Research And Evaluation Issues In Prevention Of Infertility Due To Sexually Transmitted Diseases

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

[Program Announcement 455]

RIN 0905-ZA61

Research And Evaluation Issues In Prevention Of Infertility Due

To Sexually Transmitted Diseases

Introduction

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

availability of fiscal year (FY) 1994 funds for a cooperative agreement

program to evaluate the public health impact of diagnostic,

epidemiologic, and surveillance efforts to prevent infertility due to

sexually transmitted diseases (STDs) among women of reproductive age.

The Public Health Service (PHS) is committed to achieving the

health promotion and disease prevention objectives of ``Healthy People

2000,'' a PHS-led national activity to reduce morbidity and mortality

and improve the quality of life. This announcement is related to the

priority areas of Sexually Transmitted Diseases and Family Planning.

(To order a copy of ``Healthy People 2000,'' see the section ``Where to

Obtain Additional Information.'')

Authority

These cooperative agreements are authorized under Section 318A of

the Public Health Service Act (42 U.S.C. 247c(-1)), as amended.

Applicable program regulations are found in Part 51(b), subparts A and

F of Title 42, Code of Federal Regulations.

Smoke-Free Workplace

The Public Health Service strongly encourages all grant recipients

to provide a smoke-free workplace and promote the non-use of all

tobacco products. This is consistent with the PHS mission to protect

and advance the physical and mental health of the American people.

Eligible Applicants

Applications may be submitted by:

1. Non-profit research institutions (public and private, e.g.,

universities, colleges, hospitals, laboratories);

2. Clinical public health entities (family planning clinics;

sexually transmitted disease (STD) clinics; migrant, community, and

other primary health centers; student health centers; health

maintenance organizations); and

3. Units of State or local government (e.g., public health

departments).

Applications must document collaboration between: (1)

interdisciplinary research and evaluation teams, including expertise in

clinical, epidemiologic, behavioral, (including cultural nuances of the

population being served), and health services research and laboratory

sciences, and, (2) State or local health departments and family

planning programs. Applications must also contain evidence of access to

relevant clinic populations, especially racial and ethnic minority

populations, and to laboratories.

Availability of Funds

Approximately $1,000,000 is available in FY 1994 to fund

approximately three to five awards. The awards are expected to range

from $200,000 to $300,000 beginning in September 1994, and continuing

for a 12-month budget period within a project period of up to 4 years.

Funding estimates may vary and are subject to change. Continuation

awards within an approved project period will be based on satisfactory

progress and the availability of funds.

Purpose

The purpose of these awards is to stimulate and support projects in

the research and evaluation of issues that are central to high-quality,

cost-effective STD-related infertility prevention programs in the

United States.

Program Objectives, Study Design Considerations, and Study

Populations

A. Detection: Field Effectiveness and Cost-Effectiveness of New

Screening Tests

Determine the sensitivity and specificity of recently developed

nonculture diagnostic products in urine specimens for women and men who

have symptomatic or asymptomatic chlamydial lower-genital-tract

infection. Test these products in populations of high (8% and higher)

and moderate (5-7%) chlamydia prevalence, under ideal and routine

conditions of specimen collection and transport, using laboratories

experienced in conducting nonculture tests for routine chlamydia

screening.

The study design must allow for a multicenter evaluation of the

sensitivity and specificity of recently developed nonculture diagnostic

products in urine specimens for women and men. The evaluation should

include laboratories that are experienced in performing chlamydia

nonculture screening and that will develop experience in either

polymerase chain reaction or ligase chain reaction techniques.

Involving State Public Health Department Laboratories in the

performance of some of the test methods is highly desirable.

Participating diagnostic centers should have access to patient settings

including family planning and STD clinics; access to men who are at

risk for STDs but who do not have symptoms of urethritis; and

demographic (including race and ethnic) identifiers and information on

risk factors. Gold-standard tests (including tissue culture and direct

fluorescent antibody and other tests for discrepancy analysis) should

be performed by a reference laboratory with a record of high

performance.

It is anticipated that this screening test program component will

be completed in approximately 12-24 months, less than the full project

period of 4 years.

