Taking on Gender Bias in Clinical Trials

The National Women’s Health Network (NWHN) has long advocated for the greater participation of women and other key groups in clinical trials for all drugs and devices, and particularly for products that are principally marketed and used by women.  For decades, health research was done on men and the results were assumed to apply to women. Women were treated as if they were just smaller versions of a male body.  Women’s health activists including the NWHN drew attention to that problem more than 20 years ago, and as a result things have started to change in the research world. We invited ConsumerSafety.org to create a blog post that introduces the subject to those who are new to the issue. The problem is far from over!

When clinical trials make the news, it is usually the results that people care about most. A story might report that insights from a study could lead to better healthcare practices or a breakthrough treatment for patients. But it is also common to see news stories about clinical trials gone wrong, like the tainted clinical trial for Johnson & Johnson’s blood thinner Xarelto. What the news doesn’t always emphasize are the clinical trial subjects themselves. And today, in the midst of the #MeToo era, we need to highlight a major issue that has affected clinical trial results for decades: gender bias.

Historically, women have been incredibly underrepresented in clinical trials. Part of this disparity between genders in clinical research came from the early misconception that men and women are the same. We now know that this is false; men and women are unique on a cellular level. Because of this, they react to drugs and medical therapies differently. However, early researchers, unaware of these differences, preferred working with male test subjects for two main reasons.

Firstly, male subjects experience fewer hormonal fluctuations than the average menstruating woman. Researchers worried that the frequent changes in hormone levels could affect the final results of the clinical trial. Secondly, it was taboo to test on a pregnant woman; people feared the safety risks involved for both mother and child. Therefore, women who were pregnant or could get pregnant during the length of the clinical trial were often excluded.

We might consider this a dated practice from the 1950’s to protect housewives everywhere, but even as recently as 1986 there was a study looking into the effects of obesity and its relationship to breast and uterine cancer in women. No women were actually part of this study. This male-only study missed the critical link between hormones, calcium, and osteoporosis in women.

Heart disease, too, has been studied through a narrow gender lens, and women have suffered because of it. Often labeled a man’s disease, heart disease is the leading cause of death for both men and women. Studies using a majority of male test subjects have done a disservice to women. For example, the typical signs of a heart attack are symptoms that many women don’t experience when having a heart attack; they are symptoms most commonly seen in male patients. Because of this, women experiencing a heart attack are frequently misdiagnosed. Women and even doctors have misinterpreted these “abnormal” heart attack symptoms seen in women as signs of a panic attack, too much stress, or even hypochondria. To make matters worse, studies have shown that doctors spend less time educating their female patients about heart disease.

Historically, women have been incredibly underrepresented in clinical trials.

It’s reasonable to assume that drug clinical trials study the demographics that will be using the approved drug. However, the drug industry is no exception to the practice of using men over women in clinical trials. By excluding women, drug companies and researchers miss the opportunity to study the side effects and results that only occur with female patients. A report from the U.S. Government Accountability Office (GAO) showed that between 1997 and 2001, 10 prescription drugs were pulled from the market. Eight of those drugs were removed because they negatively affected the health of women. It’s impossible to fully understand the safety and efficacy of a drug or medical device unless we include all demographics in the clinical trials. To truly understand the nature of a drug or medical device, we need to make studies inclusive, including all genders, races, ethnicities, and potentially different age groups.

To combat the gender bias in clinical trials and medical research, Congress passed the National Institute of Health Revitalization Act of 1993. It encouraged researchers to include more women and minorities in clinical trials. While this piece of legislature did generate greater awareness of the issue and start the momentum towards equality in clinical trials, the work isn’t finished. As recently as 2015, the GAO expressed the need to further study the differences experienced by male and female test subjects in clinical research. The NWHN recognizes the continued need for more inclusivity in clinical trials, for all drugs and devices, and particularly for products that are principally marketed and used by women.”

We have made progress as a country, but there is still work to be done. Clinical trials need to broaden their subject base and do a better job of representing all affected parties for the sake of equality and the generation of more rational, insightful data. Patients and healthcare professionals need great transparency and “accurate information about the medical products available to them.” Without data on the benefits and risks specific to a person’s race, ethnicity, gender, or age, how can a doctor make a safe decision for her patient?

The NWHN advocates for an explicit requirement by the FDA mandating the inclusion of sufficient numbers of women in pre-approval clinical trials to allow the agency to determine if the products are safe and effective when used by women.  The FDA continues to resist creating a mandate. However, in response to our advocacy, in 2015 the FDA created Drug Trials Snapshots. In these Snapshots, the FDA publishes the exact data about who was in trials of new drugs, so people can see the data for themselves and make informed decisions. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

The NWHN continues to urge the FDA to establish strong enforcement mechanisms to hold companies accountable. We are committed to ensuring that women have access to accurate, balanced health information and services.

Caitlin Hoff is a Consumer Advocate at ConsumerSafety and a NWHN staff member.

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