“Involving Minority and Underrepresented Women in Clinical Trials: The National Centers of Excellence in Women’s Health” (2000), by Marcia Killien, Judy Ann Bigby, Victoria Champion et al.

In 2000, Marcia Killien and colleagues published “Involving Minority and Underrepresented Women in Clinical Trials: The National Centers of Excellence in Women’s Health,” hereafter “Involving Women,” in the Journal of Women’s Health and Gender-Based Medicine. Killien and colleagues address the historical exclusion of women from participation in medical research studies and difficulties in generalizing the results of studies that exclude women. They propose strategies to improve participation of minority and underrepresented women in clinical studies and identify systemic barriers such as mistrust, lack of access, and cultural insensitivity that have historically excluded those populations from clinical trials. The article emphasizes the necessity of inclusive research to ensure that medical advancements benefit all women equitably and suggests strategies to achieve more inclusive clinical research practices.

The research team who published “Involving Women” comprised experts from the National Centers of Excellence, or CoEs, in Women's Health, which was a US federal initiative under the Office of Women’s Health within the US Department of Health and Human Services, or HHS. The HHS established the CoE program in 1996 to address gaps in women's healthcare. At the time of the article's publication, lead author Killien was a professor in the Department of Family & Child Nursing at the University of Washington in Seattle, Washington, researching maternal health and health promotion. Bigby served as the director of the CoE at Harvard Medical School in Boston, Massachusetts. There, she researched health equity among minority populations, particularly in breast and cervical cancer. Champion was a professor of nursing at Indiana University in Bloomington, Indiana, researching cancer prevention strategies and health disparities in rural women’s health. Fernández-Repollet worked as a health disparities researcher at the University of Puerto Rico Medical Sciences Campus in San Juan, Puerto Rico. Kagawa-Singer, then a researcher at the University of California–Los Angeles in Los Angeles, California, studied cancer disparities in Asian American communities. Prout studied breast cancer risk and prevention strategies at Boston University in Boston, Massachusetts, focusing especially on cancer prevention outreach with underserved communities. Jackson was a professor of Internal Medicine in the Division of Endocrinology, Diabetes, and Metabolism at The Ohio State University in Columbus, Ohio. At the time of publication, she had held multiple leadership roles in the Women’s Health Initiative, or WHI, for over twenty-five years.

The paper represents a policy analysis and a position statement from the CoE’s program. The aim of the paper is to demonstrate the historical context of the exclusion of minorities and women in clinical trials and synthesizing what they identify as evidence-based recommendations to address systemic exclusion in clinical research. There was one incident in particular that made the inclusion of women, particularly pregnant women, in clinical studies much more difficult. According to the authors of “Involving Women,” the scientific controversy surrounding thalidomide, which was a drug given to pregnant women for nausea starting in the late 1950s, contributed to the exclusion of women from clinical trials. Within several years of the widespread prescription of the drug, researchers identified that thalidomide had caused birth defects in children born in Europe, Australia, and Japan. Scientists also asserted that the drug could cause the death of the fetus while still in the mother. Most countries withdrew thalidomide from commercial markets by 1961, banning the medication by the late 1960s. While the US government never approved the drug for public usage, around 20,000 Americans still received the drug during the 1950s and 1960s as part of two clinical trials led by pharmaceutical companies Richardson-Merrell and Smith, Kline & French. According to an outreach toolkit from the National Institutes of Health, or NIH, the thalidomide incidents led to a 1977 policy from the Food and Drug Administration, or FDA, which is a governmental organization in the US that regulates food, drugs, and medical devices, recommending the exclusion of all women of childbearing age from clinical studies. That included women who used contraception to prevent pregnancy or whose husbands had undergone a vasectomy.

Because the exclusion of women from clinical trials led to limited pharmaceutical data on how medication may affect women, the NIH established a policy in 1986 that encouraged NIH researchers to recruit female participants in their studies. In July 1989, the NIH developed additional policy on the subject, this time instructing that NIH scientists need to provide rationale if they choose to exclude women or minorities from their research. However, in 1990, the Congressional Caucus for Women’s Issue, a group of Congressmembers who advocate for women’s issues, asked the General Accounting Office, or GAO, a government agency that audits federal programs and is known as the Government Accountability Office as of 2026, to conduct an investigation into the NIH’s implementation of that 1989 policy. The GAO found that the NIH had poorly communicated the policy, causing inconsistent application of their mandate across research studies. That led the NIH to establish the Office of Research on Women’s Health, or ORWH, in 1990. The ORWH worked to increase research into diseases that are unique to or are more prevalent amongst women, ensuring that women receive appropriate representation in NIH-run clinical research studies. The ORWH also conducted educational initiatives to increase the number of women in biomedical research careers. Congress codified the participation of women in clinical research into law with the NIH Revitalization Act of 1993, which mandated the inclusion of women and minorities into any NIH-funded research on 10 June 1993.

