Tackling the gap in women’s health data

Today more than ever, our world is driven by data – and missing data often leads to problems. As we reflect on International Women’s Day, sex- and gender-related data is no exception.  

“How can we fix or track a problem without fully understanding it in the first place?” asks Tasha Wibawa, a commissioning editor at 360info.  

“To better understand the lives of women and make better, more equal policy decisions, we need numbers and data to help paint a better picture.

“But more often than not, that data doesn’t exist, and we only have a partial understanding of the lives of women and girls.”

Health is an area whose ‘data gap’ is increasingly recognised as being of concern. Do we have enough data from research and clinical trials on women to effectively protect women’s health?

Lavanya Vijayasingham, a researcher at the United Nations University International Institute for Global Health in Kuala Lumpur, points to the ongoing COVID-19 pandemic as a factor that has exacerbated lack of data collection and reporting relating to sex and gender, risking downstream entrenchment of health inequalities.

“Of the 75 clinical trials on COVID-19 vaccines included in a recent review, only 24% presented their main outcome data disaggregated by sex, and only 13% included any discussion of the implications of their study for women and men,” she says.

“In 2020, less than one in five trial reports published in journals reported sex-disaggregated results.”

Why does the data gap exist?

“There is a history of perceived complexity in accounting for hormonal changes and cycles throughout women’s lives, including in puberty, pregnancy, childbirth and menopause,” says Vijayasingham.

“Women are hesitant to participate in trials, and foetal protectionary ethics in medical research lead to perceived increased liabilities, risk, and costs of including females, especially those of ‘child-bearing potential’.”

Australian experts agree that pregnancy or ‘child-bearing potential’ can be a barrier to women’s participation in some types of research.

“Essentially all the medications used in early-phase clinical trials don’t have data to support their use in pregnancy or to demonstrate that they don’t cause any issues with pregnancy,” explains Paul Griffin, an associate professor at the University of Queensland and Director of Infectious Diseases at Mater Research.

“We always err on the side of caution, which is why there are some quite strict limitations on enrolling women of childbearing age and having contraception requirements.

“So, I think inadvertently that may contribute to a slight under-representation of females in some of these clinical trials in the early-phase trials, but that’s done for safety reasons.”

Griffin says that this under-representation can generally be addressed in later phases of clinical trials, where researchers are aiming to represent as closely as possible the wider population who will be using the new medication or vaccine.

He also points out that the early-phase trials, which are less likely to include women, are generally small and contribute only a small amount to the final dataset used to approve a new therapeutic.

Aside from who is recruited to participate in a trial in the first place, there’s also the matter of whether sex- and gender-related data are collected, reported and included in analyses.

“We’ve come a really long way in recent times,” says Griffin.

“We certainly do try and make it so that we can interpret the data about by looking at all groups that are included, so we can be really confident that whatever it is [we’re] trialling is demonstrated to be safe and effective in all those different groups.”

Australia doesn’t currently have national-level requirements to include women in research or clinical trials, or to report on data that’s disaggregated (separated) by sex or gender. Researchers or organisations leading the study generally determine what variables they consider appropriate to measure and which populations to target.

According to a 2020 study published in the Medical Journal of Australia (MJA), only two out of 10 major health research funding agencies in Australia had policies regarding the collection, analysis and reporting of sex- and gender-specific health data. Four out of 10 major Australian peer-reviewed medical journals also lacked such policies.

Why does the data gap matter?

“Genetic, molecular, physiological, and biochemical sex differences exist,” says Vijayasingham.

“They influence disease risk, clinical outcomes, progress, recovery, and rehabilitation, and importantly the way people respond to treatment or medical interventions such as pharmaceuticals and vaccines.”

For example, women are more likely to be affected by rare thrombosis side-effects after adenovirus-based COVID-19 vaccines, while young men and boys are more likely to suffer cardiac complications associated with mRNA-based COVID-19 vaccines.

