Randomised controlled trial of LGBTQ-affirmative cognitive-behavioural therapy for sexual minority women’s minority stress, mental health and hazardous drinking: Project EQuIP protocol

Abstract

Introduction

Sexual minority women represent one of the highest-risk groups for hazardous drinking and comorbid mental health problems (eg, depression, anxiety). Research has identified cognitive (eg, expectations of rejection), affective (eg, emotion dysregulation) and behavioural (eg, avoidant coping) pathways through which minority stress (eg, stigma) places sexual minority women at disproportionate risk of hazardous drinking and comorbid depression/anxiety; yet no evidence-based interventions have been tested to address these pathways in this population. This article describes the design of Project EQuIP (Empowering Queer Identities in Psychotherapy), a randomised controlled trial of a transdiagnostic lesbian, gay, bisexual, transgender, queer (LGBTQ)-affirmative cognitive-behavioural therapy intervention (CBT) designed to improve minority stress coping and reduce sexual minority women’s hazardous drinking and mental health comorbidities.

Methods and analysis

This two-arm randomised controlled trial, funded by the National Institute on Alcohol Abuse and Alcoholism, has two objectives: (1) test the efficacy of 10 sessions of LGBTQ-affirmative CBT compared with 10 sessions of supportive counselling for sexual minority women in the community (anticipated n=450) who report hazardous alcohol use and meet criteria for a Diagnostic and Statistical Manual of Mental Disorders - 5 diagnosis of a depression or anxiety disorder and (2) examine psychosocial mechanisms and demographic factors as potential mediators and moderators, respectively, of the treatment-outcome relationship. This study’s primary outcome is change in the proportion of heavy drinking days. Secondary outcomes are changes in depressive and anxious symptoms.

Ethics and dissemination

The Yale University Human Subjects Committee reviewed and approved the research protocol. Results of this study will be disseminated to researchers and practitioners through peer-review publications and conference presentations, and directly to study participants.

Trial registration number

Registered on 17 August 2022 (ClinicalTrials.gov identifier: NCT05509166).

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• A randomised controlled trial can test the efficacy of this treatment against community treatment-as-usual.

• Identifying treatment mediators over 12 months can encourage treatment efficiency.

• Identifying treatment moderators can inform treatment personalisation and matching.

• Enrolled participants might not be representative of the population of sexual minority women in need of evidence-based treatment.

• The use of a single control condition limits comparisons to treatment approaches not focused on alleviating the psychosocial effects of stigma and minority stress.

Background

Sexual minority women (SMW) represent one of the highest-risk groups for hazardous drinking (HD), a risk factor for alcohol use disorder (AUD).¹,⁴ HD is increasingly recognised as a women’s health issue.^{5 6} Alcohol consumption and related morbidity and mortality are increasing more steadily among US women than men,^{7 8} and women are now recognised as being at a greater risk of certain alcohol-related cancers, cardiovascular disease and liver disease.^{9 10} Furthermore, women with AUD are about half as likely as men to perceive a need for, or to seek, treatment for alcohol-related problems.¹¹ Among SMW, these disparities are particularly acute. SMW are 6–7 times more likely than heterosexual women to meet the criteria for alcohol dependence and 8 times more likely to report seeking help for alcohol-related problems.⁴¹²,¹⁴ Given SMW’s higher rates of AUD and treatment seeking, developing interventions specifically for SMW who experience alcohol-related problems can potentially reduce population prevalence of HD. Among SMW, HD is also more likely to co-occur with depression, anxiety and post-traumatic stress disorder (PTSD), compounding treatment needs.¹⁵,¹⁹

SMW’s elevated risk of HD is linked to exposure to unique identity-related stressors, known as minority stressors (eg, family and peer rejection, discrimination and identity-based sexual or physical abuse).²⁰,²⁹ Minority stressors put SMW at risk of HD for several reasons. For instance, many SMW turn to alcohol as a coping strategy (ie, negative reinforcement).³⁰ In fact, SMW’s high rates of positive alcohol use expectancies, such as worry disengagement, partially explain their greater risk.³¹ Additionally, SMW frequently socialise in alcohol-focused venues (eg, queer bars), in part to find support and cope with stress, enhancing their normative perceptions of heavy drinking.³²,³⁶ Finally, the cumulative impact of lifetime trauma exacerbates minority stressors and stress reactions (eg, emotion dysregulation), which also helps explain the sexual orientation disparity in HD.³⁷,⁴¹ For many SMW, sexual minority stressors intersect with race/ethnicity-, class- or gender-based stress to confer even greater vulnerability to behavioural and mental health risks.⁴²,⁴⁸

