Subject: NIH GUIDE - Vol. 20, No. 10, March 8, 1991 - RFA AI9108
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Fri, 08 Mar 91 10:34 EST

Hi Paul,
   This is the last of the 3/8/9l NIH Guide.  Please post this to the
listserver as: RFAAI-91-08.910308.
   Thanks ever so much for being your kind, helpful self.   Have a
very nice weekend.
                  Dottie
 ---------------------------- Text of forwarded message -----------------------
 
$$XID RFA AI9108 AI-91-08 P1O1 *****************************************
 
RESEARCH UNITS ON PELVIC INFLAMMATORY DISEASE AND ITS SEQUELAE
 
RFA:  AI-91-08
 
P.T. 34; K.W. 0715026, 1002004, 1002027, 0710070
 
National Institute of Allergy and Infectious Diseases
 
Letter of Intent Receipt Date:  April 15, 1991
Application Receipt Date:  October 21, 1991
 
The Sexually Transmitted Disease (STD) Branch of the Division of
Microbiology and Infectious Disease (DMID) of the National Institute of
Allergy and Infectious Diseases (NIAID) invites grant applications for
program project grants to be initiated in FY 1992 that focus on pelvic
inflammatory disease (PID) and its sequelae.  In recognition of the
severe impact of PID on the health of women, the Institute wishes to
expand research in this area and to place greater emphasis on
investigations that are likely to lead to reduction of the incidence and
severity of long-term sequelae such as infertility, ectopic pregnancy
and chronic pelvic pain syndrome.  The Research Units on PID and its
Sequelae will provide a strong, interdisciplinary approach to PID
research which will draw upon expertise in clinical, epidemiological,
behavioral, and basic sciences.  Although a broad range of PID research
issues will be addressed, research in the following three areas is
particularly enthusiastically encouraged:
 
1) Long-term sequelae - Characterization of the molecular,
microbiological, immunological, and behavioral determinants of the
development of long-term sequelae of PID and use of animal models to
evaluate interventions to reduce these sequelae;
 
2) Atypical PID - Development of methods to detect atypical PID, and
definition of the epidemiology of this portion of the PID spectrum;
 
3) Diagnostic Approaches - Development and assessment of non-invasive
methods to diagnose symptomatic PID.
 
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 RFA,
Research Units on Pelvic Inflammatory Disease and its Sequelae, is
related to the priority area of Sexually Transmitted Diseases.
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, D.C. 20402-9325
(telephone 202-783-3238).
 
BACKGROUND INFORMATION
 
In the United States, PID-related sexually transmitted diseases (STDs)
have remained refractory to control efforts.
 
* Annually, approximately 2 million new cases of gonorrhea occur at an
estimated cost of almost $1 billion; 25 percent of these cases are in
teenagers.  In addition, four new types of antibiotic resistance have
emerged in the last decade.
 
* The annual incidence of chlamydial infection is approximately 4
million cases at a comprehensive cost estimated to exceed $2.18 billion.
Control of chlamydial infection is complicated by the frequency of
asymptomatic disease, the cost and technical difficulty of available
diagnostic tests, and the absence of effective, single dose therapy.
 
As a result, in 1990 PID continues to be the single most serious and
most costly common STD affecting American women.
 
* Each year, between 10 and 40 percent of women with untreated
gonococcal and chlamydial infections develop PID.
 
* It is estimated that in the United States, 10 to 15 percent of women
of reproductive age have had a least one episode of PID, and that
annually between 750,000 and 1,000,000 new cases are added to this
figure.
 
* PID frequently results in severe, irreversible sequelae.  Due to
scarring following PID, approximately 17-25 percent of women become
infertile, 15-18 percent develop debilitating chronic pelvic pain, and
20-25 percent present with recurrent PID.  In addition, a woman who has
had PID is 6-10 times more likely to have a potentially fatal ectopic
pregnancy than a woman who has never had upper genital tract infection.
These complications are particularly devastating because approximately
70 percent of women who develop PID are less than 25 years old and 75
percent have not yet had a child.
 
