Full Text AI-95-001

STD DIAGNOSTIC DEVELOPMENT GROUPS

NIH GUIDE, Volume 23, Number 43, December 9, 1994

P.T. 34

Keywords: 
  Sexually Transmitted Diseases 
  Diagnosis, Medical 


RFA:  AI-95-001

National Institute of Allergy and Infectious Diseases

Letter of Intent Receipt Date:  January 9, 1995
Application Receipt Date:  March 23, 1995

PURPOSE

The National Institute of Allergy and Infectious Diseases (NIAID)
invites applications for the establishment of Sexually Transmitted
Disease (STD) Diagnostic Development Groups (SDDG) for the research
development, manufacturing development, and evaluation of diagnostic
tests that are simple, easy-to-use, rapid and inexpensive.  The
specific focus of this initiative is the development and evaluation
of tests for the diagnosis of cervicitis and urethritis due to
Neisseria gonorrhoeae or Chlamydia trachomatis.  This solicitation
for cooperative agreements is designed to encourage and support joint
for-profit and non-profit research groups in development and
evaluation of these diagnostic tests.

HEALTHY PEOPLE 2000

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 for setting priority areas.  This Request
for Applications (RFA), STD Diagnostic Development Groups (SDDG), is
related to the priority areas of STD and HIV infection.  Potential
applicants may obtain a copy of "Healthy People 2000" (Full Report:
Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report:
Stock No. 017-001-00473-1) through the Superintendent of Documents,
Government Printing Office, Washington, DC 20402-9325 (telephone
202-783-3238).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic for-profit and non-profit
organizations, public and private organizations such as universities,
colleges, hospitals, laboratories, units of State or local
government, and eligible agencies of the Federal government.
Applications from minority individuals and women are encouraged.

MECHANISM OF SUPPORT

The administrative and funding mechanism to be used to undertake this
program will be the Cooperative Agreement (U01), an assistance
mechanism, rather than an acquisition mechanism, in which substantial
NIH scientific and/or programmatic involvement with the awardee is
anticipated during the performance of the activity.  Under the
cooperative agreement, the NIH purpose is to support and/or stimulate
the recipient's activity by involvement in and otherwise working
jointly with the award recipient in a partner role, but it is not to
assume direction, prime responsibility, or a dominant role in the
activity.  Details of the responsibilities, relationships, and
governance of a study funded under cooperative agreement(s) are
discussed later in this document under the section Terms and
Conditions of Award.

The total project period may not exceed five years.  At this time,
the NIAID is administratively limiting the duration of P01 grants to
four years; this administrative limitation may change in the future.
The anticipated award date is September 1995.  At this time, the
NIAID has not determined whether or how this solicitation will be
continued beyond the present RFA.

FUNDS AVAILABLE

The estimated total funds (direct and indirect costs) available for
the first year of support for awards under this RFA will be $2.0
million.  In Fiscal Year 1995, the NIAID plans to fund three
applications: two for diagnostic test development  and one for test
evaluation.  Depending upon the stage of development of the
diagnostic test proposed, it is anticipated that the first year
development awards will range from $300,000 to $850,000 (total cost).
Applications for test evaluation activities will be limited to
$300,000 first-year total costs.  Applicants proposing budgets larger
than these amounts must obtain approval, prior to submission, from
Dr. Hitchcock (see INQUIRIES below).  In recognition of the highly
specialized scientific expertise needed, it is anticipated that
applications for test development will focus on either N. gonorrhoeae
or C. trachomatis; for evaluation applications, it is anticipated
that the applicants will have the capability to evaluate tests for
both infections.  Although this program is provided for in the
financial plans of the NIAID, awards pursuant to this RFA are
contingent upon the availability of funds for this purpose.

The usual PHS policies governing grant administration and management
will apply.  This level of support is dependent on the receipt of a
sufficient number of applications of high scientific merit.  Funding
beyond the first and subsequent years of the grant will be contingent
upon satisfactory progress during the preceding years and
availability of funds.

