose and objectives of this 
cooperative agreement program.
    3. Capacity and Personnel:
    a. Describe past experience in conducting projects/studies similar 
to that being proposed.
    b. Describe resources, facilities, and professional personnel that 
will be involved in conducting the project. Include in an appendix, 
curriculum vitae for all professional personnel directly involved with 
the project.
    c. Because award size should reflect the number of patients on 
which data will be collected, provide in an appendix a list of all 
patients, void of personal identifiers, identified by infection control 
staff using standard NNIS definitions as having a nosocomial primary 
bloodstream infection while in an intensive care unit for at least the 
past 5 years. This list

[[Page 48512]]

must include, but not be limited to, infections associated with S. 
aureus (both methicillin-susceptible and methicillin-resistant), and 
enterocococcus spp. (both vancomycin-susceptible and vancomycin-
resistant). Other organisms of interest, and highly desirable to study 
if present in sufficient quantity, include Klebsiella pneumoniae not-
susceptible to ceftazidime or aztreonam, Candida albicans, and C. 
krusei. For each patient, the list must document the organism(s) 
associated with the nosocomial bloodstream infection, susceptibility 
status to the antimicrobial of interest (e.g., pathogens stated above), 
date of admission to hospital, date of infection, and location of 
patient at time of infection.
    d. Provide in an appendix letters of support from all key 
participating non-applicant Departments (i.e., medical informatics, 
medical records), individuals, etc., which clearly indicate their 
commitment to participate as described in the operational plan. Do not 
include letters of support from CDC personnel.
    4. Objectives and Technical Approach: a. Describe specific 
objectives for the proposed project which are measurable and time-
phased and are consistent with the purpose and goals of this 
cooperative agreement.
    b. Present a detailed operational plan for initiating and 
conducting the project which clearly and appropriately addresses all 
Recipient Activities, including the approach to collecting financial 
data.
    c. Clearly identify specific assigned responsibilities for all key 
professional personnel.
    d. Describe the nature and extent of collaboration with CDC and/or 
others during various phases of the study.
    e. Describe in detail a plan for evaluating progress toward 
achieving project objectives.
    5. Budget: Provide in an appendix, a budget and accompanying 
detailed justification for the project that is consistent with the 
purpose and objectives of this program. If requesting funds for 
contracts, provide the following information for each proposed 
contract: (1) Name of proposed contractor, (2) breakdown and 
justification for estimated costs, (3) description and scope of 
activities to be performed by contractor, (4) period of performance, 
and (5) method of contractor selection (e.g., sole-source or 
competitive solicitation).
    6. Human Subjects: Whether or not exempt from DHHS regulations, if 
the proposed project involves human subjects, document in an appendix 
that the principal investigator has obtained human subjects clearance.

F. Submission and Deadline

Application

    Submit the original and five copies of PHS-398 (OMB Number 0925-
0001) (adhere to the instructions on the Errata Instruction Sheet for 
PHS 398). Forms are in the application kit. On or before November 1, 
1998 submit the application to: Van Malone, Grants Management 
Specialist, Grants Management Branch, Procurement and Grants Office, 
Announcement #99013, Centers for Disease Control and Prevention, Room 
300, 255 East Paces Ferry Road, NE, MS E-18, Atlanta, Georgia 30305-
2209.
    If your application does not arrive in time for submission to the 
independent review group, it will not be considered in the current 
competition unless you can provide proof that you mailed it on or 
before the deadline (i.e., receipt from U.S. Postal Service or a 
commercial carrier; private metered postmarks are not acceptable).

G. Evaluation Criteria

    Applications will be reviewed and evaluated based on the following 
weighted criteria.

1. Background and Need (10 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 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 cooperative 
agreement.

