The U.S. Food and Drug Administration (FDA) is a science-based, regulatory agency with the core mission of protecting the public health (see FDA Mission Statement in the Introduction).1 The foundation of FDA’s public health and consumer protection mission is regulatory science, the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of FDA-regulated products. 2 The research under way at FDA helps FDA scientists assess the toxicity, safety, efficacy (or effectiveness), quality, and performance of the medical and other products FDA regulates. This research also contributes to advances in science and technology in general and promotes innovation in medical product development and food and cosmetic safety. FDA’s research also helps alert the Agency to potential safety issues, like product contamination, and other problems that may become apparent only after a product enters the marketplace.
In 1994, FDA’s Office of Women’s Health (OWH) established a program to support FDA research and development activities related to advancing the science of women’s health. 3 Over the past two decades, OWH has funded research projects totaling approximately $35 million.4 These projects have addressed health issues affecting women across their lifespan, including, for example, endocrine and metabolic disorders, cardiovascular disease, breast cancer, sexually transmitted infections, and issues related to pregnancy. Results from OWH-supported research have led to safety labeling changes for some medical products, guidance for industry on product development, new evidence-based communications about FDA-regulated products used by pregnant women, and regulatory decisions related to FDA-regulated products used by women.5
Since its inception, OWH has worked closely with FDA’s centers6, which is where many research activities are underway. OWH has helped to expand existing research projects and foster new collaborations. OWH has also worked with other governmental agencies, academia, women’s research organizations, and other stakeholders to foster and facilitate research projects and scientific forums. These combined efforts have helped to advance our understanding of women’s health issues. They have furthered the development of new tools and approaches for informing FDA decisions about the harm or the safety and effectiveness of FDA-regulated products that are used not only by women, but by all Americans.
The Women’s Health Research Roadmap (Roadmap), outlined in this report, builds on knowledge gained from previously funded research and is intended to assist OWH in coordinating future research activities with other FDA research programs and with external partners. The Roadmap outlines priority areas where new or enhanced research is needed. Although many critical women’s health issues may warrant further examination, future OWH-funded research should focus on areas where advancements will be directly relevant to FDA as it makes regulatory decisions. The Roadmap creates strategic direction for OWH to help maximize the impact of OWH initiatives and ultimately promote optimal health for women.
Women’s health research is critically important. We know that disease sometimes manifests differently in women than in men; sometimes women also respond differently to FDA-regulated products. A number of factors can influence these differences. Intrinsic factors (e.g., genetics, hormones, body size, sex-specific physiology), extrinsic factors (e.g., diet, sociocultural issues, environment), or interactions among these and other factors can play an important role in how women respond to therapies. Characteristics associated with female sex (e.g., size, age, co-morbidities, past pregnancies) may be associated with differences in the safety or effectiveness of a particular medical product.
Because these differences in health, disease, and treatment response can occur throughout a woman’s life―and may be substantial, depending on her stage of life―a deeper analysis is needed of how regulated products work in diverse populations of women. For example, it is important to understand whether and how hormonal changes affect product performance at the onset of puberty, during the menstrual cycle, during pregnancy, and during the transition from pre-menopause, to peri-menopause, to post-menopause. We must improve our understanding of how to identify and interpret sex differences in addition to understanding how these differences might affect treatment. This is especially important, given the many evolving new technologies and scientific fields, such as nanotechnology; pharmacogenomics; stem cells; and novel imaging techniques and methods used to improve diagnosis. Advances in our understanding in these areas will contribute to FDA’s ability to carefully evaluate the many innovative therapeutic products in the development pipeline.
New clinical trial and study designs could help ensure effective use of small samples and sub-population analyses. New methods, processes, and tools can help evaluate medical device designs, predict toxicity, or predict the safety and efficacy of FDA-regulated products and guide medication dosing for women.
Biomarkers, patient reported outcomes,7 and other tools are increasingly being used during medical product development and in the clinic to help understand disease, therapy, and patient response to therapy. Advances in the science of biomarkers could help improve our understanding of the molecular underpinnings of disease in women and provide the data necessary to evaluate the safety and effectiveness of medical products, leading to advances in personalized, or precision, medicine. 8
The information gained from this research must be clear and readily available to multiple diverse subpopulations of women to help them and their health care professionals make informed choices about the regulated products available to them. Social science research can help identify and evaluate methods for eliciting patient perspectives on disease, treatment options, and effects of treatment and for delivering information to women and determining how individual factors like sex, age, culture, and health literacy might affect consumer understanding of product labeling and other FDA communications about regulated products.
FDA is interested in any patient or population characteristics that might affect the course of a disease or condition or the toxicity, safety, or effectiveness of an FDA-regulated product available to women. The goal is not just to identify that differences exist from one subpopulation to the next. The goal is to determine when identified differences have clinically meaningful 9 effects on patient health. This information can then be used to guide clinical decisions about the optimum course of action and inform the development of better diagnostic and therapeutic products for all subpopulations of women.
By promoting collaborative research in mission critical areas, developing new tools, applying this new knowledge during FDA’s review process, and strategically coordinating the findings so that they inform regulatory and policy decisions, FDA will be better positioned to foster the advancement of innovative products that promote and protect the health of all Americans.
The goal of the Roadmap is to provide a framework for continuing to integrate women’s health science into all of FDA’s research activities. OWH will use the Roadmap to make effective and efficient funding decisions that are aligned with FDA’s research priorities. The Roadmap strengthens OWH’s previous research efforts by publicly presenting a science-based framework that aligns directly with FDA’s priorities and strategic goals10 and within which OWH can make effective and efficient funding decisions. Moreover, the Roadmap will serve as a catalyst for future collaborations and other efforts related to protecting and advancing the health of women. Finally, stakeholders external to FDA will find the Roadmap useful as they seek OWH collaborative opportunities.