Killien and colleagues split the paper into five sections. The introduction establishes the need for inclusive clinical trials and highlights the historical reliance on young White male participants and the resulting health disparities, as well as introducing the CoEs as a key initiative to address underrepresentation of diverse populations in research. The second section discusses how unethical medical experiments have instilled a sense of mistrust in academic and research institutions within minority populations, especially women of color. The third section identifies two main obstacles, conceptual barriers and structural barriers, that hinder participation of underrepresented women in clinical trials. The fourth section proposes collaborative approaches between researchers and communities to improve clinical trial accessibility and trust, emphasizing culturally sensitive study designs and inclusive research teams. Finally, the last section, future considerations, discusses the successes of the current system and systemic reforms needed across research infrastructure to achieve equity in medical research participation and outcomes. 

In the introduction, Killien and colleagues explain that researchers have tested the efficacy of medications, medical treatments, and disease prevention strategies through randomized controlled clinical trials, which is an experimental study that randomly assignments participants to a treatment group, which receives the intervention, and a control group, which receives a placebo not containing an intervention. That type of study design allows researchers to gauge the effects of medical treatments such as medications or procedures by comparing the outcomes of those two groups. However, researchers still enroll mostly young adult White men in those trials. In preclinical research, they use male mice almost exclusively to maintain consistency. The authors assert that scientists exclude women from clinical trials over concerns that the menstrual cycle or other hormonal fluctuations can confound data and make it more difficult to determine the result of the intervention being tested in the trial. Researchers also omit pregnant women, citing potential risks to fetal development. However, the results from clinical trials enrolling mainly White men still inform the medical care of many different individuals, including women, people of color, children, and geriatric populations.

As evidence accumulates that people respond differently to medical interventions by sex, race, and life stage, the authors introduce CoEs, which receive funding from the Office on Women’s Health to expand participant diversity in clinical trials and improve outcomes in overlooked communities. The authors assert that, although the scientific community generally supports the goal of increasing diversity, there are certain challenges associated with studying groups like women or minorities, which the authors will address and offer potential solutions for throughout the article.

In the second section titled “Historical and Sociocultural Context,” Killien and colleagues suggest that the underrepresentation of minorities and women in clinical trials stems from documented cases of medical exploitation, creating lasting distrust in marginalized communities. The authors review several instances that cultivated medical mistrust such as the Tuskegee syphilis study, a study lasting from 1932 to 1972 in which researchers denied medical treatment to Black men with syphilis to study the natural progression of the disease. According to the authors, the Tuskegee syphilis study caused Black Americans to be distrustful of medical research, as the coordinators of the project attempted to justify its premise by asserting the Black patients often do not comply with medical treatment anyway.

The authors also discuss how minority women and low-income women have been the target of unethical medical experimentation and reproductive legislation. They state that medical practitioners during the 1800s, such as gynecologist James Marion Sims, performed nonconsensual gynecological experiments on enslaved Black women. They also discuss forced sterilization laws targeting poor women and women from minority groups. As late as the 1970s, there were accounts of government-supported forced sterilizations on women from marginalized groups, such as Black, Native American, and Puerto Rican women. During concerns about crack cocaine use during the 1980s and 1990s, clinical trials, especially among Black pregnant women, often involved drug testing without the patient’s consent. Minority women in the US also experienced higher infection and mortality rates during the acquired immunodeficiency syndrome, or AIDS, epidemic, which began affecting people in the US in the 1980s.

The authors note that, globally but especially within developing countries, women have been the subject of sterilization campaigns. Because those campaigns sometimes used oral contraceptives to prevent pregnancies without consent, women from those countries often avoid contraceptive technology as a whole and perceive many contraceptive technologies as means of committing genocide. The authors explain that those events and other instances of medical injustice have dissuaded minority and low-income women from participating in studies. They emphasize that the low participation of those groups in medical research perpetuates disparities in healthcare, such as historically worse cancer treatment outcomes amongst Black Americans compared to White Americans.

The authors state that even protective governmental policies for harm prevention had unintended consequences of exclusion. For instance, after the thalidomide clinical trials, the Food and Drug Administration’s 1977 policy excluded women of childbearing age from trials. Institutional review boards, or IRBs, committees that review and oversee research with human participants, frequently categorized some groups of women, particularly minorities, as vulnerable populations at higher risk of harm from participating in clinical trials and created additional policy barriers to their inclusion. The authors assert that researchers hoping to include minority and low-income women in their clinical trials must be aware of feelings of medical mistrust and be willing to address those anxieties with potential research participants.

In the third section titled “Issues and Barriers,” the authors describe how clinical trials at CoEs encounter difficulties in recruiting women from minority and other underrepresented populations, with obstacles falling into two primary categories: conceptual barriers and structural barriers. Conceptual barriers stem from fundamental differences in cultural and social perspectives between researchers and potential research participants. That includes participants’ limited awareness about clinical research processes, as well as any cultural mismatches with Western biomedical or ethical models. For example, some societies do not emphasize the concept of altruism, which is the act of helping other people without expecting personal gain or reward. Participants with this cultural perspective may not be inclined to join research studies which offer primarily collective benefits.