Evidence suggests that minority stressors give rise to maladaptive identity-based cognitive, emotional and behavioural reactions. For instance, SMW’s discrimination predicts internalised stigma, concealment and chronic rejection expectations, which in turn predict HD and comorbid depression/anxiety.⁴⁹ Minority stressors also contribute to maladaptive reactions, such as emotion dysregulation, impulsivity and hypervigilance.²¹⁵⁰,⁵⁴ Because these reactions confer vulnerability to a broad range of negative outcomes—including HD, depression and anxiety—they are considered transdiagnostic.

An intervention capable of reducing maladaptive cognitive, emotional and behavioural minority stress reactions can simultaneously improve SMW’s HD and mental health comorbidities.^{55 56} Drawing on advancements in emotion science,⁵⁷ psychiatric nosology⁵⁸ and cognitive-affective neuroscience,⁵⁹ there is strong evidence that SMW’s psychosocial health challenges are highly comorbid and represent functionally similar maladaptive reactions to minority stress.^{24 55} For example, chronic exposure to the stressors that SMW often experience from an early age disrupts neurobiological stress pathways and yields rejection schemas, emotion dysregulation, unassertiveness and impulsivity,^{60 61} which are associated with HD and poor mental health.^{62 63} Researchers have developed and tested this model, depicted in figure 1, which shows that minority stressors elicit minority stress reactions that predict depression, anxiety and HD.³⁸⁶⁴,⁷⁰ Given that these stress reactions underlie SMW’s HD, depression and anxiety, a treatment that improves these reactions may improve multiple behavioural and mental health challenges simultaneously.

Figure 1. Conceptual model. CBT, cognitive-behavioural therapy; LGBTQ, lesbian, gay, bisexual, transgender, queer; SMW, sexual minority women.

Despite clear evidence of need,⁷¹,⁷⁵ few targeted HD interventions have been tested among SMW.^{4 76 77} To our knowledge, only two studies have been published, and these were narrowly focused on reducing alcohol risk through gamified normative feedback among SMW⁷⁸ or behavioural couples therapy for heavy drinking among both lesbian and gay participants with AUD.⁷⁹ Further, despite strong evidence of the role of minority stress, depression and anxiety in SMW’s HD, no intervention has addressed these factors to reduce SMW’s disproportionate risk of HD. Responding to the near-complete lack of interventions for SMW’s mental and behavioural health, the current study is designed to test the efficacy of lesbian, gay, bisexual, transgender, queer (LGBTQ)-affirmative cognitive behavioural therapy (CBT), a transdiagnostic intervention.

LGBTQ-affirmative CBT was created with extensive input from SMW, following our team’s history of developing interventions ‘by and for’ the sexual minority community.⁵⁶⁸⁰,⁸⁵ Specifically, LGBTQ-affirmative CBT is based on the Unified Protocol for the Transdiagnostic Treatment of Emotional Disorders,⁸⁶,⁹⁰ a flexible protocol that distils CBT into its core components (eg, motivational interviewing for treatment engagement, mindfulness, cognitive restructuring, behavioural exposures). The Unified Protocol shows strong efficacy across several randomised controlled trials (RCTs) for reducing depression, anxiety and HD^{89 91 92} in non-SMW samples by targeting the maladaptive cognitive, affective and behavioural processes shared across disorders involving emotion dysregulation. In pilot research, we adapted the Unified Protocol’s CBT principles and techniques to distinctly respond to SMW’s minority stress,⁹³ resulting in LGBTQ-affirmative CBT.^{94 95} In our pilot waitlist-controlled trial of LGBTQ-affirmative CBT with 60 SMW, we found large reductions in depression (Cohen’s d=0.85) and anxiety (d=0.86), and moderate reductions in emotion dysregulation (d=0.44) and HD (d=0.29).⁹⁰ In the current trial, we strengthen LGBTQ-affirmative CBT’s focus on HD (eg, through personalised feedback and weekly assessment to increase self-awareness and inform case conceptualisation), another transdiagnostic outcome driven by minority stress,⁹⁶ that co-occurs with depression and anxiety,^{97 98} and is highly suitable to being addressed by this transdiagnostic treatment.⁵⁶

