In 2017/18 the Medical Research Council (MRC) allocated less than 3% of its research expenditure on women’s health, despite the fact that a third of women experience severe reproductive health problems.1
The pharmaceutical industry has a key role to play to continue alleviating the causes of gender bias across western health systems and the impact it has on women’s health outcomes.
This article outlines how pharma might remedy the lack of female representation in clinical research, the lack of R&D into conditions exclusively affecting women and the trust problems that may exist between some female patients and healthcare professionals.
Historical exclusion of female participants in clinical research
Much of the medical community’s knowledge is based upon research using mostly male subjects. Until the 1990s, women were generally excluded from clinical research. The Food and Drug Administration (FDA) prohibited women of childbearing age from taking part in early phase clinical studies, for fear of potential risks to their reproductive systems, and any future children. Although difficult to prove, it is also possible that women were excluded from trials for ease of collecting statistically significant results – to avoid accounting for women’s perceived fluctuating hormonal states, that would make studies complex and costlier.
Researchers relied on extrapolating data from male subjects to form assumptions on how drugs would work in women. This ‘sex-based gap’ in clinical research means we are less certain that drugs are as safe and effective in women, as they are in men. In fact, a US Government Accountability study revealed that 80 percent of the drugs withdrawn from the market were due to sideeffects on women.
Excluding females from clinical research hinders our understanding of diseases in women. Research published in The Journal of the American Medical Association found younger women were less likely than men to experience chest pains when having a heart attack. This research highlighted important variation and informed medical practice, at a time when symptoms of the disease were thought to be uniform across the sexes. It’s no surprise that this important breakthrough followed a sizeable jump in female participation in cardiovascular clinical research, rising from 9% of all cardiovascular clinical trials involving women in 1970, to 41% in 2006.
The benefits of including more women in clinical trials are slowly being realised. Inclusion of women in research areas such as pain (which has historically seen underrepresentation of female participants), must continue to grow to rectify the historical imbalance of female participation in clinical studies.
Lack of R&D investment in conditions that exclusively affect women
There is a general lack of investment in conditions that are exclusive to women.
In the UK in 2017/18, the Medical Research Council’s gross research expenditure stood at £814.1 million. Of this, £20.8 million went towards women’s health research, and of that, £0.6 million was spent on endometriosis research.
Endometriosis is a condition where tissue that should grow inside the uterus, travels to other parts of the body causing considerable pain. Recently, a number of high profile women, such as author Dame Hilary Mantel and BBC presenter Emma Barnett have spoken candidly of their suffering from the disease.
If left untreated, endometriosis can cause infertility. In Australia, roughly $900,000 was allocated for endometriosis research in 2015 by the National Health and Medical Research Council (NHMRC). This constitutes about 1% of its annual budget for medical research. However, endometriosis affects 10% of women of childbearing age and is reported to cost Australian society $9.7 billion annually. Two-thirds of these costs are attributed to a loss in productivity with the remainder, approximately $2.5 billion being direct healthcare costs.
When it comes to funding research in the US, all of the conditions that exclusively affect women fall in the bottom 45 out of 288 disease/research areas (including endometriosis, Rett syndrome, uterine fibroids, pelvic inflammatory disease and vulvodynia).
Arguably, the funding allocated to research for women-only diseases is not proportional to the prevalence, impact and severity of such diseases.
The ‘Trust Gap’
The ‘trust gap’ refers to the notion that women’s health concerns are more readily dismissed than those affecting men, this leads to distrust within the female patient community.
Several reasons explain the ‘trust gap’. Consider systemic preconceptions held by medical practitioners about how female patients experience maladies. For example, a study from the University of Maryland, found that women were less likely to receive aggressive treatment when diagnosed with pain and were more likely to have their pain dismissed, despite the fact that women are more likely to suffer from pain conditions. An article published in ‘Pain Research and Management’ found that women with chronic pain are more likely assigned psychological rather than somatic causes for their pain. Biases based on gender norms can therefore have a tangible effect on treatment.
Another reason for the trust gap is that healthcare professionals do not know enough about how certain conditions affect women, particularly those that are exclusive to women. It is thought GPs may lack the ability to recognise symptoms of conditions such as Polycystic Ovary Syndrome, which has an estimated prevalence of 1 in 5 women in the UK, as well as similar conditions like endometriosis and uterine fibroids. Further, a recent study suggested that nearly four in ten women don’t trust GPs to diagnose perimenopause correctly, and a quarter say they don’t trust GPs to diagnose the menopause correctly.
The inability accurately to diagnose medical conditions in women indicates a broader issue of awareness (or lack of thereof). Whether caused by ignorance or conscious bias, this only serves to widen the trust gap.
How can industry alleviate the problem?
Firstly, more women need to be included in clinical trials. Some progress has been made: today, women represent 43 percent of clinical trial participants globally. However, it will take time to make up for women’s historical exclusion from research, redress the imbalance and improve medical understanding. There has been recent regulatory progress in this area, but more must be done. The ABPI guidelines on phase I clinical trials only go as far as stating “the inclusion of women as early as possible in drug development might be a valuable clinical strategy”. FDA regulation states that new drug application data must present safety and efficacy data by sex, which should encourage trials to have balanced samples.
Secondly, pharma could do more to unlock the value of investing in conditions that exclusively affect women. As well as the moral imperative not to neglect conditions on the basis that they affect women only, from a commercial perspective, pharma could also gain considerable profit from investing in women’s health. High prevalence conditions such as menopause, miscarriage and endometriosis currently have a dearth of effective prevention treatments. 1 in 4 pregnancies end in miscarriage and 1 in 100 women have 3 or more miscarriages in a row. Yet, research into the causes of miscarriage is severely underfunded. This is despite the fact that half of early miscarriages have underlying causes that can be cured. Further, there are currently no drugs specifically indicated for endometriosis available in the UK. It is not just the patient community calling out for something new, but the market as well.
Finally, the pharmaceutical industry should actively engage further with the gender equality narrative. With its financial might, pharma is capable of raising the profile of female health conditions. New research – backed and funded by industry – into awareness of female health conditions across UK healthcare professionals would certainly be a good start.
By Will Greenhill
1Information obtained from the Medical Research Council in 2020