If women are, as is often claimed, under-represented in clinical trials, it is not so much to do with straight exclusion as with a bias towards conditions specific to the female sex, an Australian study suggests.

At the same time, the researchers found, gender-specific reporting of trial results is sorely lacking, despite a growing body of evidence that important differences exist between women and men in the incidence of certain diseases, responses to treatment and long-term outcomes.

“The traditional model of medical research was limited by gender and racial blindness and assumed that results of research on white male participants could be easily extrapolated to the female and minority populations,” noted Drs Wendy Rogers and Angela Ballantyne of the School of Medicine at Flinders University in Adelaide, Australia.

In a review published in the May issue of Mayo Clinic Proceedings, the researchers looked at 400 clinical studies involving Australian-only participants and published in journals between 1 January 2003 and 31 May 2006 (100 per year). The goal was to assess the numbers of male and female subjects in each study as well as the presence or absence of analysis by sex (covariate adjustment, subgroup analysis or sex-specific reporting).

Sex-specific trials were also evaluated to determine whether the exclusion of one sex was biologically necessary – i.e., the research related directly to male or female biological function.

Out of a total sample of 546,824 participants, 73% were female, suggesting no pattern of routine exclusion from clinical research. However, 36 of the studies assessed were male-only and 78 were female-only. In the 286 studies that were not sex-specific, 56% of the participants were female. In the 114 sex-specific trials, segregation by sex was determined to be biologically necessary in 62% of the studies.

Some of the trials excluded women or men “for apparently arbitrary reasons”, the authors commented. Moreover, research conducted with male-only participants differed in nature and size from the female-only research.

In terms of gender-specific analysis or reporting, 28% of the studies with 30 participants or more included covariate adjustment or subgroup analysis by sex, while just 7% included sex-specific reporting of results.

“Research on women’s health continues to focus predominantly on their reproductive capacity and function, whereas research with men continues to investigate conditions that are not specific to one sex,” Rogers and Ballantyne noted. As a result, women were under-represented in research that focused on significant health issues unrelated to biological aspects of reproduction.

The authors recommended that clinical trial registries should collect data on the gender of participants “to facilitate further research in this area” and that “researchers, journal editors and peer reviewers work to standardise mechanisms for sex-specific reporting and analysis in publications”.

In an accompanying editorial, Dr Sharonne Hayes, director of the Mayo Clinic Women’s Heart Clinic, and Dr Rita Redberg of the University of California, San Francisco in the US said they had observed a similar trend in a recent review of cardiology trials, where only 25% of all studies reported results by sex.

“As heart disease is the leading cause of death in women, it is dismaying that data from cardiovascular clinical trials are so limited,” they commented.