[Federal Register Volume 64, Number 94 (Monday, May 17, 1999)]
[Notices]
[Pages 26761-26765]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-12313]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention
[Program Announcement 99104]


Notice of Availability of Funds; Innovative Demonstration 
Projects to Screen and Treat Asymptomatic Males for Chlamydia 
Trachomatis Infection Using Urine-Based Diagnostic Tests: Translational 
Research

A. Purpose

    The Centers for Disease Control and Prevention (CDC) announces the 
availability of fiscal year (FY) 1999 funds for a cooperative agreement 
program to conduct innovative demonstration projects using nucleic acid 
amplification tests on urine specimens to screen and treat asymptomatic 
males with Chlamydia Trachomatis (CT)infection. This program addresses 
the ``Healthy People 2000'' priority area of Sexually Transmitted 
Diseases. The purpose of the program is to determine the acceptability, 
feasibility, and cost associated with different approaches to screening 
asymptomatic males for CT infection. Successful applicants will 
implement demonstration projects using nucleic acid amplification tests 
on urine specimens to screen asymptomatic males for CT infection and 
will conduct research in the context of the demonstration project. 
Please reference Appendix 1 for background information relevant to this 
program announcement. Appendix 2 outlines project objectives.

B. Eligible Applicants

    Applications may be submitted by public and private non-profit 
organizations in partnership with State or local health departments. 
Any organization may be the primary applicant, but each application 
must include both an agency/institution with program implementation 
experience and an agency/institution with research experience. All 
applications must include a partnership with a State or local health 
department.

    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

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to receive Federal funds constituting an award, grant, cooperative 
agreement, contract, loan, or any other form.

C. Availability of Funds

    Approximately $750,000 is available in FY 1999 to fund two to three 
awards, with an average yearly award of 250,000, ranging from $200,000 
to $300,000. It is expected that the awards will begin on or about 
September 30, 1999, and will be made for a 12-month budget period 
within a project period of up to two years. Funding estimates may 
change.
    Continuation awards within an approved project period will be made 
on the basis of satisfactory progress as evidenced by required reports 
and the availability of funds.

Use of Funds

    Funds awarded under this program may not be used for treatment.

Funding Preferences

    Funding preference may be given to applicants to achieve geographic 
balance.

D. Program Requirements

    Recipients will work with CDC to assure a scientifically sound 
demonstration project and embedded research study. If multiple awards 
are made, the only requirement for uniformity of approach across sites 
will relate to collection of a core set of data elements (including 
those related to cost) to allow systematic comparisons between 
different approaches to male screening.
    In conducting activities to achieve the purpose of this program, 
the recipient will be responsible for the activities listed under the 
subparagraph Recipient Activities and CDC will be responsible for the 
activities listed under the subparagraph CDC Activities.

1. Recipient Activities

    a. Design and implement a demonstration project to screen 
asymptomatic males for chlamydia infection which addresses as many of 
the objectives listed in Appendix 2 as possible. At a minimum, 
recipients should gather routine data that will permit measurement of 
the prevalence of infection and male treatment rates, as well as the 
cost to detect and treat an infected male, and his infected female 
partners. Recipients are encouraged to screen in settings other than a 
sexually transmitted diseases clinic; however, a sexually transmitted 
diseases clinic could be one of several settings where screening is 
conducted, as this could provide a useful comparison to other screening 
venues developed by the recipient.
    b. Design and implement a research study that can be embedded 
within the male CT screening demonstration project and which entails 
longitudinal follow up of a subset of men in order to address as many 
of the Appendix 2 objectives requiring longitudinal follow up as 
possible (i.e., reinfection, notification of female partners, reported 
behavior change after learning a positive test result).
    c. Collaborate with other recipients in developing and collecting a 
common set of core variables to permit systematic comparison between 
different approaches (for the purpose of cost comparisons, this will 
require measurement of all relevant costs, including providers' costs 
of service delivery and participants' costs).
    d. Collaborate with other recipients during implementation of the 
demonstration project and research study. Collaboration will include 
(1) communication with CDC regarding project and study progress and (2) 
participation in quality control procedures, and in regularly scheduled 
meetings and conference calls with CDC.
    e. Recipients will use findings from their own demonstration 
project/embedded research to develop at least one publication for a 
peer-reviewed journal.
    f. Submit and receive approval of study protocol by the recipient's 
local institutional human investigation review board (IRB).

