More Women are Participating in Clinical Trials But That Doesn’t Mean the Studies are Studied

James Brown and Luciano Pavarotti weren’t being sexist when they performed the famous duet, “It’s a Man’s Man’s World” (double man’s). After all, the lyrics give us credit: “This is a man’s, man’s, man’s world | But it wouldn’t be nothing, nothing without a woman or a girl.” (Three man’s, one woman, and a girl.)

Tell that to Big Pharma and the medical research community because their collective MO has a longstanding tradition of sexism. These industries, until recently dominated by males, have famously slighted women because, if you will, females are a different, more complicated organism than men on account of ever-changing hormones. Some say it’s bias.

Is there any improvement today over a decade ago? One study says yes, and no.

Female participation in general human clinical trials is up from 28% in 2009 to 49%. But the studies are not being analyzed for findings, experts say. The underlying issue traces back to the ancient taboo of menstruation. Believe it or not, “hormone variation” is blamed for women’s exclusion from trials or, if participating, lack of resulting analysis of the findings. Fluctuating hormones render the female a more complicated organism, less stable and inferior, as subjects go. So they say.

Women have been poorly under-represented in drug trials since 1977 when the FDA banned all women with “childbearing potential” from empirical trials to protect their unborn from exposure to experimental chemicals. The decision was precluded by a disaster involving the drug thalidomide, prescribed for morning sickness and resulting in serious birth defects until the connection was made.

During those 16 years, abundant information was collected about the impact of drugs and trials on cisgender males (men who identify with their birth gender). So began a tradition whereby male responses became accepted as the norm for both sexes.

Prior to the women’s health movement: “Many clinical trials ran under an unspoken assumption that the only difference between women and men was their sexual and reproductive organs. Women were, in essence, considered small men.” – Regine Douthard, NIH Office of Research on Women’s Health

The 1977 ban lasted until 1993 when the FDA published a revised guideline requiring new applications for drugs to examine and include safety and efficacy data by gender, age and race. Together with the NIH Revitalization Act of 1993, it was a beginning. The FDA has since adhered to a policy of inclusion in clinical trials, especially regarding prescription drugs.  It’s working: we’re at nearly 50%.

The passage of the Revitalization Act, long overdue, was significantly brought to fruition by many civil liberty movements, and popular literature like the book Our Bodies, Ourselves, which comfortably addressed women’s health and sexuality.

Hardly any drug on the market today, except Ambien (zolpidem), specifies separate doses based on sex, but it makes sense: women are smaller, they have different composition in terms of body fat and generally slower metabolism, not to mention hormone variations. As a result of clumping the sexes, 80% of drugs pulled from shelves in 1997 were found to cause more adverse side effects and health risks in women.

One recent discovery, within the context of research sex equity, has been that diseases may present differently in women than men. Heart disease, for example, kills 1-4 women in America, making it the highest cause of female deaths in the US. But women with cardiovascular disease more often go undiagnosed or misdiagnosed simply because they don’t exhibit classic symptoms (e.g., the appearance of plaque is smaller in women than men), resulting in underdiagnosis or less aggressive treatment than called for.

On average women with heart disease are diagnosed 7-10 years after an unidentified attack, when secondary complications may have developed and the chances for survival are diminished. Even aspirin affects women differently (aspirin lessens men’s risk of heart attack but not stroke; the opposite is true for women).

Women are severely under-represented in cancer trials, though the female incidence for lung cancer, melanoma, and pancreatic cancer is higher than men’s (excluding breast and prostate cancer in this analysis).

“Given the significant sex differences from biology to behavior, excluding females means one cannot assume that any findings would apply to females,” said Vineet Arora of The University of Chicago Pritzker School of Medicine.

Every cell in a person’s body has a sex. The situation may be improving but the lack of recognizing the difference, especially when there is data for analysis, is a wrong that research must begin to right. To many, the attitude seems more lax than life-and-death.