B. Targeting: Risk Factors for Recurrent Chlamydia Infection in

Adolescent and Young Adult Women

1. Determine the strength of association between recurrent lower-

genital-tract chlamydial infection in women aged 15 to 34 years and

risk factors such as inadequate treatment at the time of initial

infection, inadequate treatment of their infected partners at the time

of initial infection, the presence of new partners, the use of an oral

contraceptive, coinfection with other STDs, diagnostic method,

inconsistent use of condoms, and factors related to the host's

immunologic characteristics.

2. Determine the attributable risk associated with behavioral risk

factors and related cultural and linguistic issues for recurrent lower-

genital-tract chlamydial infection in women 15 to 34 years of age.

3. Determine the effectiveness and the cost-effectiveness of

various strategies for preventing recurrent chlamydial infection in

women aged 15 to 34 years, e.g., patient versus provider referral,

therapy delivered to male partners at the clinic versus through the

mail or through a female partner.

This project requires the evaluation of strategies for the

prevention of recurrent infection in women: for example,

characteristics of the health care system that influence the

probability of successful treatment of the male partner (patient versus

provider referral, alone or in combination with the requirement of a

clinic visit for treatment) versus an alternative form of treatment

(through the mail or through the female partner). Because the risk of

reinfection attributable to the failure of any of these strategies may

vary by source of care, it is important that this be a multicenter

study, including family planning clinics, STD clinics, student health

clinics, primary care centers, and HMOs. Although it is not essential

that each of the participating sites enroll patients from each of these

clinic settings, inclusion of as many of these settings as possible is

preferable. Inclusion of family planning clinics and STD clinics is

essential.

C. Program Evaluation: Methods to Measure Infertility Related Health

Events

Develop a system of measurements and culturally relevant

methodologies that will accurately assess the following in a community:

1. The prevalence, incidence, and trends of chlamydial and

gonococcal lower-genital-tract infection among sexually active young

women;

2. The extent of recurrent chlamydial and gonococcal infection

among sexually active young women;

3. The incidence of acute urethritis among sexually active young

men, the proportion of acute symptomatic urethritis attributable to

chlamydia and gonorrhea, and the extent of recurrent chlamydial and

gonococcal infection;

4. The prevalence of asymptomatic chlamydial and gonococcal

infection among sexually active young men;

5. The incidence and trends in acute and chronic PID and ectopic

pregnancy; and

6. The number of laboratory tests for chlamydia and gonorrhea,

including the proportion of positive tests.

This project requires research to develop procedures for monitoring

symptomatic and asymptomatic chlamydia and gonorrhea infections in

women and men. Special outreach to appropriate racial and ethnic

minorities should be included in the trials. Monitoring should include

estimates of recurrent infection, PID, ectopic pregnancy, and estimates

of chlamydia and gonorrhea screening and testing practices in the

community as measured by the number of laboratory tests performed.

Specifically, the chlamydia and gonorrhea research centers

supported by this announcement will be expected to use epidemiologic

surveillance principles to develop well-reasoned, systematic, and

culturally relevant approaches to establish ongoing surveillance

systems in a defined community.

Because of the high proportion of asymptomatic infection in women,

chlamydia and gonorrhea prevalence and trends should be estimated in

populations of young women who undergo routine chlamydia and gonorrhea

screening. Screening is performed routinely in a variety of settings.

Determining the summary positivity rates of chlamydia and gonorrhea at

periodic intervals is one approach to estimating prevalence in

adolescent and young adult women.

In addition to assessing prevalence, it is desirable to be able to

compare infected and noninfected women by demographic characteristics

and risk variables. This information can be obtained by selecting

sentinel sites for this purpose. The gaps in data on minority

populations such as Hispanics are significant. The sentinel sites may

provide an opportunity to start closing these gaps.

Proposals should contain a provision for establishing a small

number of sentinel surveillance sites in which chlamydia and gonorrhea

screening will be conducted in accordance with a standardized protocol

for the collection of detailed demographic and epidemiologic data on

the clinic populations. At a sentinel site, all patients or a given

number of consecutive patients should be screened, regardless of chief

complaint or symptom status. In addition, it is desirable that (1)

sentinel surveillance sites provide care for a community sub-population

of interest (e.g., subgroups of minority populations, women seeking

contraception or prenatal services, persons seeking evaluation and

treatment for an STD, sexually active adolescents); (2) populations

served by the site have relatively stable characteristics (age, race,

ethnicity, gender, geographic area of residence, socioeconomic status,

and reason for seeking care); (3) the staff at the sites be familiar

with chlamydia and gonorrhea screening, diagnosis, and treatment; and

(4) the site have or will be able to develop an information system that

can satisfy the data management requirements of this project.

