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

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

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(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