Though evenly split overall, research shows that women and men in disease trials are not represented according to the population affected.
Clinical trial sample populations should be proportionate to the population affected by the disease, as some diseases are more prevalent or manifest differently in one sex versus the other. Neglecting one sex in clinical trials can skew medical evidence toward therapies for the neglected population.
The study cross-analysed over 20 000 US clinical trials between 2000-2020, and found that women are underrepresented in clinical trials in cardiology, oncology, neurology, immunology and haematology. Meanwhile, men are underrepresented in clinical trials in musculoskeletal disease and trauma, psychiatry and preventive medicine.
This study, published JAMA Network Open, is the first to examine sex bias in all US human clinical trials relative to disease burden (which is the prevalence of disease based on factors such as sex and ethnicity).
“Sex bias in clinical trials can negatively impact both men and women by creating gendered data gaps that then drive clinical practice,” said first study author Dr Jecca Steinberg, a medical resident in the department of obstetrics and gynecology at Northwestern University Feinberg School of Medicine. “Neglecting one sex in clinical trials — the gold standard scientific exploration and discovery — excludes them from health innovation and skews medical evidence toward therapies with worse efficacy in that sex.”
Underrepresentating either sex in clinical trials can lead to less optimal health outcomes; differences exist for women and men in medical test results, disease progression, treatment response, drug metabolism and surgical outcomes, Dr Steinberg said.
These differences stem from variations in body size, composition, and hormones. Women’s smaller body sizes and higher fat contents typically result in varied drug responses. One study showed that aspirin has differential effects on the sexes with regard to primary protection against strokes and heart attacks. Aspirin only lowered women’s risk of stroke but had no effect on the risk of myocardial infarction or death.
“Identifying areas of research in which sex bias disadvantages males is important to improving population health,” Dr Steinberg said. “Our novel finding that men are underrepresented in trials related to mental health and trauma assumes greater urgency in American society where suicide, violence and substance use increasingly contribute to growing morbidity and premature male mortality in the US.”
Clinical trials for preventative medicine are more likely to have greater enrollment of women, the study found, adding credence to the notion that women, more than men, seek out preventive services and access to health care.
Women-specific underrepresentation remains
“One of the top reasons for Food and Drug Administration drug recall is adverse effects in women,” Dr Steinberg said. “Millions and millions of dollars go into these trials, so to relatively neglect women in the trial population is a waste.
“A greater allocation of resources for female-focused trials could be critical to improving care for women and discerning the heterogenous manifestations of diseases within the female population.”
For example, women with heart disease often have different reactions to medications and experience different symptoms from men, such as feeling abdominal pain rather than their left arm. If a clinical trial implements its intervention based on symptoms predominantly exhibited by the male population, it could miss testing interventions in women with cardiac arrest.
The reduced representation of women relative to disease burden specifically in oncology and cardiology clinical trials is especially troubling, said Steinberf, because cardiologic and oncologic diseases are among the leading causes of death among women in the US.
Participating in clinical trials is also one of the only ways to access cutting edge therapies, especially oncology, so the relative deficiency of one sex contributes to disparities in health outcomes, Steinberg said.
“One of our hopes from this study is that scientists and physicians will read about our findings and be inspired to say, ‘Why is that happening in my field?’ and then address it,” Dr Steinberg said.
Source: Northwestern University