RESEARCH OBJECTIVES

Background

The HIV pandemic has focused attention on STDs, both because HIV
infection is a fatal STD and because other STDs are implicated as
risk factors for sexual transmission of HIV.  Current global
estimates indicate that 14 million people are infected with HIV, the
cause of Acquired Immunodeficiency Syndrome (AIDS).  The majority of
these infections were acquired through sexual intercourse.  Unless
effective prevention measures to stop sexual transmission of HIV are
implemented, the number of AIDS cases will continue to grow.

Several clear lines of experimental evidence indicate that STDs
increase sexual transmissibility of HIV infection.  Recent studies
indicate that both discharge STDs (chlamydial infection, gonorrhea,
and trichomoniasis) and ulcerative STDs (genital herpes, syphilis,
and chancroid) increase HIV transmission.  Although individual risk
associated with the genital ulcer diseases appears to be higher (up
to nine fold) compared to the discharge diseases (ranging from three
to five fold), the higher prevalence of the discharge diseases means
the population attributable risk for the discharge diseases is
greater than that of the ulcerative diseases.  Several mechanisms of
action are likely to play a role in altered susceptibility/
infectiousness.  These include disruption of mucosal epithelium
(providing opportunities for bidirectional trafficking of HIV),
alteration of normal (protective) flora, cellular inflammation
including the recruitment of CD4+ target cells to the mucosal
surface, molecular interactions between the pathogens, and immune
suppression/stimulation.  Significant reductions in the rates of HIV
transmission are likely to result from a focused effort to control
the spread of these more common STDs, particularly those due to N.
gonorrhoeae or C. trachomatis.

Separate and apart from the HIV epidemic, STDs cause significant
morbidity and mortality and contribute greatly to increasing health
care costs.  In the United States in 1993, an estimated 12 million
cases of STDs occurred; people less then 24 years old accounted for
64 percent of these and three million were in teenagers.  In 1992,
costs associated with these infections approached $6 billion.

STDs disproportionately affect the female, the fetus, and the
newborn.  Gonococcal and chlamydial infections cause pelvic
inflammatory disease, infertility, and ectopic pregnancy.  These STDs
adversely affect pregnancy and result in spontaneous abortion,
stillbirth, chorioamnionitis, premature rupture of membranes, pre-
term delivery, and postpartum endometritis.  Neonatal infections
include gonococcal/chlamydial conjunctivitis, which may lead to
blindness, and chlamydial pneumonia, which may lead to chronic
respiratory disease.

The importance of STD prevention as a means to prevent HIV infection,
as well as the morbidity and mortality associated with the major
sequelae of STDs in women and infants, are compelling reasons for the
development of simple, easy-to-use, rapid, and inexpensive diagnostic
tests.  These will enable effective screening and antibiotic therapy
for infections caused by N. gonorrhoeae or C. trachomatis.  Ideally,
the needed tests would be administered to a patient without the need
to obtain invasive specimens and would be so rapid that an
etiological diagnosis would be obtained before the end of the clinic
visit.  These tests are needed for both high and low prevalence
settings and therefore must have appropriate (i.e., high) sensitivity
and specificity.  Several new and innovative tests have recently been
developed.  For example, PCR and similar methods have been applied.
While these tests are highly specific and sensitive, the unrelenting
problem with the application of these technologies is that they are
complicated, relying on sophisticated technical equipment and highly
trained technical staff.  Finally, it is important to highlight that
the tests must be inexpensive; a manufacturing cost of less than
$1.00 per test is the target.  The availability of a sensitive,
accurate, inexpensive test will enable/encourage screening and case
finding - a critical approach to controlling these asymptomatic
infections, preventing HIV infection, chronic sequelae, and
decreasing health care costs.

In a 1991 workshop on STD Diagnostics, co-sponsored by the National
Institute of Allergy and Infectious Diseases, STD researchers and
representatives from funding agencies, health care delivery agencies,
and industry convened to examine the potential for and constraints on
developing STD diagnostics.  The participants considered the special
requirements of such tests and recommended that useful STD diagnostic
tests should be similar in format and simplicity to the occult fecal
blood card or the urine glucose dipstick; no such STD diagnostic
tests exist that have the required sensitivity and specificity.

