Applied Research in Emerging Infections Hepatitis C Virus Infection

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

[Announcement Number 779]

Applied Research in Emerging Infections Hepatitis C Virus

Infection

Introduction

The Centers for Disease Control and Prevention (CDC) announces the

availability of fiscal year (FY) 1997 funds for competitive cooperative

agreements and/or grants to support applied research on emerging

infections--epidemiologic studies of hepatitis C virus (HCV) infection.

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

CDC strongly encourages all grant recipients to provide a smoke-

free workplace and to promote the non-use of all tobacco products, and

Public Law 103-227, the Pro-Children's 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 non-profit

organizations and governments and their agencies. Thus, universities,

colleges, research institutions, hospitals, other public and private

organizations, 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 non-

profit businesses are eligible to apply.

Availability of Funds

Approximately $150,000 is available in FY 1997 to fund one award.

It is expected the award will begin on or about September 30, 1997, and

will be made for a 12-month budget period within a project period of up

to three years. Funding estimate may vary and is subject to change.

Continuation awards within the project period will be made on the

basis of satisfactory progress and availability of funds.

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 determine whether a grant or cooperative agreement is

the appropriate instrument based upon the need for substantial CDC

involvement in the project.

Use of Funds

Restrictions on Lobbying

Applicants should be aware of restrictions on the use of Department

of Health and Human Services (HHS) funds for lobbying of Federal or

State legislative bodies. Under the provisions of 31 U.S.C. Section

1352 (which has been in effect since December 23, 1989), recipients

(and their subtier contractors) are prohibited from using appropriated

Federal funds (other than profits from a Federal contract) for lobbying

Congress or any Federal agency in connection with the award of a

particular contract, grant, cooperative agreement, or loan. This

includes grants/cooperative agreements that, in whole or in part,

involve conferences for which Federal funds cannot be used directly or

indirectly to encourage participants to lobby or to instruct

participants on how to lobby.

In addition, the FY 1997 Departments of Labor, HHS, and Education,

and Related Agencies Appropriations Act, which became effective October

1, 1996, expressly prohibits the use of 1997 appropriated funds for

indirect or ``grass roots'' lobbying efforts that are designed to

support or defeat legislation pending before State legislatures.

Section 503 of this new law, as enacted by the Omnibus Consolidated

Appropriations Act, 1997, Division A, Title I, Section 101(e), Pub. L.

No. 104-208 (September 30, 1996), provides as follows:

Sec. 503(a) No part of any appropriation contained in this Act

shall be used, other than for normal and recognized executive-

legislative relationships, for publicity or propaganda purposes, for

the preparation, distribution, or use of any kit, pamphlet, booklet,

publication, radio, television, or video presentation designed to

support or defeat legislation pending before the Congress, * * * except

in presentation to the Congress or any State legislative body itself.

(b) No part of any appropriation contained in this Act shall be

used to pay the salary or expenses of any grant or contract recipient,

or agent acting for such recipient, related to any activity designed to

influence legislation or appropriations pending before the Congress or

any State legislature.

Background

Once expected to be eliminated as a public health problem,

infectious diseases remain the leading cause of death worldwide. In the

United States

[[Page 36547]]

and elsewhere, infectious diseases increasingly threaten public health

and contribute significantly to the escalating costs of health care.

In 1992, the Institute of Medicine of the National Academy of

Sciences published a report entitled Emerging Infections, Microbial

Threats to Health in the United States highlighting the threat of

emerging infections and making specific recommendations to address the

threat. This report emphasized a critical leadership role for CDC in a

national effort to detect and control infectious disease threats.

In partnership with other Federal agencies, State and local health

departments, academic institutions, and others, CDC has developed a

plan for revitalizing the nation's ability to identify, contain, and

prevent illness from emerging infectious diseases. The plan, Addressing

Emerging Infectious Disease Threats; A Prevention Strategy for the

United States, identifies objectives in four major areas: surveillance;

applied research; prevention and control; and infrastructure.