Structural barriers present more tangible obstacles to participation, and the authors examine them through three key dimensions. The first is availability, which refers to whether trials are offered at convenient locations and times. The second is accessibility, which encompasses practical challenges like transportation limitations, childcare needs, language barriers, and safety concerns. The third, acceptability, involves overcoming participants’ historical mistrust of medical institutions and ensuring cultural sensitivity in research protocols. The authors discuss possible solutions to structural barriers such as van pools, local research sites, and flexible clinic hours. However, they emphasize that conceptual barriers require building trust over time. For example, participants from minority populations have reported that they feel as if medical institutions always take from the community but never provide anything in return. The authors reiterate the need to understand and empathize with those perspectives to build trust and improve clinical trial recruitment not just with minority women, but women who may be LGBTQ+, low-income, disabled, or undocumented.

In the fourth section, titled “Strategies to Enhance Participation in Clinical Trials,” Killien and colleagues discuss strategies to overcome structural and conceptual barriers to participation. The main strategy encourages collaboration between the researchers and the participants, shifting from a traditional recruitment model to a community-based approach. Instead of researchers solely seeking volunteers for pre-designed studies, the community-based model involves active participation from community members in designing and implementing the research. Effective strategies for linking with communities in clinical trials involve deepening existing relationships between the research institution and the community, especially by engaging community leaders, such as healthcare providers, religious figures, or community elders, as liaisons between researchers and potential participants. The authors also assert that the research process and outcomes should benefit the community, such as hiring members as research staff and planning research that addresses community health concerns. Additionally, researchers can build trust by actively participating in community activities beyond the research context, demonstrating respect and fostering collaborative relationships. The authors state that CoEs have used those strategies to conduct research with diverse, underrepresented women as participants. Finally, the section concludes by stating the research team should reflect the diversity of the population being studied, as some participants may prefer to interact with researchers of similar gender, race, or cultural background. The author asserts that studies could hire clinical researchers based on the participants’ preferences in order to promote engagement.

In the final section titled “Future Considerations,” the paper discusses the increasing focus on women's participation in clinical trials, highlighting key studies such as the Women’s Health Initiative, or WHI, the Breast Cancer Prevention Trial, or BCPT, and the Black Women’s Health Study. Researchers developed those studies specifically for women’s health issues. Although those trials have developed methods for effectively recruiting and informing women, many challenges remain. Issues such as premature trial closures result in difficulties in analyzing the long-term effects of medical interventions, and the underrepresentation of women who do not regularly receive preventive care services affects the generalizability of the results of prevention trials. Furthermore, some consent forms are long and contain complex language, which may alienate potential participants with limited educational backgrounds. The demographic differences in race and gender between the researchers and the participants also may discourage the recruitment of women, especially those belonging to minority groups. Despite efforts like the NIH Revitalization Act of 1993, which mandates the inclusion of women and minorities in research, the authors point out that significant gaps in representation remain, particularly among women from minority groups.

The paper concludes by stressing the need for comprehensive strategies to overcome barriers to participation and retention in clinical trials. The authors explain that it is important to reduce the demographic differences between scientific researchers and the medically underserved populations that they study, especially in terms of gender, race and socioeconomic class. When academic institutions produce a diverse workforce of scientists, the clinical research process naturally becomes more culturally competent due to that diversity. As well as by promoting leadership in academic health science disciplines among women from diverse backgrounds and improving community outreach, those efforts can help ensure that clinical research is more inclusive, and its findings are applicable to all communities.

"Involving Women” by Killien and colleagues addressed the issue of including diverse populations in clinical research, as well as potential strategies for improving recruitment. As of 2025, fifty-seven studies have referenced “Involving Women,” according to the NIH scientific literature search engine PubMed. However, the issue of representation of women, particularly women from ethnic or racial minority groups, in clinical trials has continued into the 2020s. A 2022 publication by Barbara Bierer, a co-director of the clinical trials center at Brigham and Women’s Hospital in Boston, Massachusetts, and her colleagues, asserts that, although the presentation of women in clinical trials generally increased over time, there are certain types of therapeutic research trials that still under-enroll women. Furthermore, women of color continue to lack representation in clinical trials. For example, between 2015 and 2016, only 3.2 percent of women enrolled in global cardiovascular drug trials were African American. They also point out the issues with the reporting of diversity metrics, as trials will report the number of women participants and the proportion of Black participants, but not the intersection of both categories. Thus, as of 2022, Bierer and her colleagues emphasize that there still remain issues with the involvement of underrepresented women in medical research. 

The US government defunded the CoE program in 2007, leading to the closure of many centers that relied entirely on federal funding. At its peak, the program created a network of forty-eight CoEs across forty states and Puerto Rico, forming a nationwide network that emphasized interdisciplinary care and the integration of sex and gender in medical practices. In 2022, former CoE leaders discussed the need to adapt the CoE model to address evolving health care challenges, such as including sex- and gender-based women’s health in clinical care, education, and research.

The work by Killien and colleagues addressed the issues regarding the involvement of women in clinical trials, especially women from medically underrepresented backgrounds. Historically, women were often excluded from studies, which led to gaps in research findings and a limited understanding of how certain treatments affected them. The strategies outlined in the article, such as more inclusive recruitment methods and tailored study designs, suggested ways to improve inclusivity in medical research and led to more representative clinical trials.

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