The workshop participants reviewed the available biotechnology, and
concluded that the principal obstacle for the development of these
tests was in the application of technological innovation to obtain
appropriate tests.  Recent advances and possible modifications of
older diagnostic approaches may lead to tests that are useful.  Most
promising are inexpensive biochemical tests for enzymes and
metabolites and immunodiagnostics, including antigen detection tests
and serological assays, using newer, simpler formats.

Research Objective and Scope

The objective of this RFA is to develop and evaluate tests for
gonorrhea and chlamydial infection through collaborative research
between private sector and academic scientists.  The collaboration
will facilitate the research development, manufacturing development
and evaluation of new diagnostic tests for sexually transmitted
discharge diseases through original and innovative approaches focused
on the antigens, nucleic acids, biochemical metabolites of and immune
responses to chlamydial infection and gonorrhea.  Ultimately this
research should lead to commercially available diagnostic tests for
gonorrhea or chlamydial infection that:

o  utilize a non-invasive or minimally invasive clinical sample,
i.e., urine or a finger stick sample of blood would be acceptable)
that requires minimal processing;

o  utilize stable, inexpensive, and readily available reagents;

o  are simple to use and provide results within 10 to 20 minutes of
application of the clinical sample;

o  have sensitivities and specificities to detect
cervicitis/urethritis due to gonorrhea and chlamydial infection
comparable to culture; and

o  are small and simply packaged.

SPECIAL REQUIREMENTS

Applicants may apply for either a test development or the test
evaluation award, but not both.  Applicants who wish to develop tests
for gonorrhea and for chlamydial infection must submit a separate
application for each test development effort.

Test Development

The scope of test development includes all activities required to
improve the basic test system such that it has the desired
performance characteristics and all activities required to take the
prototype test format through the complete manufacturing development
phase including all steps involved in the scale up, quality control
assessment, and the production of three lots of 10,000 tests.  The
budget should reflect this research effort.

Test Evaluation

The scope of test evaluation includes all activities required to
determine and report the characteristics of experimental/prototype
tests including: (a) determination of sensitivity and specificity of
the test using a panel of prepared laboratory specimens; (b)
determination of the sensitivity and specificity of the test using
appropriate human clinical specimens, such as blood, urine, cervical
swabs, saliva or other suitable specimens; and (c) comparison of the
experimental test results to those obtained by culture of the
appropriate sample from the same patient.  (If the results are
discrepant, a confirmatory test that is based on a different target
should be used.)  The budget should reflect this effort.

A.  Minimum Requirements

Test Development:

o  The applicant should describe, in detail, the basic assay concept
and the marker that will be used as well as the functional test
system.

o  A description of the sensitivity and specificity of the prototype
tests determined by evaluating a limited number of clinical
specimens.  The other characteristics of the prototypes and the
appropriateness of different types of clinical specimens (e.g., urine
or vaginal secretions) should be included.

o  If discrepancies exist between performance characteristics of the
prototypes at the time of submission of the application and required
characteristics of the final tests, the applicant should provide a
justification and a research plan for achieving the desired
characteristics in the final product.

o  The applicant should describe the capabilities for production of
tests by a manufacturing process that can be fully validated for
regulatory approval.

o  Plans for establishing good manufacturing procedures (GMP)
standards and placing the tests on real time and accelerated
stability schemes using appropriate protocols should be included by
the applicant.

o  The applicant should include plans for the final component
specifications including raw materials, work-in-progress, finished
goods, and unit costing.

Test Evaluation:

o  Applicants should describe the capability to conduct laboratory
evaluations of diagnostic tests for gonorrhea and chlamydial
infection using laboratory prepared and human clinical specimens and
conduct "gold standard" diagnostic tests (i.e., culture) using human
clinical specimens.