* Serologic data from infertility and ectopic pregnancy patients suggest
that atypical PID may be responsible for a substantial proportion of
both conditions.  "Silent" salpingitis and subsequent tubal scarring
probably account for the majority of tubal infertility and a significant
proportion of ectopic pregnancies.
 
* The long-term, devastating consequences of PID disproportionately
affect minority women.  Although non-white women comprise only 17
percent of the total female population of the United States, they
represent 33 percent of consultations for PID.  Ectopic pregnancies, 50
percent of which are caused by previous PID, are the principal cause of
pregnancy-related mortality among black women in the United States.
Furthermore, minority teenagers with ectopic pregnancies are almost six
times as likely to die as their Caucasian counterparts.
 
* The highest annual PID incidence among sexually active women is in the
adolescent group.  Sexually active 15-19 year old females have
approximately a one in eight risk of developing PID.
 
* PID has an enormous personal and economic impact at the time of the
acute episode and again when sequelae of PID (infertility, ectopic
pregnancy and chronic pelvic pain) manifest.  It is estimated that in
the United States, PID and its sequelae will cost more than $4.2 billion
in 1990.  If the incidence of PID remains constant, at the current rate
of inflation, projected comprehensive costs of PID for the year 2000
will be almost $10 billion.
 
RESEARCH OBJECTIVES AND SCOPE
 
Research Objectives
 
The goal of this program is to encourage investigators to undertake
research that will provide the microbiological, immunological, clinical,
epidemiological and behavioral information needed for the eventual
control of PID and its long-term sequelae.  In addition to other
important research issues, data that are needed to design and conduct
intervention trials to reduce the incidence and severity of sequelae of
PID are of high priority.  It should be understood that such a trial is
not a component of this solicitation nor has the NIAID developed
specific plans for such a trial at this time.  However, one of the major
purposes of this RFA is to stimulate exceptionally high quality,
multi-disciplinary research on those aspects of the epidemiology,
pathogenesis and detection of PID, which are likely to be critical in
the design of such trials.
 
Programmatic Parameters
 
In addition to the importance of utilizing a multi-disciplinary
approach, specific programmatic requirements and constraints are as
follows:
 
* Structure of Program Projects:  Each program project must consist of
at least three individual subprojects which are synergistically
inter-related.  Each subproject should have clearly described research
objectives and each should be headed by a project leader, with a
research staff and a separately identifiable budget.  It is the primary
responsibility of the project leader to clearly state the objectives and
approaches of the project, to plan and conduct the research stipulated
in the proposal and to ensure that the results obtained are analyzed and
published in a timely manner.
 
The Program Director of the Research Unit will be responsible for the
overall direction and administration of the total program project.  It
is the Program Director's responsibility to promote effective
coordination and strong interaction among the research staff of
individual subprojects, directed towards resolving the problems of PID
and its sequelae.  The concept of a team effort is an especially
important one; the strength of the team approach can have a major impact
on the review of these applications.
 
* Clinical Facility:  In order to bridge the basic research and clinical
arenas, the PID program project must offer a strong clinical facility
with accessible patient populations that are appropriate to answering
PID research questions.  Adolescents and inner city minority groups are
examples of populations which should be considered for special attention
in the context of these program project grants.
 
* Exposure of Pre- and Postdoctoral Candidates:  Efforts should be made
within the setting of the program project to advance learning
experiences in PID research and to make medical students, house staff
and postdoctoral candidates more aware of the research opportunities in
PID at both the clinical and basic science levels.  A selected program
of training that also involves student stipends, however, will not be
considered part of this program.  Formal training programs at either the
clinical or basic sciences level that include stipends for these
students are supported by other funding mechanisms at the NIH, such as
the National Research Service Awards/Institutional Training Grants
(T32s) and do not, therefore, fall within the purview of this program
request.
 
Research Scope
 
A broad range of research questions is potentially relevant to the goal
of this program.  Specific research issues of high priority include but
are not limited to the following:
 
Microbiology and Pathogenesis
 
* Definition of the chronological and molecular relationships among
lower tract infection, tubal infection, and subsequent scarring.
 
