Gender equity in clinical trials an unresolved issue for nephrology


By Mardi Chapman

21 Mar 2024

Women are underrepresented as lead authors on published randomised controlled trials in nephrology and there has been no sign of progress over the past decade, a study has found.

The systematic review, published in Kidney International Reports [link here], identified 395 nephrology RCTs that met the criteria including being published in high-impact journals from general medicine, nephrology, and kidney transplantation between 2011 and 2021.

It found the proportion of women in lead authorship positions was 22.5% overall. Rates of female corresponding, first and last authorship positions on the RCTs were 22%, 28%, and 19% respectively, without change over the study period.

Female lead authorship was low among general medicine journals with the highest impact factors such as JAMA (15.0%), NEJM (15.0%) and The Lancet (17.6%).

Among nephrology journals, the American Journal of Kidney Diseases had the highest proportion of women in lead authorship positions (38%) followed by the Clinical Journal of the American Society of Nephrology (26.1%).

The median percentage of women participants in the trials was 40.2% across the whole study period.

The study also noted that most trials did not report sex-specific eligibility criteria (71.1%) or perform gender-specific subgroup analysis (87.3%).

However RCTs led by women nephrologists were more likely to have sex-specific eligibility criteria than not.

“Overall, women were less likely to be enrolled in nephrology RCTs as participants but more likely to be enrolled when women were lead authors,” the study authors said.

“Participation is crucial given the sex disparities in kidney disease pathogenesis and progression and can lead to better health outcomes for women with kidney disease.”

The authors said their findings demonstrate ongoing underrepresentation of women in nephrology trial leadership despite improved representation in leadership and presidency positions in organisations including the International Society of Nephrology.

“However, gaps remain with women underrepresented in national conferences and academic grand rounds, receiving fewer achievement awards, and are less likely to be listed as first author,” they said

“These disparities can contribute to women being left out of leadership roles and can impact their growth and promotion.”

Australian perspective

ANZSN president Associate Professor Rathika Krishnasamy, from the Sunshine Coast University Hospital and University of Queensland, told the limbic that the findings were not surprising given the wider gender equity issues in nephrology.

She said ANZSN had already identified the issues locally – see 2022 workforce survey findings here – and had been working towards gender equity in the workplace, academic science and research.

The Society’s 2023 Statement on Equity, Diversity and Inclusion in the Workforce [link here], commits to identifying and actively addressing inequities “particularly driven by gender and race…”

Associate Professor Krishnasamy said that having more women in leadership roles meant that there would be a conscious effort to enrol more female participants.

“The changes will come if there is a change from the top so what we’ve put as a statement is looking at a diverse leadership and how we can actually make that diverse leadership happen.”

She said local initiatives include a mentorship program that will be officially launched at the ANZSN ASM this year.

Associate Professor Krishnasamy said she was optimistic for gender equity in research leadership and participation but that change takes time.

“Change is never something that happens overnight. In some of the trials that we’re doing now, we’re having that honest conversation about looking at diversity on many levels including gender, race and representation of difference … having a proper representation of people from different backgrounds. So, we are looking at diversity from a trial perspective at a broader level but as I said, the change is going to take time.”

She said without adequate representation of women as participants in clinical trials, the impact of factors such as smaller kidney size and hormones on kidney disease could be overlooked.

Harms and benefits 

An accompanying Commentary article in the journal [link here], coauthored by Queensland paediatric nephrologist Dr Anna Francis said female representation in trial participation was also an issue, given that renal tubular structure and function were different in men and women, likely due in part to the effect of sex chromosomes and sex hormones.

“Major life events such as the onset of menarche, pregnancy, breastfeeding, and menopause affect the female body, with associated changes in function and disease risk. The failure to recruit women proportionately, and the failure to include sex-stratified analyses, leads to a knowledge gap in differences in both health outcomes and safety data for men and women.”

The Commentary said that drugs and interventions may also have differing harms in men and women.

“Thus, if there is insufficient enrolment of women in trials, we may miss harm signals. Furthermore, because there are differences in risks of CKD progression and death between men and women, the risk-benefit balance for some drugs may also be impacted. Differences in biology may affect pharmacokinetics, pharmacodynamics, and effect; while differences in social environments may impact both drug acceptability and drug adherence.”

The authors said trials need to be designed to encourage the involvement of women participants.

“This includes women in leadership roles designing and implementing the trials. The lived experience of women can inform female-friendly trial design and though sex equity is the responsibility of all, women may be more likely to advocate for increased female participation.”

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