
==== Front
Intensive Care Med
Intensive Care Med
Intensive Care Medicine
0342-4642
1432-1238
Springer Berlin Heidelberg Berlin/Heidelberg

39012536
7541
10.1007/s00134-024-07541-1
Letter
Sex representation within intensive care trials in Australia and New Zealand
http://orcid.org/0000-0002-0062-3705
Modra Lucy lucy.modra@austin.org.au

12
Bone Allison 34
Pilcher David 356
Woodward Mark 78
Thompson Kelly 89
1 https://ror.org/01ej9dk98 grid.1008.9 0000 0001 2179 088X Department of Critical Care, University of Melbourne, Melbourne, Australia
2 https://ror.org/010mv7n52 grid.414094.c 0000 0001 0162 7225 Intensive Care Unit, Austin Hospital, 145 Studley Rd Heidelberg, Victoria, 3084 Australia
3 https://ror.org/02bfwt286 grid.1002.3 0000 0004 1936 7857 Australia and New Zealand Intensive Care Research Centre, Monash University, Clayton, Australia
4 https://ror.org/00jrpxe15 grid.415335.5 0000 0000 8560 4604 Intensive Care Unit, University Hospital Geelong, Geelong, Australia
5 https://ror.org/04scfb908 grid.267362.4 0000 0004 0432 5259 Department of Intensive Care, Alfred Health, Commercial Road, Prahran, VIC 3004 Australia
6 grid.489411.1 0000 0004 5905 1670 ANZICS Centre for Outcomes and Resource Evaluation, High Street, Prahran, VIC 3004 Australia
7 grid.7445.2 0000 0001 2113 8111 The George Institute for Global Health, School of Public Health, Imperial College London, London, UK
8 grid.1005.4 0000 0004 4902 0432 The George Institute for Global Health, UNSW, Sydney, Australia
9 Nepean Blue Mountain Local Health District, Kingswood, Australia
16 7 2024
16 7 2024
2024
50 9 15291531
25 6 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
http://dx.doi.org/10.13039/501100000925 National Health and Medical Research Council APP1194058 APP1174120 Woodward Mark Thompson Kelly issue-copyright-statement© Springer-Verlag GmbH Germany, part of Springer Nature and European Society of Intensive Care Medicine 2024
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pmcDear Editor,

Recruiting a representative study population helps to ensure the generalizability of a trial’s findings across demographic groups. It also promotes trust and fair access to trial participation among the target population of affected patients [1]. Nonetheless, women remain under-represented in some fields including oncology, cardiology and infectious diseases trials [2, 3]. Regarding critical care trials, Kristensen and colleagues found that a minority of participants were women, however they did not compare sex balance between study populations and their respective target populations [4].

We examined sex-based representativeness in randomized controlled trials (RCTs) endorsed by the Australia and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group and completed 2014–2023 (supplement Fig. 1). The ANZICS Adult Patient Database (APD) was taken to represent the general population of intensive care unit (ICU) patients, as it captures 90% of ICU admissions in Australia and New Zealand [5]. The database records patient sex—the focus of our study—defined as the biological distinction between female and male [5].Fig. 1 a Percentage of women in study population compared to target populations. Lines connecting triangles and circles represent the arithmetic difference in the percentage of women in the study population and target population. Pink lines indicate more women in study than target population; blue lines indicate less women in study than target population (adapted from Steinberg et al. [2]). References 6–29 are provided in the electronic supplementary materials. b. Forest plot of sex balance in study population compared to target populations

For each trial, the study population was compared with a matched target population identified from the APD using the trial’s own eligibility criteria (supplement Table 1). Quality of matching was assessed using pre-specified criteria; target populations were considered well-matched if matched in at least 4 of 5 domains (supplement Table 2). We calculated the arithmetic difference between the percentage of women in each study population minus the percentage women in each target population, with estimated 95% confidence interval. We used random effects meta-analysis to calculate pooled differences, using STATA 17 BE (Statacorp, Texas USA) for all analyses.

There were 24 eligible trials with 68,968 participants in total (36.3% women). The sex balance ranged from 16.7 to 47.8% women (Fig. 1a). Each trial recorded patient sex but not gender and no trial included a third sex category, e.g., intersex. Therefore, sex and gender-based minorities were not represented.

There were 2,017,197 admissions (42.9% women) recorded in the APD during the trials’ cumulative recruitment period October 2008 to November 2021. There were substantially less women in the pooled study population than the general ICU population represented by the APD (arithmetic difference − 6.6%, 95% confidence interval [CI] − 69 to − 6.2%).

When compared to matched target populations, there was no significant disparity in sex balance between the study populations and target populations overall (pooled arithmetic difference − 0.5%, 95% CI − 2.2% to 1.2%; Fig. 1b). This finding was robust to sensitivity analysis including only trials with well-matched target populations (supplement Fig. 2).

On diagnostic subgroup analysis, women were under-represented in cardiac arrest trials [arithmetic difference − 5.5% (95% CI − 8.6 to − 2.4%)] and sepsis trials [arithmetic difference − 2.9% (95% CI − 5.1% to − 0.7%)], compared to the target populations of ICU patients with these diagnoses. There was no sex-based disparity in trauma trials or trials including multiple diagnostic categories (supplement Fig. 3).

We found critical care trials in Australia and New Zealand recruited representative proportions of women and men overall, when compared to target populations defined by their own eligibility criteria, suggesting that screening and enrolment of participants was not affected by patient sex. However, the pooled study population had substantially less women than the general population of ICU patients in Australia and New Zealand. This suggests the trials examined relatively male-dominated groups of ICU patients by design, related to study question, participating sites or eligibility criteria. Many trials examined conditions predominantly affecting men, including trauma or cardiac arrest, rather than female-dominated conditions such as subarachnoid haemorrhage or asthma [5].

Concordant with previous research, women were under-represented in cardiac arrest and sepsis trials [2]. This may relate to the decision-making of surrogate decision-makers or clinicians in high-risk situations. Further research is needed to identify effective strategies for improving sex-based representation in these trials.

Supplementary Information

Below is the link to the electronic supplementary material.Supplementary file1 (DOCX 614 KB)

Acknowledgements

The authors and the ANZICS CORE management committee would like to thank clinicians, data collectors and researchers at the contributing sites listed in the online Supplement Table 4. The authors would also like to acknowledge Neil Orford, Priya Nair and Rinaldo Bellomo for their contribution to revising and improving this manuscript.

Declarations

Conflicts of interest

KT is supported by a National Health and Medical Research Council of Australia (NHMRC) Investigator Grant (APP1194058). MW is supported by a similar NHMRC grant (APP1174120). LM is a member of the Women in Intensive Care Medicine Network of the Australia and New Zealand Intensive Care Society (WIN-ANZICS).

Ethics statement

Ethics approval was obtained from Alfred Health Human Research Ethics Committee.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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References

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