A requirement for consideration of award is the inclusion of

sentinel site activities for chlamydia and gonorrhea screening in at

least two family planning (reproductive health) clinics and at least

one health maintenance organization (HMO) or migrant or community

health center (CHC).

In selecting sentinel sites, give priority to clinics that (1)

conduct an average of at least 10 chlamydia tests on women each day

(for initial rather than follow-up visits); (2) have demonstrated an

ability to screen for chlamydia and gonorrhea that can be expanded to

meet these guidelines (i.e., active programs and the personnel for

chlamydia screening and control, or for gonorrhea screening and

control, or both); and (3) serve women from various demographic,

racial, and ethnic groups and socioeconomic strata.

For components A-C of this program, develop the specific research

questions in the light of your interpretation of current findings and

the research objectives and background sections of this program

announcement. In the proposed research design, address specifically the

definition and measurement of outcomes; the choice of study

populations; the criteria for selection, exclusion, and follow-up; the

rates required for participation; the definition of comparison groups;

potential confounders; types, direction, and magnitude of bias; and

ways of controlling for the effects of confounders and systematic bias.

Many of the issues relevant to this program announcement have

different patterns and magnitudes in different populations and may be

affected by different factors in different populations. Describe study

populations carefully and discuss the implications of the choice of

study population. You are encouraged to include more than one study

population to allow comparison between populations.

Program Goals

The first goal is to help redefine the components of a more

effective STD-related infertility strategy by evaluating:

A. New diagnostic tools assessing the field effectiveness of

recently developed noninvasive diagnostic tests of acceptable

sensitivity and specificity;

B. New approaches to target services identifying the relative

importance of risk factors, including cultural nuances, for recurrent

chlamydial infection among women aged 15-34 years in various

populations; and

C. The impact of services defining methodologies for assessing the

magnitude of the burden of chlamydial and gonococcal infections and

pelvic inflammatory disease (PID) in specified populations, with

emphasis on racial and ethnic minority populations, and monitoring

trends in such burden through the epidemiologic surveillance of

selected populations (e.g., those attending family planning clinics,

migrant and community health centers, health maintenance organizations,

student health centers, and detention centers).

In addition, this program will contribute to the establishment of

multicenter collaborations between family planning programs and health

departments and research institutions that will:

1. Conduct multidisciplinary, program-oriented research and

evaluation including clinical, epidemiologic, behavioral, and health

services approaches that are culturally relevant and linguistically

appropriate; and

2. Provide potential sites for future multicenter studies and

opportunities for interaction among investigators working in the

prevention of STD-related infertility.

Although collaborations among family planning programs, health

departments, and research institutions should be established in

geographic proximity when feasible, this is not a requirement. Health

departments in one area of the country may collaborate with research

institutions located in another area of the country. All applicants

must participate in the three components (A, B, and C) mentioned

earlier.

The program will encourage synergy among the components, and the

exploration of additional research and evaluation questions by

providing a multidisciplinary, systematic, sustained culturally

competent approach to infertility research and evaluation. Two

additional areas of substantive interest are:

1. The identification of factors that facilitate and factors that

impede effective integration of family planning and STD prevention

services; and

2. The assessment of culturally relevant and linguistically

appropriate approaches in improving accessibility to diagnostic,

therapeutic, and risk-reduction services to populations at risk for

chlamydial and gonococcal infection.

Program Requirements

In conducting activities to achieve the purpose of this program,

the recipient will be responsible for the activities under Recipient

Activities, and CDC will be responsible for the activities listed under

CDC Activities.

Recipient Activities

1. Participate with other recipients and CDC representatives in

meetings at which core standardized protocols and instruments for

program areas A, B, and C will be developed.

2. Implement the standardized protocol and collect the data as

specified in the protocol. In addition, recipients are encouraged to

evaluate related questions and issues which they consider important,

such as the identification of factors that facilitate or impede the

integration of family planning and STD prevention services; and the

culturally appropriate assessment of approaches to improve

accessibility of diagnostic, therapeutic, and risk-reduction services

to populations at risk for chlamydial and gonococcal infection.

