VULVODYNIA - SYSTEMATIC EPIDEMIOLOGIC, ETIOLOGIC OR THERAPEUTIC STUDIES

RELEASE DATE:  March 27, 2002 

PA NUMBER: PA-02-090 (This PA has been reissued, see PA-06-302) 

EXPIRATION DATE:  March 1, 2005, unless reissued.

National Institute of Child Health and Human Development (NICHD)
 (http://www.nichd.nih.gov) 
Office of Research on Women's Health (ORWH) 
 (http://www4.od.nih.gov/orwh/)

THIS PA CONTAINS THE FOLLOWING INFORMATION

o Purpose of the PA
o Research Objectives
o Mechanism of Support 
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations

PURPOSE

This PA replaces PA-98-112.

The Center for Population Research (CPR) of the National Institute of Child 
Health and Human Development (NICHD) invites new and experienced basic 
scientists, epidemiologists, and clinical investigators to submit research 
grant applications to further our understanding of the epidemiology, 
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.  

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.  This announcement was followed by another initiative, 
Pathophysiology, Epidemiology and Treatment of Vulvodynia (RFA-HD-00-008) in 
February 2000.  It was anticipated that studies in this under-researched 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, subsequent PA, and RFA, 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 PA represents a continuation 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 
research agenda 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 announcement 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 chronicity and inclusion/exclusion criteria for refining 
the definition for and diagnosis of vulvodynia and its subtypes.  Rigorous 
definitions will permit uniform study designs leading to comparability at the 
national and international levels. 

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 clinical trials of novel therapeutic 
interventions. 

o  Assessment of the natural history of vulvodynia.  Creation and validation 
of 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  Initiation and implementation of controlled clinical epidemiological 
studies to determine if at-risk groups can be identified for prospective or 
interventional studies.

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  Initiation and implementation of well-controlled multidisciplinary 
clinical trials of therapeutic protocols for treating vulvodynia in a well-
defined population. 

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 WHERE TO SEND INQUIRIES, below.

MECHANISM OF SUPPORT

This PA will use the NIH Research Project Grant (RO1) award mechanism.  As an 
applicant, you will be solely responsible for planning, directing, and 
executing the proposed project.  

This PA uses just-in-time concepts.  It also uses the modular as well as the 
non-modular budgeting formats (see 
http://grants.nih.gov/grants/funding/modular/modular.htm).  Specifically, if 
you are submitting an application with direct costs in each year of $250,000 
or less, use the modular format.  Otherwise, follow the instructions for non-
modular research grant applications.

ELIGIBLE INSTITUTIONS

You may submit an application if your institution has any of the following 
characteristics: 

o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, hospitals, 
and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic or foreign

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with their institution to 
develop an application for support.  Individuals from underrepresented racial 
and ethnic groups as well as individuals with disabilities are always 
encouraged to apply for NIH programs.

WHERE TO SEND INQUIRIES

We encourage your inquiries concerning this PA and welcome the opportunity to 
answer questions from potential applicants.  Inquiries may fall into two 
areas:  scientific/research and financial or grants management issues:

o Direct your questions about scientific/research 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
Email:  ep61h@nih.gov

o Direct your questions about financial or grants management matters to:

Ms. Kathy Hancock
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A17, MSC 7510 
Bethesda, MD  20892-7510
Telephone:  (301) 496-5482
FAX:  (301) 402-0915
Email:  kathy.hancock@nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  The PHS 398 is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 435-0714, 
Email: GrantsInfo@nih.gov.

APPLICATION RECEIPT DATES:  Applications submitted in response to this 
program announcement will be accepted at the standard application deadlines, 
which are available at http://grants.nih.gov/grants/dates.htm.  Application 
deadlines are also indicated in the PHS 398 application kit.

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS:  Applications 
requesting up to $250,000 per year in direct costs must be submitted in a 
modular grant format.  The modular grant format simplifies the preparation of 
the budget in these applications by limiting the level of budgetary detail.  
Applicants request direct costs in $25,000 modules.  Section C of the 
research grant application instructions for the PHS 398 (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step 
guidance for preparing modular grants.  Additional information on modular 
grants is available at 
http://grants.nih.gov/grants/funding/modular/modular.htm.

SPECIFIC INSTRUCTIONS FOR APPLICATIONS REQUESTING $500,000 OR MORE PER YEAR:  
Applications requesting $500,000 or more in direct costs for any year must 
include a cover letter identifying the NIH staff member within one of NIH 
institutes or centers who has agreed to accept assignment of the application.   

Applicants requesting more than $500,000 must carry out the following steps:
	
1) Contact the IC program staff at least six weeks before submitting the 
application, i.e., as you are developing plans for the study; 

2) Obtain agreement from the IC staff that the IC will accept your 
application for consideration for award; and,
  
3) Identify, in a cover letter sent with the application, the staff member 
and IC who agreed to accept assignment of the application.  

This policy applies to all investigator-initiated new (type 1), competing 
continuation (type 2), competing supplement, or any amended or revised 
version of these grant application types.  Additional information on this 
policy is available in the NIH Guide for Grants and Contracts, October 19, 
2001 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html. 

SENDING AN APPLICATION TO THE NIH:  Submit a signed, typewritten original of 
the application, including the checklist, and five 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)

APPLICATION PROCESSING:  Applications must be mailed on or before the receipt 
dates described at 
http://grants.nih.gov/grants/funding/submissionschedule.htm.  

