Until 1993 it was not required to include women in clinical research. In fact, they were actively excluded from studies until the United States’ Congress passed the NIH Revitalization Act, which required the representation of women and minorities in clinical trials. 30 years have passed and while there has been a lot of headway, we still have a long way to go to reach gender equality in healthcare.
Inclusion of women in clinical research. Why in 1993?
In the 1950s, the use of Thalidomide was approved in pregnant women to treat morning sickness, but it tragically resulted in the birth of thousands of newborns with malformations. As a response, the U.S. Food and Drug Administration (FDA) established a policy protection for research subjects and the Public Health Service increased efforts to ensure the safety of participants, especially those who were more vulnerable due to physical, mental, or social reasons. Through this, it was considered safest not to include women of childbearing age, to avoid any possible effects on unborn children. Their participation was seen as dangerous and of little individual worth. In the following decades, women were not only excluded from clinical trials, but also all female healthcare was ignored and for years, women were incorrectly diagnosed or were given inadequate treatment.
Yet, there was more than safety behind this decision. The exclusion of women in clinical research was not only due to fear, but also to the belief that the female and male bodies were the same and drugs would have the same effect in both sexes, thus it was not necessary to test them in women, even though their anatomy and physiology was different. Evidently, this belief was incorrect and in the late 1980s, the scientific community recognized that the differences between men and women explained why diseases could manifest differently according to sex. The delayed acceptance of this fact means that most of modern medicine is based on research on male bodies. This gender health gap had (and continues to have) repercussions on women’s care.
History of women in clinical trials.
Because women were excluded from clinical trials early on, there was very little information available on women’s health and how drugs affected them. To remedy this, in 1985 the Public Health Service Task Force set in motion an investigation of the biological and social factors affecting women’s health. The Task Force presented a series of recommendations to ensure progress in women’s healthcare, one of which was expanding biomedical and behavioral research, with an emphasis on conditions and diseases more prevalent in women of all age groups. The following year, the National Insitute of Health (NIH) released a new policy encouraging researchers to include women in their studies, but it was not a legal requirement. In the early 90s an investigation by the now US Government Accountability Office, and driven by Congressional Caucus for Women’s Issues, revealed that the policy had been poorly communicated and was seldom applied in practice.
A key turning point in the women’s health advocacy occurred in 1991, when Dr. Bernadine Healy launched the Women’s Health Initiative. It consisted in a series of clinical trials involving more than 1,500 postmenopausal women, which were carried out over a period of 15 years to understand the hormonal changes after going through menopause and the effect of possible treatments.
For the next few years, the inclusion of women in clinical research was an NIH policy but not law. Finally, in 1993, the U.S. Congress passed the NIH Revitalization Act creating guidelines to ensure and enforce the inclusion of women and minorities in clinical research.
At the same time in Europe, although the importance of gender balance in research was acknowledged and even promoted by the European Commission, there were concerns regarding the protection of participant safety based on the principles outlined by the Helsinki Declaration. Because of this, almost 20 years went by before a new clinical trial regulation was passed in 2014, stating that participation in clinical trials must be representative of both male and female populations, unless otherwise justified. It also emphasized the need to protect participants that may be considered as vulnerable, such as minors, pregnant or lactating women, and is fully aligned with the Helsinki Declaration.
Research gender gap in the present
Women’s scarce participation throughout the history of clinical trials has inevitably resulted in a gap of health information and data that persists nowadays. Following the assumption that risk factors and disease states are similar in men and women, researchers have been more concerned with finding treatments for acute symptoms or conditions, focusing less on chronic pathologies that are more common in women, such as migraines, headaches, anxiety disorders, among others. Not only that, but also because of the lack of inclusion and participation of women in the drug development process, many drugs were never tested on female subjects. To this day, there is still a lack of precise information on how women react to many treatments, including what their adequate dosage should be, their efficacy, and the possible side effects in women.
This gender gap in research has been demonstrated in many studies over the years. For example, the University Hospital Miguel Servet in Spain carried out a study on the influence of gender in clinical research in 2004. Their objective was to analyze differences in participation in clinical trials according to sex. They looked at 101 clinical trials that had been carried out previously, where both men and women had participated, and found that overall, twice as many men were included in the trials than women.
Next steps for women’s health in clinical research
Equal participation is key
For a new trial to be inclusive, it is important for researchers not only to foster diversity and inclusion in participants, but also be able to correctly interpret results. Considering gender differences to analyze results and the effect of the new drug or treatment being studied is a fundamental step to bridging the gender health gap.
Consideration for women-specific needs
The female body can go through a wide range of changes during a lifetime: pregnancy, lactation, menopause, hormonal variations, etc. These should be considered and represented in research to truly understand the different needs, conditions, and drug tolerance of women throughout their life, as well as to ensure their safety and access to treatment options.
An important step in this direction was taken in 2018, when the FDA drafted specific guidelines on scientific and ethical considerations for enrolling pregnant women in clinical trials, emphasizing that pregnant women can enroll in clinical trials that pose the least risk to the fetus.