3. Compile and analyze data from the local project and disseminate

results as appropriate in scientific, programmatic, and policy-making

forums, including community planning and decision making.

4. Collaborate with CDC to compile and analyze data in the

aggregate or in multisite format.

5. Participate in semiannual workshops coordinated by CDC for key

investigators in the program.

CDC Activities

1. Help recipients develop, pilot test, and implement standard core

protocols and instruments.

2. Help compile and analyze an aggregate or multisite database;

present aggregate results in scientific, programmatic, and policy-

making forums.

3. Coordinate semiannual workshops for key investigators in the

program.

Review Conditions and Evaluation Criteria

To be referred to the independent review group for consideration,

applications must meet the following conditions:

1. Address the specific requirements in all three components.

2. Include culturally relevant interdisciplinary approaches by

multidisciplinary research and evaluation teams, including expertise in

clinical, epidemiologic, behavioral and health services research and in

laboratory science.

3. Give evidence of close collaborations between family planning

programs and State or local health departments and research

institutions.

4. Give evidence of access to relevant clinic populations,

especially people of color.

5. Verify access to a reference laboratory whose performance is of

high-quality as evidenced by published evaluations of chlamydia

diagnostic tests compared with culture testing.

6. Document the laboratory's (at least 1 year) experience in

performing at least two tests to detect Chlamydia trachomatis and

describe the laboratory's quality assurance standards for specimen

processing.

7. Document willingness to participate in implementing a core

standard protocol for the quality assurance of all laboratory

procedures including culture testing and amplification techniques,

coordinated by CDC.

Applications that meet the above conditions will be reviewed and

evaluated according to the following criteria:

1. Understanding of the objectives of this research and evaluation

program as reflected in statement of research background and research

questions. (10 points) (application narrative items 1 and 2)

2. The quality of the study design, internal and external validity,

appropriateness of the study design for the research questions. (20

points) (application narrative item 3)

3. The quality of the plan for data analysis, its appropriateness

for the data collected, and its relevance to the experience of racial

and ethnic minority study populations, to the study design, and to the

research questions. (15 points) (application narrative item 4)

4. Overall ability (that of the applicant and the proposed sites)

to perform the technical aspects of the project(s) as reflected in the

availability of qualified and experienced personnel for a

multidisciplinary team; facilities and plans for the administration of

the project(s), including a detailed and realistic schedule for the

specified activities and access to study populations. (20 points)

(application narrative items 5, 6, and 7)

5. The extent to which the research approach is interdisciplinary

and culturally and programmatically relevant and the extent to which

collaborations among family planning programs, health departments,

research institutions, and participating communities are likely to be

sustained for the duration of the project. (10 points) (application

narrative item 9)

6. The extent to which additional research questions will be

addressed during the research on major program components. (5 points)

(application narrative item 10)

7. The extent to which proposed component projects reinforce one

another. (5 points) (application narrative item 11)

8. Creativity and originality in the proposed research approaches.

(15 points)

In addition, consideration will be given to the extent to which the

budget is reasonable, clearly justified, and consistent with the

intended use of the funds.

Funding Priorities

The geographic distribution of project sites will be considered in

funding applicants. In addition, the following will be considered:

For projects focusing on the evaluation of risk factors for

recurrent chlamydia infections among young women, applicants with

access to minimum of 300 chlamydia infections in women per year

(including all sites) and areas where chlamydia is legally reportable

with unique identifiers and line-listed data will be preferred (to

follow reinfection passively, after the funding period has ended).

For projects focusing on the procedures for monitoring the disease

burden related to chlamydial and gonococcal lower genital tract

infections in a community, metropolitan areas with more than 200,000

persons (1990 U.S. Census) and reported gonorrhea case rates of at

least 225 per 100,000 population in 1992 (as reported in the CDC

Sexually Transmitted Disease Surveillance 1992 Report, published in

July 1993), and sites that choose (and provide data to support their

choice of) clinics and health care providers that meet the requirements

of an effective sentinel site and provide health care to women from

various demographic groups and socioeconomic strata will be preferred.

