Who Are We Missing? Reporting of Transgender and Gender-Expansive Populations in Clinical Trials

HomeJournal of the American Heart AssociationAhead of PrintWho Are We Missing? Reporting of Transgender and Gender‐Expansive Populations in Clinical Trials Open AccessRapid CommunicationPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toOpen AccessRapid CommunicationPDF/EPUBWho Are We Missing? Reporting of Transgender and Gender‐Expansive Populations in Clinical Trials Eli N. Rice, Roy H. Lan, Julio C. Nunes, Rushil Shah, Kira Clark, Vyjeyanthi S. Periyakoil, Jonathan H. Chen, Bryant Lin, Melvin Echols, Christopher Awad, Muhammed Y. Idris, Erin Rose Cruz, Peter D. Poullos, Eldrin F. Lewis, Cati Brown‐Johnson, Joseph Igwe, Sa Shen, Latha Palaniappan, Marcia L. Stefanick, Victor Ritter, Priscilla Pemu, Fatima Rodriguez, Brototo Deb, Krishna Pundi and Paul J. Wang Eli N. RiceEli N. Rice https://orcid.org/0000-0001-9729-1251 , Stanford University School of Medicine, , Stanford, , CA, , USA, Search for more papers by this author , Roy H. LanRoy H. Lan https://orcid.org/0000-0001-8168-7438 , Stanford University School of Medicine, , Stanford, , CA, , USA, Search for more papers by this author , Julio C. NunesJulio C. Nunes , Yale University School of Medicine, , New Haven, , CT, , USA, Search for more papers by this author , Rushil ShahRushil Shah , Stanford University School of Medicine, , Stanford, , CA, , USA, Search for more papers by this author , Kira ClarkKira Clark https://orcid.org/0000-0003-1102-7885 , Stanford University School of Medicine, , Stanford, , CA, , USA, Search for more papers by this author , Vyjeyanthi S. PeriyakoilVyjeyanthi S. Periyakoil https://orcid.org/0000-0001-5438-9902 , Stanford University School of Medicine, , Stanford, , CA, , USA, Search for more papers by this author , Jonathan H. ChenJonathan H. Chen https://orcid.org/0000-0002-4387-8740 , Stanford University School of Medicine, , Stanford, , CA, , USA, Search for more papers by this author , Bryant LinBryant Lin https://orcid.org/0000-0002-7284-0522 , Stanford University School of Medicine, , Stanford, , CA, , USA, Search for more papers by this author , Melvin EcholsMelvin Echols https://orcid.org/0000-0001-6630-5761 , Morehouse School of Medicine, , Atlanta, , GA, , USA, Search for more papers by this author , Christopher AwadChristopher Awad https://orcid.org/0000-0002-8845-3076 , Emory University School of Medicine, , Atlanta, , GA, , USA, Search for more papers by this author , Muhammed Y. IdrisMuhammed Y. Idris https://orcid.org/0000-0002-3899-3728 , Morehouse School of Medicine, , Atlanta, , GA, , USA, Search for more papers by this author , Erin Rose CruzErin Rose Cruz https://orcid.org/0009-0003-5986-1868 , Stanford University School of Medicine, , Stanford, , CA, , USA, Search for more papers by this author , Peter D. PoullosPeter D. Poullos https://orcid.org/0000-0002-8335-5725 , Stanford University School of Medicine, , Stanford, , CA, , USA, Search for more papers by this author , Eldrin F. LewisEldrin F. Lewis , Stanford University School of Medicine, , Stanford, , CA, , USA, Search for more papers by this author , Cati Brown‐JohnsonCati Brown‐Johnson https://orcid.org/0000-0002-5415-3665 , Stanford University School of Medicine, , Stanford, , CA, , USA, Search for more papers by this author , Joseph IgweJoseph Igwe https://orcid.org/0000-0002-2753-3865 , Stanford University School of Medicine, , Stanford, , CA, , USA, Search for more papers by this author , Sa ShenSa Shen , Stanford University School of Medicine, , Stanford, , CA, , USA, Search for more papers by this author , Latha PalaniappanLatha Palaniappan https://orcid.org/0000-0002-1245-665X , Stanford University School of Medicine, , Stanford, , CA, , USA, Search for more papers by this author , Marcia L. StefanickMarcia L. Stefanick , Stanford University School of Medicine, , Stanford, , CA, , USA, Search for more papers by this author , Victor RitterVictor Ritter https://orcid.org/0000-0002-1676-9573 , Stanford University School of Medicine, , Stanford, , CA, , USA, Search for more papers by this author , Priscilla PemuPriscilla