We expect that LGBTQ-affirmative CBT will result in a greater reduction of HD, depression and anxiety compared with treatment-as-usual (TAU). To test this hypothesis, participants from the community will be randomised to receive LGBTQ-affirmative CBT or TAU, and all participants will complete assessments of alcohol use, mental health and minority stress reactions at baseline, 4, 8 and 12 months. We further expect that LGBTQ-affirmative CBT will be more efficacious than TAU in reducing stress reactions, including those specific to sexual minority identity (eg, rejection expectations, internalised stigma, identity concealment) and those elevated among sexual minority people because of minority stress (eg, emotion dysregulation, impulsivity). Longitudinal assessments at baseline, 4, 8 and 12 months will be used to determine if reductions in the intended psychosocial mechanisms of LGBTQ-affirmative CBT (eg, internalised stigma, rejection sensitivity, emotion dysregulation) mediate reductions in heavy drinking. To advance personalised medicine (ie, person-to-treatment matching), we will also examine whether LGBTQ-affirmative CBT is differentially efficacious across key demographic factors, including race and ethnicity, sexual identity (eg, lesbian, bisexual), gender identity and expression, and stigma exposure at three socioecological levels: individual (eg, internalised stigma), interpersonal (eg, discrimination) and structural (eg, local laws and policies in the cities/counties in which participants live).

Methods

Design

In this two-arm RCT starting on 1 February 2023 and anticipated to end 1 June 2027, LGBTQ-affirmative CBT will be compared with TAU (ie, LGBTQ-affirmative supportive counselling) to test the benefit of LGBTQ-affirmative CBT regarding (1) the primary outcome: the change in proportion of heavy drinking days in the past 30 days; and (2) the secondary outcomes: reduction in WHO risk drinking level, the absence of a major depression and anxiety disorder diagnosis, and reduction in depression and anxiety symptoms. Both LGBTQ-affirmative CBT and TAU groups receive 10 sessions of therapy—both delivered remotely via telehealth—and complete weekly surveys to track symptoms and alcohol use. Baseline and follow-up assessments at 4, 8 and 12 months will allow us to determine whether LGBTQ-affirmative CBT successfully improves minority stress reactions (see figure 2 for study flow).

Figure 2. Study flow. CBT, cognitive-behavioural therapy; DIAMOND, Diagnostic Interview for Anxiety, Mood, OCD and Related Neuropsychiatric Disorders; LGBTQ, lesbian, gay, bisexual, transgender, queer; TAU, treatment-as-usual; TLFB, timeline follow-back.

Study data were collected and managed using Research Electronic Data Capture (REDCap) electronic data capture tools hosted at Yale University.^{99 100} REDCap is a secure, web-based software platform designed to support data capture for research studies, providing (1) an interface for validated data capture, (2) audit trails for tracking data manipulation and export procedures, (3) automated export procedures for seamless data downloads to common statistical packages and (4) procedures for data integration and interoperability with external sources.

Recruitment

Participants are recruited in the states of New York, New Jersey and Pennsylvania.¹⁰¹ Recruitment staff post ads on online platforms (eg, Instagram, Lex, Facebook), on streets in various neighbourhoods and in venues frequently visited by SMW (eg, bars, bookstores, restaurants/cafes). Staff speak directly with prospective participants at SMW-oriented venues, community events and through social media platforms. Additional recruitment methods rely on community-based organisations (eg, health centres, community organisations), school/university groups and local LGBTQ sports teams to spread information about the study.

Eligibility

Inclusion criteria

SMW are eligible if they report (1) being 18 years of age or older; (2) being fluent in English; (3) self-identifying as lesbian, bisexual, queer, pansexual or other non-heterosexual identity; (4) drinking ≥8 standard drinks/week, on average, in the past 30 days, or report at least two heavy drinking days (≥ 4 drinks in 1 day) in the past 30 days; (5) current Diagnostic and Statistical Manual of Mental Disorders (DSM-5) depression or anxiety disorder (screened initially using a cut-off of ≥2 on the Brief Symptom Inventory-4 and further confirmed by diagnostic interview via the Diagnostic Interview for Anxiety, Mood, OCD and Related Neuropsychiatric Disorders (DIAMOND)); (6) at least minimum motivation to reduce drinking (measured by the Readiness Ruler) and (7) living in New York, New Jersey or Pennsylvania and planning to stay for at least the next 4 months.

