Drugs are a necessity in medicine and their creation and innovation has exponentially increased along with our knowledge of science. With these improvements we’ve seen increased regulations in order to keep patients safe – one of which is clinical trials.
A clinical trial allows researchers to compare the effects of different treatments, ensuring that drugs are safe and effective before being marketed. They are split into different phases which each test for specific things:
Phase 1:
Involves giving the drug to humans for the first time. It is used to research for side effects and calculate the correct dosage for the treatment, by starting with a small dose, and increasing it if there are no side effects. Typically, the volunteers are healthy.
Phase 2:
The drug is then used on a larger group of people who are ill in order to understand its effects on the illness in the short term.
Phase 3:
If the drug has passed the first two phases, it is tested on a larger group of people (several thousand) who are ill against a drug which is already used, or a placebo, to see if it is better or if it has significant side effects. This is done over a longer period.
If a medicine passes these phases, it can be giving a marketing licence, which makes it available on prescription, (though the side effects and effectiveness of the drug are still monitored while it is being used). In theory, these trials should be diverse, so that many different people can effectively benefit from the drug’s use, and for researchers to know how medicines affect these different groups of people. But clinical trials are still failing to sufficiently represent one of the largest groups on the planet: women.
The representation of women in Phase 1 is very low (around 22%), and while it increases in Phase 2 and 3 (around >40%), this isn’t good enough. By this point, treatments are being adjusted to make them better, not being tested for efficacy, so drugs that could be effective on women are being overlooked, and those that aren’t effective are reaching production. The second most common adverse reaction is drugs not working on women (but working on men), and this is a clear consequence of the failure to include women in research.
A paper was published that assessed the participation by sex in recent clinical trials in the USA (2016-19) across different areas such as adult cardiovascular, psychiatric and cancer drugs, in trials that planned to enrol both sexes. Researchers found that over 1433 trials, with over 300,000 participants, on average only 41.2% were female. 49% of people with cardiovascular disease are women but only 41.9% of the participants were female. Heart disease remains one of the leading causes for death for women, both in the US and the UK, and yet clinical trials’ participant numbers do not reflect this. Even more worryingly, in diseases with a higher female disease population, the numbers also fell short. 60% of psychiatric patients are women, but “the mean participation of females in clinical trials was 42.0%”. [1] Furthermore, trials for cancer drugs showed only 41% of female participants, when 51% of cancer patients are female. As the researchers state,“for each therapeutic area analysed, the participation of females in clinical trials fell short of the benchmark…from national…data”. 1
But this negligence doesn’t end at human clinical trials. 90% of pharmacological articles describe studies done only on male animals, even on diseases that are more prevalent in women, such as depression. When it comes to studies on diseases that primarily affect and kill women, this is seen often. And findings that use male mice have been proven not to generalise to female mice. [2]
This is important because it has been proven that sex differences can be substantial. There are differences present in heart mechanics, lung capacity (even when normalised to height) and the causes of disease, which can vary even to a cellular level. Furthermore, some conditions, such as autoimmune diseases, disproportionately affect women (±80% of affected).
The lack of drug testing on women has been found to lead to worse medical care and outcomes for female patients and is likely a part of the reason why women are more likely to experience adverse reactions to prescription drugs than men. [3]
The reasons behind this exclusion are numerous but come down to deep rooted sexism within medicine. Female bodies are claimed to be too complex, variable and costly to test on, supposedly an extra burden on research variables. Some claim that biological sex doesn’t matter, or that the lack of comparable historical data is an issue. And sometimes, it is claimed that drugs for female patients just aren’t worth the funding.
Period pain (or dysmenorrhea) leads to 600 million lost work hours each year in the USA, and yet no effectively treatment exists for it. Currently ibuprofen and other non-steroidal anti-inflammatory drugs are the most frequently used for relief, but these can cause ulcers and kidney damage through prolonged use. Endometriosis, a condition which causes intensely painful periods, takes eight years on average to diagnose in the UK and ten in the USA – despite the fact that it affects an estimated 10% of women. [4]
Sildenafil (better known as Viagra), was used in a double blind, randomised, controlled clinical trial, and demonstrated total pain relief for periods over four hours. But researchers working on it were not able to meet their sample size due to loss of funding and were rejected twice by the NIH when they applied for more, with comments suggesting it was not a priority public health issue.
Cardiovascular symptoms in women are different to men’s, leading to slower identification or misdiagnosis of heart attacks in women, as these symptoms are not taught as often, if at all. Women are less likely to fare well in the short and long term after heart attacks – and women made up only 25% of participants for congestive heart failure across 31 landmark trials between 1987 and 2012.
Women’s pain is often not taken seriously by primary care. Women are being underrepresented in research and it is killing them.
However, there have
been recent attempts by some bodies to force the inclusion of an “an equal
balance of male and female cells, tissues, and animals” [5]
in research, such as by health research funding agencies in the USA and Canada.
The issue is that independent drug manufacturers can do what they want, and
women typically aren’t their priority. The 1995 Beijing Declaration and
Platform for Action also condemned medical interventions for women that were
based on research carried out mainly on men. An article in the British Medical
Journal states that “a critical first step is for regulatory agencies to stop
framing women as a “subgroup” for analysis”, which sums up the attitude change
that needs to happen. Healthcare must stop treating women as smaller men, or as
some kind of medical “other”, but instead as women, and therefore as people.
[1] https://www.sciencedirect.com/science/article/pii/S1551714422000441?via%3Dihub
[2] https://www.bmj.com/content/371/bmj.m3808
[3] https://doi.org/10.1016/j.eclinm.2019.10.001
[4] https://pubmed.ncbi.nlm.nih.gov/19196878/
[5] https://www.bmj.com/content/371/bmj.m3808
