[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
[[Page 26762]]
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
[[Page 26763]]
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.
[[Page 26765]]
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