PATHOPHYSIOLOGY, EPIDEMIOLOGY AND TREATMENT OF VULVODYNIA 

Release Date:  February 7, 2000

RFA:  HD-00-008

National Institute of Child Health and Human Development 
Office of Research on Women’s Health 

Letter of Intent Receipt Date:  March 15, 2000
Application Receipt Date:  May 5, 2000

THIS RFA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS.  IT INCLUDES 
DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED 
WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS RFA.

PURPOSE

The Center for Population Research (CPR) of the National Institute of Child 
Health and Human Development (NICHD) and the NIH Office of Research on 
Women’s Health (ORWH) invite new and experienced basic scientists, 
epidemiologists, and clinical investigators to submit research grant 
applications to further our understanding of the etiology, prevalence, 
criteria for accurate diagnosis, underlying pathophysiology and pain 
mechanisms, and treatment strategies for vulvodynia.  Research grant 
applications are encouraged that address preclinical or clinical, biomedical 
and/or behavioral research that concentrates on studies of relevance to 
vulvodynia.  This solicitation is intended to stimulate and strengthen a 
multidisciplinary approach to this complex, underresearched area of women’s 
health and form a framework for assessing future research needs.  The goal is 
to build a substantive scientific knowledge base related to this debilitating 
condition.  This initiative continues and expands the scientific objectives 
represented in PA-98-112, “Vulvodynia – Systematic Epidemiologic, Etiologic 
or Therapeutic Studies,” and is responsive to the FY 2000 House and Senate 
Appropriations Report Language directives recommending that NICHD expand and 
intensify vulvodynia research.

HEALTHY PEOPLE 2010

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), Pathophysiology, Epidemiology and Treatment of 
Vulvodynia, is related to one or more of the priority areas.  Potential 
applicants may obtain  "Healthy People 2010" at 
http://odphp.osophs.dhhs.gov/pubs/hp2000.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign 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.  Racial/ethnic minority individuals, 
women, and persons with disabilities are encouraged to apply as Principal 
Investigators.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) research project 
grant (R01) award mechanism.  Responsibility for the planning, direction, and 
execution of the proposed project will be solely that of the applicant.  This 
RFA is a one-time solicitation.  Future unsolicited competing continuation 
applications will compete with all investigator-initiated applications and be 
reviewed according to the customary peer review procedures.  The anticipated 
award date is September 29, 2000.

Specific application instructions have been modified to reflect "MODULAR 
GRANT" and "JUST-IN-TIME" streamlining efforts being examined by the NIH. 
Complete and detailed instructions and information on Modular Grant 
applications can be found at 
http://grants.nih.gov/grants/funding/modular/modular.htm

For this RFA, funds must be requested in $25,000 direct cost modules, up to a 
total direct cost of $200,000 per year.

FUNDS AVAILABLE

The NICHD and ORWH intend to commit approximately $1 million in total costs 
(direct plus Facilities and Administrative [F & A] costs) in FY 2000 to fund 
four to six new grants in response to this RFA.  An applicant may request a 
project period of up to five years and a budget for direct costs of up to 
$200,000 per year, including F & A costs on consortium arrangements.  Because 
the nature and scope of the research proposed may vary, it is anticipated 
that the size of awards also will vary.  Although the financial plans of the 
NICHD and ORWH provide support for this program, awards pursuant to this RFA 
are contingent upon the availability of funds and the receipt of a sufficient 
number of meritorious applications.  