o  The applicant should describe, identify, and demonstrate access to
appropriate populations as a source of clinical specimens.  These
populations should include: symptomatic and asymptomatic women and
men with gonorrhea and/or chlamydial infection; and sub-populations
with ranges in disease burden to support evaluation of chlamydial and
gonococcal diagnostic tests in high, intermediate and low prevalence
settings.  For gonorrhea, low prevalence is defined as less than 2%,
intermediate as 2-8%, and high as greater than 8%.  For chlamydial
infection, these are defined as less than 4%, 4-7% and greater than
7%, respectively.  Additionally, NIH policies for inclusion of women
and minorities in the clinical studies must be met (see STUDY
POPULATIONS - Inclusion of Women and Minorities in Research involving
human subjects below).

o  The diagnostic laboratory should have access to a minimum of 7500
subjects per year.  For the purpose of determining the budget, in
year 1 it is anticipated that 3000 tests will be evaluated and in
years 2-5 that 7500 tests per year will be evaluated.

o  The applicant should include detailed examples of (1) protocols
for culture and confirmatory test; (2) consent forms; (3) reports of
test results and other information on test performance
characteristics.

o  Letters of collaboration from all participating clinics/clinicians
are necessary.  These letters shall describe in detail the agreed
upon plans for obtaining informed consent of the patients, assuring
confidentiality of the patient, for the collection of
additional/different samples, collecting appropriate information
about the patient, and the procedures for handling, labeling,
storing, and transporting the clinical samples.

o  Since it is theoretically possible that the requirements for the
experimental or prototype tests will include application of the
sample to the test format at the time of specimen collection, the
abilities of the collaborating clinics/clinicians to accommodate the
evaluation of the test "at the bedside" (i.e., in the clinical
setting) should be described.

o  The applicant should include a plan for administration of the
diagnostic test evaluations, specifying methods to record and report
the results of the diagnostic test evaluations, to calculate the
sensitivity and specificity of the tests.  This may include
developing the specifics of the protocols; purchasing of commercially
available tests (supplies for years 1 and 2 should include the
purchase of 1000 commercially available tests at $5/test); receiving
and shipping of reagents and samples; coding of patients, reagents,
and samples, and coordinating all of the collaborators' activities
(and subcontractors', if applicable).  This may also include
development of an organized, complete system for entering and
tracking data on test results; and documentation of the conduct of
all clinical evaluations.

B.  Definitions

1.  SEXUALLY TRANSMITTED DISEASES DIAGNOSTIC DEVELOPMENT GROUP
(SDDG):  In this RFA, the terms Sexually Transmitted Diseases
Diagnostic Development Group, SDDG and "Group" are synonymous.  An
SDDG is composed of a test development awardee and the test
evaluation awardee.  Each SDDG will have a scientific steering
committee.

2.  SCIENTIFIC STEERING COMMITTEE:  For each SDDG, a steering
committee comprised of the Principal Investigators from the
development and evaluation cooperative agreements, the NIAID
Scientific Coordinator, and two to three peers from the scientific
community will be established.  The role of the Steering Committee is
to provide direction and oversight of the Group's activities and is
defined below under Terms and Conditions of Award.

3.  NIAID SCIENTIFIC COORDINATOR:  This is a Senior Scientist of the
NIAID extramural staff who coordinates NIAID's participation in the
STDG.  Within NIAID, this individual oversees the entire research
program on sexually transmitted diseases, maintains the overall
scientific balance in NIAID's diagnostic development program
commensurate with new research, field observations and emerging
research opportunities, and ensures that the diagnostic development
program is consistent with NIAID's missions and goals.  For role in
the SDDG, see NIAID Staff Responsibilities, below.

C.  Patent Coverage

Because the discovery of innovative, non-invasive, rapid, sensitive,
specific and reliable diagnostic tests to identify active infection
due to N. gonorrhoeae or C. trachomatis is the goal of this effort,
and since active involvement by the private sector is facilitated by
the existence of adequate patent coverage, it is essential that
applicants provide plans to ensure such coverage.  With the potential
for involvement of several institutions, the patent situation could
be complicated.  Each applicant for a test development award must,
therefore, provide a detailed description of the approach to be used
for obtaining patent coverage and for licensing where appropriate, in
particular where the invention may involve investigators from more
than one institution.  Each applicant must provide a detailed
description of the procedures to be followed for the resolution of
legal problems that may develop. Attention is drawn to  the reporting
requirements of 35 U.S.C. Parts 200-212 and 37 CFR Part 401 or FAR
52.227-11.  Instructions were also published in the NIH Guide for
Grants and Contracts, Vol. 19, No. 23, June 22, 1990.  Note that non-
profit organizations (including universities) and small business
firms retain the rights to any patent resulting from Government
contracts, grants, or cooperative agreements.

