Awareness of the importance of sex and gender issues in medical research may be increasing but evidence shows the issues are inconsistently addressed in study design, analysis, and interpretation of Australian cancer clinical trials.

The findings of a study, published in Research Integrity and Peer Review [link here], suggest implementation of the Sex and Gender Equity in Research (SAGER) guidelines has been patchy.

“Despite growing recognition of the importance of sex and gender in biomedical research, our findings reveal that adherence to sex and gender reporting remains inconsistent and, in many aspects, suboptimal,” the study said.

“These findings reinforce the need for stronger implementation of sex and gender reporting guidelines and the systematic integration of sex and gender considerations across all stages of the research process.”

“Such efforts are essential to improve research rigor and equity, scientific integrity, and the applicability of findings to diverse populations,” it concluded.

Little progress

The study reviewed 128 eligible cancer RCTs of any phase, in adults, and conducted in Australia or led by Australian investigators. The most common cancer types were colorectal (20%), skin including melanoma (14%), and lung (11%).

The RCTs were published between 2014 and 2024 across 68 journals including Supportive Care in Cancer (12%), BMC Cancer (5%), and Journal of Clinical Oncology (5%). The time period covered before and after publication of the SAGER guidelines in 2016 [link here] and its subsequent implementation checklist in 2022 [link here].

Among the study’s dismal findings:

• 50% of RCTs used sex/gender terminology appropriately
• 16% described how sex/gender was considered in the study design
• 5% of RCT introductions included references to prior studies addressing sex/gender differences
• 10% of RCTs included complete sex/gender breakdown for all categories of results
• 2% included adverse event data disaggregated by sex/gender
• 11% discussed the potential implications of sex/gender on the study results
• No RCTs offered a rationale for the absence of sex/gender analysis or discussed the implications of this omission
• No RCTs defined how participants’ sex or gender was determined (e.g. self report, genetic testing).

When compared over time, pre- and post-SAGER, there was an improvement in some criteria such as the appropriate use of sex/gender terminology, reporting of sex/gender breakdowns in abstracts, and inclusion of separate rows for male and female participants in the patient demographic tables.

However other practices declined over time – citations of prior sex/gender research, mention of sex/gender as a relevant variable in the introductions, consideration of sex/gender in study design, proportion of studies presenting data disaggregated by sex/gender, and the reporting of sex- or gender-based analyses regardless of outcome.

The study also found that there was little difference in the sex/gender reporting practices between journals that did and did not endorse SAGER guidelines.

The investigators, led by Dr Vikneswary Batumala from The George Institute for Global Health and UNSW Sydney, said their findings align with prior literature showing that while awareness of sex and gender issues may be increasing, practical implementation remains limited and inconsistent.

“This disconnect raises concerns about the depth of engagement with equity-focused guidelines like SAGER and suggests that their uptake may be more superficial than substantive,” they said.

Why it matters

Yet the gap between guidelines and practice matters for both efficacy and safety outcomes.

“On the efficacy side, clinical studies and meta‑analyses across cancer types have identified sex‑related differences in treatment effectiveness and survival outcomes including for immunotherapy, chemotherapy, targeted therapy, and radiotherapy, underscoring the need for consistent sex‑disaggregated reporting to judge generalisability,” they said.

“On the safety side, reviews of adverse events by sex indicate higher risks of severe treatment‑related adverse events for women across modalities, particularly with immunotherapy, reinforcing the need to present adverse events by sex and to justify dosing and monitoring approaches.”

They suggested implementation challenges included limited statistical power for sex- or gender-stratified analyses in many trials, insufficient practical guidance for researchers, and inconsistent enforcement of reporting expectations during peer review.

As well, they said Australia lags behind international standards in its policy approach to sex and gender in health research.

Some of their proposed solutions included:

• research institutions should embed education and support structures around study design that accounts for sex/gender into research training.
• broader engagement across the research sector to build understanding of how sex and gender influence health, and to ensure these considerations are integrated from study conception through to translation and implementation
• stronger editorial compliance mechanisms for journals and clearer expectations during manuscript submission and peer review.

Dr Batumala said in a statement from The George Institute that critical information about safety and effectiveness of interventions is lost when clinical trials don’t report data separately for men and women.

“That’s not a minor reporting gap. That’s information clinicians need to make informed decisions for their patients,” she said.

Senior investigator Professor Mei Ling Yap, also from The George Institute, said the findings suggest that voluntary guidelines were not enough to improve sex and gender reporting in clinical trials.

“Journals endorsing the SAGER guidelines made virtually no difference to reporting quality in practice. What we need are funding mandates, stronger editorial enforcement and genuine investment in researcher education. Sex and gender need to be built into study design from the very beginning, not treated as an afterthought at the point of publication,” she said.