RESEARCH OBJECTIVES

Background

Vulvodynia is one of the poorly understood complex focal pain syndromes, 
representing a complex, multifactorial clinical syndrome of unexplained 
vulvar pain, sexual dysfunction, and psychological disturbance.  On April 2-
3, 1997, the NICHD, in collaboration with the Office of Research on Women’s 
Health, Office of Rare Diseases, and the National Institute of Arthritis, 
Musculoskeletal and Skin Diseases, convened the “Vulvodynia Workshop:  
Current Knowledge and Future Directions” to explore the state-of-the-science 
by reviewing current definitions, etiology, epidemiology, and treatment 
modalities.  In response to recommendations made at the conclusion of this 
workshop, emphasis was placed on stimulating clinically relevant research on 
promising biomedical, clinical or behavioral studies that would expand our 
knowledge of vulvodynia.  The Program Announcement (PA-98-112), “Vulvodynia – 
Systematic Epidemiologic, Etiologic or Therapeutic Studies,” was published on 
September 29, 1998.  It was anticipated that studies in this underresearched 
area would form a foundation for assessing future research needs and 
complement our overall commitment to support research important to women’s 
health.  As a result of the workshop and subsequent PA, the research 
community was made aware of our interest in this area.  Notwithstanding this 
programmatic emphasis, additional efforts are now needed to strengthen the 
science base.  This RFA represents an expansion of ongoing research efforts 
to reduce the burden of this disease and ultimately improve the quality of 
life for women affected with this disorder.  Moreover, this initiative 
reflects the NICHD and ORWH research agendas for identifying and 
characterizing the pathophysiologic factors, and potential avenues for 
treatment related to benign gynecologic disorders.

Vulvodynia is a clinical condition with several different and poorly defined 
antecedents.  There is a need to increase knowledge and understanding about 
vulvodynia and the biological processes that lead to its development and 
long-term sequelae.  The factors influencing a patient’s decision to seek 
care and the criteria by which the clinician selects therapy are not uniform.  
Patients frequently experience dyspareunia, persistent vulvar irritation, 
burning and pain.  Symptoms also may be associated with the urinary and 
gastrointestinal tracts.  In addition, diagnostic criteria that define the 
categories and subtypes of vulvodynia are neither well defined nor utilized 
consistently by many clinicians.  While the true prevalence of vulvodynia 
remains unknown, there are several common diagnostic subtypes that are 
recognized, including (1) vulvar vestibulitis, (2) dysesthetic vulvodynia, 
and (3) vulvar dermatosis and dermatitis.  Vulvar vestibulitis, thought to be 
the most common subtype, has been found in 15 percent of patients in a 
general clinical practice in some studies.  While histologic studies suggest 
a chronic inflammatory reaction, the causes of the inflammation as well as 
its significance remain unclear.  The role of pelvic floor dysfunction as a 
catalyst for the development of vulvar pain syndromes, particularly 
dysesthethic vulvodynia, has been proposed in several published studies, but 
its true impact is uncertain.  Published studies also comment on the 
influence of neurophysiological parameters as a potential association that 
should be taken into account. 

Surgery has been reported to be a successful intervention for selected cases 
of vulvar vestibulitis, and is reserved for women with severe and long-
standing symptoms.  However, optimum surgical management is still 
undetermined and very few well-designed, long-term studies document the 
outcome of surgical procedures.  In addition, pharmacological and behavioral 
therapies would benefit from treatment standardization and prospective 
clinical studies. 

Despite the use of surgery, pharmaceutical regimens, psychological support, 
physical therapy, and pain management techniques, such as biofeedback and 
behavior modification, there is no consensus on which procedure(s) offers the 
most improvement and patient satisfaction.  A combination of therapies is 
frequently utilized and, while there are several options available for the 
treatment of vulvodynia, most of the literature supports the conclusion that 
cures for vulvodynia are uncommon and a specific inciting cause can be 
diagnosed in a relatively small percentage of patients.  Consideration of 
these factors must be an integral part of the management of patients with 
vulvodynia and this underscores the need to examine this condition in a 
multidisciplinary context.  

This elusive pain syndrome has many unexplored questions.  Therefore, an 
overall strategy of augmenting and strengthening a multidisciplinary approach 
to this distressing condition, leading to improved diagnosis and therapy, is 
warranted.  Improvements in pain management, as well as approaches to the 
treatment and prevention of vulvodynia will require insight and increased 
knowledge of the underlying etiology and pathophysiological mechanisms. 

Research Scope 

Several research strategies are deemed important for the potential 
development of new leads or approaches.  Examples of the scope of research 
areas considered responsive to this RFA include, but are not limited to, the 
following:

o  Elucidation of pathogenic antecedents involved in stimulating the 
biological processes that lead to the development and long-term sequelae of 
vulvodynia.  Evaluation of the role of pathologic vaginal microbial and viral 
agents or altered vagina flora in this process. 

o  Development of novel experimental preclinical or clinical studies in 
animal models and/or humans to evaluate normal and dysfunctional 
neurophysiological parameters and mechanisms.  Determination of the role of 
neurogenic irritability and/or regional autonomic dysfunction and its 
influence on symptoms, muscle instability, tissue injury, and repair in 
vulvodynia. 