FDA is interested in patient or population characteristics that might influence the presentation, course, or outcome of a disease, thus affecting the toxicity or the safety, effectiveness, and security of an FDA-regulated product that is used by women. The task is not just to identify that differences exist from one subpopulation to the next. The task is to identify when sex differences have clinically meaningful11 effects on patient health. To develop better diagnostic and therapeutic products for all subpopulations of women, it is important to examine more closely the possible roles sex differences play.
The process of developing the Roadmap was under way before FDA issued its report Collection, Analysis, and Availability of Demographic Subgroup Data for FDA-Approved Medical Products. However, because it is such an important component of FDA activities in this area, the Roadmap was subsequently designated a key FDA commitment in the August 2014 Action Plan to Enhance the Collection and Availability of Demographic Subgroup Data, referred to in that report. 12 Considered a living document, the Roadmap will be refined and expanded as needed to reflect present and future women’s health regulatory questions, needs, and priorities.
To foster transparency within and outside FDA, OWH will post the Roadmap on its Women’s Health Research website,13 where information about OWH, including research initiatives, is available. FDA’s OWH will launch the Roadmap for use beginning with the fiscal year 2017 grants cycle.
OWH has identified the following seven broad goals, areas where additional or new research around FDA-regulated products that are used by women would be beneficial to women’s health.
Advance Safety and Efficacy: Advance the safety and efficacy and reduce the toxicity of FDA-regulated products used by women
Improve Clinical Study Design and Analyses: Improve clinical study design and conduct to better identify and evaluate possible sex differences related to FDA-regulated products
Novel Modeling and Simulation Approaches: Evaluate and promote the adoption of novel modeling and simulation approaches that can aid in regulatory evaluation of FDA-regulated products
Advances in Biomarker Science: Develop tools and methods that can help identify, evaluate, and qualify predictive or prognostic clinical and non-clinical biomarkers and surrogate endpoints
Expand Data Sources and Analysis: Identify, develop, and evaluate data sources and efficient techniques for data mining, data linkage, and large data set analysis that can be used to assess the postmarket toxicity or the safety and effectiveness of FDA-regulated products
Improve Health Communications: Develop, evaluate, and use tools and methods to foster the creation and easy availability of clear and useful information about FDA-regulated products used by women to help women and their health care professionals make informed health-related decisions
Emerging Technologies: Support the identification of sex differences related to the use of emerging technologies
Next Section: Introduction
2 FDA’s Strategic Plan for Advancing Regulatory Science. Accessed June 24, 2015.
3 See the OWH Reserch website.
4 From 1994 to 2015, OWH funded 340 research projects supporting the advancement of the science of women’s health.
5 Obias-Manno D, Scott PE, Kaczmarczyk J, et al. The Food and Drug Administration, Office of Women’s Health: Impact of Science on Regulatory Policy. J Women’s Health 2007 July-Aug; 16(6)807-17, available at http://www.ncbi.nlm.nih.gov/pubmed/17678451. Accessed March 22, 2015.
6 FDA’s centers are the (1) Center for Biologics Evaluation and Research, (2) Center for Drug Evaluation and Research, (3) Center for Devices and Radiologic Health, (4) Center for Food Safety and Applied Nutrition, (5) National Center for Toxicological Research, (6) Center for Tobacco Products, and (7) Center for Veterinary Medicine. For more on FDA centers, see http://www.fda.gov/AboutFDA/CentersOffices/OrganizationCharts/ucm2006146.htm, Accessed November 2015.
7 A patient reported outcome (PRO) is any report of the status of a patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else. In clinical trials, a PRO instrument can be used to measure the effect of a medical intervention on a symptom or group of symptoms, on effects on a particular function or group of functions, or on a group of symptoms or functions shown to measure the severity of a health condition. PRO instruments have proved useful in assessing medical product labeling claims. See, for example, FDA guidance. Accessed June 26, 2015.
8 Also known as individualized treatment, or targeted therapy, precision medicine makes use of blood tests, images of the body, or other technologies to measure individual factors called biomarkers. These biomarkers can then be used to determine who is most likely to benefit from a treatment, who is at higher risk of a side effect, or who needs a different dose. For more, see http://blogs.fda.gov/fdavoice/index.php/2015/03/fda-continues-to-lead-in-precision-medicine/.
9 The definition of clinically meaningful can vary depending on the disease or condition being considered, the therapy under consideration, and the goal of therapy. Generally, however, it can be understood to mean a measurable medical or statistical benefit to a patient or subgroup, respectively, in a given situation.
10 FDA’s Regulatory Science Priorities, Accessed June 28, 2015.
11 The definition of clinically meaningful can vary depending on the disease or condition being considered, the therapy under consideration, and the goal of therapy. Generally, however, it can be understood to mean a measurable medical or statistical benefit to a patient or subgroup, respectively, in a given situation.
12 FDA’s report Collection, Analysis, and Availability of Demographic Subgroup Data for FDA-Approved Medical Products Accessed June 29, 2015. FDA’s Action Plan to Enhance the Collection and Availability of Demographic Subgroup Data responds to a provision in section 907 of the Food and Drug Administration Safety and Innovation Act of 2012 (P.L. 112-144, July 9, 2012). See priority 1 in FDA’s Action Plan.
13 See the OWH Reserch website.