Invisible Women: and now for something really wacky
Invisible Women: and now for something really wacky
sex disaggregating adverse events and sexist snow gritting
My dear GFPs, welcome to the newsletter you were MEANT to get a couple of weeks ago when I decided instead to take a detour into the miserable world of male violence against women. Which I’m glad I did, as it seemed to resonate with so many of you. Maybe I’ll indulge in some more detours in the future…but for now, let’s return to our regularly scheduled programming and (the lack of) sex disaggregated data in heart failure research.
Gender data gap of the week
Toward the end of last year a really useful review paper came out that analysed the state of sex disaggregation in heart failure research. Second to original research studies that properly sex disaggregate and sex analyse 😍, this is my favourite kind of paper, as it’s always very useful to have an up-to-date round-up of where we are even if the answer is usually, as it is here, quite depressing/enraging.
So where are we? Well, nowhere very good. This paper, which analysed 224 random controlled heart failure trials between 2000 and 2020 found that women made up only 28% of participants. This is…suboptimal given heart disease is the leading cause of death for women in the US and Europe. Only 33% did any sex analysis of the primary outcome and only 28% tested for interaction between sex and the intervention, ie the drug or device they were studying. A grand total of zero (0) trials reported sex-disaggregated data on adverse effects.
Let’s take a pause here to reflect on a section of Invisible Women where I wrote about adverse effects and women:
Some drugs used to break up blood clots immediately after a heart attack can cause ‘significant bleeding problems in women.’ Other drugs that are commonly prescribed to treat high blood pressure have been found to lower men’s mortality from heart attack – but to increase cardiac-related deaths among women.’ […] In 2000 the FDA forced drug manufacturers to remove phenylpropanolamine, 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. Drug-induced acute liver failure has also been reported more often in women, and certain HIV medications are six to eight times more likely to cause an adverse drug reaction (ADR) in women.
[…]
The second-most common ADR for women (after nausea) is that the drug simply doesn’t work at all, and data on the number of deaths that occur as a result of the drug failing to work is not available. We do know, however, that women are more likely to be hospitalised following an ADR, and more likely to experience more than one . A 2001 US study found that 80% of drugs that had been recently removed from the market caused more ADRs in women, while a 2017 analysis points to the ‘large number’ of medications and medical devices removed from the market by the FDA that posed greater health risks to women.
None of this should surprise us, because despite obvious sex differences, the vast majority of drugs, including anaesthetics and chemotherapeutics, continue with gender-neutral dosages, which puts women at risk of overdose. At a most basic level, women tend to have a higher body-fat percentage than men, which, along with the fact that blood flow to fat tissue is greater in women (for men it’s greater to skeletal muscle) can affect how they metabolise certain drugs. Acetaminophen (an ingredient in many pain relievers), for example, is eliminated by the female body at approximately 60% of the rate documented in men. Sex differences in drug metabolism is in part because women’s lower lean body mass results in a lower base metabolic rate, but it can also be affected by, among other things: sex differences in kidney enzymes; in bile acid composition (women have less); and intestinal enzyme activity. Male gut transit times are also around half the length of women’s, meaning women may need to wait for longer after eating before taking medications that must be absorbed on an empty stomach. Kidney filtering is also faster in men, meaning some renally excreted medications (for example digoxin – a heart medication) ‘may require a dosage adjustment’. [IW, pp.214-5)
The really enraging thing about all this is that, as this paper points out, thanks to the failure of researchers to systematically sex disaggregate and sex analyse their data most of this information about adverse drug reactions in women is not uncovered during the trial stage, but instead become apparent years after the drug or device has been approved for use in patients:
Indeed, sex differences in treatment effect are common but often discovered in observational data years after RCTs are published. Observational data have revealed that females benefit from angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and beta blockers at lower doses than those informed by RCTs (with predominantly male participants). Similarly, females incur higher bleeding risk post percutaneous coronary intervention, experience greater benefit from cardiac resynchronization therapy, and have higher complication rates post-surgical revascularization than males. Sex differences in cardiac chamber and coronary artery size, volume of distribution, and pharmacokinetics are well documented; these may influence tolerability, treatment effect, and adverse events following drug, device, and surgical interventions.
All seems like stuff you might like to discover before releasing a new drug onto the market by, you know, doing something wacky like sex disaggregating you adverse outcome data or something 🤪
Default male of the week
I was delighted to see this story appearing in my mentions this week. Alex Beckett is Cambridgeshire’s lead counsel for highways and as Daisy says, he’s preaching the Invisible Women message, which obviously, we love to see:
Cllr Beckett […]argued current [gritting] routes need to work better for active travel users – cyclists and pedestrians – and for those engaged in social care, rather than being focused on business users.
He told councillors: “We do need to review the network. It’s currently years out of date and primarily focused on getting men to work in cars. It’s a network focused on businessmen and councillors, not representative of normal people and their lives.
