Male participants will no longer be the norm in medical research

Medical studies have historically excluded female subjects from foundational medical research, and there are increasing calls for greater inclusion of gender diversity.

There are changes on the horizon for sex and also gender participant parity in medical research.

The National Health and Medical Research Council (NHMRC) and the Department of Health and Aged Care (responsible for the Medical Research Future Fund [MRFF]) are planning to release a statement promoting greater inclusion of sex and gender diversity in foundational medical research.

“This is really a big step forward, because – as far as I am aware – it’s the first time such initiative is happening in Australia,” said Associate Professor Séverine Lamon, who was a panellist at the NHMRC–MRFF Statement on sex and gender in health and medical research workshop.

Associate Professor Lamon told InSight+ that even a first step towards sex and gender equity in foundational medical research is a significant one. Associate Professor Lamon puts the sex and gender bias in foundational medical research front and centre of her recent work and was pleased to participate in a long-awaited review of sex and gender in foundational medical research studies.

Male-based research has been the norm

“Up until roughly 20 years ago, it was the norm to only study males in basic biomedical research, the only exception being diseases that mostly occur in females, such as breast cancer,” Associate Professor Lamon said. “The reason behind this … was this idea that males are less variable than females and perfectly stable in terms of hormonal fluctuations, which now is being questioned, anyway.”

Associate Professor Lamon’s own research includes a study funded by the Australian Research Council, “Understanding the determinants of age-related muscle wasting in females”, which highlights the need for an increased understanding of evidence-based best practice anti-ageing strategies in women and found that research in female populations was limited.

“Nearly everything we know about muscle ageing is through studies conducted on males. This is because there has historically been a lack of research on female muscle,” Associate Professor Lamon told InSight+.

Even animal research has been historically conducted on overwhelmingly male rats and mice.

“Foundational research is important because it informs what research will be translated to the clinic,” Associate Professor Lamon said. “If the preclinical research is only done on half of the population, this will introduce a bias into the research. For example, which drugs might be targeted. If you haven’t done fundamental testing on female models, how do you know that this drug doesn’t have side effects in females that is not going to have in males? It’s important to have disparate preclinical models as a first checkpoint that the drug is doing what it’s meant to do in a female model.”

Associate Professor Lamon said it comes down to how much it costs to account for variables such as hormonal fluctuations and a majority of women using some sort of hormonal contraception.

“Sex- and gender-balanced studies are around 1.5 to two times more expensive than a male study only,” Associate Professor Lamon said.

Steps in the right direction

Lamon says that steps such as those being taken by the NHMRC and MRFF are significant and positive. The potential is for the Australian foundational medical research to have a sex and gender quality requirement, such as is governed by the National Institutes of Health (NIH) in the United States.

“In Australia, there are currently recommendations but absolutely no enforcement that would incentivise researchers to study female populations or male versus female populations. So up until a decade or two ago, there was even very little talk of including female cohorts,” Associate Professor Lamon said.

“I think it will take even longer to achieve a situation similar to the one in the US, where you must demonstrate a gender- or sex-balanced study design to get to funding.”

Other medical organisations are falling in line. Associate Professor Lamon will attend a workshop in the coming weeks hosted by the Association of Australian Medical Research Institutes (AAMRI), during which similar initiatives will be explored. “The AAMRI had representatives at that [NHMRC and MRFF] workshop, and it is now following suit. It is going to formulate guidelines to complement the activities currently being undertaken by the NHMRC and MRFF,” Associate Professor Lamon said.

“This is the chief organisation of all medical research institutes and associations in Australia, and therefore it is huge. They are showing a real willingness to take on the issue.”

In a separate move regarding funding for sex- and gender-diverse research, the Australian Government this year announced a $26 million investment under the MRFF to explore models of care for sexuality and gender diverse people and people with innate variations of sex characteristics. This is the largest ever investment in LGBTIQA+ health and medical research by an Australian Government.

Public consultation on the NHMRC draft Statement on sex and gender in health and medical research is planned for the second half of 2023.

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