2. CDC Activities

    a. Provide technical assistance and scientific expertise. CDC staff 
will provide current scientific and programmatic information relevant 
to the design and conduct of the demonstration project and embedded 
research study.
    b. As needed, provide technical advice to awardees in developing 
and collecting a common set of core variables to enable comparisons 
between different approaches, including those needed to accurately and 
completely measure costs, and which would allow for cross-site 
comparisons that could include a cost effectiveness analysis. 
Collaborative activities may include technical advice on awardee-
development of common data collection instruments. As needed, CDC may 
assume responsibility for developing a centralized system for data 
management for the core set of data elements collected by each of the 
funded projects.
    c. Assist in analysis and dissemination of results; as needed, 
assist each site in analyzing data and in dissemination of study 
results.
    d. Monitor and Evaluate Scientific and Operational Accomplishments 
of the Project: This will be accomplished through periodic site visits, 
telephone calls, and review of technical reports and interim data 
analysis.
    e. Submit and receive approval of study protocol by the Centers for 
Disease Control and Prevention IRB. 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 25 double-spaced pages, 
printed on one side, with one inch margins, and size 12 font. 
Appendices may include letters of support, data tables, and 
bibliography only.

F. Submission and Deadline

Letter of Intent (LOI)

    A letter of intent must be submitted on or before June 14, 1999 to 
the Grants Management Specialist listed in the ``Where to Obtain 
Additional Information'' section of this announcement. No applications 
will be accepted without a letter of intent. Letters of intent must be 
no more than one page, must be prepared with a Courier 12-point font 
and must include the following: statement of intent to apply, reference 
to Program Announcement 99104, title of the proposed project and the 
names, phone numbers, and email addresses for the lead investigators 
representing each collaborating institution or agency.

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 August 2, 1999 
submit the application to the Grants Management Specialist listed in 
the ``Where to Obtain Additional Information'' section of this 
announcement.
    Deadline: Applications shall be considered as meeting the deadline 
if they are either received on or before the deadline date or sent on 
or before the deadline date and received in time for independent 
review. (Applicants must

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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.) Applications that do not meet these criteria will not be 
considered and will be returned to the applicant.

G. Evaluation Criteria

    Each application will be evaluated individually against the 
following criteria by an independent review group appointed by CDC.

1. Background and Rationale for the Male Screening Demonstration 
Project and Embedded Research Study (10 Points)

    Degree to which the applicant (a) Describes the local prevalence of 
CT infection (with stratification by age, gender, and ethnicity); (b) 
demonstrates knowledge of the medical/public health literature 
describing urine testing to identify asymptomatic men infected with CT; 
(c) demonstrates insight into factors that could influence the 
effectiveness of a male screening strategy for primary prevention among 
women; (d) demonstrates insight into the logistic and ethical 
challenges of offering diagnostic testing to an asymptomatic population 
in non-traditional and non-clinical settings; (e) presents a compelling 
rationale for their proposed approach to screening asymptomatic males 
for Chlamydia infection; (f) provides data to support their choice of 
screening venues; (g) describes any previous or existing male screening 
programs in their locality and describes how the proposed demonstration 
project compares to any existing local male screening programs, and (h) 
presents a rationale for their selection of research objectives from 
among those in Appendix 2.

2. Objectives (5 Points)

    Extent to which the application addresses the research objectives 
outlined in Appendix 2 of this program announcement.

