Sex and Gender Reporting in Epilepsy Clinical Trials for US Food and Drug Administration Approvals: 30 Years of Inadequate Reporting
Abstract number :
2.283
Submission category :
4. Clinical Epilepsy / 4E. Women's Issues
Year :
2024
Submission ID :
964
Source :
www.aesnet.org
Presentation date :
12/8/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Judy Chen, BS – McGill University
Liam Cooper-Brown, MD – University of Toronto
Luc Wilson, Msc – McGill University - The Neuro
Jacqueline Chen, BHSc – McMaster University
Arya Ebadi, BHSc – McMaster University
Jim Xie, MD – University of Toronto
Boris Bernhardt, PhD – McGill University
Esther Bui, MD – University of Toronto
Rationale:
Sex and gender are related but distinct determinants of disease, treatment response, and research reproducibility, whose consideration is increasingly required for research funding. In epilepsy, sex hormones at different life stages can impact epilepsy drug therapy1. In 2016, the NIH has required that sex be considered an important biological variable to be considered in research design and reported appropriately. Nevertheless, the appropriateness of sex and gender reporting amongst trials used in US Food and Drug Administration (FDA) approvals remains unknown.
Methods:
This cross-sectional review of all peer-reviewed randomized controlled trials (RCTs) published between 1990 and 2023 and cited in the US FDA approvals of epilepsy therapeutics following the PRISMA reporting guideline. The Drugs@FDA database was screened by two independent reviewers and disagreements were resolved by a third party to identify all epilepsy drugs. For each identified drug, the FDA label, medical, and statistical reviews were used to identify all published trials cited in the approval. Data of study characteristics, sex/gender terminology and analysis of sex and gender were extracted by two independent reviewers. All analyses conducted with continuous variables used logistic regression, while between-group differences for categorical variables used Fisher exact tests.
Results:
Data were extracted from 55 trials describing 17 unique drugs (Table 1). Eighty-five percent of trials were industry-funded with a median sample size of 198. Forty-seven percent (27/55) of studies achieved statistical power to detect significant effects, 41% (23/55) of studies used sex- or gender-associated terms correctly, and 56% (31/55) either used sex and gender terms interchangeably or incorrectly. Statistical analyses reveal no association between year of publication and appropriate sex and gender, sex, or gender reporting of clinical trials (p > 0.05) but reveal anon-significant trend toward more appropriate sex/gender reporting pre- versus post-2016. Reporting of sex and gender variables in adverse events and primary and secondary outcomes was uncommon (Fig 1); only 2 trials reported the gender distribution of their primary outcome, 8 reported the sex distributions of any outcome. Fewer trials reported the sex distributions of adverse events, while none reported the gender distributions. Only 2 trials discussed gender disaggregation for any outcome assessed.
Conclusions:
Despite literature demonstrating the importance of sex and gender considerations in epilepsy therapeutics1,2, there exists pervasive inadequate reporting and analysis of sex and gender variables among FDA approved epilepsy drugs. The development of a common process and accountability for sex and gender reporting and analysis may be prudent to address these shortcomings.
1Hophing L, et al. Int Rev Neurobiol. 2022;164:235-276.
2Samba Reddy D, et al. Neurosci Lett. 2021; 750:135753.
Funding: This work was supported by the University of Toronto's University Health Network Women's Health summer scholarship.
Clinical Epilepsy