o  Documentation of the use and evaluation of the effects of adjunctive 
therapy in clinical trials, including behavioral, surgical, and medical 
treatment, in women with vulvodynia.  Investigation and translation of 
promising, innovative, preclinical findings into clinical research 
applications, including designing small clinical trials of novel therapeutic 
interventions. 

o  Assessment of the natural history of vulvodynia.  Creation and validation 
of small population-based epidemiological studies that assist in defining the 
prevalence and resolution of vulvodynia and its subtypes.  Feasibility and 
effectiveness of risk factor modification for prevention of vulvodynia.

o  Assessment of normal tissue structure, muscle integrity, cellular 
mechanisms, structural defects, and the factors involved in the transition 
between latent injury, symptoms, and tissue rehabilitation in vulvodynia.  
Detection of the role of nerve damage, muscular damage, and/or direct tissue 
disruption.

o  Determination of the influence of risk factors such as race, ethnicity, 
and co-morbid medical conditions or previous surgery associated with the 
occurrence of vulvodynia, treatment outcomes, and complications.

Prospective applicants are encouraged to consider relevant topics other than 
those listed here and to discuss their ideas with the program staff listed 
under INQUIRIES.

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 are 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,” published in the Federal Register of March 28, 1994 (FR 59 14508-
14513) and in the NIH Guide for Grants and Contracts, Vol. 23, No. 11, March 
18, 1994, and available at: 
http://grants.nih.gov/grants/guide/notice-files/not94-100.html.
 
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 subject research, conducted or supported by the 
NIH, unless there are 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,” published in the NIH Guide for Grants and 
Contracts, March 6, 1998, and available at: 
http://grants.nih.gov/grants/guide/notice-files/not98-024.html.

Investigators also may obtain copies of these policies 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 a letter of intent that includes a 
descriptive title of the proposed research, the name, address, and telephone 
number of the Principal Investigator, the identities of other key personnel 
and participating institutions, and the number and title of this RFA.  
Although a letter of intent is not required, is not binding, and does not 
enter into the review of a subsequent application, the information that it 
contains allows NICHD staff to estimate the potential review workload and 
avoid conflict of interest in the review.

The letter of intent is to be sent to Dr. Estella Parrott, by March 15, 2000, 
at the address listed under INQUIRIES.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) is to be used in 
applying for these grants.  These forms are available at most institutional 
offices of sponsored research, on the Internet at 
http://grants.nih.gov/grants/funding/phs398/phs398.html, and from the 
Division of Extramural Outreach and Information Resources, National 
Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-
7910, telephone 301-435-0714, E-mail: Grantsinfo@nih.gov.

Application Instructions

The modular grant concept establishes specific modules in which direct costs 
may be requested as well as a maximum level for requested budgets. Only 
limited budgetary information is required under this approach.  The 
just-in-time concept allows applicants to submit certain information only 
when there is a possibility for an award. It is anticipated that these 
changes will reduce the administrative burden for the applicants, reviewers 
and Institute staff.  The research grant application form PHS 398 (rev. 4/98) 
is to be used in applying for  these grants, with the modifications noted 
below.

Modular Grant applications in response to this RFA will request direct costs 
in $25,000 modules, up to a total direct cost request of $200,000 per year.  
The total direct costs must be requested in accordance with the program 
guidelines and the modifications made to the standard PHS 398 application 
instructions described below:

o FACE PAGE: Items 7a and 7b should be completed, indicating Direct Costs (in 
$25,000 increments up to a maximum of $200,000) and Total Costs [Modular 
Total Direct plus Facilities and Administrative (F&A) costs] for the initial 
budget period.  Items 8a and 8b should be completed indicating the Direct and 
Total Costs for the entire proposed period of support.

o DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD:  Do not complete Form Page 4 
of the PHS 398.  It is not required and will not be accepted with the 
application.

o BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT:  Do not complete the 
categorical budget table on Form Page 5 of the PHS 398.  It is not required 
and will not be accepted with the application.

o NARRATIVE BUDGET JUSTIFICATION:  Prepare a Modular Grant Budget Narrative 
page. (See http://grants.nih.gov/grants/funding/modular/modular.htm for 
sample pages.) At the top of the page, enter the total direct costs requested 
for each year.  This is not a Form Page.