3. Demonstration Project Activities (20 Points)

    Extent to which the application describes the proposed activities 
with detailed plans for implementation of the demonstration project, 
including: (a) A detailed and realistic time line for the specified 
activities; (b) specific information on the site where screening will 
be conducted, hours that screening will be offered, staffing, 
provisions for urine specimen collection (e.g., restrooms convenient to 
the site where males are being invited for screening, adherence to CLIA 
(Clinical Laboratory Improvement Amendments) requirements for specimen 
collection); (c) plans for obtaining informed consent (if needed); (d) 
plans for males to learn test results and receive treatment; and (e) 
plans to seek, screen, and treat the female sex partners of infected 
males.

4. Potential Influence of the Demonstration Project on Public Health 
Practice (15 Points)

    Extent to which the applicant presents a detailed and logical plan 
for conducting a screening program that will provide access to a male 
population with a high prevalence of CT infection; particularly males 
who may contribute disproportionately to infecting females. Points will 
also be given for the extent to which the study population is 
representative of a large pool of potentially infected men and the 
likelihood that such a population could be identified and accessed in 
other locations across the United States. Points will be awarded to 
applicants describing a demonstration project that could be 
incorporated into the array of public health activities with a minimum 
of additional training, resources, and infrastructure. Points will also 
be awarded to applications that describe a plan for integrating partner 
services into the demonstration project.

5. Design of Research Study Requiring Longitudinal Follow Up (20 
Points)

    Extent to which the embedded research study is (a) both an 
appropriate and optimal means of addressing research objectives in 
Appendix 2 that require longitudinal follow up; (b) will achieve the 
research objectives without interfering with assessments of 
acceptability and feasibility (which could be biased if measured in 
study subjects consenting to participate in a study requiring 
longitudinal follow up); (c) includes clear and valid calculations for 
the sample sizes that would be required to measure effects related to 
each of the applicants chief research objectives; (d) provides clear 
description of appropriate comparison groups in each aspect of the 
study; and (e) if the study includes adolescents, displays familiarity 
with the legal and ethical issues surrounding elicitation of 
information regarding sexual activity between adolescents and older sex 
partners, (including the particulars of relevant State legislation), 
and demonstrates a means of adhering to such legislation in the 
proposed study.

6. Program and Research Capacity (25 Points)

    The overall ability of the applicant to perform the technical 
aspects of the project. The quality of the applicant's: (a) Proposed 
collaboration with State or local health departments and partners for 
either research or program implementation (including letters of 
support); (b) availability and identification of personnel with the 
needed experience and competence in community outreach and program 
implementation, sexually transmitted disease service delivery, partner 
services, study design and conduct, data collection, analysis, and 
dissemination; (c) assurance that staff can be hired within an 
appropriate amount of time; (d) ability and willingness to collaborate 
in the development and collection of a common set of variables to 
permit cross-site comparisons; (e) demonstration of access to the data 
needed to permit true costs of service delivery to be determined so 
that a cost effectiveness evaluation can be done, e.g., demonstration 
of the ability to identify and collect data to measure the costs for 
screening that include testing and treatment costs, provider costs for 
wages and overhead, and participants' travel and time costs, as well as 
costs for partner services; (f) documentation of the availability of 
adequate laboratory, clinical, and administrative facilities and 
resources to conduct the proposed research, including a letter of 
agreement from the laboratory that will be conducting nucleic acid 
amplification testing on urine specimens and a letter of agreement from 
the administrative or managerial director of the proposed screening 
site (and board of directors or community board if appropriate); (g) 
access to cost-efficient, locally available staff to complete data 
entry and data management.

7. The Degree to Which the Applicant Has Met the CDC Policy 
Requirements Regarding the Inclusion of Ethnic and Racial Groups in the 
Proposed Research. (5 Points)

    This includes:
    1. The proposed plan for the inclusion of 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

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community(ies) and recognition of mutual benefits.
    5. This program specifically seeks applications describing male 
screening programs, with a long term objective to develop strategies 
that can increase public health capacity to detect and treat infected 
females. Applicants need not address the inclusion of women in their 
response to evaluation criterion 7.