Pemu https://orcid.org/0000-0002-2443-6613 , Morehouse School of Medicine, , Atlanta, , GA, , USA, Search for more papers by this author , Fatima RodriguezFatima Rodriguez https://orcid.org/0000-0002-5226-0723 , Stanford University School of Medicine, , Stanford, , CA, , USA, Search for more papers by this author , Brototo DebBrototo Deb https://orcid.org/0000-0001-8800-0002 , Georgetown University School of Medicine, , Washington, , DC, , USA, Search for more papers by this author , Krishna PundiKrishna Pundi https://orcid.org/0000-0002-1230-367X , Stanford University School of Medicine, , Stanford, , CA, , USA, Search for more papers by this author and Paul J. WangPaul J. Wang * Correspondence to: Paul J. Wang, MD, Division of Cardiovascular Medicine, Stanford University, 300 Pasteur Dr Room A260, MC 5233, Stanford, CA 94305. Email: E-mail Address: [email protected] https://orcid.org/0000-0002-5467-5877 , Stanford University School of Medicine, , Stanford, , CA, , USA, Search for more papers by this author Originally published10 Nov 2023https://doi.org/10.1161/JAHA.123.030209Journal of the American Heart Association. 2023;0:e030209Transgender and gender‐expansive individuals are a growing segment of the population and have elevated risks of certain cardiac conditions, such as myocardial infarction and venous thromboembolism.1 However, few large cardiovascular clinical trials have studied or reported clinical outcome data explicitly regarding this patient population. In this research letter, we characterized the reporting and language used for transgender and gender‐expansive populations in cardiovascular randomized clinical trials.We did a systematic review of randomized clinical trials across 4 cardiovascular areas (coronary artery disease, hypertension, atrial fibrillation, and diabetes) using ClinicalTrials.gov, which included 79 recently completed (2018–2022) interventional studies in the United States with published results for each area. Our research was exempted from the Stanford University Institutional Review Board approval, and no informed consent was required.A total of 451 807 participants were included (Table). We collected reporting of populations for sex and gender descriptions, as well as the inclusion and exclusion criteria. Almost all studies reported sex or gender as a single outcome variable. We inferred this to denote sex unless it was specified otherwise. All studies reported sex, with women representing 42% of all participants. Women represented the minority of study participants in coronary artery disease (30%), atrial fibrillation (42%), and diabetes (48%) clinical trials, but the majority of participants in hypertension trials (67%). Gender identity, including the option other, was reported in only 1 trial (<1%). No studies reported data regarding transgender or gender‐expansive identification. Several trials included pregnant women and lactating women as exclusion criteria, as well as man and woman as inclusion criteria. Our complete findings are available from the corresponding author upon request.Table 1. Gender Diversity by Clinical Trial SubtypeAtrial fibrillationCoronary artery diseaseHypertensionDiabetesTotalTrials, n2020201979Trials reporting sex, n (%)20 (100)20 (100)20 (100)19 (100)79 (100)Total participants, n424 923*11 934273612 214451 807*Men, n (%)242 207 (57)8312 (70)904 (33)6410 (52)257 833 (57)Women, n (%)179 206 (42)3622 (30)1832 (67)5804 (48)190 464 (42)Reporting gender, n (%)1 (5)0001 (1)*N=3510 are included other and nonreport category.Our findings confirm that there is a lack of commitment in current cardiovascular randomized clinical trials to the Sex and Gender Equity in Research guidelines.2 and the Measuring Sex, Gender Identity, and Sexual Orientation Report.3 These guidelines and report describe how to record and report sex and gender identification systematically within clinical research.Furthermore, the National Institutes of Health has defined the difference between sex, “the biological differences between females and males, including chromosomes, sex organs, and endogenous hormonal profiles, and is typically assigned at