Exclusion criteria

SMW are ineligible under the following conditions: (1) reporting current mental health treatment ≥1 day/month; (2) having received any CBT in the past 3 months, although participants are not ineligible on enrolling in the study if they seek concomitant care and interventions after enrolment; (3) reporting current alcohol or drug use disorder treatment, except mutual self-help (eg, Alcoholics Anonymous); (4) exhibiting a need for alcohol detoxification, based on an adapted Clinical Institute Withdrawal Assessment for Alcohol-Revised¹⁰²; (5) exhibiting active psychosis or active mania, as initially assessed by a trained research assistant (RA) and confirmed by a study clinician; (6) exhibiting active suicidality or active homicidality, as assessed by the Suicidal Ideation Attributes Scale (SIDAS)¹⁰³ and confirmed by a study clinician; (7) reporting being currently legally mandated to attend treatment or (8) demonstrating gross cognitive impairment, as assessed with the St. Louis University Mental Status Cognitive Assessment,¹⁰⁴ and confirmed by a study clinician.

Screening and consent

Prospective participants complete an eligibility screener via Qualtrics. After the preliminary assessment for eligibility, participants attend a Zoom screening interview with an RA, and study clinician if indicated, to determine if participants are ineligible due to (1) geographical location, (2) need for alcohol detoxification, (3) active psychosis or active mania, (4) active suicidality or (5) gross cognitive impairment. Once individuals are deemed eligible to continue in the study, a research staff member reviews the full study consent form and clarifies any points of confusion. Individuals still interested in participating give consent electronically via Qualtrics.

Participants receive compensation as follows: $45 for completing the baseline assessment, $50 for completing the 4-month follow-up assessment, $55 for completing the 8-month follow-up assessment, $60 for completing the 12-month follow-up assessment and $5 for completing the survey after each of 10 intervention sessions.

Randomisation

The research staff conducting baseline and follow-up assessments are masked to study condition assignment. Participant conditions are hidden from masked staff in REDCap to prevent them from becoming unmasked. At the end of the Zoom portion of the baseline assessment, the unmasked project coordinator randomises the participant into the LGBTQ-affirmative CBT or TAU condition in a 1:1 ratio using the REDCap randomiser and orients the participants to their condition.

LGBTQ-affirmative CBT condition

LGBTQ-affirmative CBT is a 10-session, individually delivered intervention based on the Unified Protocol. Sessions will be delivered remotely from the offices of an academic research centre. The intervention has demonstrated efficacy in reducing stress-sensitive mental health disorders (eg, depression, anxiety) and enhancing emotion regulation skills, reducing avoidance patterns and improving motivation and self-efficacy for behaviour change. LGBTQ-affirmative CBT was created with input from LGBTQ community members and expert treatment providers over a multistage intervention development process.^{82 93} Figure 1 summarises LGBTQ-affirmative CBT’s principles and box 1 outlines its techniques. These principles and techniques infuse the Unified Protocol to normalise the adverse impact of minority stress, reduce internalised stigma and rejection schemas, reduce avoidant coping patterns and validate SMW’s unique strengths. The Unified Protocol employs modules for motivation enhancement, interoceptive and situational exposure, cognitive restructuring, mindfulness and self-monitoring techniques. Modules were adapted to help SMW identify minority stress experiences; track unhealthy reactions to minority stress, focusing on avoidance reactions (eg, substance use); attribute distress to minority stress rather than to personal failure; and assert themselves against minority stress in safe situations. In this trial, participants complete ten 50 min sessions via videoconferencing software within a 4-month period and are encouraged to complete one session per week.

Box 1. Techniques of LGBTQ-affirmative CBT.

Module 1: motivation enhancement for LGBTQ-affirmative CBT engagement

• Discuss alcohol use and its health impact.

• Review normative HD feedback report against SMW norms.

• Clarify primary and behavioural health goals.

• Build motivation to address mental and behavioural health.

• Review SMW’s unique strengths.

