Gender Disparity in Clinical Trials on Hereditary Hemorrhagic Telangiectasias. a Retrospective Study

Introduction

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder characterized by malformations of the blood vessels with symptoms varying from patient to patient but commonly manifests with epistaxis & gastrointestinal (GI) bleeding. However, this disorder is significantly associated with the development of visceral arteriovenous malformations (AVM) with resultant life-threatening complications depending on the location including significant hemorrhage, stroke, cirrhosis and heart failure (Zhang et al, Blood Adv, 2023). Clinical manifestations of HHT tend to be more severe in women, though the reasons for this disparity are not well understood (Mora-Lujan et al, Orphanet J Rare Dis, 2020). HHT is considered an understudied condition, despite the high morbidity seen among women, creating inequity in the field of hematology & understanding these disparities is crucial for improving patient outcomes (Zhang et al, Blood Adv, 2023). This descriptive, retrospective study aims to analyze clinical trials conducted over a 28 year period to provide insights into participants' gender and highlight potential disparities in the research.

Methods

In this study, we conducted a comprehensive search of multiple databases, including PUBMED and ClinicalTrials.gov, with the aim of identifying publications on clinical trials focused on HHT treatments that were conducted from January 1996 to July 2024, including both full manuscripts and abstracts. Articles that were unavailable in English and articles that lacked preliminary results were excluded. For the eligible studies, we extracted data on several key variables: the number of participants, gender distribution, year of publication, and the year the study was initiated. We performed descriptive statistical analyses, obtaining proportions and measurements of frequency to summarize these variables and explore gender distribution.

Results

We identified a total of 32 studies comprising 2,248 individuals with HHT. Of these studies, 66% (n=21/32) were randomized clinical trials (RCT). Among the total individuals in these studies, 56% (n=1,264) were female & the total male-to-female ratio was 0.75. Interestingly, the male-to-female ratio varied across different time periods. For studies conducted between 1996 and 2000, the ratio was 1.37, compared to 0.78 in studies conducted between 2000 and 2009 and 0.87 in studies conducted between 2010 and 2020. There was a notable increase in the amount of clinical trials that were performed over the studied period, demonstrated by 3% (n=1/32) of the studies were developed before the year 2000 compared to 81% (n= 26/32) after the year 2010. Notably, none of the studies that were found treated pregnant patients.

Conclusions

The findings in this study reflects the research efforts in HHT over the past 28 years. A significant portion of our clinical trials were randomized, indicating a strong emphasis in obtaining robust clinical data. Initially, there was a more pronounced gender disparity in the enrollment of interventional studies in the early clinical trials, with a higher number of male participants than females. However, this trend has shifted over time, resulting in an enrollment with a more balanced distribution between sexes, although now, the ratio of male to female is marginally inverted. Despite HHT being the second most prevalent bleeding disorder, it appears to be understudied. Additionally, the exclusion of pregnant patients in these studies highlights a significant gap in research & suggests further investigation in this population.

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