From “The Gift of Participation” by Ken Getz, Founder & Board Chair, CISCRP
Gender mix in clinical trials, overall, appears to be relatively balanced. Research conducted by the Center for the Study of Drug Development at the Tufts University School of Medicine found that, in clinical trials conducted in support of drugs submitted to the FDA, 52% of all patients who participated were men and 48% were women.
There is no question, however, that protocol designs have historically addressed disease as it manifests in adult males. Beginning in the early 1990s, public pressures fueled stricter government requirements for the presentation of data by gender in market applications to the FDA and valid analysis by gender at the NIH. In 2000, the FDA further specified that a clinical trial excluding persons having reproductive potential could be placed “on hold,” preventing further product development. This requirement helped ensure that women of childbearing potential were included in studies.
Pharmaceutical and biotechnology companies have also sought ways to increase the market potential for new and existing drugs by gathering clinical data to make specific claims about drug safety and effectiveness among women. As a result, clinical trials are increasingly being designed to assess the safety and efficacy of gender-specific medical treatment, and medical treatments are being “personalized” for gender differences in response.
Many diseases behave differently in women than in men. Risk factors, symptoms, the clinical course, and response to treatment can all be gender-specific. Among a long list of differences, men and women vary by:
- body size, composition, and metabolism
- the ways their bodies change during the aging process, e.g., puberty and midlife
- endogenous hormones
- exogenous hormones
Due to these differences and to other factors researchers have discovered that:
- Lung cancer kills more women than any other cancer.
- Alzheimer’s disease is twice as prevalent in women.
- Men and women experience pain differently.
- Women are two to three times more likely to experience depression, due to less serotonin uptake in the brain.
- About 75% of autoimmune diseases occur in women, most frequently during childbearing years.
- Urinary incontinence and dysfunction are more common in women and often have an entirely different cause than the same conditions in men.
- Cardiovascular disease kills approximately 250,000 more women each year than all forms of cancer combined, accounting for 58% of all deaths. Within a year of the first myocardial infarction, 44% of women die, compared to 27% of men. Hormone-replacement therapy does not prevent heart disease, as was previously assumed.
- The initial HIV viral load may be significantly lower in women, who represent an estimated 30% of new infections, but both sexes develop AIDS at the same rate
Although the FDA recommended in 1993 that clinical studies include enough women to understand the unique ways in which their bodies respond to drugs, women are still underrepresented in small, phase I trials. And when eligibility is restricted by age, older women are disproportionately excluded from studies of diseases that are more common in women at older ages. Although regulations prohibit the explicit exclusion of women of childbearing potential, the possibility of becoming pregnant can result in women in their childbearing years not being included in studies.
Generally, a woman capable of conceiving a child won’t be considered for a clinical trial unless she’s not pregnant and agrees to use birth control. Some studies require that women of childbearing age use two forms of contraception to participate in a study. Pharmaceutical companies don’t want their drugs tested among women who are—or might get—pregnant, mostly because the risk of exposure or a lawsuit by the mother is too high. Even in normal pregnancies, 1% to 2% end with an abnormal birth. Many parents are quick to blame poor birth outcomes on drugs. Some doctors erroneously believe that certain drugs cause fetal abnormalities. But genes and chromosomes are the primary culprits, according to Marilynn C. Frederiksen, M.D., associate professor of obstetrics and gynecology at Northwestern University Medical School.
“All of this presents a major barrier to clinical trial participation by women who don’t want, can’t afford, or are religiously opposed to contraception,” says Frederiksen.
Things aren’t bound to change unless the NIH comes up with the funds to conduct special dosing studies in pregnant women. And that probably won’t happen quickly or easily.
The NIH has an Office of Research on Women’s Health to help strengthen policies requiring inclusion of women in clinical research and to help translate new knowledge into clinical practice, but it doesn’t have any institutes that devote research dollars specifically to female health issues. As a direct result of the 1993 NIH Revitalization Act, NIH-sponsored clinical research now routinely includes sufficient numbers of non-pregnant women. In 2001, additional protections were given to pregnant women (as well as human fetuses and neonates) that spell out the conditions under which they can be involved in federally funded research— if earlier studies provide data on the potential risks, for example, and the risk to the fetus is caused solely by interventions that could directly benefit either the women or the fetus. Participation of women in NIH-funded studies, overall, is proportional to the percentage of women in the general population when sex-specific studies are excluded.
The participation of women in clinical trials is essential. The exclusion of women from early-phase studies, in particular, delays the discovery of sex-specific dosing requirements and the identification of gender-specific side effects, limiting the identification of drugs that are useful just for women. The problem is compounded by the fact that animal studies, when scientists learn about many of a drug’s potential adverse reactions, also tend to exclude females. Limiting studies to a single gender requires fewer study subjects (animal or human) and, thus, shorter and less costly studies.
There are many hopeful signs of change. Pharmaceutical companies are devoting a tremendous amount of money to trials focusing on diseases and conditions that only affect women.
For more information on clinical trials and making informed decisions about volunteering for clinical research, read “The Gift of Participation” by Ken Getz, Founder and Board Chair, CISCRP.
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