Gender minority patients in dermatology clinical trials

Introduction

Patients who identify as part of the lesbian, gay, bisexual, transgender, and queer (LGBTQ+) community often face unique health disparities (Yeung et al., 2019). The term “gender minority” refers to individuals who identify outside of their assigned birth sex, including transgender and gender nonbinary (TGNB) people (Wood and Spach, 2018). The transgender population is a smaller group within the LGBTQ + community who face additional challenges in dermatology, often related to varying stages of transitioning (Sullivan et al., 2019). Accurate estimates of the U.S. TGNB population are unknown. Most population-based surveys do not collect data on gender identity; however, recent studies have reported the prevalence of TGNB identity to be between 0.39% and 2.7% (Nolan et al., 2019). Undoubtedly, the number of individuals self-identifying as TGNB is growing, with particularly higher proportions in young generations. The increase in the TGNB population has been related to greater societal acceptance and awareness of TGNB individuals, which has contributed to increased self-identification (Nolan et al., 2019).

Challenges of caring for gender minority patients

Current clinical trial structures do not adequately accommodate TGNB patients. The recent unprecedented surge in therapeutics (including immunomodulators and small molecule inhibitors) under investigation in dermatology highlights the importance of optimizing clinical trial access and enrollment for all patient populations. As we strive to improve enrollment of underrepresented minorities in clinical trials, striving to provide care that acknowledges gender diversity is equally important. Facilitating the enrollment of TGNB patients in clinical trials begins with the first step of health care providers, industry, and regulatory bodies recognizing and acknowledging these patients as an important population to include in clinical trials, followed by establishing trust with these patients and improving their access to care. LGBTQ + individuals often experience stigma, perceived stigmatization, and prior negative experiences with health care providers that can lead to delays in seeking medical treatment (Yeung et al., 2019). Delays in medical treatment contribute to further disease burden and health disparities.

As a whole, dermatologists and clinical staff need training on how to care for LGBTQ + patients, especially due to often limited exposure in medical school and other training curricula. In addition, changes are needed across multiple levels to improve culturally competent and inclusive care for TGNB individuals participating in clinical trials. Providing participants with the option to disclose their unique gender identities, encouraging the development of more inclusive protocols, and updating industry and regulatory body (e.g., institutional review board, U.S. Food and Drug Administration) definitions can spearhead inclusive care in dermatology clinical trials.

Clinical trial resources

Using correct pronouns is the first step in fostering a comfortable and welcoming environment for TGNB patients. Currently, most clinical trials, particularly sponsored trials, use demographic collection platforms and source documents that only elicit biological sex. The U.S Food and Drug Administration reported demographic information for all global clinical trials from 2015 to 2016, but only “male” and “female” were used to describe gender and there was no specification of assigned gender or gender identity (Jenkins et al., 2017). ClinicalTrials.gov also only specifies male and female when classifying trial participants.

Awareness of the specific needs in caring for TGNB patients has grown in dermatology, spearheaded by recognized limitations in the iPLEDGE system for isotretinoin. Recently, patient advocates have called for change to the gender-binary categorization model within the iPLEDGE system for prescribing isotretinoin (Boos et al., 2019). The current model poses challenges, particularly for transgender men (biological female to male), who are often misidentified as female due to the requirement of two forms of birth control in those of childbearing potential. Using gender-neutral language and only focusing on childbearing potential affirms the patient’s right to self-identify while still allowing for safe and reliable care.

A similar approach can be adapted for clinical trials in dermatology. Many clinical trials require contraception methods for patients with childbearing potential. Emphasizing the presence or absence of childbearing potential may be most beneficial in affirming TGNB patients while ensuring safe clinical trial participation. This method also helps to clarify the need for pregnancy tests and contraception methods for transgender patients who may be in differing stages of the gender affirmation process.