* Elucidation of the structure and function of bacterial and host
factors which play a role in the pathogenesis of long-term sequelae of
PID.  It may be particularly productive in these studies to compare
women with localized cervicitis and with clinical salpingitis stratified
by pathogen and to evaluate host determinants in a multi-dimensional
fashion including innate genetic determinants, immune responses,
behavioral factors, sperm factors, myometrial contractions, poor
reproductive history, and endocrinologic factors.
 
* Further development and use of animal models to better define the
relationship between lower and upper genital tract infection.  Relevant
questions include the immunologic mechanisms that promote both
protective and pathogenic responses to C. trachomatis infection and the
effects of immunomodulators and oral contraceptives on ascending
chlamydial infection.
 
* Characterization of the full etiological spectrum of both symptomatic
and atypical PID.  Definition of the relative role of STD and non-STD
pathogens in the development of PID and it sequelae will be important to
the development of effective control efforts.
 
Epidemiology/Behavioral Research
 
* Further elucidation of the descriptive epidemiology of PID with
particular emphasis on atypical infections.  Cervicitis patients without
lower abdominal pain and women with menorrhagia are two populations in
which the latter issue may be explored.
 
* The definition of the role of specific behavioral risk factors and
risk markers in the development of PID and its sequelae.  Factors
requiring additional study include douching, intercourse during menses,
contraceptive practices, and provider behaviors.  It may be useful to
design research approaches that attempt to distinguish among factors
affecting risk of lower tract infection, risk of spread to the upper
tract, and risk of long-term sequelae.
 
* Assessment of the role of the male in the development of PID and its
sequelae.  Issues include whether the stage of infection and/or the
inoculum size in the male alters the risk of upper tract infection in
female partners.
 
Detection and Diagnosis
 
* Design and evaluation of diagnostic algorithms based on epidemiologic,
clinical, and simple laboratory data.  These studies should use
well-defined standards such as laparoscopy, or laparoscopy and
endometrial biopsy to provide standardized assessments.
 
* Development and evaluation of diagnostic criteria for atypical or
"silent" PID.  Use of broad inclusion criteria and data on women
initially misdiagnosed with other diseases may be helpful in these
studies.
 
* Development and assessment of non-invasive methods to diagnose PID and
to identify individuals at high risk of developing sequelae.  Examples
of relevant approaches might include vaginal probe ultrasonography, and
organism or host-specific markers.
 
MECHANISM OF SUPPORT
 
Successful applicants funded under this RFA will be supported through
program project grants (PO1).  This type of funding mechanism is
utilized when it is desired to encourage multi-disciplinary
investigator-initiated research on a broad range of problems which are
linked by a common theme.  This solicitation represents a single
competition with a specified deadline for receipt of applications.
Although there are no present plans to reissue this request for
applications at any future time, NIAID may invite competitive renewal
applications upon expiration of the initial funding period, contingent
on the availability of funds for this purpose.  NIAID anticipates making
three program project grant awards as a result of this RFA.
 
FOR A PROGRAM PROJECT TO BE CONSIDERED FOR FUNDING, IT MUST CONTAIN AT
LEAST THREE APPROVED, INTER-RELATED RESEARCH PROJECTS.  Program project
grants are awarded to an institution on behalf of a program director for
the support of a broadly based, multi-disciplinary, long-term research
program that has a specific major objective or basic theme.  A program
project generally involves the organized efforts of relatively large
groups of investigators, whose members conduct research projects that
focus on various components of the overall program objective.  The grant
can provide support for the projects and for certain shared basic
resources (cores) which will facilitate the total research effort.  Each
project supported under a program project grant is expected to
contribute to the common theme of the program; the individual projects
must be scientifically meritorious in their own right, and must also
demonstrate an essential element of unity, interdependence, and synergy.
 