The CSR will not accept any application in response to this PA 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 a substantial revision of an application 
already reviewed, but such application must include an Introduction 
addressing the previous critique.

PEER REVIEW PROCESS

Applications submitted for this PA will be assigned on the basis of 
established PHS referral guidelines.  An appropriate scientific review group 
convened in accordance with the standard NIH peer review procedures 
(http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific 
and technical merit.  

As part of the initial merit review, all applications will:

o Receive a written critique
o Undergo a selection process in which only those applications deemed to have 
the highest scientific merit, generally the top half of applications under 
review, will be discussed and assigned a priority score
o 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.  In 
the written comments, reviewers will be asked to discuss the following 
aspects of your application in order to judge the likelihood that the 
proposed research will have a substantial impact on the pursuit of these 
goals: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
  
The scientific review group will address and consider each of these criteria 
in assigning your application's overall score, weighting them as appropriate 
for each application.  Your 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, you 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 your study address an important problem? If the aims 
of your application are achieved, how do they advance scientific knowledge?  
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?  Do you acknowledge potential problem areas and consider alternative 
tactics?

(3) INNOVATION:  Does your project employ novel concepts, approaches or 
methods? Are the aims original and innovative?  Does your project challenge 
existing paradigms or develop new methodologies or technologies?

(4) INVESTIGATOR: Are you appropriately trained and well suited to carry out 
this work?  Is the work proposed appropriate to your experience level as the 
principal investigator and to that of other researchers (if any)?

(5) ENVIRONMENT:  Does the scientific environment in which your 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?

ADDITIONAL REVIEW CRITERIA:  In addition to the above criteria, your 
application will also be reviewed with respect to the following:

PROTECTIONS:  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.

INCLUSION:  The adequacy of plans to include subjects from both genders, as 
appropriate, all racial and ethnic groups (and subgroups), and children as 
appropriate for the scientific goals of the research.  Plans for the 
recruitment and retention of subjects will also be evaluated. (See Inclusion 
Criteria included in the section on Federal Citations, below)

DATA SHARING:  The adequacy of the proposed plan to share data, if 
appropriate.
 
BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.

AWARD CRITERIA

Applications submitted in response to a PA will compete for available funds 
with all other recommended applications.  The following will be considered in 
making funding decisions:  

o Scientific merit of the proposed project as determined by peer review
o Availability of funds 
o Relevance to program priorities

REQUIRED FEDERAL CITATIONS 

MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD:  Research components 
involving Phase I and II clinical trials must include provisions for 
assessment of patient eligibility and status, rigorous data management, 
quality assurance, and auditing procedures.  In addition, it is NIH policy 
that all clinical trials require data and safety monitoring, with the method 
and degree of monitoring being commensurate with the risks (NIH Policy for 
Data Safety and Monitoring, NIH Guide for Grants and Contracts, June 12, 
1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH:  It is the policy of 
the NIH that women and members of minority groups and their sub-populations 
must be included in all NIH-supported clinical research projects unless a 
clear and compelling justification is provided indicating 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 clinical research should read the AMENDMENT "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research - Amended, October, 2001," published in the NIH Guide for Grants and 
Contracts on October 9, 2001 (http://grants.nih.gov/grants/guide/notice-
files/NOT-OD-02-001.html); a complete copy of the updated Guidelines are 
available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.  
The amended policy incorporates:  the use of an NIH definition of 
clinical research; updated racial and ethnic categories in compliance with 
the new OMB standards; clarification of language governing NIH-defined Phase 
III clinical trials consistent with the new PHS Form 398; and updated roles 
and responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) 
all applications or proposals and/or protocols must provide a description of 
plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable; 
and b) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS:  
The NIH maintains a policy 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 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 is available at 
http://grants.nih.gov/grants/funding/children/children.htm.

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS:  NIH 
policy requires education on the protection of human subject participants for 
all investigators submitting NIH proposals for research involving human 
subjects.  You will find this policy announcement in the NIH Guide for Grants 
and Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

HUMAN EMBRYONIC STEM CELLS (hESC):  Criteria for federal funding of research 
on hESCs can be found at http://grants.nih.gov/grants/stem_cells.htm and at  
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).  
It is the responsibility of the applicant to provide the official NIH 
identifier(s)for the hESC line(s)to be used in the proposed research.  
Applications that do not provide this information will be returned without 
review. 

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT:  The 
Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) 
cited publicly and officially by a Federal agency in support of an action 
that has the force and effect of law (i.e., a regulation) may be accessed 
through FOIA.  It is important for applicants to understand the basic scope 
of this amendment.  NIH has provided guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application. In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES:  All applications and proposals 
for NIH funding must be self-contained within specified page limitations. 
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) 
should not be used to provide information necessary to the review because 
reviewers are under no obligation to view the Internet sites.  Furthermore, 
we caution reviewers that their anonymity may be compromised when they 
directly access an Internet site.

HEALTHY PEOPLE 2010:  The Public Health Service (PHS) is committed to 
achieving the health promotion and disease prevention objectives of "Healthy 
People 2010," a PHS-led national activity for setting priority areas. This PA 
is related to one or more of the priority areas. Potential applicants may 
obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

AUTHORITY AND REGULATIONS:  This program is described in the Catalog of 
Federal Domestic Assistance No. 93.864, and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.  Awards are made under authorization of Sections 301 
and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and 
administered under NIH grants policies described at 
http://grants.nih.gov/grants/policy/policy.htm and under Federal Regulations 
42 CFR 52 and 45 CFR Parts 74 and 92. 

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the 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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