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The Office of Women's Health Scientific Research Program
Introduction
Regulating products that impact the health of women is an integral part of the Food and Drug Administration's (FDA) overall mission to ensure that food is safe and wholesome and those medical products are safe and effective. FDA's Office of Women's Health (OWH) was established in 1994 to provide leadership and policy direction for the agency regarding issues of women's health, to coordinate efforts to establish and advance a women's health agenda for the agency and to serve as the agency's liaison with other agencies, industry and professional associations with regard to the health of women. To help fulfill this mandate and promote women's health throughout the agency, in 1994, OWH established an intramural scientific research program to 1) address gaps in current knowledge, 2) encourage new directions, and 3) set new standards of excellence in women's health. OWH resources are used to stimulate and support quality projects aimed at protecting and improving the agency's policies and decisions on women's health issues. OWH funded projects display rigorous thought, are well focused, can accomplish meaningful results in the allotted time, and have scientific and regulatory merit.
The program has completed its seventh year of funding. It has funded over 90
research projects and spent about 8.5 million dollars on women's health related
projects from all parts of the agency. OWH has funded projects over a wide range
of traditional women's health topics including contraceptives, estrogens, pregnancy,
developmental and reproductive toxicology, gynecological and breast cancer,
breast implants, cosmetics. In addition to ensuring the safety and effectiveness
of products used primarily or exclusively by women, the agency assures the safety
and effectiveness of products used to treat diseases and conditions that affect
women differently from men. Thus, in addition to funding projects that address
traditional issues in women health, the program has sought out and funded projects
in areas that are not traditionally viewed as women's health. For example, OWH
has funded projects investigating questions on autoimmune disease, cardiovascular
disease, post marketing surveillance, and gender differences in adverse reactions
to medical products. OWH has also funded projects aimed at assessing and preventing
inequality or inadvertent gender bias in determining the safety and efficacy
of products used for both men and women.
OWH monitors the success of the research program by tracking objective measures of success including the completion rate, the number of papers published, and if the project has lead to additional research or other outcomes. To date, the completion rate is 64%. The results of OWH funded research have been published in 40 papers in peer-review journals. An additional 21 papers have been submitted to peer reviewed journals. OWH funded projects have also lead to further research projects. Animal models developed with OWH fund have been used for other research and regulatory projects. Also, OWH monitors the impact of OWH funded projects on regulatory decision-making including guidance documents issued, label changes and standard development.
Competitive Funding Process 2000
The program utilizes a competitive peer review process to select the highest quality projects with an emphasis on projects that significantly contribute to FDA's actions on women's health. Briefly, the process for selecting research projects for funding in FY 2000 is as follows:
- Determination of priority topics - During August and September, OWH worked with the OWH Research Program Center Coordinators and Center management to identify and prioritize topics of mutual interest for scientific research in FY 2000.
- Announcement - On October 1 1999, OWH sent to a letter to the Center OWH Research Coordinator announcing the anticipated availability of FY 2000 funds for scientific research and the priority research topics for FY 2000. (Table 1: Priority Research Topics). The announcement requested that 1-2 page concept papers related to priority topic areas be forwarded to OWH through Center management and the OWH Coordinator.
- Review of concept papers - On October 20, 1999, concept papers were forwarded to OWH from the Center coordinators. OWH received 58 concept papers on a broad range of topics. The wide range of topics reflected the breath of women's health issues before the agency and need to conduct bridging research in a wide number of areas to improve regulatory decision-making.
- Selection of concept papers - Between October 21 and November 21, 1999, OWH met with the Center OWH Coordinators and managers to rate and rank the concept papers. During internal meetings, OWH decided to aim for a 50-60% funding rate across all Centers. Based on the anticipated budget, OWH selected 22 concept papers for development into full proposals. When requested, representatives from OWH would meet with or speak to or Centers to aid in proposal development. On November 22, OWH informed the Center, OWH Coordinators of the concept papers that were chosen for development in research proposals (Table 2: Concept Papers Selected for Proposal Development).
- Proposal Development - Between November 22 and January 5, principal investigators (PIs) developed their proposals. When requested, representatives from OWH met with Centers to aid in proposal development. Concurrently, OWH identified internal and external reviewers for each proposal.
- Proposal Review - On January 5, 2000, twenty-two research proposals, approved by Center management, were submitted to OWH through the Center Coordinators. Internal and external reviewers provided written evaluations of select proposals. Each proposal was reviewed by at least two internal reviewers to ensure that the research was relevant to FDA's regulatory mission. Each proposal was also reviewed by at least two external reviewers to ensure that the research was up to current standards. In addition, OWH staff reviewed all proposals. OWH used the internal/external evaluations for guidance in selecting proposals to be funded.
