A Systematic Review of Sex-Based Reporting in Topical Glaucoma Medication Clinical Trials

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology. Glaucoma Pub Date : 2025-07-01 DOI:10.1016/j.ogla.2025.03.010

Helen Zhao BA , Rachel E. Davis MD , Alexander S. Davis MD, PhD , Susan L. Meoli RPh, PharmD , Elizabeth A. Cretara MD

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引用次数: 0

Abstract

Topic

The National Institutes of Health (NIH) issued guidance in 2016 that sex should be treated as a biological variable in clinical studies; however, previous research has shown that biomedical studies still fail to include sex as a biological variable (SABV) in study design and analysis. We hypothesize that despite evidence for sex-specific glaucoma risk factors, clinical trials for glaucoma topical medications also fail to treat SABV.

Clinical Relevance

Prior studies have found sex-specific genetic and hormonal risk factors for glaucoma suggesting that biological sex may influence the disease course.

Methods

We performed a systematic review on Pubmed and Google Scholar using terms including generic names of common glaucoma medications, and filters “randomized control trial” and “clinical trial.” Resulting studies were reviewed and included if they met inclusion criteria including randomized controlled trial design, testing of topical glaucoma medications in patients with open-angle glaucoma or ocular hypertension, and published between 2002-2022. Included studies were read and assessed on metrics pertinent to SABV including sex reporting and matching, sex-based analysis of medication efficacy, adverse events (AEs), and mention of SABV in the discussion and conclusion.

Results

We identified 543 studies; 122/543 (22.5%) met inclusion criteria representing 31 644 subjects; 16 656/31 644 (52.6%) were women. Sex of subjects was reported in 109/122 (89%) studies. However, only 5/122 (4%) mentioned sex in data analysis, including efficacy (1), AEs (1), and mention of sex in the discussion or conclusion (4). We found that studies published after the NIH guidance on SABV in 2016 and studies funded by the NIH were not more likely to include SABV, however only 3 of 122 (2.5%) studies were NIH-funded. Pregnancy or lactation were exclusion criteria for 31/122 (25%) studies.

Conclusions

While the majority of glaucoma topical medication clinical trials reported sex and achieved sex-matching, they failed to include sex-based analysis of medication efficacy or AEs. Opportunities remain to include SABV to improve our understanding of the impact of biological sex on glaucoma treatment, although that may require increases in sample size.

Financial Disclosure(s)

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

查看原文本刊更多论文

局部青光眼药物临床试验中基于性别报告的系统综述。

目的：美国国立卫生研究院（NIH）于 2016 年发布指南，规定在临床研究中应将性别作为生物变量处理；然而，以往的研究表明，生物医学研究仍未能将性别作为生物变量（SABV）纳入研究设计和分析。我们假设，尽管有证据表明存在性别特异性青光眼风险因素，但青光眼局部用药的临床试验也未能将性别作为生物变量：对象、参与者和/或对照组：我们使用包括常见青光眼药物通用名称在内的术语以及 "随机对照试验 "和 "临床试验 "过滤器对 Pubmed 和 Google Scholar 进行了搜索：方法、干预或测试：对所获研究进行审查，如果符合纳入标准（包括随机对照试验设计、开角型青光眼或眼压过高患者的青光眼局部用药研究、2002-2022 年出版年份），则予以纳入。我们对纳入的研究进行了阅读，并对与 SABV 相关的指标进行了评估：我们对性别报告和匹配进行了分析。我们评估了基于性别的药物疗效、不良事件（AEs）以及讨论和结论中提及 SABV 的分析。我们根据国家、期刊、药物类别、资金来源和发表年份对结果进行了分组：我们确定了 543 项研究；122/543（24.9%）项符合纳入标准，代表 31,644 名受试者；16,656/31,644（52.6%）名受试者为女性。109/122（89%）项研究报告了受试者的性别。然而，只有 5/122 项（4%）在数据分析中提及性别，包括疗效 1/122 项（0.8%）、AEs 1/122 项（0.8%），以及在讨论或结论中提及性别的 4/122 项（3.3%）。我们发现，81/122（67%）项研究发表于 2016 年之前，3/122（2.5%）项研究由美国国立卫生研究院资助。性别报告最详细的五项试验发表于 2016 年之前，由非美国国立卫生研究院资助，评估前列腺素类似物，分别来自日本、美国、塞尔维亚和韩国。怀孕和/或哺乳期是31/122（25%）项研究的排除标准：结论：虽然大多数青光眼局部用药临床试验都报告了性别并实现了性别匹配，但它们都没有对药物疗效或AEs进行基于性别的分析。尽管这需要增加样本量，但仍有机会纳入SABV，以提高我们对生理性别对青光眼治疗影响的认识。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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