Determining If Sex Bias Exists in Human Surgical Clinical Research

Abstract

Importance: Sex is a variable that is poorly controlled for in clinical research.

Objectives: To determine if sex bias exists in human surgical clinical research, to determine if data are reported and analyzed using sex as an independent variable, and to identify specialties in which the greatest and least sex biases exist.

Design, setting, and participants: For this bibliometric analysis, data were abstracted from 1303 original peer-reviewed articles published from January 1, 2011, through December 31, 2012, in 5 surgery journals.

Main outcomes and measures: Study type, location, number and sex of participants, degree of sex matching of included participants, and inclusion of sex-based reporting, statistical analysis, and discussion of data.

Results: Of 2347 articles reviewed, 1668 (71.1%) included human participants. After excluding 365 articles, 1303 remained: 17 (1.3%) included males only, 41 (3.1%) included females only, 1020 (78.3%) included males and females, and 225 (17.3%) did not document the sex of the participants. Although female participants represent more than 50% (n = 57 688 606) of the total number (115 377 213) included, considerable variability existed with the number of male (46 111 818), female (58 805 665), and unspecified (10 459 730) participants included among the journals, between US domestic and international studies, and between single vs multicenter studies. For articles included in the study, 38.1% (497 of 1303) reported these data by sex, 33.2% (432 of 1303) analyzed these data by sex, and 22.9% (299 of 1303) included a discussion of sex-based results. Sex matching of the included participants in the research overall was poor, with 45.2% (589 of 1303) of the studies matching the inclusion of both sexes by 50%. During analysis of the different surgical specialties, a wide variation in sex-based inclusion, matching, and data reporting existed, with colorectal surgery having the best matching of male and female participants and cardiac surgery having the worst.

Conclusions and relevance: Sex bias exists in human surgical clinical research. Few studies included men and women equally, less than one-third performed data analysis by sex, and there was wide variation in inclusion and matching of the sexes among the specialties and the journals reviewed. Because clinical research is the foundation for evidence-based medicine, it is imperative that this disparity be addressed so that therapies benefit both sexes.

Figure 1. Sex of Subjects Included

Number and percent of manuscripts which state the sex of the human subjects included in (A) all manuscripts and (B) by journal. The distribution of rates of sex stated/not stated was different between journals (p<0.0001). (C) Number and percent of manuscripts that include male only, female only, and male and female subjects.

Figure 2. Sex-Based Data Reporting

(A) Percent of manuscripts that reported the data by sex. (B) Percent of manuscripts that statistically analyzed the data by sex. (C) Percent of manuscripts that included a discussion of the results by sex.

Figure 3. Number of Male and Female Subjects Included

Absolute number of male, female, and unspecified subjects included in (A) all manuscripts, (B) by journal, (C) in US domestic and international studies. Distribution of included males, females, and unspecified subjects between journals and between domestic and international studies was different (p<0.0001). (D) Number of male subjects included by specialty. (E) Number of female subjects included by specialty. (F) Number of unspecified subjects included by specialty. Distribution of included males, females, and unspecified subjects was different by specialty (p<0.0001).

Figure 4. Sex Matching of Subjects

(A) Degree of sex matching in all manuscripts and (B) by specialty. There is a statistically significant difference in distribution of 50% or greater matching across all specialties (p<0.0001).