Australian medical research that considered sex as a biological variable: a meta-analysis

Subjects in medical research have predominantly been male (1). Women experience 50-75% more adverse drug responses (2) resulting in withdrawn medications (3). While sex differences in metabolism, disease and treatment response are increasingly recognised, sex-informed medicine is lagging. In 2016, USAs National Institutes of Health (NIH) formulated the Sex as a Biological Variable policy (4), stating that grant recipients must consider sex in experimental design, planning, analysis and reporting of their findings. Australian data is lacking on the inclusion of both males and females as well as appropriate analysis of sex differences. We analysed the 219 Medical Journal of Australia (MJA) research articles over 2019-2023 (Box 1). We tallied when; i) both males and females were included in the study, ii) sex differences were reported and/or considered, and iii) the analysis was appropriate to support sex-related claims. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/24310791v1_figB1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@157d654org.highwire.dtl.DTLVardef@1b832d2org.highwire.dtl.DTLVardef@108b50org.highwire.dtl.DTLVardef@2a3a73_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOBox 1.C_FLOATNO Analysis of Original Research Articles in the Medical Journal of Australia in the last five years (2019-2023). Of 219 Original Research Articles, 146 included both male and female participants. 37 of those also considered sex as a biological variable. C_FIG We found that articles published in MJA are including males and females, however testing of sex differences is uncommon and appropriate statistical analysis is lacking. We hope that this article will bring attention to this fundamental issue and improve future efforts to investigate sex differences.