Module 2: the nature and emotional impact of minority stress

• Review minority stress’s impact on mental and behavioural health.

• Identify early and ongoing forms of intersectional minority stress.

• Discuss current coping strategies, including alcohol use.

Module 3: tracking emotional experiences

• Raise awareness of the emotional impact of early and ongoing minority stress and trauma.

Module 4: awareness of minority stress reactions

• Raise awareness of behavioural impact of minority stress and trauma.

• Teach mindful, present-focused reactions to minority stress.

• Teach distress tolerance skills for managing the emotional impact of trauma.

Module 5: cognitive appraisal and reappraisal

• Connect minority stress and trauma to maladaptive thinking patterns.

• Identify thoughts driven by minority stress and learn to update them.

Module 6: emotion avoidance

• Learn how avoiding strong emotions can lead to HD.

• Discuss how minority stress and trauma might lead to avoidance of certain people, places or experiences.

Module 7: emotion-driven behaviours

• Focus on how minority stress and trauma can lead to avoidant coping.

• Discuss intimacy, relationships and alcohol use.

• Create an emotional and behavioural avoidance hierarchy.

Module 8: behavioural experiments

• Engage SMW in behavioural experiments in which previously avoided experiences are gradually confronted.

• Increase tolerance of strong emotions in uncomfortable situations.

Module 9: behavioural skills training

• Continue graduated behavioural experiments.

• Focus on assertiveness training for coping with minority stress.

Module 10: relapse prevention

• Review new cognitive, affective and behavioural coping strategies and their application to future minority stress experiences.

TAU condition

Participants in the TAU condition receive 10 sessions of individually delivered LGBTQ-affirmative supportive counselling, the current standard of care for LGBTQ individuals, from a community clinic in New York City. Sessions will be delivered remotely. LGBTQ-affirmative supportive counselling is defined, for example, as a diverse set of supportive practices informed by general guidelines of the American Psychological Association (APA) that broadly direct clinicians to be aware of the distinct influences on sexual minority individuals’ mental health and address them in a manner that respects the individual’s autonomy to choose their treatment goals while validating their identities.¹⁰⁵ We selected LGBTQ-affirmative supportive counselling as our control because it is recommended by the APA and is likely to be safe and acceptable for SMW participants. Otherwise, by design, LGBTQ-affirmative supportive counselling was selected as the TAU because it does not follow a standard protocol prescribed by the study. In previous research on LGBTQ-affirmative supportive counselling, we have found a relatively low degree of both CBT content and psychodynamic-interpersonal content in recorded sessions of this counselling.¹⁰⁶ Therapists provide TAU online to match the videoconferencing delivery modality of LGBTQ-affirmative CBT. TAU participants complete the ten 50 min sessions within a 4-month period and are encouraged to complete one session per week.

Therapist training and fidelity monitoring

Therapists across both conditions are master’s- or PhD-level therapists or trainees (eg, advanced graduate students or postdoctoral fellows in clinical psychology); different therapists deliver each condition. Each therapist is assigned to deliver either the intervention or TAU. Before delivering LGBTQ-affirmative CBT, study therapists who deliver that condition receive approximately 16 hours of training involving didactics on the minority stress model and experiential exercises applying the model through CBT techniques. Sessions are audio-recorded with participants’ consent. Clinical supervisors review approximately 20% of all study sessions using fidelity checklists created for this treatment.⁹⁰ Fidelity is also reviewed in weekly supervision and shortfalls are remediated. All LGBTQ-affirmative CBT therapists receive weekly individual supervision from a clinical supervisor. A a licensed clinical psychologist and study principal investigator, leads biweekly group supervision with all study therapists and supervisors. A clinical protocol guides the handling of participant suicidality and distress. All staff receive training in the clinical protocol at the beginning of their study involvement and in the event of a protocol deviation. TAU therapists receive clinical supervision from a licensed psychologist at the community clinic. Study staff will also review audio-recordings from TAU sessions using standard CBT rating schemes to assess for CBT contamination on enrolment of 50 participants into the TAU condition. If we find that the coded sessions include substantial CBT content, we will discuss results with directors at the TAU community site so that future TAU participants only meet with therapists who do not practise CBT.¹⁰⁷

Study assessments

Participants complete assessments at four timepoints: baseline, and 4-, 8- and 12-month follow-ups (figure 2). Each assessment consists of a self-report online assessment of alcohol use, mental health, minority stress and universal mechanisms of mental health risk, as well as an interviewer-administered assessment of alcohol use and mental health via Zoom. We facilitate retention of participants across 12 months by (1) providing evening and weekend availability for sessions and assessments, (2) verifying contact information at all appointments and 3) collecting multiple forms of contact information.

