Women in Clinical Trials
The facts remain that many women were not included in clinical trials which a hole in the testing wider when the numbers are compared to Men in Clinical Trials. No doubt, there is a difference in reaction to various medicines.
Throughout history, doctors have considered women’s bodies atypical and men’s bodies the “norm,” despite women accounting for nearly half the global population and outnumbering men in the United States since 1946. Though policy and social changes in the 1990s have helped turn the tide, women remain underrepresented in research, sometimes grossly so. Many medical researchers avoided conducting studies on female mice due to greater costs associated with purchasing and housing both sexes and concerns that the fluctuating hormones and reproductive systems of female mice might confound the study results. Hence issues . . .
History of Women in Clinical Trials: Overcoming Bias & Exclusion
The exclusion of women from clinical trials can be traced back to the early 1970s when men were still viewed as the ‘dominant’ gender and few women were working in the field of medicine. The prevailing belief at the time was that Caucasian males constituted a ‘normal’ study population, alongside concerns about females’ fluctuating hormone levels making them a more complex group to study, leading to their exclusion from biomedical research.
Many clinicians also voiced concerns about pregnant women being a ‘vulnerable’ group and these fears were only magnified by incidents such as the thalidomide tragedy, in which expectant mothers who were given the drug gave birth to babies with severe limb defects. This led to the Food and Drug Administration (FDA) issuing guidelines in 1977 which banned expecting mothers from participating in phase I/II clinical trials. However, this ruling also applied to single women, those using contraception, or those whose husbands were vasectomized. Unfortunately, this cautious approach has had a deleterious impact, with a lack of research about a new drug or treatments’ effect on the female body leading to various safety concerns.
In the late 1980s, the National Institutes of Health (NIH) began to put policies in place recommending the inclusion of women in scientific studies and in 1991 appointed their first female director who launched the Women’s Health Initiative, to study a range of conditions predominantly affecting postmenopausal women7. However, it wasn’t until 1993, when the FDA’s 1977 guidelines were reversed and the inclusion of women in clinical trials became part of Federal law, that the numbers of female patients steadily began to increase.
While the inclusion of women in clinical trials has improved since the 1990s, disparities in biomedical research remain. Women, along with other underrepresented populations, continue to be enrolled at lower rates in many studies, leading to gaps in understanding sex- and gender-specific responses to treatments. To address this, the Food and Drug Omnibus Reform Act (FDORA) of 2022 introduced Diversity Action Plans (DAPs), requiring clinical trial sponsors to implement strategies for improving enrollment diversity8. In 2024, the FDA issued draft guidance reinforcing these efforts, emphasizing the need for equitable representation in drug research to enhance the safety and efficacy of medical treatments across populations.
A Woman’s Right to Safe Healthcare Outcomes, Angry Bear and NPR
Fact: Women make up over half of the U.S. population.
As reported by the GAO, women have been underrepresented in NIH supported clinical research which lead to unidentified differences in treatment results between men and women when incurring a disease. There have been instances of women experiencing different and also adverse effects to medications and treatments than what was experienced by men in NIH Clinical trials. It is thought the NIH’s
Inclusion Policy established requirements governing women’s inclusion in its clinical research may have led to this issue.
Some study examples:
The Baltimore Longitudinal Study of Aging started in 1958 did not include women until 1978 in its study even though women lived 6 years longer than men. 1000 men were initially in the study and no women. Another study, the Physicians Health Study concluded in 1989, the taking of low-dose aspirin might lower your risk for heart disease. It included 22,000 men and zero women. A study investigating the possible interactions between the libido-boosting drug Flibanserin (also known as “female Viagra”) and alcohol used a study group of 25 participants which included twenty-three men. It raises the question, why and how would we ever know the impact of drugs on women if only men are used in trials?
Why the Under Representation?
The driving factor for the lack of women in tests is not necessarily driven by bias as much as a lack of knowledge of the biological differences determining how disease symptoms may present in each gender. A broad-based assumption was made of the test findings of men, the results of which could also apply to women, and the testing of men was simpler as men are not subject to the hormonal fluctuations of women. As sound(?) as this reasoning may be in minimizing the number of trials, this appears to be more of a financial decision without considering the biological differences between the genders.
Reports of birth defects from the use of Thalidomide during the 1950s and 60s lead to FDA guidelines excluding potential child bearing women from participation in Phase 1 and 2 clinical studies until reproductive toxicity studies were conducted and evidence of effectiveness and safety was available. The FDA guide lines were misinterpreted and applied to all clinical study phases even though it was not intended to exclude women.
Dangers of Under Representation
Assumptions from an 11 year NIH study on moral development in children using only boys concluded little girls are morally inferior to little boys. Females are simply different and arrive at conclusions different than men and just as moral. Eight of 10 approved drugs were pulled from the market due to health risks for women which were not risky for men. More women than men used four of the drugs and for 4 other drugs women and men used them equally. The differences in men and women between the two sets revealed itself in the later set of 4 with women experiencing serious side effects more often than men. Hence, emphasizing the need to have women equally represented in clinical studies. “Excluding women makes a difference: If women had been included before 1978, the link between osteoporosis-calcium-estrogen and progesterone would have been discovered in time to help their mothers”.
Resolution
In 1993 the Health Revitalization Act was passed which incorporated the use of women and minorities in NIH clinical studies. In 2000, Congress asked the GAO to assess the progress of the NIH. While progress was made to include women and minorities in trials, the GAO recommended the NIH to improve reporting format. Later years the GAO again assessed the NIH recommending the NIH improve the consistency of reporting by sex so as to allow researchers to “identify potentially important sex differences that may ultimately affect patient care.”
Globally the representation in 43% women and 57% men in clinical trial representation. In the US, the representation has improved to 49% women and 51% men. There is still work to be done. Most recently, the 21st Century Cure Act was passed with one of its intents being to move new drugs to market faster through testing in the public sector. “Without detailed clinical trials and studies, there is effectively no way to determine the extent of potential side effects and other issues the current detailed trials and studies provide.” Numbers predicting probability versus clinical trial experience, we will have to see how this plays out.