[Federal Register Volume 59, Number 120 (Thursday, June 23, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-15246]


[[Page Unknown]]

[Federal Register: June 23, 1994]


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

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