- Awarding Grants - In March, 2000, OWH selected 9 research projects for funding based upon the comments of the reviewers and the internal deliberations of OWH staff. OWH provided Principle Investigators (PI) and Center management with announcements of grant awards. Transfer of funds followed OWH's receipt of a signed Letter of Agreement (Table 3: OWH Funded Projects for FY 2000). A brief summary of each of these projects is included in the Abstracts Section.
- Grantee Orientation - On May 4, representatives from OWH met with this year's OWH grants awardees to congratulate the recipients, review expectations and discuss common research interests.
- Project Tracking - Project progress is tracked throughout the life of the project. Periodic phone calls from OWH Project Officers to PIs are made to assess progress and/or resolve problems. Two interim written progress reports are required from PIs for every year of funding. OWH Project Officers review these reports and comments are sent to PIs for clarification. Site visits are conducted by OWH on an as needed annual basis. A final report is due 6 months after the completion of the project. Principle investigators are asked to provide OWH with copies of any outcome document (such as manuscripts (draft and final), abstracts, posters, guidance documents, labeling, presentations, etc) which were created as a result of OWH funding. In addition, OWH is now requesting that investigators inform the office of any other projects or initiatives that were undertaken as a result of OWH funding.
- Project Completion - OWH reviews and approves the final report. Once approved,
the investigator is informed the project is closed.
Monitoring of On-Going Research Projects
At six-month intervals throughout the project, PI's are required to submit
a progress report to OWH. The progress report summarizes the accomplishments
since project initiation or since the last progress report. PI's are required
to describe problems encountered as well as the solution or recommendation
for solutions that have been implemented. If the project is not proceeding
as originally projected, the PI's must supply a revised timeline. In addition,
the PI's are requested to submit any completed publications or presentations
as well as note any anticipated activities related to the project. OWH reviews
the progress reports and sends a response to the PI noting that the progress
report is acceptable or requesting additional information.
In November 1999, OWH received 21 progress reports for ongoing projects and
2 final reports. OWH review of these reports noted that several of the projects
were presented at scientific meeting and 13 abstracts of these presentations
were provided. There were 17 papers published or prepared for publication.
Also many of the projects showed evidence that additional work was being conducted
based on the initial results of the OWH funding (see Outcomes Section for
a more detailed summary).
Other Activities
In keeping with these program goals, OWH staff recently conducted a site
visit of the National Center for Toxicological Research (NCTR). The purpose
of the site visit was to assess the program's successes from FY 1994 through
to the present, to review the progress of ongoing OWH funded research and
to discuss the future direction of women's health research at the NCTR. At
the end of this site visit, OWH and NCTR agreed to work together to develop
a Women's Health Research Initiative at NCTR. This program will identify one
or two high priority women's health issues and develop a 5 year research plan.
OWH also recognizes that internal research expertise and facilities do not
exist to address all the research questions related to women's health. Therefore,
OWH will be exploring opportunities for studies to be completed at non-FDA
facilities, such as DHHS Centers of Excellence in Women's Health.
OWH provides information about its scientific program to external stakeholders
by reporting on activities and outcomes of the program in the quarterly newsletter,
The OWH Update, making this information available via the internet, and encouraging
the publication and presentation of profit results.
Conclusions
The OWH Scientific Research Program has been a remarkable success. The program
has consistently funded research projects aimed at improving the health of
women and the results of these projects has been incorporated into agency
policies and regulatory decision making. Over the years, OWH staff has found
creative ways of leveraging OWH funding including forming collaborations with
FDA's product Centers and co-funding projects with the National Institutes
of Health. In the future, the Scientific Program will focus its efforts on
improving the quality of funded research projects by increasing OWH oversight
of on-going projects, and improving the dissemination of project results to
internal and external stakeholders.