It is also noted that a Presidential memorandum of February 18, 1983
extended to all business concerns, regardless of size, the first
option to the ownership of rights to inventions as provided in P.L.
96-517.  As a result of this memorandum, the relationships among
industrial organizations and other participants are simplified, since
all Group members can now be full partners in the research and in any
inventions resulting therefrom.  The specific patenting arrangements
among institutions may vary and could include joint patent ownership,
exclusive licensing arrangements, etc.  Applicants are encouraged to
develop an arrangement that is most suitable for their own particular
circumstances.

Federal regulation clause 37 CFR 401 and HHS Inventions regulations
at 45 CFR Parts 6 and 8 require that NIH be informed of inventions
and licensing occurring under NIH funded research.  Invention and
licensing reports must be submitted to Extramural Invention Reports
Office, Office of Extramural Research, Building 31, Room 5B41, NIH,
9000 Rockville Pike, Bethesda, MD 20892.

D.  Terms and Conditions of Award

The following terms and conditions will be incorporated into the
award statement and provided to the Principal Investigator as well as
the institutional official at the time of award.

These special Terms of Award are in addition to, and not in lieu of,
otherwise applicable OMB administrative guidelines, HHS Grant
Administration Regulations at 45 CFR part 74 and 92, and other HHS,
PHS, and NIH Grant Administration policy statements.

The administrative and funding instrument used for this program is
the Cooperative Agreement (U01), an "assistance" mechanism (rather
than an "acquisition" mechanism), in which substantial NIH scientific
and/or programmatic involvement with the awardee is anticipated
during the performance of the activity.

Under the Cooperative Agreement, the NIH purpose is to support and/or
stimulate the recipient's activity by involvement in and otherwise
working jointly with the award recipient in a partner role, but it is
not to assume direction, prime responsibility, or a dominant role in
the activity.

Consistent with this concept, the dominant role and prime
responsibility for the activity resides with the awardee(s) for the
project as a whole, although specific tasks and activities in
carrying out the study will be shared among the awardees and the
NIAID Scientific Coordinator.

Under the cooperative agreement, a relationship will exist between
the award recipient(s) and the NIAID in which the performers of the
activities (1) are responsible for the requirements and conditions
described below and (2) agree to accept program assistance from the
named NIAID Scientific Coordinator in achieving project objectives.

Failure of an awardee to meet the performance requirements, including
these special terms and conditions of award, or significant changes
in the level of performance, may result in a reduction in budget,
withholding of support, or suspension and/or termination of the
award.

1.  Awardee Rights and Responsibilities

The awardee is responsible for:

a.  Research design and development, including definition of
objectives and approaches, planning, implementation, data collection,
quality control, interim data and safety monitoring, final data
analysis and interpretation, and publication of results.

b.  Establishing a mandatory Steering Committee to coordinate and
manage the test development and test evaluation studies.

c.  Implementing the data collection strategy and methods
collectively decided upon by the Steering Committee.  For each study
involving multiple institutions, it is the responsibility of each
awardee/site to ensure that data will be collected and submitted in a
timely way following such procedures as agreed to by the Steering
Committee.

d.  Establishing mechanisms for quality control and monitoring.
Awardees are responsible for ensuring the accurate and timely
assessment of the progress of the study, including development of
procedures to ensure that data collection and management are adequate
for quality control and analysis.

e.  Preparing and submitting interim progress reports, when requested
(not more than quarterly), to the NIAID Scientific Coordinator
including, as a minimum, summary data on diagnostic test performance
results.   Such reports are in addition to the annual awardee
noncompeting continuation progress reports.

f.  Establishing procedures, where applicable, for all participating
institutions in coordinated awards to comply with FDA regulations for
studies involving investigational agents or devices and to comply
with the requirements of 45 CFR Part 46 for the protection of human
subjects.

