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Researchers aim to shed light on just how rampant sex bias is in clinical trials.
Image credit: Francesco Carta fotografo/Getty Images
  • A new cross-sectional study shows that both males and females face underrepresentation in clinical trials, though in different areas of medical study.
  • The research found that females were most underrepresented in the area of oncology, while males were most underrepresented in the areas of musculoskeletal disorders and trauma.
  • The authors warn that bias could lead to poorer standards of care for members of the underrepresented sex.

A note about sex and gender

Sex and gender exist on spectrums. This article will use the terms “male,” “female,” or both to refer to sex assigned at birth. Click here to learn more.

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Researchers evaluate the effectiveness of medical treatments based on outcomes in clinical trials. These studies aid in the development of safe and effective treatments for various diseases.

The results of clinical trials can be used to improve the overall health of the population, increase knowledge about diseases, and promote the distribution and implementation of effective treatments.

Researchers are concerned about accurately representing the population that will be affected by new treatments. This includes having adequate representation of male and female participants in clinical trials.

One cross-sectional study, published in JAMA Network Open, examines female participation in clinical trials over the last 20 years.

The authors wanted to see whether female participants were represented accurately in relation to disease prevalence, something that has not received much attention in data analysis.

As the Food and Drug Administration (FDA) explains, there are several reasons why it is important to have accurate, diverse representation in clinical trials. The participants in these trials need to reflect the people who will likely receive the treatment in the future.

If a treatment will be widely available to the general population, the clinical trials for that treatment need to include participants who reflect the general population.

Because people respond to treatments differently, including a diverse group of participants helps with complete data collection. This better ensures the safety of everyone.

As the researchers behind the present study note, historically, women were not included in clinical trials. Lead study author Dr. Jecca Steinberg told Medical News Today:

“Clinical trials represent the gold standard of evidence for the progression of medical care. Sex bias in clinical trials leads to treatments with understudied efficacy in the neglected sex. The historic underrepresentation of females in trials has contributed to the relative deficiency in knowledge on the prevention strategies, disease manifestations, prognosis, and treatment of disease in females.”

The researchers set out to investigate whether female participants were being accurately represented in relation to the number of females affected by a particular disease in the general population. They also examined factors related to clinical trials that influenced the enrollment of females, such as study funding and study design.

With the data collected, they discovered areas in which females were underrepresented — and others in which males were underrepresented.

The team collected data using the database provided by the National Library of Medicine. They examined enrollment based on sex in clinical trials dating from March 2000 to March 2020.

The researchers then compared levels of enrollment with disease prevalence using the Global Burden of Disease Study 2016 database. The compiled data included 20,020 clinical trials and their collective enrollment of more than 5 million participants.

Considering the disease prevalence, females were most underrepresented in the area of oncology.

They were also underrepresented in the following areas of specialty:

  • neurology
  • immunology
  • sex-nonspecific nephrology and genitourinary disease
  • hematology
  • cardiology

The main positive finding was a higher likelihood of enrolling in trials that focused on disease prevention. However, females were particularly unlikely to enroll in pediatric and cardiology trials, as well as any that involved a medical device, biologic drug, or supplement.

Dr. Steinberg described highlights of the study’s findings and suggested that more focus on females in clinical trials could improve health outcomes: “Cardiology and pediatric trials showed [the] greatest negative associations with female enrollment, while prevention trials had a positive association… A greater allocation of resources for female-focused trials could be critical to improving care for females.”

Males were also underrepresented but in different areas. The greatest underrepresentation was in trials related to musculoskeletal disease and trauma.

The researchers also identified underrepresentation for males in the following areas:

  • ear, nose, and throat, a specialty called otolaryngology
  • psychiatry
  • congenital studies
  • nutritional and metabolic studies
  • gastroenterology
  • endocrinology
  • pulmonology

They were also less likely to enroll in studies of mental health and prevention.

Dr. Steinberg noted that sex bias in relation to male health is an understudied area. She told MNT that the study’s “novel finding that men are underrepresented in trials related to mental health and trauma may provide novel insights into areas of research where male health has been neglected.”

Expert in men’s health Dr. Derek M. Griffith explained to MNT:

“Men’s underrepresentation in clinical trials in psychiatry is particularly troubling, given men’s high rates of suicide and substance abuse. There [has] also been important evidence from clinicians that men may exhibit different symptoms of depression, for example, than women.”

The team behind the present study notes that sex bias in clinical trials is still prevalent, despite immense efforts to improve representation. Future research may need to be tailored to ensure an accurate representation of males and females, based on disease prevalence, in clinical trials.

The study provides thorough data to determine males’ and females’ representation in clinical trials related to 17 disease categories.

The methods of analysis allowed the researchers to examine areas of underrepresentation that need to be addressed in the future. The study also dealt with how the representation of males and females in clinical trials should be examined in relation to disease prevalence.

However, the researchers did not include information about whether potential participants were approached to take part in clinical trials, a factor that could influence representation.

It was also unclear what barriers to enrollment exist. Additional limitations include a lack of reported results from clinical trials, limitations concerning the database, and changes in disease prevalence.

Also, the study authors acknowledge that health data about transgender and nonbinary participants was lacking and that more transgender and nonbinary people will need to be included in clinical trials to increase their accuracy.

Ultimately, the study shed light on sex-related bias, concerning males and females, that still exists in clinical trials. Researchers need to understand which areas of study may have over- or under-representation in clinical trials and adjust their participant selection accordingly.