The Clinical Trial Gap: Why Diversity in Scientific Research Matters

A focus on male mice models in clinical trials has big implications for the benefits of scientific research.

There’s been a lot of talk about gender discrimination in the work place. But what about gender discrimination in the petri dish? It turns out that male cells and male animal models are much more likely to be studied in clinical research—and this could have negative impacts on women’s health. 

Though it’s tempting to think that all cells, and even all mice, will react similarly to medical testing despite gender, a new study published in Nature Communications found otherwise. Researchers from the Wellcome Trust Sanger Institute reported that many genetic traits in the mice that are used for clinical studies varied due to gender. This finding has big implications for the benefits of scientific research.

According to the study, a reliance on male mice models may be harming women. Animal research trials that are overwhelmingly focused on the male species risk missing key differences in male and female biology that could make treatments and medications less effective — or even dangerous — for the female members of the species.

“This was a scientific blind spot that we really thought needed exploration,” said Natasha Karp, a biostatistician and the lead author of the Sanger Institute study, in a press statement. “A person’s sex has a significant impact on the course and severity of many common diseases, and the consequential side effects of treatments – which are being missed.”

The team looked at 234 traits and found that most quantitative traits (things like height, weight, and blood pressure) varied significantly between male and female mice. They also discovered that even in research where both sexes were studied, two-thirds of the time the results were not analyzed by differences in gender.

“Regardless of research field or biological system,” the researchers concluded, “consideration of sex is important in the design and analysis of animal studies for studies where sex differences could occur.”

This isn’t the first time that the issue of the science research gender gap has been raised. In 1993, the National Institutes of Health (NIH) Revitalization Act was passed into law in order to promote gender and racial diversity in human clinical research. It was effective — today more than half of participants in clinical trials are women.

But the gender gap persists in pre-clinical animal and cell studies. In 2014, more than 20 years after the Revitalization Act, the NIH passed another policy that requires trial applicants to report how they plan to balance the study of male and female animals and cells. The policy was implemented last year.

As is often the case when gender equality is brought up, not everyone was thrilled.

“The rule would be a huge waste of resources,” wrote a male researcher in an op-ed when the policy was introduced in 2014. “Modifying experiments to include both males and females costs money,” he noted, and requires “time that researchers might not have to spare or that might be better spent conducting other research.”

This line of thinking, though practical at first glance, could be hazardous. Lack of representation in scientific research could potentially leave women sick or vulnerable to adverse side effects that men may not experience.

Even illnesses that disproportionally affect women are still not likely to be equally studied between genders. One example is insomnia, which affects women more than men. Yet it was discovered in 2014 that insomniac women don’t need to take as much of the sleep medication Ambien as men because they typically weigh less. In fact, the FDA recommended that the dosage for women be cut in half to diminish the likelihood of morning impairment.

Other studies of maladies that affect women more than men, such as cardiovascular diseases, also generally base their recommendations on male research. One analysis found that even in cases that study female-prevalent diseases, only 12 percent of the studies that described the gender of their animal models looked at females.

The authors of that study stressed that the preclinical biomedical mammal and cell studies are the “foundation for subsequent clinical research and medical decision-making.” “It is imperative that this disparity be addressed,” they warned, “because conclusions derived from such studies may be specific to only one sex.”

Gender isn’t the only area where clinical research is lacking diversity. There are many instances of ethnic and racial minorities being underrepresented in research, even though some ethnicities experience different genetic or environmental traits that can impact medical risks. For example, less than 5 percent of NIH-funded respiratory research studies between 1993 and 2015 reported the inclusion of racial and ethnic minorities, despite the fact that minorities are much more likely to have respiratory diseases such as asthma.

Diversity has been shown to be beneficial in many areas, including at school and in the workplace. Though it may demand more resources, these studies imply that focusing on a broader sample of animal testing models and cells would benefit science as a whole — as well as our collective health.