Table 1: Priority Research
Topics
Pre-clinical
models
- Predicting
toxicity in regulated medical
products, foods (including
dietary supplements/botanicals),
and cosmetics
- Animal
models of disease (e.g. gynecological
cancers, cardiovascular disease,
osteoporosis)
- Biomarkers
for studying diseases in
women
- Pharmacokinetic/Pharmacodynamic
differences of regulated
products by sex and species
- Mechanisms
of toxicity & disease
(e.g., skin cancer and phototoxicity,
environmental contaminants,
mechanism of action of lightening
agents, ingredient safety
of cosmetics)
Regulated
Product use in Pregnancy and
Lactation
- Analysis
of data on human use of medical
products (drugs, devices,
biologics), functional foods/neutraceuticals
and dietary supplements during
pregnancy/lactation
- Use
of regulated products and
impact on the developing
fetus
- Reproductive
toxicity of retinol
Clinical
Models
- Regulated
product(s) interaction and
toxicity
- Dietary
supplements/Botanicals (i.e.,
clinical evaluation of the
safety and efficacy of botanicals)
- Product
performance in pre- and post-menopausal
women
Risk
assessment/Risk management
- Allergenicity
of regulated products (i.e.,
seafood, sulfites)
- Sunscreens
(i.e., UV radiation)
- Cosmetic
ingredient safety
- Labeling
comprehension of products
used predominantly by women
(i.e., botanicals, cosmetics,
devices used during labor
and delivery)
Marketing
surveillance/pharmacovigilence
- Strengthening
the current knowledge base
in adverse event reporting
- Sex
differences in toxicity profiles
of medical products
Inclusion
of women in clinical trials
- Data
analysis of participation
of women in clinical trials
- Analysis
of gender differences and
special populations
- Clinical
evaluations of alternative
medicines
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Table 2: Concept Papers Selected
for Proposal Development
Center for Biologics Evaluation
and Research (CBER)
- DNA
vaccination in pregnancy
- Gender
differences in adverse events
following vaccines and biological
products
____________________________________________________________________________________________
Center for Drug Evaluation
and Research (CDER)
- The
acute liver failure active
surveillance program
- Vaginal
volume: optimizing vaginal
deployment of topical microbicides
- Women's
participation in randomized
drug trials for cardiovascular
disease
- Evaluation
of the Tg.AC transgenic mouse
as a model for predicting
photocarcinogenicity
of pharmaceuticals and cosmaceuticals
____________________________________________________________________________________________
Center for Devices and
Radiological Health (CDRH)
- A
more consistent and useful
method for presenting ultrasound
bone sonometer results to
practitioners
- Potential
minimally-invasive breast
tumor therapy
- Surveillance
of sex-specific utilization,
morbidity, and mortality
associated with transmyocardial
revasularization
- Relationship
of ultrasonic properties
to microarchitectual properties
of trabecular bone
- Role
of gender specific cell death
in angioplasty balloon-induced
stenosis of swine coronary
arteries
____________________________________________________________________________________________
Center for Food Safety
and Applied Nutrition (CFSAN)
- Feeding
practices related to food
allergy and mother's understanding
of food allergy in infants
- A
laboratory investigation
of the teratogenic potential
of cosmetic treatment products
containing retinol and retinyl
palmitate
- Product
safety implications of cosmetics
labeling claims
____________________________________________________________________________________________
Center for Veterinary Medicine
(CVM)
- Use
of a unique animal model
to study placental and milk
transfer of enrofoxacin from
the dam to the offspring
during the perinatal period
- Effect
of gender on development
of arthritis in a swine model
system
____________________________________________________________________________________________
Office of Regulatory Affairs
(ORA)
- Development
of HSV-1 and HSV-2 quality
control serum panel
- Analysis
of dioxins/furan levels in
tampons
____________________________________________________________________________________________
National Center for Toxicological
Research (NCTR)
- Chemical
differences and toxicological
effects of Dong Quai Root
preparations
- Evaluation
of the effects of genistein
on the mutagenicity and carcinogenicity
of the model mammary carcinogen
7, 12-dimethylbenz(a)anthracene
in female transgenic rats
- Evaluation
of the Tk KO mouse as a model
for systemic lupus erythematous
- Measurement
of K-ras mutation in endometrial
tissue and analysis of tamoxifen-associated
changes in K-ras mutant frequency
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Table 3: OWH Funded Projects
for FY 2000
- Debra
Birnkrant, M.D., Ajaz Hussain,
Ph.D., CDER, "Vaginal Volume:
Optimizing vaginal deployment
of topical microbicides"
- Ronald
Honchel, Ph.D., Frank Sistare,
Ph.D., CDER, "Evaluation
of the Tg.AC transgenic mouse
as a model for predicting
the photocarcinogenicity
of pharmaceuticals and cosmeceuticals"
- Ann
Farrell, M.D., Lilia Talarico,
M.D., CDER, "Women's participation
in clinical drug trials for
unstable angina and myocardial
infarction"
- Brad
Astor, Ph.D., CDRH, "Surveillance
of sex-specific utilization,
morbidity, and mortality
associated with transmyocardial
revascularization"
- Richard
Kotz, Ph.D., CDRH, "A study
to evaluate the consistency
of T-scores among ultrasound
bone measurement devices
and the usefulness of these
devices for monitoring bone
status"
- Jeffrey
Yourick, Ph.D., Thomas Collins,
Ph.D., CFSAN, "Teratogenic
potential of cosmetic products
containing Retinol (Vitamin
A) and Retinyl Palmitate"
- Phase 1
- Jurgen
von Bredow, Ph.D., CVM, "Use
of a unique animal model
to study placental &
milk transfer of ciprofloxicin
from the dam to the offspring
during the perinatal period"
- Anane
Aidoo, Ph.D., NCTR, "Evaluation
of the effects of daidzein
and genistein on the genotoxic
and carcinogenic activity
of the model mammary carcinogen
7,12-dimethylbenz(a)anthracene
(DBMA) in ovariectomized
transgenic Big Blue rats"
- Vasily
Dobrolovsky, Ph.D., NCTR,
"Evaluation of the Tk knockout
(TkKO) mouse as a model of
systemic lupus erythematosus"
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