g.  Cooperating in the reporting of the study findings.  The NIAID
will have access to and may periodically review all data generated
under an award.  Where warranted by appropriate participation, plans
for joint publication with NIAID of pooled data and conclusions, are
to be developed by the Principal Investigator or Steering Committee,
as applicable.  NIH policies governing possible co-authorship of
publications with NIAID staff will apply in all cases.  In general,
to warrant co-authorship, NIAID staff must have contributed to each
of following areas:  (a) design of the experiments or concepts being
tested; (b) performance of significant portions of the activity; and
(c) preparation and authorship of pertinent manuscripts.  The awardee
will retain custody of and have primary rights to the data developed
under these awards, subject to Government right of access consistent
with current HHS, PHS, and NIH policies.  Contents of reports of
study results are solely the responsibility of the authors and do not
necessarily represent the views of NIAID.

2.  NIAID Staff Responsibilities

It is expected that the dominant role and prime responsibility for
the activity will reside with the awardee(s) for the project as a
whole.  However, specific tasks and activities will be shared among
the awardee(s) and the NIAID Scientific Coordinator.  As required for
the coordination of activities and to expedite progress, the NIAID
Scientific Coordinator may designate additional NIAID staff to
provide advice or assistance to the awardee(s) on specific
scientific, technical, or management issues.  The NIAID Scientific
Coordinator shall retain overall programmatic responsibility for the
award(s) and will clearly specify to the awardee(s) the name(s) and
role(s) of any such additional individuals and the lines of reporting
authority.

a.  Interacting with the principal investigator(s) on a regular basis
to monitor study progress.  Monitoring may include:  (a) regular
communications with the principal investigator and staff, (b)
periodic site visits for discussions with awardee research teams, (c)
observation of laboratory, manufacturing, data collection and
management techniques, quality control, fiscal review, and other
relevant matters, as well as (d) attendance at and participation in
Scientific Steering Committee.

b.  Convening the first meeting of and subsequent participation in
the Scientific Steering Committee that oversees study conduct.  The
NIAID Scientific Coordinator will be a full participant and voting
member of the Scientific Steering Committee.

c.  Serving as a resource with respect to ongoing NIAID activities
that may be relevant to the research to facilitate compatibility and
avoid unnecessary duplication.

d.  Substantial assistance in the design and coordination of research
activities for awardees including:

1.  Assisting by providing advice on the management and technical
performance of the investigations.

2.  Providing access to and use of, when appropriate, reagents and
assays, and other resources available through NIAID contractors and
awardees.

3.  Technical advice and assistance with meeting FDA requirements.

4.  Reviewing and approving study designs to insure that they are
within the scope of peer review and for adequacy of safety, human
subjects, and representation of women and minorities, as required by
Federal regulations.

5.  Reviewing and providing advice regarding the establishment of
mechanisms for quality control and study monitoring.

e.  Making recommendations for continued funding based on: (1)
overall study progress, including study subject and/or data accrual;
(2) cooperation in carrying out the research (e.g., attendance at
Steering Committee meetings, implementation of group decisions,
compliance with terms of award and reporting requirements); and/or
(3) maintenance of a high quality of research which will allow
pooling of data and comparisons across multiple cooperative agreement
awards for common data elements.

3.  Joint Responsibilities

In addition to the interactions defined above, awardees and NIAID
staff shall share responsibility for the organization of and
participation on a Scientific Steering Committee.  A Scientific
Steering Committee for each SDDG organized by the Principal
Investigators of a test development awardee and the test evaluation
awardee and the NIAID Scientific Coordinator will be the main
oversight body of the study.  The steering committee will be
comprised of the Principal Investigators from a development and the
evaluation cooperative agreements, the NIAID Scientific Coordinator,
and two to three peers from the scientific community.  The peers from
the scientific community shall be selected jointly by the Principal
Investigators and the NIAID Scientific Coordinator.