8. Budget (Not Scored)

    The budget should anticipate the salaries of appropriate staff, 
travel for principal investigator and project supervisor to meet with 
CDC annually, supplemental needs related to diagnosis, management, and 
treatment of CT and other concurrently diagnosed STDs, including 
anticipated partner tracing activities, longitudinal participation, and 
other needs. The applicant should provide a line-item first year budget 
(with a budget narrative that justifies each line item). Budgets will 
be evaluated on the appropriateness of budget estimates in relation to 
the proposed research, and the extent to which the budget is 
reasonable, clearly justified, and consistent with the intended use of 
funds.

9. Human Subjects (Not Scored)

    Does the application adequately address the requirements of Title 
45 CFR Part 46 for the protection of human subjects?

H. Other Requirements

    Technical Reporting Requirements For Award Recipients Provide CDC 
with original plus two copies of
    1. Semi-annual progress reports;
    2. financial status report, no more than 90 days after the end of 
the budget period; and
    3. final financial status and performance reports, no more than 90 
days after the end of the project period.
    Send all reports to the Grants Management Specialist listed in the 
``Where to Obtain Additional Information'' section of this 
announcement.
    The following additional requirements are applicable to this 
program. For a complete description of each, see Attachment 1 in the 
application kit.

AR-1  Human Subjects Requirements
AR-2  Requirements for Inclusion of Women and Racial and Ethnic 
Minorities in Research
AR-6  Patient Care
AR-7  Executive Order 12372 Review
AR-8  Public Health System Reporting Requirements
AR-9  Paperwork Reduction Act Requirements
AR-10  Smoke-Free Workplace Requirements
AR-11  Healthy People 2000
AR-12  Lobbying Restrictions

I. Authority and Catalog of Federal Domestic Assistance Number

    This program is authorized under sections 301(a) and 317 of the 
Public Health Service Act [42 U.S.C. 241 and 247b], as amended. The 
Catalog of Federal Domestic Assistance number is 93.978.

J. Where To Obtain Additional Information

    To receive additional written information and to request an 
application kit, call 1-888-GRANTS4 (1-888-472-6874). You will be asked 
to leave your name and address and will be instructed to identify the 
announcement number of interest. If you have questions after reviewing 
the contents of all documents, business management technical assistance 
may be obtained from: Curtis Meusel, Grants Management Specialist, 
Grants Management Branch, Procurement and Grants Office, Announcement 
99104, Centers for Disease Control and Prevention (CDC), 2920 
Brandywine Road, Mail Stop E15, Atlanta, Georgia 30341, Telephone (770) 
488-2738, Email address [email protected].
    Complete application information is also available on the CDC home 
page on the Internet: HTTP://WWW.CDC.GOV
    For program technical assistance, contact: Julie Schillinger, MD, 
Centers for Disease Control and Prevention (CDC), 1600 Clifton Road, 
Mail Stop E02, Atlanta, GA 30333, Telephone: (404) 639-8368, Email: 
[email protected].

    Dated: May 11, 1999.
John L. Williams,
Director, Procurement and Grants Office, Centers for Disease Control 
and Prevention (CDC).