Level and Duration of Support
 
NIAID anticipates making three program project grant awards as a result
of this RFA.  The final number of awards to be made is dependent upon
the availability of funds.  The initial year's direct and indirect costs
should not exceed $800,000 for each award.  Awards will be made for a
project period of up to four years.  The earliest possible award date is
July 1, 1992.  Funding beyond the first and subsequent years of the
award will be contingent upon satisfactory progress during the preceding
years and upon availability of funds.  If a Request for Applications
(RFA) is not issued about a year prior to termination of the grant, the
program director must contact NIAID program staff if there is intention
to submit a competing renewal application.  It is NIAID policy to accept
a program project application only with prior contact with and approval
of the program officer.
 
Allowable Costs
 
Award funds may be utilized to support the following research-related
activities:
 
* Scientific and Professional Personnel Costs:  The requested percentage
of an individual's salary may not exceed the percentage of effort
devoted specifically to activities associated with the PID program
project grant.  Information substantiating this level of effort must be
included in the application.
 
* Administrative Costs:  This category includes the costs necessary for
the central administration and fiscal management of the program project,
such as salaries of the Chief Administrator and secretarial support.
Those costs may not duplicate or replace costs included in the
institution's indirect cost base.
 
* Shared Research Resources (Cores):  The PID program project grant may
include funds for equipment, supplies and services to expand and/or
maintain clinical, laboratory, biostatistical, and behavioral facilities
which are shared by research staff from at least two research projects.
 
In addition to the above categories, budget requests within each project
may include research-related costs for supplies, patient involvement and
medical care, funds for limited investigator travel, and costs of
publication.  An applicant whose institution has an NIH-supported
General Clinical Research Centers (GCRC) must first attempt to utilize
such a Center for relevant categories of patient care before requesting
budgets for such costs.  Because the program project cannot provide
funds for new construction, adequate physical facilities must be
available to meet the primary needs of the project.
 
ELIGIBILITY - ONLY DOMESTIC INSTITUTIONS ARE ELIGIBLE TO APPLY.
 
MINIMUM REQUIREMENTS FOR APPLICATION
 
Before preparing an application, the applicant should read the
information brochure which accompanies each RFA:  Program Project and
Center Grants, NIAID.  Instructions outlined in the brochure for the
formatting of the application should be followed carefully.  Failure to
follow the instructions may result in unnecessary delays in the review
process.  Particular attention should be given to the following areas
when responding to the application instructions found in the brochure.
 
* The detailed description of each research project should demonstrate
how it contributes to the attainment of the program project objectives.
Furthermore, in addressing the Organization and Administrative structure
of the program project grant, the mutually reinforcing
inter-relationships among the investigators should be clearly described.
This section must include an organizational chart showing the name, the
organization and the scientific discipline of the Principal
Investigator, the Project Leaders, and the key personnel for the
projects and cores.
 
* In describing the clinical and laboratory facilities available to
conduct each project, specific information should be included on the
institution's present PID patient load and projections for patient
involvement and patient follow-up in clinical investigations as well as
on the availability of appropriate biohazard facilities and safety
procedures.
 
* SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL
RESEARCH STUDIES - For projects involving clinical research, NIH
requires applicants to give special attention to the inclusion of women
and minorities in study populations.  By the nature of this program,
subjects will consist largely of women.  Applicants are urged to give
added attention, where feasible and appropriate, to the inclusion of
minorities in study populations for PID program project grants.  If
minorities are not included or adequately represented in the study
populations for clinical studies, a specific justification for this
exclusion or inadequate representation must be provided.  Applications
without such documentation will not be accepted for review.
 
The composition of the proposed study population must be
described in terms of gender and racial/ethnic group.  In
addition, gender and racial/ethnic issues should be addressed in
developing a research design and sample size appropriate for the
scientific objectives of the study.  This information should be
included in the form PHS 398 in Section 2, A-D of the Research
Plan AND summarized in Section 2, E, Human Subjects.
Applicants/offerors are urged to assess carefully the feasibility
of including the broadest possible representation of minority
groups.  However, NIH recognizes that it may not be feasible or
appropriate in all research projects to include representation of
the full array of United States racial/ethnic minority
populations (i.e., Native Americans (including American Indians
or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics).
 
The rationale for studies on single minority population groups
should be provided.
 
