VULVODYNIA - SYSTEMATIC EPIDEMIOLOGIC, ETIOLOGIC OR THERAPEUTIC STUDIES

Release Date:  September 29, 1998

PA NUMBER:  PA-98-112 (see replacement PA-02-090)

P.T.

National Institute of Child Health and Human Development

PURPOSE

The Center for Population Research of the National Institute of Child Health
and Human Development (NICHD) invites research grant applications from
institutions interested in performing clinically relevant research on
promising biomedical or behavioral research that will expand our knowledge of
vulvodynia in the human. The purpose of this Program Announcement (PA) is to
increase research efforts designed to establish the prevalence, criteria for
accurate diagnosis, underlying pathophysiologic mechanisms,and effective
therapeutic interventions for vulvodynia in the human. The studies proposed in
applications responding to this PA may address preclinical or clinical
biomedical and/or behavioral research approaches focused, as appropriate, on
systematic epidemiologic, etiologic, diagnostic or therapeutic studies of
relevance to human vulvodynia.

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 PA, Vulvodynia: Systematic
Epidemiologic, Etiologic or Therapeutic Studies, is related to the priority
area of family planning. Potential applicants may obtain a copy of "Healthy
People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock
No.017-001-00473-1) through the Superintendent of   Documents, Government
Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by foreign and domestic, for-profit and non-
profit organizations, public and private, such as universities, colleges,
hospitals, laboratories, units of State and local governments, and eligible
agencies of the Federal government.  Applications may be from a single
institution or may include arrangements with one or more institutions (e.g.,
subcontracted subproject components)if appropriate. Racial/ethnic minority
individuals, women, and persons with disabilities are encouraged to apply as
principal investigators.

MECHANISM OF SUPPORT

Support of this program will be through the National Institutes of Health
(NIH) research project grant (R01) mechanism. Applicants will be responsible
for the planning, direction, and execution of the proposed project.  All PHS
and NIH grants policies will apply to applications received and awards made in
response to this PA. Grants made for the support of research projects
responsive to this PA may be renewable in accord with relevant NIH and PHS
policies and guidelines. Competitive continuation of projects developed under
this program will be through the R01 research grant mechanism. Applications
for the R01 grant mechanism may not request more than five years of support.
Awarded applications will be administered under PHS grants policy as stated in
the Public Health Service Grants Policy Statement, PHS Publication No. (OASH)
94-50.000 (Rev. April 1,1994).

RESEARCH OBJECTIVES

Background

Although a number of focal pain syndromes of the urogenital area have been
well described, they remain underrecognized and poorly understood. 
Vulvodynia, one of the types of focal pain syndromes in the female, is a
complex, multifactorial, underdiagnosed clinical syndrome of unexplained
vulvar pain, sexual dysfunction and psychological disability.  An earlier
controversy surrounding this group of disorders ranged from opinions
questioning their existence to suggestions that they were of a purely
psychosomatic origin. More recently, this has been largely counterbalanced by
an extensive recent literature attesting to the organic nature of these
disorders.  At present, neither the prevalence nor the etiology of this
enigmatic condition is accurately known.  A specific secondary cause can
usually be diagnosed in only a small minority of the patients experiencing the
symptoms of vulvodynia. Only empirical treatment options are available at
present.  While cures are uncommon, some measure of pain relief can be
achieved in nearly all patients using a multidisciplinary approach involving
pain medications, local treatment regimens, physical therapy and psychological
support.  Medical management usually employs medication protocols designed to
treat neuropathic pain and has been under-investigated to date.  Pain
management techniques such as biofeedback and behavior therapy have been
reported in some instances to provide positive outcomes.  Surgery involving
invasive and often irreversible therapeutic procedures has been stated,
arguably, to be the treatment option with the highest success rate for certain
subtypes of vulvodynia.