The Steering Committee has primary responsibility to design joint
research activities, establish priorities, develop common methods and
procedures including data recording forms, establish and maintain
quality control among awardees, review progress, coordinate and
standardize data management, and cooperate on the publication of
results.  Major scientific decisions regarding data will be
determined by the Steering Committee.  The Steering Committee will
document progress in written reports to the NIAID Scientific
Coordinator and will provide periodic supplementary reports upon
NIAID request.

An initial meeting of the Steering Committee will be convened early
after award by the NIAID Scientific Coordinator.  The final structure
of the Steering Committee will be established at the first meeting.
The NIAID Program Officer will have voting membership on the Steering
Committee.  After the initial meeting, the Steering Committee will
meet 1-2 times per year.

A Chairperson, other than the NIAID Program Officer, will be selected
by vote of the members.  The Chairperson is responsible for
coordinating the Committee activities, for preparing meeting agendas,
for scheduling and chairing meetings, and for preparing and
disseminating a concise summary of each meeting to members of the
Committee.

4.  Arbitration Process

Any disagreement that may arise on scientific/programmatic matters
(within the scope of the award), between award recipients and the
NIAID may be brought to arbitration.  An arbitration panel will be
composed of three members -- one awardee designee, one NIAID
designee, and a third designee with expertise in the relevant area
and chosen by the other two.  This special arbitration procedure in
no way affects the awardee's right to appeal an adverse action that
is otherwise appealable in accordance with PHS regulations 42 CFR
Part 50, Subpart D and HHS regulation at 45 CFR Part 16.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
SUBJECTS

It is the policy of the NIH that women and members of minority groups
and their subpopulations must be included in all NIH supported
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification is provided
that inclusion is inappropriate with respect to the health of the
subjects or the purpose of the research.  This new policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43) and supersedes and strengthens the previous policies
(Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations), which
have been in effect since 1990. The new policy contains some
provisions that are substantially different from the 1990 policies.

All investigators proposing research involving human subjects should
read the "NIH Guidelines For Inclusion of Women and Minorities as
Subjects in Clinical Research," which have been published in the
Federal Register of March 28, 1994 (FR 59 14508-14513) and reprinted
in the NIH Guide for Grants and Contracts, March 18, 1994, Volume 23,
Number 11.

Investigators also may obtain copies of the policy from the program
staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.

LETTER OF INTENT

Prospective applicants are asked to submit, by January 9 1995, a
letter of intent that includes a descriptive title of the overall
proposed research, the name, address and telephone number of the
Principal Investigator, the number and title of this RFA, and a list
of the key investigators and their institution(s). Although the
letter of intent is not required, is not binding, does not commit the
sender to submit an application, and does not enter into the review
of subsequent applications, the information that it contains allows
NIAID staff to estimate the potential review workload and to avoid
conflict of interest in the review.

The letter of intent is to be sent to Dr. Olivia Preble at the
address listed under INQUIRIES.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these grants.  These forms are available at most
institutional offices of sponsored research; from the Office of
Grants Information, Division of Research Grants, National Institutes
of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892,
telephone 301/710-0267; and from the program administrator listed
under INQUIRIES.

Applications must address the items stated in the section "SPECIAL
REQUIREMENTS" above and must specifically agree to the Terms and
Conditions of Award presented in the SPECIAL REQUIREMENTS section.

Should the Group wish to place all inventions and discoveries
resulting from these studies within the public domain, a letter to
that effect must be submitted to Dr. Hitchcock in lieu of the patent
agreement prior to submission of the application.  The letter must be
co-signed by the Principal Investigator and each of the business
officials representing the respective institutions.

The RFA label available in the PHS 398 (rev. 9/91) application form
must be affixed to the bottom of the face page of the application.
Failure to use this label could result in delayed processing of the
application such that it may not reach the review committee in time
for review.  In addition, the RFA title and number must be typed on
line 2a of the face page of the application form and the YES box must
be marked.

Submit a signed, typewritten original of the application, including
the checklist, and three signed, exact, single-spaced photocopies in
one package to:

Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**

At the time of submission, also submit two additional exact copies of
the application, and five sets of the appendix and reprints directly
to Dr. Olivia Preble at the address listed under INQUIRIES.