Under the objective for applied research, the plan proposes to

integrate laboratory science and epidemiology to optimize public health

practice in the United States. One component of these efforts is to

implement an extramural program for research in emerging infectious

disease surveillance, epidemiology, and prevention which will fill the

gaps in existing support for such research. In FY 1996, CDC initiated

the Extramural Applied Research Program in Emerging Infections (EARP)

and made grant or cooperative agreement awards to seven institutions

for projects in the areas of antimicrobial resistance and tickborne

diseases. This grant/cooperative agreement announcement specifically

addresses the area of hepatitis C virus infection (HCV).

In the United States, HCV is an important cause of acute and

chronic liver disease, although the natural history of this infection

is not well understood. An estimated 3.9 million persons are

chronically infected with HCV and are a potential source of

transmission to others. In the absence of pre-or post-exposure

prophylaxis, preventing the transmission of HCV and providing infected

persons with specific information about the risk and consequences of

infection are dependent on a better understanding of the natural

history and the risk of transmission in different settings.

In studies conducted to date, an average of 5 percent of infants of

anti-HCV positive mothers are infected perinatally; however, little is

known about the natural history of infection in these infants.

Understanding the outcome of perinatal HCV infection is essential for

developing recommendations and providing appropriate information to HCV

infected persons regarding any special precautions or restrictions

related to pregnancy, as well as determining the need for development

of therapeutic interventions in pediatric populations.

Case-control studies conducted prior to the discovery of HCV showed

that household contact with a person with hepatitis was a risk factor

for acquiring acute non-A, non-B hepatitis. Since the discovery of HCV,

cross sectional studies of household contacts of persons with chronic

HCV infection have demonstrated an average seroprevalence of 4 percent;

however, none of these studies was done in the United States, none

conclusively demonstrated that transmission occurred within the

household, and none had a sufficient sample size to estimate the risk

if such transmission occurred. To determine if specific recommendations

are needed for preventing transmission of HCV in the household setting,

the risk of, and risk factors for, household transmission of HCV need

to be addressed.

Follow-up studies among infants and other household contacts of

HCV-infected women identified through prenatal testing can address

questions regarding the natural history of perinatal HCV infection and

regarding household transmission of HCV.

Purpose

The purpose of this grant/cooperative agreement announcement is to

provide assistance for projects addressing HCV infection. Specifically,

applications are solicited for projects addressing the natural history

of perinatal HCV infection and household transmission of HCV:

a. Follow a cohort of infants with perinatal HCV infection through

the first five years of life.

b. Assess the incidence of and risk factors for HCV infection among

household contacts of HCV-infected women of childbearing age.

Program Requirements

In conducting activities to achieve the purpose of this program,

the recipient will be responsible for the activities under A.

(Recipient Activities), and CDC will be responsible for conducting

activities under B. (CDC Activities):

A. Recipient Activities

1. Natural history of perinatal HCV infection:

a. Identify an existing group of at least 10 perinatally-infected

infants with follow-up data, including serial results of appropriate

laboratory testing available from birth until at least 2 years of age.

Infants should be anti-HIV negative;

b. Perform additional follow-up clinical evaluations for all HCV-

infected infants in the group for a 3-year period (until children are

5 years of age), including history, physical examination,

laboratory testing, and liver biopsy, as appropriate according to

clinical practice standards.

2. Risk for household transmission of HCV infection:

a. Identify an existing cohort of at least 200 anti-HCV positive

women of childbearing age and their household contacts with the

following characteristics:

(1) Majority of women anti-HIV negative,

(2) Women who gave birth to at least one child since their anti-HCV

status was confirmed,

(3) Anti-HCV status (baseline) of all household contacts known,

(4) A complete history of risk factors for HCV infection for all

women and their household contacts.

b. Determine the incidence of HCV infection among anti-HCV negative

household contacts by conducting anti-HCV testing and obtaining history

of potential risk factors for transmission at least 3 years after

baseline testing. Employ methods to maintain participation of the

cohort during the interim period between baseline and follow-up

testing.

c. For incident HCV infections in households, identify virus-

specific factors that may be responsible for transmission and confirm

the identity of virus strains in household contact-pairs when both are

infected.

3. Publish results.

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.

[[Page 36548]]

2. Cooperative Agreements

A cooperative agreement implies that 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 may collaborate by: (a) providing

technical assistance in the design and conduct of the research; (b)

performing selected laboratory tests as appropriate and necessary;(c)

participating in data management, the analysis of research data, and

the interpretation and presentation of research findings; and (d)

providing biological materials as necessary for studies, etc.

