Throughout the past few decades, studies indicate that the inclusion of women in clinical trials has improved marginally, but there is still a need for better representation of women in research. “The equal inclusion of men and women in clinical trials is important from both a medical and surgical standpoint,” says Melina R. Kibbe, MD. “Men and women have dissimilar health issues, metabolize and react to some drugs differently, and respond to medical devices differently. Both males and females can have diverse outcomes after medical interventions.”
Recent analyses have shown that there appears to be sex bias in surgical biomedical research. “Based on the results of these investigations and pressure from advocacy groups, the NIH announced that sex must be considered a variable in all NIH-funded studies,” says Dr. Kibbe. Despite this decree, it is still unknown if sex bias still occurs in human surgical clinical research.
Considering that men and women can experience different postoperative outcomes, complication rates, and readmission rates, Dr. Kibbe says it is important to determine if this problem of sex bias is pervasive in surgery. “Controlling for sex as a variable is important because the data derived from clinical research are the foundation to evidence-based medicine,” she says.
Taking a Closer Look
For a study published in JAMA Surgery, Dr. Kibbe and colleagues investigated if sex bias exists in human surgical clinical research. They also sought to determine if data are reported and analyzed using sex as an independent variable and to identify specialties in which there were the most and least sex biases. The research team conducted a bibliometric analysis, using data from more than 1,300 original peer-reviewed articles published from 2011 to 2012 in five commonly-read surgery journals.
According to the results, only about 80% of published studies included both males and females. “Alarmingly, about 17% did not even document the sex of the participants in the study,” Dr. Kibbe says. The study team also found that there were slight differences regarding studies reporting data separately for male and female participants, studies that performed statistical analyses on data collected by sex, and articles addressing sex-based results in the discussion section (Figure below). These data were similar between domestic and international studies.
“Overall, sex matching of the included participants in our study was also poor,” says Dr. Kibbe. Only about 45% of the studies matched the inclusion of both sexes by half. A wide variation in sex-based inclusion, matching, and data reporting was also seen. Endocrine surgery, surgical oncology, and colorectal and thoracic surgery had the best matching of male and female participants whereas breast, bariatric, and cardiac surgery had the worst.
Dr. Kibbe says that although gender reporting and bias has improved over time, more work is needed to reduce the disparities seen in clinical research. “For example, it’s possible some drugs, therapies, and devices may be developed that are more effective for one sex than another,” she says. “Without collecting sex-based data, we cannot know which sex benefits more from a particular treatment.” She adds that performing independent data analyses and reporting can produce findings that offer more valuable contributions to the health and well-being of men or women independently.
The study group notes that it is possible that some therapies and drugs in development may be abandoned if they have an overall low efficacy in men and women when the data are combined. Furthermore, it is possible therapies may be developed that have undesirable adverse effects in the opposite sex.
In the past, there has been criticism surrounding the inclusion of both sexes and considering sex differences in clinical research. “We recommend that there be an FDA mandate requiring that drugs, devices, and new therapies be tested equally in men and women in clinical trials before they reach market approval,” says Dr. Kibbe. The study suggests that medications which have been recalled due to adverse effects in one sex should be tested independently in both sexes. It is possible that these drugs may be considered for rerelease with different dosing parameters for each sex.
“There should be a mandate by research funding agencies to include males and females in clinical research and report results independently for these participants so that sex may be examined as an independent variable,” Dr. Kibbe says. “Journal editors should also require study authors to include the sex of all participants involved in the investigation and require sex-based reporting, analysis, and discussion of this data. Additionally, government monitoring of sex-based inclusion of participants, sex as an independent variable, and sex-based data reporting should be required.”
Considering that clinical research is the foundation for evidence-based medicine, Dr. Kibbe emphasizes the importance of addressing the disparities seen in the analysis. She notes that inclusion of data on men and women in scientific clinical research has been mandatory for other many other countries throughout the world, and says the United States should follow suit and also mandate such requirements.
Melina R. Kibbe, MD, has indicated to Physician’s Weekly that she has or has had no financial interests to report.
Readings & Resources (click to view)
Mansukhani NA, Yoon DY, Teter KA, et al. Determining if sex bias exists in human surgical clinical research. JAMA Surg. 2016 Aug 17 [Epub ahead of print]. Available at: http://archsurg.jamanetwork.com/article.aspx?articleid=2542659.
Kim AM, Tingen CM,Woodruff TK. Sex bias in trials and treatment must end. Nature. 2010;465:688-689.
Prins MH, Smits KM, Smits LJ. Methodologic ramifications of paying attention to sex and gender differences in clinical research. Gend Med. 2007;4(suppl):S106-S110.
Check Hayden E. Sex bias blights drug studies. Nature. 2010;464:332-333.