Gender bias in clinical trials of biological agents for severe asthma: A systematic review

Abstract

Asthma is one of the most common chronic diseases characterized by sex disparities. Gender bias is a well-documented issue detected in the design of published clinical trials (CTs). International guidelines encourage researchers to analyze clinical data by sex, gender, or both where appropriate. The objective of this work was to evaluate gender bias in the published CTs of biological agents for the treatment of severe asthma. A systematic review of randomized controlled CTs of the biological agents (omalizumab, benralizumab, reslizumab, mepolizumab or dupilumab) for the treatment of severe asthma was conducted. The literature search was performed using PubMed and EMBASE without language restrictions. This study followed the corresponding international recommendations. We identified a total of 426 articles, of which 37 were finally included. Women represented 60.4% of patients included. The mean percentage of women in these trials was 59.9%, ranged from 40.8% to 76.7%. The separate analysis by sex of the main variable was only performed in 5 of the 37 publications included, and none of the trials analyzed secondary variables by sex. Only 1 of the articles discussed the results separately by sex. No study included the concept of gender in the text or analyzed the results separately by gender. The proportion of women included in CTs was higher compared to publications of other disciplines, where women were under-represented. The analysis of the main and secondary variables by sex or gender, even the discussion separately by sex, was insufficient. This gives rise to potential gender bias in these CTs.

Sex differences in adult asthma and COPD therapy: a systematic review

“…A first step to manage this important and discriminatory scientific lack could be to make the data from large investigational clinical trials in asthma and COPD available specifically for each sex rather than as overall results. Moreover, considering that clinical trials in asthma and COPD are characterized by imbalanced enrollment ratio between men and women leading to possible sex bias in measured outcomes [ 9 , 80 ], it is expected that the randomization procedures of future RCTs will be set to equally enroll both sexes. Finally, but not less important, pre-specified analyses in men and women should be planned in the trial protocols, a necessary condition that should be requested also by the regulatory agencies.…”

Sex Disparities in Asthma Development and Clinical Outcomes: Implications for Treatment Strategies

“…1 , 127 , 163 However, gender differences in the efficacy of the biologics in severe asthma have not been extensively investigated. 163 , 164 Some randomized trials explored gender differences in responsiveness to these biologics and did not find differential responses between women and men. 165–171 To our knowledge, no human studies have looked at the effects of these biologics on hormonal activity.…”

Sex, Allergic Diseases and Omalizumab

“…Omalizumab is the first biologic drug launched for asthma, and its trials began with a smaller proportion of women. Only in the two most recent trials of omalizumab was an analysis by sex performed [ 107 , 108 , 109 , 110 , 111 ]. It is therefore important to consider sex as a variable when evaluating the response, as well as the other indicators, in order to understand if this can provide additional predictive information.…”