Are Sex and Gender Considered in Neurological Drug Approvals? A Systematic Review
Judy Chen1, Liam Cooper-Brown2, Jacqueline Chen4, Arya Ebadi4, Aaliya Saquib4, Luc Wilson1, Jim Xie3, Boris Bernhardt1, Esther Bui2
1McGill University, 2Neurology, 3Opthalmology, University of Toronto, 4McMaster University
Objective:
This systematic review aims to examine all randomized controlled trials (RCT) leading to Food and Drug Administration (FDA) neurological drug approvals for: 1) sex and gender terminology accuracy; 2) sex- and gender-based analysis.
Background:
Sex and gender are distinct concepts each associated with independent health outcomes. Sex is a biological variable, whereas gender is a multidimensional psychosocial and cultural construct. Despite increasing recognition of sex and gender issues in neurology, they may be conflated or under-reported in the evaluation of neurological therapeutics.
Design/Methods:
The drugs@FDA database was screened by two independent reviewers to identify all therapeutics approved by the FDA for a neurological indication between Jan 1, 1985 and Dec 31, 2023. All available RCTs cited in these approvals were included. Study characteristics, definitions and uses of sex and gender, sex- and gender-based analyses and mentions of sex and gender in discussion sections were extracted. Descriptive statistics and logistic regressions for associations between sex and gender variables and study characteristics were performed.
Results:
216 RCTs (109,442 participants) associated with 98 approved therapeutics were included. The most represented subspecialties of indication were epilepsy (25%), movement disorders (18%), headache (16%) and autoimmune neurology (14%). Overall, 82/216 RCTs (38%) reported sex using sex-related terms accurately, and eighteen (8.4%) used gender-related terms accurately. Four studies reported sex-stratified results for the primary outcome, and 14 did so for any outcome. For gender, 4 studies stratified results for the primary outcome, and 12 for any outcome. Two studies disaggregated sex when reporting adverse events, while no studies did so for gender. Logistic regression model did not show any significant associations between accurate sex/gender reporting and year of study publication, number of study centers or sample size.
Conclusions:
Our results identify shortcomings in reporting and analyzing sex and gender among neurological drug RCTs with no significant improvement over time.
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