Women are generally more likely to experience adverse events after vaccination (not just against COVID), and also tend to exhibit a stronger antibody response than men.

Cheryl Carcel, a researcher from the George Institute for Global Health, co-authored the aforementioned MJA study, which outlined the need to update Australian policy on sex and gender in health research.

She says that there are two key reasons the data gap on women’s health needs to be closed: generalisability and access to treatment.

“If you have only 20% women in a drug trial, how can you adequately say that this is okay for both sexes?” she asks.

“If a drug trial is 70–80% men, clinicians will see that and say, ‘this might not be good for women, so I will not be able to give her that drug’. There’s a missed opportunity there.”

The MJA study points to the example of zolpidem, a drug that was found to remain at higher levels in the blood of women than men, affecting their alertness and raising safety concerns, after it had already been made available to the public. The US and Canada subsequently halved the recommended dose of zolpidem for women.

Experts also highlight the need for sex and gender data collection that transcends the typical male-female binary.

“Long-term hormone therapy (oestrogen or testosterone) in transgender, intersex and gender-diverse people produces changes in body physiology, composition and biochemistry,” Vijayasingham points out.

“This can affect how people respond to pharmaceuticals, and there’s also the issue of how hormone therapies interact with other medications.”

Adopting a more nuanced approach to sex- and gender-related data would also help tease apart the myriad factors that can underlie sex- and gender-related differences in health outcomes – be they physiological (such as hormones), social (such as experiences of sexism or discrimination), or both.

Sex and gender aren’t necessarily relevant to every single study, says Andrew McLachlan, a professor in the school of pharmacy at the University of Sydney – but we can’t always predict whether they will be at the outset.

“Simply analysing something because it’s there is not good practice, you have to usually have to have a biologically plausible reason to suspect the difference,” he says.

“But there’s a chicken-and-egg scenario – if we don’t study those things, we won’t know to look for them.”

How can we close the data gap?

The data gap is a systemic issue that will require change across many aspects of science to fully address.

“Public demand and advocacy – champions in all parts of the science ecosystem – are likely to shift attitudes and help overcome existing resistance, regulations and guidelines that hamper the delivery of sex-disaggregated data,” says Vijayasingham.

Carcel identifies three major stakeholder groups who need to take action to address the problem: funding bodies, researchers, and journals.

“For this field, the issue is that we need to have clear, accessible policies on the inclusion of women or females in cell lines, in animal models, and in humans,” she says.

“When that’s done, we need an educational campaign so that everyone will know that these policies exist.

“And then we need a way to implement them and then evaluate them later on whether they’re working or not.”

Her ongoing research in this field is planned to include the creation of policy framework templates for stakeholder groups so that they can more easily develop these new policies. Australia can learn from examples from the US, Canada and Europe of policies that have already begun to be implemented and evaluated.  

There are promising signs that the tide is turning.

In 2020, the Australian Bureau of Statistics released an updated Standard for Sex, Gender, Variations of Sex Characteristics and Sexual Orientation Variables. These updated guidelines will influence how these variables are measured and reported by other federal government agencies and research institutes, such as the Australian Institute for Health and Welfare.

McLachlan points out that the National Health and Medical Research Council’s (NHMRC) Statement on Ethical Conduct of Human Research now requires researchers to provide evidence to justify why a study is only being done on one sex.

“We’re certainly seeing a shift away from simply only doing early-phase research in healthy males,” McLachlan says.

“Most scientists are always trying to control their experiments, they’re trying to control for variables that they think might be important so they can study their key research hypothesis,” he muses.

“In doing so, sometimes they have excluded one sex from their experiments, and that does mean that the applicability of that data may be uncertain.

“I think there has been a really good pendulum swinging back towards the idea of more balance, and national guidelines now support this.”

Asked why Australia appears to be lagging behind in addressing the data gap, Carcel is optimistic.  

“I think Australia needs champions in the area who want to push the agenda and I think we’re starting to have that,” she says. “Somebody just needs to drive it.”

This article was published in partnership with 360info.org