Funding will be provided to at least one site in one of the four Public

Health Service (PHS) regions in which regional chlamydia prevention

programs have already been established (Region III, VII, VIII, and X)

and at least one sentinel surveillance system in one of the other six

PHS regions.

Comments on the proposed funding priorities are invited. All

comments received on or before July 15, 1994, will be considered before

the application due date. If funding priority should change as a result

of any comments received, a revised announcement will be published in

the Federal Register. Written comments should be addressed to Elizabeth

M. Taylor, 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, Atlanta, GA

30305.

Executive Order 12372 Review

STD Accelerated Prevention Campaign applications are subject to

review as governed by Executive Order (E.O.) 12372, Intergovernmental

Review of Federal Programs. E.O. 12372 sets up a system for State and

local government review of proposed Federal assistance applications.

Applicants should contact their State Single Point of Contact (SPOC) as

early as possible to alert them to the prospective applications and

receive any necessary instructions on the State process. A current list

of SPOCs is included in the application kit. If SPOCs have any State

process recommendations on applications submitted to CDC, they should

forward them no later than 60 days from the due date of the application

to Elizabeth Taylor, 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, Atlanta, GA

30305.

Public Health System Reporting Requirement

This program is subject to the Public Health System Reporting

Requirements. Under these requirements, all community-based

nongovernmental applicants must prepare and submit the items identified

below to the head of the appropriate State and/or local health

agency(s) in the program area(s) that may be impacted by the proposed

project no later than the receipt date of the Federal application. The

appropriate State and/or local health agency is determined by the

applicant. The following information must be provided:

A. A copy of the face page of the application (SF424); and

B. A summary of the project that should be titled ``Public Health

System Impact Statement (PHSIS),'' not exceed one page, and include the

following:

1. A description of the population to be served;

2. A summary of the services to be provided; and

3. A description of the coordination plans with the appropriate

State and/or local health agencies.

If the State and/or local health officials should desire a copy of

the entire application, it may be obtained from the State Single Point

of Contact (SPOC) or directly from the applicant.

Catalog of Federal Domestic Assistance Number

The Catalog of Federal Domestic Assistance Number is 93.978,

Preventive Health Services--Sexually Transmitted Diseases Research,

Demonstration, and Public Information and Education Grants.

Other Requirements

Paperwork Reduction Act

Projects that involve the collection of information from 10 or more

individuals and funded by 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 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 assurance in accordance with the appropriate guidelines and

form provided in the application kit.

Letters of Intent

Letters of intent are desired. On or before July 15, 1994, submit

the original and two copies of a letter of intent to submit an

application to Elizabeth M. Taylor, 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,

Atlanta, GA 30305.

Application Submission and Deadline

The original and two copies of the application PHS Form 5161-1

(Revised 7/92, OMB Control Number 0937-0189) must be submitted to

Elizabeth M. Taylor, 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, Atlanta, GA

30305, on or before August 12, 1994.

Deadline: Applications shall be considered as meeting the deadline

if they are either:

1. Received on or before the deadline date, or

2. 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 the U.S. Postal Service. Private

metered postmarks are not acceptable as proof of timely mailing.)

Applications which do not meet the criteria in 1. or 2. 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, information on application

procedures, an application package, and business management technical

assistance may be obtained from Linda Long, Grants Management

Specialist, Grants Management Branch, Procurement and Grants Office,

Centers for Disease Control and Prevention (CDC), 255 East Paces Ferry

Road, NE., Room 300, Atlanta, GA 30305, telephone (404) 842-6640.

Programmatic technical assistance may be obtained from Sevgi O.

Aral, Ph.D., Division of STD/HIV Prevention, National Center for

Prevention Services, Centers for Disease Control and Prevention (CDC),

1600 Clifton Road, NE., Mailstop E-02, Atlanta, GA 30333, telephone

(404) 639-8259.

Please refer to Announcement 455 when requesting information and

submitting an application.

You 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) mentioned in the ``Introduction,'' from the

Superintendent of Documents, Government Printing Office, Washington, DC

20402-9325, telephone (202) 783-3238.

Dated: June 17, 1994.

Ladene H. Newton,

Acting Associate Director for Management and Operations, Centers for

Disease Control and Prevention (CDC).

[FR Doc. 94-15246 Filed 6-22-94; 8:45 am]

BILLING CODE 4163-18-P