Vulvar pain syndrome (vulvodynia, burning vulvar syndrome) was first described
as a syndrome at the end of the last century.  Although more than a hundred
years have passed in the interim, the cause(s) of the disorder remain(s)
undiscovered.  Several subtypes of vulvodynia have, however, now been
recognized and identification of the distinct subset of patients presenting
with vulvodynia has been stated to be a prerequisite for its successful
management.  The most common subtypes recognized are vulvar vestibulitis
syndrome, cyclic vulvovaginitis,and dysesthetic vulvodynia.  Vulvar
vestibulitis, thought to be the major subtype of vulvodynia, has been found in
some studies to be present in as many as 15% of patients in a general clinical
practice.  Vulvar vestibulitis syndrome (VVS) characterized by severe, chronic
pain on vestibular touch or attempted vaginal entry is thought to be the most
frequent cause of dyspareunia in premenopausal women.  Other frequently
misdiagnosed vulvar or vaginal conditions which can also cause vulvodynia are
vulvar papillomatosis, cytolytic vaginosis, lactobacillosis, and desquamative
inflammatory vaginitis.  In addition, many vulvar dermatoses can cause acute
or chronic vulvar itching or pain, and are a frequent confounding problem in
the differential diagnosis of vulvodynia.  While studies have been reported
that describe the histological abnormalities observed in patients with vulvar
vestibulitis as the result of a chronic inflammatory reaction of the mucosa of
the vulvar vestibule, the cause of the latter remains unclear.  Reports
proposing a clinical role of urinary oxalates as nonspecific irritants,
contact allergy, candidiasis or human papilloma virus (HPV) infection in women
presenting with vulvodynia remain without consensus and are controversial.

Scope

Systematic epidemiologic, etiologic, and therapeutic studies of vulvodynia
should be undertaken to better define its prevalence, establish diagnostic
criteria for discriminating between its major and minor subtypes, elucidate
its underlying pathophysiology, clarify its mechanism of pain and develop
improved clinical therapy options designed to either cure it or alleviate its
symptoms.

Examples of hypothesis-driven research approaches that are encouraged include,
but are not limited to:

o  Conducting experimental preclinical or clinical studies in animals and/or
humans, respectively, designed to evaluate the presence and extent of abnormal
neurophysiological mechanisms that underlie inappropriate sensory and motor
pathway activities associated with vulvar pain.

o  Determining the role of neurogenic inflammation in vulvodynia, including
vulvar vestibulitis.

o  Evaluating whether there is widespread or regional autonomic dysfunction in
patients presenting with vulvar pain.

o  Developing chronicity and inclusion/exclusion features/factors as criteria
for refining the definition for and diagnosis of vulvodynia and its subtypes.
A rigorous definition will permit uniform study design leading to
comparability at the national and/or international levels of study.

o  Carrying out population-based epidemiology studies to define the prevalence
of vulvar vestibulitis and other subtypes of vulvodynia. Conducting case
controlled epidemiological studies to determine if a group at high risk of
vulvodynia can be identified for prospective or interventional studies.
Accomplishing population-based epidemiology studies that include psychological
measures useful in defining the psycho-social component of vulvodynia.

o  Conducting well-controlled clinical studies of therapeutic protocols for
treating vulvodynia in a well-defined population with rigorous
inclusion/exclusion enrollment criteria. Studies might include multi-
disciplinary therapeutic trial designs involving medication, aerobic exercise,
and cognitive behavioral therapy. For vulvar vestibulitis only, the use of
surgical procedures for treating this disorder might be explored,  especially
with regard to both the roles of pre- and post- surgical interventions and
surgical therapy outcomes.

o  Defining the vaginal microflora in patients with vulvodynia, including the
role of past or present candidiasis, bacterial vaginosis, trichomoniasis,
gonorrhea, chlamydia, Herpes Simplex Virus (HSV) and/or Human Papilloma Virus
(HPV) colonization or infection.

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 policy results from the NIH Revitalization Act of 1993
(Section 492B of Public Law 103-43).

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 in the NIH Guide for Grants and Contracts, Volume 23,
Number 11, March 18,1994.

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.

NIH POLICY AND GUIDELINES ON THE INCLUSION OF CHILDREN AS PARTICIPANTS IN
RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age of 21)
must be included in all human subjects research, conducted or supported by the
NIH, unless there are clear and compelling scientific and ethical reasons not
to include them.  This policy applies to all initial (Type 1) applications
submitted for receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines on the Inclusion of Children as Participants in
Research Involving Human Subjects" that was published in the NIH Guide for
Grants and Contracts, March 6, 1998, and is available at the following URL
address:  http://www.nih.gov/grants/guide/notice-files/not98-024.html

APPLICATION PROCEDURES

Applications are to be submitted on the grant application form PHS 398 (rev.
5/95) and will be accepted on the standard application deadlines as indicated
in the application kit.  Application kits are available at most institutional
offices of sponsored research and may be obtained from the Division of
Extramural Outreach and Information Resources, National Institutes of Health,
6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/710-0267, Email: [email protected].