Alternatively, clinical trials could also implement a process of eliciting assigned gender at birth as well as gender identity with the inclusion of gender diverse terms, such as transgender, gender nonbinary, intersex, genderqueer, and other. Efforts should be made to ensure that patients are referred to by their preferred pronouns and allowed to express their gender identity. Eliciting both assigned gender and gender identity also allows for quantification of transgender and gender nonbinary participants to examine participation in clinical trials over time. In addition, it may shed light on any potential health concerns affecting this population.

Clinical trial staff education

As the TGNB population increases, research, clinic, and sponsor staff education is needed to best serve and support gender diverse populations. The National LGBT Health Center (www.lgbthealtheducation.org) provides learning modules with the goal of advancing health equity, addressing and eliminating health disparities, and optimizing health care access for LGTBQ + populations. Encouraging health care providers to complete educational modules, such as those provided by the National LGBT Health Center, will help promote inclusive care and enhance patient outcomes. Additional resources for health care providers interested in optimizing care for LGBTQ + patients were presented in a recent article describing dermatologic care for LGBTQ + people (Yeung et al., 2019).

Study protocol optimization

Study protocols should be developed to accommodate and match the psychosocial and physical needs of TGNB participants. Inquiring about patients’ sexual orientations and gender affirmation treatments and procedures can help direct decisions for patient safety. Clear guidance should be included in trial protocols and eligibility criteria for transgender patients who may be undergoing varying stages of the gender affirming process. For example, patients transitioning from male to female would not need pregnancy tests or contraception methods because they are biologically male. Meanwhile, patients transitioning from female to male may require pregnancy tests and contraception unless they have undergone gender affirmation surgery. In addition, clarifying the protocol requirements for patients of childbearing potential who exclusively have sex with others of childbearing potential should be considered. Making the protocol clear for investigators allows for thoughtful conversations that describe necessary safety measures while still affirming the patients’ identity.

At the trial design stage, communication with specialists with knowledge regarding LGBTQ + populations may be beneficial for industry and dermatology investigators. Their expertise may be constructive in improving inclusiveness of source documents and protocol design throughout screening, enrollment, and follow-up. For example, e-diaries and electronic data entry sites could allow participants to include a preferred name and preferred pronoun in addition to their legal name and assigned gender at birth. Protocols should also take into consideration common health and dermatologic issues that TGNB patients may face in general and throughout clinical trial participation (Sullivan et al., 2019). After clinical trial completion, outcome and data reporting should also include a variety of gender identities to more accurately reflect gender diversity in participation.

Looking into the future

We have entered an era of an unprecedented surge in pipeline medications in dermatology for conditions such as atopic dermatitis, hidradenitis suppurativa, and psoriasis. Similarly, there is a parallel increase in self-identification of TGNB populations. Throughout these periods of growth, it is imperative to modify and improve clinical trial designs to optimize inclusion of TGNB patients while providing culturally mindful and sensitive care to this often-stigmatized population.

Financial Disclosures

Dr. Vivian Y. Shi is a stock shareholder of Learn Health and has served as an advisory board member, investigator, and/or received research funding from Sanofi Genzyme, Regeneron, AbbVie, Eli Lilly, Novartis, SUN Pharma, LEO Pharma, Pfizer, Menlo Therapeutics, Burt’s Bees, GpSkin, Altus Labs, and Skin Actives Scientific. Dr. Afsaneh Alavi has received an unrestricted educational grant from AbbVie and has served as an advisory board member, investigator, and/or received research funding from Janssen, Novartis, Sanofi Genzyme, Regeneron, AbbVie, Eli Lilly, SUN Pharma, LEO Pharma, Pfizer, Xoma, Infla Rx. There were no incentives or transactions, financial or otherwise, relevant to this manuscript. Ms. Kyla N. Price and Dr. Jennifer L. Hsiao have no conflicts of interest to declare relevant to this manuscript.

Conflicts of interest

None.

Funding

None.

Study Approval

N/A.