For the purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, epidemiology,
prevention (and preventive strategies), diagnosis, or treatment
of diseases, disorders or conditions, including but not limited to
clinical trials.
 
The usual NIH policies concerning research on human subjects also
apply.  Basic research or clinical studies in which human tissues
cannot be identified or linked to individuals are excluded.
However, every effort should be made to include human tissues
from women and racial/ethnic minorities when it is important to
apply the results of the study broadly, and this should be
addressed by applicants.
 
For foreign awards, the policy on inclusion of women applies
fully; since the definition of minority differs in other
countries, the applicant must discuss the relevance of research
involving foreign population groups to the United States'
populations, including minorities.
 
If the required information is not contained within the
application, the application will be returned.
 
Peer reviewers will address specifically whether the research
plan in the application conforms to these policies.  If the
representation of women or minorities in a study design is
inadequate to answer the scientific question(s) addressed AND the
justification for the selected study population is inadequate, it
will be considered a scientific weakness or deficiency in the
study design and will be reflected in assigning the priority
score to the application.
 
All applications for clinical research submitted to NIH are
required to address these policies.  NIH funding components will
not award grants or cooperative agreements that do not comply
with these policies.
 
* Included in information under the "Other Support" section must be an
explicit written plan which explains how applicant Principal
Investigators who also hold Principal Investigator status on grants
unrelated to the PID program project application (particularly on
Center, Training or other program project grants) will be able to
successfully and fully meet the responsibilities demanded by both
endeavors.
 
* The application must include a signed letter of agreement from each
collaborator and/or consultant to the program indicating 1) willingness
to participate in the program, and 2) the exact nature of the
participation.  Applicants from institutions which have a General
Clinical Research Center (GCRC) funded by the NIH National Center for
Research Resources may wish to identify the GCRC as a resource for
conducting the proposed research.  In such a case, a letter of agreement
from either the GCRC program director or Principal Investigator must be
included with the applications.
 
REVIEW PROCEDURES AND PEER REVIEW CRITERIA
 
Review Procedures
 
Applications that are judged to be non-responsive to this RFA will be
screened out by NIAID staff upon receipt and returned to the applicant
without further consideration.  Those applications that are complete and
responsive to the RFA may be subjected to triage review by a NIAID peer
review group to determine their scientific merit relative to the other
applications received in response to the RFA.  The NIAID will withdraw
from competition those applications judged by the triage peer review
group to be noncompetitive for award, and will notify the applicant and
the institutional business office.  Those applications considered to be
competitive for award will be reviewed for scientific and technical
merit on or about November 1991 by a committee convened by the Division
of Extramural Activities, NIAID.  The second level of review will be
provided by the National Advisory Allergy and Infectious Diseases
Council in May 1992.  The earliest award date is July 1, 1992.
 
Peer Review Criteria
 
It is again emphasized that prospective applicants should carefully read
the information brochure "PROGRAM PROJECT AND CENTER GRANTS, NIAID"
which accompanies each RFA.  The brochure describes program projects and
other large, multi-disciplinary grants; outlines review criteria for
such programs; and includes other important information that will aid in
formatting the application.  The review criteria outlined in the
brochure are the review criteria to be used by the peer review group in
the evaluation of applications received in response to this RFA.
Specifically, proposals will be evaluated for scientific merit including
the originality, uniqueness and technical excellence of the research
projects.  Programmatic relevance, overall responsiveness to the
research objectives stated within this RFA and the degree of synergy of
the projects will, of course, also be considered.
 
In addition to the review criteria stated above, proposals must satisfy
the previously mentioned specific programmatic requirements which are
summarized below.  These requirements appear in greater detail in
Section III - "RESEARCH OBJECTIVES AND SCOPE" and applicants are urged
to review this section.
 
Requirements
 
* A minimum of three projects which are linked synergistically to a
common research focus or theme.
*  A multi-disciplinary approach to the research issues.
*  A clinical facility with appropriate patient populations.
 
Applicants are also strongly encouraged but not required to address
issues in:
 
i)   Development of long-term sequelae;
ii)  Characterization of atypical PID;
iii) Improved and less invasive diagnosis.
 