Under Personnel, list key project personnel, including their names, percent 
of effort, and roles on the project. No individual salary information should 
be provided. However, the applicant should use the NIH appropriation language 
salary cap and the NIH policy for graduate student compensation in developing 
the budget request.

For Consortium/Contractual costs, provide an estimate of total costs (direct 
plus facilities and administrative) for each year, each rounded to the 
nearest $1,000.  List the individuals/organizations with whom consortium or 
contractual arrangements have been made, the percent effort of key personnel, 
and the role on the project.  Indicate whether the collaborating institution 
is foreign or domestic.  The total cost for a consortium/contractual 
arrangement is included in the overall requested modular direct cost amount.  
Include the Letter of Intent to establish a consortium.

Provide an additional narrative budget justification for any variation in the 
number of modules requested.

o BIOGRAPHICAL SKETCH:  The Biographical Sketch provides information used by 
reviewers in the assessment of each individual's qualifications for a 
specific role in the proposed project, as well as to evaluate the overall 
qualifications of the research team.  A biographical sketch is required for 
all key personnel, following the instructions below.  No more than three 
pages may be used for each person.  A sample biographical sketch may be 
	viewed at:  http://grants.nih.gov/grants/funding/modular/modular.htm. 

- Complete the educational block at the top of the form page;
- List position(s) and any honors;
- Provide information, including overall goals and responsibilities, on 
research projects ongoing or completed during the last three years;
- List selected peer-reviewed publications, with full citations.

o CHECKLIST:  This page should be completed and submitted with the 
application.  If the F&A rate agreement has been established, indicate the 
type of agreement and the date.  All appropriate exclusions must be applied  
in the calculation of the F&A costs for the initial budget period and all 
future budget years.

o The applicant should provide the name and phone number of the individual to 
contact concerning fiscal and administrative issues if additional information 
is necessary following the initial review. 

Submission Instructions

The RFA label available in the PHS 398 (rev. 4/98) application form must be 
stapled to the bottom of the face page of the application and must display 
the RFA number HD-00-008. A sample RFA label is available at 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.   Please note this 
is in the pdf format.  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 2 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 photocopies, in one package 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)
At the time of submission, two additional copies of the application should be 
sent to:

Director
Division of Scientific Review 
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 5E03, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service)

Applications must be received by May 5, 2000.  If an application is received 
after that date, it will be returned to the applicant without review.

The Center for Scientific Review (CSR) 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 
CSR will not accept any application that is essentially the same as one 
already 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.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the CSR and 
for responsiveness to the RFA by NICHD and ORWH.  Incomplete and/or non-
responsive applications will be returned to the applicant without further 
consideration.  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 NICHD in accordance with the review criteria stated below.  
As part of the initial merit review, all applications will receive a written 
critique and may undergo a process in which only those applications deemed to 
have the highest scientific merit will be discussed, assigned a priority 
score, and receive a second level review by the National Advisory Child 
Health and Human Development Council.

Review Criteria

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to discuss the following 
aspects of the application 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 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 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?

In addition to the above criteria, in accordance with NIH policy, all 
applications also will be reviewed with respect to the following:

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

o  The reasonableness of the proposed budget and duration in relation to the 
proposed research

o  The adequacy of the proposed protection for humans, animals or the 
environment, to the extent they may be adversely affected by the project  
proposed in the application.

SCHEDULE

Letter of Intent Receipt Date:    March 15, 2000
Application Receipt Date:         May 5, 2000
Peer Review Date:                 June 2000
Council Review:                   September 2000
Earliest Anticipated Start Date:  September 29, 2000

AWARD CRITERIA

Criteria that will be used to make award decisions include:

o  scientific merit (as determined by peer review)
o  availability of funds
o  programmatic priorities.

INQUIRIES

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:

Estella Parrott, M.D., M.P.H.
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
E-mail:  ep61h@nih.gov

Direct inquiries regarding fiscal matters to:

Michael J. Loewe
Lead Grants Management Specialist
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A17J, MSC 7510 
Bethesda, MD  20892-7510
Telephone: (301) 435-7008
FAX:  (301) 402-0915
E-mail:  ml70m@nih.gov    

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.864.  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 NIH grants policies and Federal 
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.  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 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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