Applications must be received by March 23, 1995.  If an application
is received after that date, it  will be returned to the applicant
without review.  The DRG will not accept any application in response
to this RFA that is essentially the same as one currently pending
initial review, unless the applicant withdraws the pending
application.  The DRG will not accept any application that is
essentially the same as one already reviewed.  This does not preclude
the submission of a substantial revision of an application already
reviewed, but such applications must include an introduction
addressing the previous critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by DRG
and responsiveness by the NIAID.  Incomplete applications will be
returned to the applicant without further consideration.  If the
application is not responsive to the RFA, DRG will return the
application to the applicant.

Applications that are complete and responsive to the RFA will be
evaluated for scientific and technical merit by an appropriate peer
review group convened by the NIAID in accordance with the review
criteria stated below.

As part of the initial merit review, a process (triage) may be used
by the initial review group in which applications will be determined
to be competitive or non-competitive based on their scientific merit
relative to other applications received in response to the RFA.
Applications judged to be competitive will be discussed and be
assigned a priority score.  Applications determined to be non-
competitive will be withdrawn from further consideration and the
principal investigator/program director and the official signing for
the applicant organization will be promptly notified.  The second
level of review will be provided by the National Advisory Allergy and
Infectious Diseases Council.

Review Criteria

Based on the PURPOSE, RESEARCH OBJECTIVES, and SPECIAL REQUIREMENTS
of this Request for Applications, the following review criteria will
apply:

o  scientific, technical, and manufacturing merit or medical
significance and originality of proposed research;

o  appropriateness and adequacy of the experimental/methodological
and manufacturing approaches proposed to carry out the research;

o  qualifications and research/manufacturing experience of the
Principal Investigator and staff, particularly, but not exclusively,
in the area of the proposed research;

o  availability of the resources necessary to perform the research;

o  appropriateness of the proposed budget and duration in relation to
the proposed research;

o  adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
evaluated.

The initial review group will also examine the provisions for the
protection of human and animal subjects and the safety of the
research environment.

AWARD CRITERIA

Awards will be made on the basis of scientific and technical merit as
determined by peer review, program needs and balance, and the
availability of funds.  It is anticipated that one award will be made
for test development for gonorrhoea, one award will be made for test
development for chlamydial infection, and one award will be made for
evaluation of tests.

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged.
The opportunity to clarify any issues or questions from potential
applicants is welcome.

Direct inquiries regarding programmatic issues to:

Dr. Penelope J. Hitchcock
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
Solar Building, Room 3A16
6003 Executive Boulevard
Bethesda, MD  20892-7630
Telephone:  (301) 402-0443
FAX:  (301) 402-0659 or 1456
Email:  penny@exec.niaid.pc.niaid.nih.gov

Direct letters of intent, and inquiries regarding application
preparation and review to:

Dr. Olivia T. Preble
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4C16
6003 Executive Boulevard
Bethesda, MD  20892
Telephone:  (301) 496-0818
FAX:  (301) 402-2638
Email:  olivia preble@exec.niaid.pc.niaid.nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Sharie Bernard
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4B22
6003 Executive Boulevard
Bethesda, MD  20892
Telephone:  (301) 496-7075
FAX:  (301) 480-3780
Email:  sharie bernard@exec.niaid.pc.niaid.nih.gov

Schedule

Letter of Intent Receipt Date:  January 9, 1995
Application Receipt Date: March 23, 1995
Scientific Review Date:   July 1995
Advisory Council Date:    September 1995
Anticipated Award Date:   September 1995

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance, No. 93.856 - Microbiology and Infectious Diseases
Research and No. 93.855 - Immunology, Allergic and Immunologic
Diseases Research.  Awards will be made under the authority of the
Public Health Service Act, Title IV, Part A (Public Law 78-410, as
amended by Public Law 99-158, 42 USC 241 and 285) and administered
under PHS grants policies and Federal Regulations 42 CFR Parts 52 and
45 CFR Part 74 [and Part 92 when applicable for State and Local
governments].  This program is not subject to the intergovernmental
review requirements of Executive Order 12372 or Health Systems Agency
review.

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.

.

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	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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