Thalidomide is a medication used to treat a number of cancers and skin conditions including complications of leprosy. The developers of the drug claimed that they “could not find a dose high enough to kill a rat” and so thalidomide was freely available since 1950s in stores as a mild over-the counter medication in many countries.In 1960, doctors began prescribing it to pregnant women who suffered from morning sickness.
It turned out that while the drug didn’t kill rats, it did affect foetal development. Before it was finally taken off the market in 1962, over 10,000 children had been born around the world with thalidomide-related disabilities! You can read a detailed story by NY Times.
Because of this scandal, the FDA (Food and Drug Administration) issued guidelines in 1977 excluding women of childbearing potential from drug trials!
But what happens when you exclude a certain group from clinical trial? Be it pregnant women or women altogether?
Over the last few weeks I have been reading a super insightful book – Invisible Women: Exposing Data Bias in a World Designed for Men by Caroline Criado Perez. Actually, I had started to read it long back (last year I think), but then got overwhelmed by the data / insights and had to take a break. I am glad I resumed. It is still overwhelming but one must read as much as one can.
Caroline essentially quotes examples after examples of how almost everything that is made / designed in the ‘man’-made world, miserably fails to take into account the specific needs of women. This reflects in design of roads to malls to phones to piano to drugs to vaccines.
Just because something works for men in a certain way does not mean it will necessarily work the same way for women. And that’s a problem when women are not represented adequately in any kind of user impact study.
In 2000 for example, the FDA had to force drug manufacturers to remove phenyl-propanolamine, a component of many over-the-counter medications, from all products because of a reported increased risk of bleeding into the brain or into tissue around the brain in women, but not in men.
To understand the difference between male and female bodies, at the most basic level you need to realize that women typically tend to have a higher body-fat percentage than men. This, along with the fact that blood-flow to fat tissue is greater in women, affects how women metabolise certain drugs. Also, male gut transit times are about half the length of women’s! This means women may need to wait for longer after eating before taking medications that need to be absorbed on an empty stomach.
When it comes to vaccine, it is well proven that women develop higher antibody responses and have more frequent and severe adverse reactions to vaccines.
The mechanisms leading to these differences can be:
- hormonal (i.e. the different effects of testosterone, oestrogens or progesterone);
- genetic (biological females have two X chromosomes while males have only one); or
- related to differences in intestinal bacteria.
And yet, most phase 1 clinical trials – a) don’t bother to study sex specific results and b) don’t enroll women in adequate numbers in the first place! How many drugs that would work for women are being ruled out at phase 1 trials just because they don’t work in men? Nobody knows!
Sex matters even in animal trials. In a 2007 analysis of animal studies where rats of both sexes were identified, it was observed that in over half the studies, the drug-effect depended upon the sex of the animal! And yet, most animal tests don’t bother to sex-tag the results (if they at all get enough of male and female animals in the first place).
By the way sex and gender have different implications – and to those not clear on the difference between the two terms, the below figure is self explanatory.
So how are we doing gender / sex wise in terms of analyzing Covid’s effect or vaccine development?
Most states are doing a bad job of reporting sex / gender aggregated data.
Bad quality of sex / gender aggregated data = a vaccine / drug that is designed mostly for men.
In a still to be peer-reviewed study, researchers have found that only 416 of the 2,484 Covid-19 clinical trials mention sex / gender as a recruitment criterion on the ClinicalTrials.gov database. [Source]
During the time of ancient Greeks, the female body was seen as a ‘mutilated male’ body – ovaries were female testicles and didn’t have a name for themselves till the 17th century! For millennia, medicine has functioned on the assumption that male bodies can represent humanity as a whole. A 2008 analysis of a range of textbooks recommended by ‘twenty of the most prestigious universities in Europe, US and Canada’ revealed that across 16,000+ images, male bodies were used three times as often as female!
For things to change in the future, we all need to be at least aware of the implicit data bias that exists in every single aspect of our lives – before enough people can even begin to make noticeable noise about it. I can only hope that happens sooner than later.
If you found the insights in this blog fascinating and yet reading an entire book on this topic is a bit much, at least check out this Guardian article that has a lot more examples of data bias for women and how it affects them, even kills them.