“There is a large body of evidence that gritting routes defined like this can be sexist and can leave active travel users counting the costs with broken limbs.
Bestill our beating hearts, Alex!
Naturally one of his fellow councillors wasted no time in making the obvious hilarious wilfully obtuse joke:
Cllr Steve Tierney (Con, Wisbech West), said Cllr Beckett “seems to think only men drive to work and then amusingly accuses others of sexism”.
Excuse us while we…
Thankfully, our hero of the hour, Cllr Beckett was ready to set his fellow councillors straight: “It might be surprising to you but prioritising routes used by business over those used for social caring responsibilities can disproportionately affect women. (And yes I really do think we need to get more of us men into social caring responsibilities).”
SING IT, ALEX!
Meanwhile, over at The Times, Carol Midgley is doing sterling work for the cause proving that it’s not just men who can be tediously obtuse and incapable of understanding how systemic discrimination and averages work:
Apparently it’s not obvious that literally no one would suggest that no women drive, nor that pointing out that men are more likely to drive to work while women are more likely to take public transport (and therefore more likely to use pavements) is not the same as saying that no women drive, nor even that snow clearing and gritting schedules are the result of deliberate dastardly misogyny rather than, you know, just a historical artefact based on typical default male travel patterns that now needs revising?
It’s a facile cheap shot and one I can again only respond to with this:
OH GOD all right then, and this:
We lack consistent, sex-disaggregated data from every country, but the data we do have makes it clear that women are invariably more likely than men to walk and take public transport. In France, two-thirds of public transport passengers are women; in Philadelphia and Chicago in the US, the figure is 64% and 62% respectively. Meanwhile, men around the world are more likely to drive. and if a household owns a car, it is the men who dominate access to it – even in the feminist utopia that is Sweden.
And the differences don’t stop at the mode of transport: it’s also about why men and women are travelling. Men are most likely to have a fairly simple travel pattern: a twice-daily commute in and out of town. But women’s travel patterns tend to be more complicated. Women do 75% of the world’s unpaid care work and this affects their travel needs. A typical female travel pattern involves, for example, dropping children off at school before going to work; taking an elderly relative to the doctor and doing the grocery shop- ping on the way home. This is called ‘trip-chaining’, a travel pat- tern of several small interconnected trips that has been observed in women around the world.
In London women are three times more likely than men to take a child to school and 25% more likely to trip-chain; this figure rises to 39% if there is a child older than nine in the household. The disparity in male/female trip-chaining is found across Europe, where women in dual-worker families are twice as likely as men to pick up and drop off children at school during their commute. It is most pronounced in households with young children: a working woman with a child under the age of five will increase her trip-chaining by 54%; a working man in the same position will only increase his by 19%.
What all these differences meant back in Karlskoga was that the apparently gender-neutral snow-clearing schedule was in fact not gender neutral at all, so the town councillors switched the order of snow-clearing to prioritise pedestrians and public-transport users. After all, they reasoned, it wouldn’t cost any more money, and driving a car through three inches of snow is easier than pushing a buggy (or a wheelchair, or a bike) through three inches of snow.
What they didn’t realise was that it would actually end up saving them money. Since 1985, northern Sweden has been collecting data on hospital admissions for injuries. Their databases are dominated by pedestrians, who are injured three times more often than motorists in slippery or icy conditions and account for half the hospital time of all traffic-related injuries. And the majority of these pedestrians are women. A study of pedestrian injuries in the Swedish city area of Umeå found that 79% occurred during the winter months, and that women made up 69% of those who had been injured in single-person incidents (that is, those which didn’t involve anyone else). Two-thirds of injured pedestrians had slipped and fallen on icy or snowy surfaces, and 48% had moderate to serious injuries, with fractures and dislocations being the most common. Women’s injuries also tended to be more severe.
A five-year study in Skåne County uncovered the same trends – and found that the injuries cost money in healthcare and lost productivity. The estimated cost of all these pedestrian falls during just a single winter season was 36 million Kronor (around £3.2 million). (This is likely to be a conservative estimate: many injured pedestrians will visit hospitals that are not contributing to the national traffic accident register; some will visit doctors; and some will simply stay at home. As a result, both the healthcare and productivity costs are likely to be higher.)
But even with this conservative estimate, the cost of pedestrian accidents in icy conditions was about twice the cost of winter road maintenance. In Solna, near Stockholm, it was three times the cost, and some studies reveal it’s even higher. Whatever the exact disparity, it is clear that preventing injuries by prioritising pedestrians in the snow-clearing schedule makes economic sense. (IW, pp.29-31)
Hope that’s not too sexist for you Carol and Steve!
Poppy pic of the week
Phew! Let’s palate cleanse with a good dose of Poppy, first of her name:
Aaaahhhhh, much better!
That’s it for now, folks, (only kidding my dear GFPs 😘) until next time…xoxoxo