birth,” and gender, “socially constructed and enacted roles and behaviors which occur in a historical and cultural context and vary across societies and over time.”4 We found that the distinction between sex and gender was almost nonexistent when it came to reporting participants within these randomized clinical trials, with many studies misreporting sex as gender. We emphasize Sex and Gender Equity in Research's recommendation that “authors should avoid confusing sex with gender and reducing complex or interactionist explanations to overly simple ones.” We encourage modification of the National Institutes of Health reporting guidelines to similarly require both gender and sex in reporting for human subject research.Even when studies are not powered to detect statistical differences for gender‐diverse populations, researchers and authors should consider the implication of how they summarize all populations, as clinical recommendations and guidelines are frequently extrapolated incorrectly toward minoritized groups. Additionally, we strongly recommend welcoming transgender and gender‐expansive individuals into trials by replacing the category other with transgender woman/transfeminine, transgender man/transmasculine, nonbinary person, and prefer to self‐describe or another option that invites individuals to participate, instead of immediately othering them.5In summary, transgender and gender‐expansive individuals are not currently reported in almost all current cardiovascular clinical trials, despite being vulnerable populations with additional cardiovascular risk. Without careful collection of gender identity data, we will never fully understand the depth and breadth of disparities in this population. Recent national guidelines have called for full reporting of gender and appropriate usage of gender‐inclusive language in randomized clinical trials. Future cardiology trials should abide by the Sex and Gender Equity in Research guidelines and other expert recommendations to better represent and care for these populations.Source of FundingSupport for this project is from the American Heart Association.DisclosuresNone.Footnotes* Correspondence to: Paul J. Wang, MD, Division of Cardiovascular Medicine, Stanford University, 300 Pasteur Dr Room A260, MC 5233, Stanford, CA 94305. Email: pjwang@stanford.eduThis manuscript was sent to Mahasin S. Mujahid, PhD, MS, FAHA, Associate Editor, for review by expert referees, editorial decision, and final disposition.For Disclosures, see page 2.References1 Streed CG, Beach LB, Caceres BA, Dowshen NL, Moreau KL, Mukherjee M, Poteat T, Radix A, Reisner SL, Singh V, et al. Assessing and addressing cardiovascular health in people who are transgender and gender diverse: a scientific statement from the American Heart Association. Circulation. 2021; 144:136–148. doi: 10.1161/CIR.0000000000001003LinkGoogle Scholar2 Heidari S, Babor TF, De Castro P, Tort S, Curno M. Sex and Gender Equity in Research: rationale for the SAGER guidelines and recommended use. Res Integr Peer Rev. 2016; 1:1–9. doi: 10.1186/s41073-016-0007-6CrossrefMedlineGoogle Scholar3 National Academies of Sciences, Engineering, and Medicine . Preface. In: Bates N, Chin M, Becker T, eds. Measuring Sex, Gender Identity, and Sexual Orientation. The National Academies Press; 2022:vii–x.Google Scholar4 Sex & Gender . Office of Research on Women's Health. National Institutes of Health. Accessed March 15, 2023. https://orwh.od.nih.gov/sex‐genderGoogle Scholar5 Spiel K, Haimson OL, Lottridge D. How to do better with gender on surveys. Interactions. 2019; 26:62–65. doi: 10.1145/3338283CrossrefGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetails Article InformationMetrics Copyright © 2023 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley BlackwellThis is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.https://doi.org/10.1161/JAHA.123.030209PMID: 37947088 Manuscript receivedApril 18, 2023Manuscript acceptedJuly 31, 2023Originally publishedNovember 10, 2023 Keywordsdisparitiestransgenderclinical trialsgendergender nonconformingPDF download SubjectsCardiovascular DiseaseDisparitiesHealth Equity