Why Sex Bias Occurs in Clinical Trials and How We Can Change It

by Karen Appold •

Areas to Focus On

Given that sex bias in clinical trials still exists, Dr. Farzal said researchers need to ensure that they strive for equal representation of both sexes in all trials. “We also need to report the sex of the subjects in all studies and analyze data by sex so that any sex-based differences are evident,” she added.

For basic science studies, Dr. Farzal recommends making sure that new treatments or tests are performed in both male and female animals or cells prior to going live in a human testing trial phase.

Additionally, otolaryngology journals need to follow other periodicals, such as the Journal of the American Medical Association network journals, in setting requirements for sex reporting and statistical analysis by sex, Dr. Farzal added.

In his work, Dr. Senior saw that the best rates of sex-based analysis were found in database studies. Randomized controlled trials (RCT), however, were found to perform sex-based analysis in only 40% of cases. “Given the fact that much of our evidence-based medicine dogma and treatment algorithms are derived from RCTs, this problem area seems particularly important to tackle,” he said. “Researchers need to take care to perform sex-based matching when appropriate and to perform sex-based analysis of their results.”

Action Steps

By making the otolaryngology research community aware of sex bias in clinical research, Dr. Senior hopes that researchers will address these issues. Furthermore, journal editors can help by mandating that only studies following current recommendations on reporting and data analysis by sex be published. Single-sex studies should provide a
rationale for exclusion.

Karen Appold is a freelance medical writer based in New Jersey.

History of Women’s Participation in Clinical Trials in the U.S.

1974 National Research Act is signed and outlines basic ethical principles underlying the conduct of research involving human participants.

1977 FDA releases a recommendation that essentially bans women of “childbearing potential” from participating in early phase clinical trials due to “risk of pregnancy” and subsequent risk of harm to a fetus.

1986 NIH recommends that grant applicants include women in studies; if they are not, a clear rationale must be provided.

1990 NIH establishes the Office of Research on Women’s Health.

1993 FDA issues “Guideline for the study and evaluation of gender differences in the clinical evaluation of drugs,” reversing the 1977 guidance.

1993 NIH Revitalization Act requires that women be included in all relevant research studies.