Editor’s note: This is the second part of a two-article series investigating gender bias in otolaryngology. Part one, which focused on gender bias in research funding, was published in the May 2019 issue of ENTtoday.
Explore This IssueJune 2019
Sex bias favoring males in clinical trials has been pervasive for decades. The many reasons include concerns that women’s estrogen hormonal variation may create biologic and physiologic inconsistencies, creating unknown variables in studies. In addition, unknown hazards of drugs tested in clinical trials could impact women’s childbearing potential. Furthermore, studies performed on men or male animals were presumed to translate directly to women.
However, it’s now known that men and women have different disease prevalence and risks, said Brent Senior, MD, the Nathaniel and Sheila Harris Distinguished Professor of otolaryngology–head and neck surgery at the University of North Carolina at Chapel Hill.
In 1986, The National Institutes of Health (NIH) changed its policy to include women of childbearing age in research. Then, the NIH Revitalization Act of 1993 mandated the inclusion of women and minorities in clinical research. However, in the 1990s and 2000s, data continued to reveal that inclusion of women didn’t increase significantly in clinical trials despite this legislation, said Zainab Farzal, MD, resident physician and researcher in the department of otolaryngology/head and neck surgery at the University of North Carolina at Chapel Hill. Furthermore, there was evidence that drugs were not being tested on both male and female animals before moving to the human testing phase. The scientific community continued to pressure the NIH to investigate and, in 2016, the NIH issued a policy requiring all funding proposals to consider sex as a biological variable in all human and animal research.
This didn’t solve everything, however, said Dr. Farzal. “This policy didn’t mandate that a certain percentage of women be included in every study and had no jurisdiction over research not funded by the NIH,” she said. “Consequently, sex bias continues to be a major force in our field.”
Studies that don’t take into account women’s metabolism and concerns don’t honor the differences between women and men and may result in incorrect or harmful care for female patients. —Sujana Chandrasekhar, MD
The Status Quo
Based on her work with Dr. Senior and other colleagues, Dr. Farzal hasn’t seen a corresponding increase in sex-inclusive research in otolaryngology despite mandates and policies for sex-inclusive research (Laryngoscope. 2019;129:858–864; Laryngoscope. 2019;129:613–618).
In reviewing otolaryngology clinical literature, Drs. Farzal and Senior and their colleagues found that only 46.7% of studies analyzed data by sex. Additionally, only 330 studies included at least half as many participants of one sex in a study as they had the other. When the researchers specifically analyzed randomized controlled trials, they noted that 40% of otolaryngology trials analyzed data by sex, which was even lower than clinical otolaryngology literature.
Dr. Senior added that, when comparing today’s trials with those from past decades, he and his colleagues found that inclusion of sex-based analyses and under-inclusion of one sex has marginally improved. For example, in the 40 years between 1949 and 1989, a study found that 32% to 45% of publications in human research journals studied both sexes (Neurosci Biobehav Rev. 2011;35:565–572). That number climbed to greater than 60% for articles published between 1999 and 2009. In addition, the researchers reported that sex-unspecified publications decreased from greater than 20% in the earlier time period to 7% in the latter. However, significant disparities still exist today; a 2011 study concluded that 75% of 86 human research articles that were federally funded lacked sex-based analysis (J Womens Health (Larchmt)). 2011;20:315–320).