2. Capacity (50 Points Total)

    A. The extent to which applicant has the appropriate organizational 
structure, administrative support, and ability to access the defined 
target population, and that this access will ensure an adequate sample 
size and representation so that epidemiologic analysis of patient 
outcomes and excess costs will be appropriate and statistically valid. 
Considerable attention will be given to the quantity of patients having 
had nosocomial bloodstream infections caused by the targeted 
antimicrobial resistant pathogens (i.e., potential cases) and those 
caused by the corresponding susceptible pathogen (i.e., potential 
controls) documented by the recipient. Considerable attention will be 
given to the recipient's capacity to access cost data for potential 
cases and matched controls, and the ability to link cost data to 
specific categories of costs and/or date of costs during patient's 
hospitalization. (40 points)
    b. Extent to which applicant documents that professional personnel 
involved in the project are qualified, by training and experience 
(i.e., NNIS hospital personnel must have the essential understanding of 
definitions of nosocomial infections used in the NNIS system); and have 
an appropriate projected level of effort directed toward accomplishment 
of the proposed objectives. (10 points)

3. Objectives and Technical Approach (i.e., Plan) (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 cooperative agreement program and which are measurable and time-
phased. (10 points)
    b. Extent to which applicant presents a detailed operational plan 
for performing the matching process to pick controls for the case-
control study. (10 points)
    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.
    c. 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. (20 points)

4. Budget (Not Scored)

    The extent to which the budget is reasonable (i.e., in proportion 
to the number of patients for which data will be collected), clearly 
justified, and consistent with the intended use of cooperative 
agreement funds.
    5. Does the application adequately address the requirements of 45 
CFR Part 46 for the protection of human subjects?
    ________ YES ______No

[[Page 48513]]

    Comments: ______

H. Other Requirements

Technical Reporting Requirements

    Provide CDC with original plus two copies of:
    1. Progress reports. Narrative progress reports are required every 
6 months. An original and two copies of reports are due within 30 days 
after first 6 months and 90 days following end of project period. 
Progress reports should address progress toward overall objectives as 
represented in the Purpose and Recipient Activities sections of this 
announcement including status report of case and control selection, 
enrollment, and progress of data abstraction.
    2. Financial status report, no more than 90 days after the end of 
the budget period. Send all reports to: Van Malone, Grants Management 
Specialist, Grants Management Branch, Procurement and Grants Office, 
Centers for Disease Control and Prevention, Room 300, 255 East Paces 
Ferry Road, NE, M/S E-18, Atlanta, GA 30305-2209.
    The following additional requirements are applicable to this 
program. For a complete description of each, see Attachment 1 (included 
in the application kit).

AR-1  Human Subjects Requirements
AR-2  Requirements for Inclusion of Women and Racial and Ethnic 
Minorities in Research
AR-10  Smoke-Free Workplace Requirements
AR-7  Executive Order 12372 Review
AR-11  Healthy People 2000
AR-12  Lobbying Restrictions

I. Authority and Catalog of Federal Domestic Assistance Number

    This program is authorized under the Public Health Service Act 
Section(s) 301(a)[42 U.S.C. 241(a)], 317(k)(2)[42 U.S.C. 247b(k)(2)], 
as amended. The Catalog of Federal Domestic Assistance number is 
93.283.

J. Where to Obtain Additional Information

    Please refer to Program Announcement 99013 when you request 
information. For a complete program description, information on 
application procedures, an application package, and business management 
technical assistance, contact: Van Malone, Grants Management 
Specialist, Grants Management Branch, Procurement and Grants Office, 
Announcement [99013], Centers for Disease Control and Prevention (CDC), 
Room 300, 255 East Paces Ferry Road, N.E., [E-18], Atlanta, GA 30305-
2209, telephone (404) 842-6872, Email address [email protected].
    See also the CDC homepage on the Internet: http://www.cdc.gov
    For program technical assistance, contact Scott K. Fridkin, 
Hospital Infections Program, National Center for Infectious Diseases, 
Centers for Disease Control and Prevention, 1600 Clifton Road, N.E., 
Mailstop E-55, Atlanta, Georgia 30333. Facsimile: (404) 639-6436. E-
mail address: [email protected]
John L. Williams,
Director, Procurement and Grants, Centers for Disease Control and 
Prevention (CDC).
[FR Doc. 98-24257 Filed 9-9-98; 8:45 am]
BILLING CODE 4163-18-P