Technical Reporting Requirements

An original and two copies of a narrative progress report are

required semiannually. The first semiannual report is required with

each year's non-competing continuation application and should cover

program activities from date of the previous report (or date of award

for reporting in the first year of the project).

The second semiannual report and Financial Status Report (FSR) are

due 90 days after the end of each budget period and should cover

activities from the date of previous report. Progress reports should

address the status of progress toward specific project objectives and

should include copies of any publications resulting from the project.

The final performance report and FSR are required no later than 90 days

after the end of the project period.

All reports should be directed to the CDC Grants Management Officer

at the address referenced in the following section.

Application Process

Notification of Intent to Apply

In order to assist CDC in planning 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 AS SOON AS POSSIBLE PRIOR TO THE APPLICATION DUE

DATE BUT NOT LATER THAN 10 BUSINESS DAYS PRIOR TO THE APPLICATION DUE

DATE. Notification should cite this Announcement Number 779 and

include: (1) name and address of institution and (2) name, address, and

phone number of contact person. Notification can be provided by

facsimile, postal mail, or electronic mail (E-mail) 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, facsimile (404) 842-6513 or E-mail [email protected].

Application Content

All applicants must develop their application(s) in accordance with

the PHS Form 398, information contained in this grant/cooperative

agreement announcement, and the instructions outlined below. In order

to ensure an objective, impartial, and prompt review, applications must

conform to these instructions.

General Instructions

Due to the need to reproduce copies of the applications for the

reviewers, ALL pages of the application must be in the following

format:

1. The original and two copies must be unstapled and unbound.

2. All pages must be clearly numbered, and a complete index to the

application and its appendices must be included.

3. All materials must be typewritten, single-spaced, using a font

no smaller than size 12, and on 8-\1/2\'' by 11'' white paper.

4. Any reprints, brochures, or other enclosures must be copied onto

8-\1/2\'' by 11'' white paper by the applicant. NO BOUND MATERIALS WILL

BE ACCEPTED.

5. All pages must be printed on ONE side only, with at least 1''

margins, headers, and footers.

Special Instruction

The application narrative must not exceed 10 pages (excluding

budget and appendices). 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 appendices. 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.

Clearly identify the type of award that is being applied for: grant or

cooperative agreement.

2. Background and Need:

Discuss the background and need for the proposed project.

Demonstrate a clear understanding of the purpose and objectives of this

grant/cooperative agreement program.

3. Capacity and Personnel:

Describe applicant's past experience in conducting projects/studies

similar to that being proposed. Describe applicant's resources,

facilities, and professional personnel that will be involved in

conducting the project. Include in an appendix curriculum vitae for all

professional personnel involved with the project. Describe plans for

administration of the project and identify administrative resources/

personnel that will be assigned to the project. Provide in an appendix

letters of support from all key participating non-applicant

organizations, individuals, etc., which clearly indicate their

commitment to participate as described in the operational plan. Do not

include letters of support from CDC personnel. Letters of support from

CDC will not be accepted. Award of a cooperative agreement implies CDC

participation as outlined in the Program Requirements section of this

announcement.

4. Objectives and Technical Approach:

Present specific objectives for the proposed project which are

measurable and time-phased and are consistent with the Purpose and

Recipient Activities of this Program Announcement. Present a detailed

operational plan for initiating and conducting the project which

clearly and appropriately addresses these objectives (if proposing a

multi-year project, provide a detailed description of first-year

activities and a brief overview of subsequent-year activities). Clearly

identify specific assigned responsibilities for all key professional

personnel. Include a clear description of applicant's technical

approach/methods which are directly relevant to the above objectives.

Describe specific study protocols or plans for the development of study

protocols. Describe the nature and extent of collaboration with CDC (if

applying for a cooperative agreement) and/or others during various

phases of the project. Describe in detail a plan for evaluating study

results and for evaluating progress toward achieving project

objectives.