Descriptive behavioral research and inclusion of minority/adolescent
populations are also encouraged as part of this RFA.
 
METHOD OF APPLYING
 
Letter of Intent
 
Prospective applicants are asked to submit, by April 15, 1991, a short
letter of intent that includes a descriptive title and the names and
affiliations of proposed key investigators for each of the proposed
research projects.  The letter of intent is requested to provide an
indication of the number and scope of applications to be reviewed.  The
letter of intent does not commit the sender to submit an application,
nor is it a requirement for submission of an application.
 
The letter of intent should be sent to:
 
Dr. Olivia Preble
Chief, Microbiology and Immunology Review Section
Program and Project Review Branch
National Institute of Allergy and Infectious Diseases
National Institutes of Health
Westwood Building, Room 3A10
Bethesda, MD  20892
Telephone:  (301) 496-8208
 
Format of Applications
 
Applications must be submitted on form PHS 398 (rev.  10/88), the
application form for research grants.  To assure the identification of
your application with this RFA, the application must have "RFA AI-91-08,
Research Units on Pelvic Inflammatory Disease and its Sequelae" typed on
item 2 of the face page of the application.  Application kits are
available at most institutional business offices, and may be obtained
from:
 
Office of Grants Inquiries
Division of Research Grants
Westwood Building, Room 449
5333 Westbard Avenue
Bethesda, MD  20892
 
Application Procedure
 
A signed, typewritten original of the application, including the
checklist, and four (4) signed, exact, single-sided copies should be
sent or delivered, in one package, to:
 
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**
 
TWO ADDITIONAL COPIES MUST ALSO BE SENT DIRECTLY TO DR.  OLIVIA PREBLE
AT THE ADDRESS GIVEN ABOVE.
 
THE RFA LABEL AVAILABLE IN THE 10/88 REVISION OF APPLICATION FORM 398
MUST BE AFFIXED TO THE BOTTOM OF THE FACE PAGE.  FAILURE TO USE THIS
LABEL COULD RESULT IN DELAYED PROCESSING OF YOUR APPLICATION SO THAT IT
MAY NOT REACH THE REVIEW COMMITTEE IN TIME FOR REVIEW.
 
Consequences of Late Applications
 
To ensure their review, applications must be received by both DRG and
Dr. Olivia Preble by October 21, 1991.  Applications received after
October 21, 1991, will be returned without review.  If the application
submitted in response to this RFA is substantially similar to a research
grant application already submitted to the NIH for review, but has not
yet been reviewed, the applicant will be asked to withdraw either the
pending application or the new one.  Simultaneous submission of
identical applications will not be allowed, nor will essentially
identical applications be reviewed by different review committees.
Therefore, an application cannot be submitted in response to this RFA
that is essentially identical to one that has already been reviewed.
This does not preclude the submission of substantial revisions of
applications already reviewed, but such applications must include an
introduction addressing the previous critique.
 
INQUIRIES
 
Investigators seeking information relevant to this RFA should contact:
 
Dr. Judith Wasserheit
Chief, Sexually Transmitted Diseases Branch
Westwood Building, Room 749
National Institute of Allergy and Infectious Diseases
National Institutes of Health
9000 Rockville Pike
Bethesda, MD  20892
Telephone:  (301) 402-0443
 
Questions regarding review procedures should be addressed to Dr. Preble,
at the address given above.
 
Questions regarding fiscal matters should be addressed to:
 
Mr. Todd Ball
Grants Management Branch
Division of Extramural Activities
NIAID, NIH
Westwood Building, Room 726
Bethesda, MD  20892
Telephone:  (301) 496-7075
 
Support is authorized by the Public Health Service Act, Public Law
78-410, as amended.  The Catalog of Federal Domestic Assistance citation
is Sec. 93.856, Microbiology and Infectious Diseases Research.  Awards
will be administered under PHS grant policies and Federal Regulations 42
CFR Part 52 and 45 CFR Part 74.  This program is not subject to the
intergovernmental review of Executive Order 12372 or Health System
Agency review.