Appendix 1--Background

    The bulk of the morbidity associated with CT infection appears 
to be borne by women, in whom infection can lead to pelvic 
inflammatory disease with subsequent infertility, ectopic pregnancy, 
and chronic pelvic pain. Women with CT infection have an associated 
increased risk for acquisition of HIV, and are at an increased risk 
for adverse outcomes of pregnancy (low birth weight, prematurity); 
there is also an increased risk for morbidity among infants born to 
infected mothers (neonatal pneumonia and ocular infections). For 
these reasons, efforts to reduce the morbidity associated with CT 
infection have focused on identifying and treating infected women, 
relying largely on widespread screening of asymptomatic women, with 
subsequent treatment of infected women and, to a lesser extent, 
their infected sexual partners. Regions of the country with active 
chlamydia prevention programs have demonstrated reductions of 36-59% 
in the measured prevalence of infection among women served in 
specific settings. There remains, however, substantial variation in 
CT-prevalence measured in different regions of the U.S., and it is 
not clear what strategies would be most effective in reducing 
disease below the threshold (3.9-7%) achieved in regions with 
aggressive prevention programs.
    The application of nucleic acid amplification technology to the 
development of a urine-based diagnostic test for CT infection has 
broadened the potential for conducting screening of asymptomatic 
women, and, for the first time, presents a feasible means of 
screening asymptomatic men. Although urine-based diagnostic tests 
have been approved for use in men and are being used in select 
settings, because available data suggest that severe sequelae of Ct 
infection are relatively infrequent in men, several important 
questions must be answered before national chlamydia control efforts 
and resources are directed to widespread screening for men. First, 
what approaches to male screening for CT infection are most 
acceptable and feasible, and second, is male screening an effective 
means of reducing disease in women? To address these questions it 
will be necessary to explore the prevalence of infection in 
different asymptomatic male populations which may be accessed by 
urine screening, to determine the acceptability and feasibility of 
screening these populations, and to measure the cost of detecting 
and treating an infected male and his infected female sex partners. 
To evaluate the comparative value of different approaches to 
screening asymptomatic males, screening would need to be conducted 
in a variety of different venues, including sexually transmitted 
diseases clinics. Ultimately, the value of screening males for CT 
infection must be measured against the alternative of using the same 
resources to screen women. Research to further knowledge of 
reinfection rates among males, changes in sexual behavior resulting 
from diagnosis with asymptomatic CT infection, and men's willingness 
to name and assist in locating female sex partners will be useful in 
interpreting the value of male screening.

Appendix 2--Research Objectives for Innovative Demonstration Projects 
and Embedded Research Studies

1. Objectives Related to Prevalence

    a. To measure the prevalence of CT infection among populations 
of males accessible with urine-based screening programs.
    b. To determine whether there is a trend in prevalence over the 
study period (are infections accessible to screening programs 
exhausted over a short time period?).
    c. To identify predictive characteristics of infected males.

2. Objectives Related to Acceptability

    a. To measure the proportion of males accepting urine-based 
testing.
    b. To measure the characteristics of males who refuse/accept 
screening.

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    c. To characterize the reasons that males do not accept urine-
based testing for Ct.
    d. To identify other settings in which males would avail 
themselves of urine testing for Ct.

3. Objectives Related to Feasibility

    a. To measure the proportion of tested males who return or 
otherwise learn their test results.
    b. To determine the proportion of infected males who receive 
treatment.
    c. To measure the median time until patients return for their 
test results.
    d. To determine how many female sex partners infected males 
identify/name/notify.
    e. To measure the characteristics of identified, named, and 
located partners.
    f. To measure the infection rate among located partners.
    g. To determine the proportion of located female sex partners 
who were notified by their male partner.
    h. To determine if screened males access other sites where they 
could be screened.
    i. To determine which strategies or approaches enhance 
completeness of timely treatment of infected men.

4. Objectives Related to Cost Estimates

    a. To measure the cost to detect and treat an infected 
asymptomatic male.
    b. To measure the costs of partner services associated with 
finding and treating the female sex partners of an asymptomatic 
infected male?
    c. To measure the overall cost to identify an infected female 
using male screening.

5. Objectives Requiring Longitudinal Follow Up

    a. To determine whether a positive screening test influences a 
man's intended future sexual behavior (including condom use, partner 
selection, partner number, health seeking behavior).
    b. To determine the proportion of treated males who are re-
infected at defined intervals after initial screening.
    c. To ascertain how many males report that their partner has 
been treated at a follow up visit.

[FR Doc. 99-12313 Filed 5-14-99; 8:45 am]
BILLING CODE 4163-18-P