5. Budget:

Provide a line-item budget and accompanying detailed, line-by-line

justification that demonstrates the request is consistent with the

purpose and objectives of this program. If requesting funds for

contracts, provide the following information for each proposed

contract: (a) Name of proposed contractor, (b) breakdown and

justification for estimated costs, (c) description and scope of

activities to be performed by contractor, (d) period of performance,

and (e) method of

[[Page 36549]]

contractor selection (e.g., sole-source or competitive solicitation).

Note: If indirect costs are requested from CDC on a new or

continuation application, a copy of the organization's current

negotiated Federal indirect cost rate agreement or cost allocation

plan must be provided.

6. Human Subjects:

Whether or not exempt from DHHS regulations, if the proposed

project involves human subjects, describe in an appendix adequate

procedures for the protection of human subjects. Also, ensure that

women, racial and ethnic minority populations are appropriately

represented in applications for research involving human subjects.

Evaluation Criteria

The applications will be reviewed and evaluated according to the

following criteria:

1. Background and Need (10 Points)

Extent to which applicant demonstrates a clear understanding of the

subject area and of the purpose and objectives of this grant/

cooperative agreement program.

2. Capacity (45 Points)

Extent to which applicant describes adequate resources and

facilities (both technical and administrative) for conducting the

project. 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. If applicable, extent

to which applicant includes letters of support from non-applicant

organizations, individuals, etc., and the extent to which such letters

clearly indicate the author's commitment to participate as described in

the operational plan.

3. Objectives and Technical Approach (45 Points Total)

a. Extent to which applicant describes 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'' for the specific

project area being addressed in the application. Extent to which

applicant clearly identifies specific assigned responsibilities of 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 approach/methods are appropriate and

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.

Extent to which applicant describes adequate and appropriate

collaboration with CDC (if applying for a cooperative agreement).

Extent to which women, racial and ethnic minority populations are

appropriately represented in applications involving human research. (30

points)

c. Extent to which applicant provides a detailed and adequate plan

for evaluating progress toward achieving project process and outcome

objectives. If the proposed project involves notifiable conditions, the

degree to which applicant describes an adequate process for providing

necessary information to appropriate State and/or local health

departments. (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 Department of Health and Human Services (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,

(2) protections appear adequate, but there are comments regarding the

protocol, (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 and

protection against the risks are inadequate as to make the entire

application unacceptable.

Executive Order 12372 Review

This program is not subject to Executive Order 12372 Review.

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 and approval 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 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. The applicant will be responsible for

providing evidence of this assurance in accordance with the appropriate

guidelines and form provided in the application kit.

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

an American Indian community is involved, its tribal government must

also approve that portion of the project applicable to it.

Women, Racial and Ethnic Minorities

It is the policy of the CDC and the 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 exist 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 of

subjects. Further guidance to this policy

[[Page 36550]]

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 five copies of each application PHS Form 398

should be submitted to Sharron 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, on or before August 25, 1997.

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 and will be returned to the

applicant.

Where to Obtain Additional Information

To receive additional written information call (404) 332-4561. You

will be asked to leave your name, address, and telephone number and

will need to refer to Announcement 779. You will receive a complete

program description, information on application procedures, and

application forms.

If you have questions after reviewing the contents of all the

documents, business management technical assistance may be obtained

from Oppie M. Byrd, Grants Management Specialist, Grants Management

Branch, Procurement and Grants Office, Centers for Disease Control and

Prevention (CDC), 255 East Paces Ferry Road, NE., Room 314, Mailstop E-

18, Atlanta, Georgia 30305, telephone (404) 842-6546, facsimile (404)

842-6513, E-mail [email protected].

Programmatic technical assistance may be obtained from Harold S.

Margolis, M.D., National Center for Infectious Diseases, Division of

Viral and Rickettsial Diseases, Centers for Disease Control and

Prevention (CDC), 1600 Clifton Road, NE., Mailstop A-33, Atlanta,

Georgia 30333, telephone (404) 639-2339, E-mail address [email protected].

Please refer to Announcement 779 when requesting information

regarding this program.

You may also obtain this and other CDC announcements 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, D.C. 20402-9325, telephone (202) 512-1800.

Dated: July 1, 1997.

Joseph R. Carter,

Acting Associate Director for Management and Operations, Centers for

Disease Control and Prevention (CDC).

[FR Doc. 97-17704 Filed 7-7-97; 8:45 am]

BILLING CODE 4163-18-P