Applicants planning to submit an investigator-initiated new (type 1),
competing continuation (type 2), competing supplement, or any amended/revised
version of the preceding grant application types requesting $500,000 or more
in direct costs for any year are advised that he or she must contact the
Institute or Center (IC) program staff before submitting the application, i.e,
as plans for the study are being developed.  Furthermore, the application must
obtain agreement from the IC staff that the IC will accept the application for
consideration for award. Finally, the applicant must identify, in a cover
letter sent with the application, the staff member and Institute or Center who
agreed to accept assignment of the application.  This policy requires an
applicant to obtain agreement for acceptance of both any such application and
any such subsequent amendment.  Refer to the NIH Guide for Grants and
Contracts, March 20, 1998 at
http://www.nih.gov/grants/guide/notice-files/not98-030.html


The title and number of the program announcement must be typed in Section 2 
on the face page of the application.

The completed original application and five legible copies must be sent or
delivered to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

REVIEW CONSIDERATIONS

Applications will be assigned on the basis of established Public Health
Service referral guidelines.  Applications will be reviewed for scientific and
technical merit by study sections of the Center for Scientific Review (CSR),
in accordance with the standard NIH peer review procedures.  As part of the
initial merit review, all applications will receive a written critique and
undergo a process in which only those applications deemed to have the highest
scientific merit, generally the top half of applications under review, will be
discussed, assigned a priority score, and receive a second level review by the
appropriate national advisory council or board.

Review Criteria

The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.  The
reviewers will comment on the following aspects of the application in their
written critiques in order to judge the likelihood that the proposed research
will have a substantial impact on the pursuit of these goals.  Each of these
criteria will be addressed and considered by the reviewers in assigning the
overall score weighting them as appropriate for each application.  Note that
the application does not need to be strong in all categories to be judged
likely to have a major scientific impact and thus deserve a high priority
score.  For example, an investigator may propose to carry out important work
that by its nature is not innovative but is essential to move a field forward.

1.  Significance.  Does this study address an important problem? If the aims
of the application are achieved, how will scientific knowledge be advanced? 
What will be the effect of these studies on the concepts or methods that drive
this field?

2.  Approach.  Are the conceptual framework, design, methods, and analyses
adequately developed, well-integrated, and appropriate to the aims of the
project?  Does the applicant acknowledge potential problem areas and consider
alternative tactics?

3.  Innovation. Does the project employ novel concepts, approaches or methods? 
Are the aims original and innovative? Does the project challenge existing
paradigms or develop new methodologies or technologies?

4.  Investigator. Is the investigator appropriately trained and well suited to
carry out this work?  Is the work proposed appropriate to the experience level
of the principal investigator and other researchers (if any)?

5.  Environment. Does the scientific environment in which the work will be
done contribute to the probability of success?  Do the proposed experiments
take advantage of unique features of the scientific environment or employ
useful collaborative arrangements? Is there evidence of institutional support?

The initial review group will also examine: the appropriateness of the
proposed project budget and duration; the adequacy of plans to include (or
justifications for not including) both genders, minorities and their
subgroups, and children as appropriate for the scientific goals of the
research and plans for the recruitment and retention of subjects; the
provisions for the protection of human and animal subjects; and the safety of
the research environment.

AWARD CRITERIA

Applications will compete for available funds with all other approved
applications. The following will be considered in making funding decisions:
Quality of the proposed project as determined by peer review, availability of
funds, and program priority.

INQUIRIES

The opportunity to clarify any issues or questions from potential applicants
is welcome.

Direct inquiries regarding scientific programmatic issues to:

Louis V. De Paolo, Ph.D
Center for Population Research
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8B01 - MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-6515
FAX:  (301) 496-0962
Email:  [email protected]

Direct inquiries regarding fiscal matters to:

Ms. Melinda Nelson
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8B17 - MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-5481
FAX:  (301) 402-0915
Email:  [email protected]

AUTHORITY AND REGULATIONS

This Program is described in the Catalog of Federal Domestic Assistance No.
93.864, Population Research.  Awards are made under authorization 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 52 and 45 CFR Part 74. This program is
not subject to the intergovernmental review requirements of Executive Order
12372 or Health Systems Agency review.

The PHS strongly encourages all grant and contract recipients to provide a
smoke-free workplace and promote the non-use of all tobacco products.  In
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking
in certain facilities (or in some cases, any portion of a facility) in which
regular or routine education, library, day care, health care or early
childhood development services are provided to children.  This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.

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