Primary outcome

Alcohol use

The primary outcome of the study is change in past-30-day proportion of HD days, as measured through the 30-day timeline follow-back (TLFB), a semi-structured interview.¹⁰⁸,¹¹⁰ The TLFB collects participants’ report of daily number of drinks over the past 30 days. These estimates are then used to calculate average past 30-day drinks per week and HD days (defined as four or more drinks within 1 day) at all timepoints. The TLFB is administered by a trained RA over Zoom and recorded for quality assurance purposes.

Secondary outcomes

Mental health

The DIAMOND¹¹¹ is a semistructured diagnostic interview based on the DSM-5 that enables non-clinician RAs to determine the presence and severity of mood, anxiety and stress-/trauma-related disorders. The DIAMOND is administered at each of the four timepoints over Zoom by a trained RA. Participants complete the Brief Symptom Inventory,¹¹² the Beck Anxiety Inventory,¹¹³ the Center for Epidemiology Studies Depression Scale,¹¹⁴ the Overall Anxiety and Depression Severity and Impairment Scale,^{115 116} the SIDAS¹⁰³ and the PSTD Checklist for DSM-5¹¹⁷ via an online survey at each timepoints.

Alcohol and substance use

In addition to the TLFB, participants complete the following assessments of alcohol and substance use and associated impairment via online survey at each timepoint: the Patient-Reported Outcomes Measurement Information System Alcohol Use Short Form,¹¹⁸ the Brief Comprehensive Effects of Alcohol Scale,¹¹⁹ the Daily Drinking Questionnaire,¹²⁰ the Alcohol Abstinence Self-Efficacy Scale,¹²¹ the Drug Use Disorders Identification Test,¹²² and the Cannabis Use Disorder Identification Test.¹²³

Mediators and moderators

Minority stress mediators

All participants complete the Lesbian, Gay, Bisexual Identity Scale (LGBIS),¹²⁴ the LGBTQ-Hypervigilance Scale¹²⁵ and the LGBTQ-Specific Parental Disclosure & Support Scale¹²⁶ at all timepoints through an online survey to measure LGBTQ-specific identity concealment motivations, internalised stigma, acceptance concerns, hypervigilance and parental acceptance, respectively. Identity-specific minority stressors are assessed at all timepoints through an online survey and include the following: the Bisexual-Specific Stress Scale,¹²⁷ the Gender Minority Stress and Resilience Measure¹²⁸ and the LGBT People of Color Microaggressions Scale.¹²⁹

Universal mechanism mediators

Universal mechanism mediators are hypothesised to be operating for all individuals in CBT and are assessed through online surveys at all four timepoints. Measures include the Perceived Stress Scale,¹³⁰ the UCLA Loneliness Scale,¹³¹ the Difficulties in Emotion Regulation Scale—Short Form,¹³² the Response Style Questionnaire Rumination Scale,¹³³ the Rathus Assertiveness Scale—Short Form,¹³⁴ the Interpersonal Support Evaluation List¹³⁵ and the Social Safety Scale.¹³⁶

Treatment moderators

Several participant demographics and stigma-related variables are assessed via the same online survey as potential moderators of treatment efficacy. Demographics are collected at baseline and include age, race, ethnicity, gender identity, sexual orientation, relationship status, level of education, employment status, income and general health, as assessed by items from the Behavioral Risk Factor Surveillance Survey.¹³⁷ Stigma-related variables that might serve as potential treatment efficacy moderators, assessed at all four time points, include individual-level stigma (ie, internalised stigma measured using the LGBIS), interpersonal-level stigma (measured by the Heterosexist, Rejection, and Discrimination Scale¹³⁸), and structural-level stigma (measured by the Perceived Structural Stigma Scale¹³⁹). We also assess endorsement of traditional gender roles (measured by the Traditional Masculinity-Femininity Scale¹⁴⁰) as a potential treatment efficacy moderator, consistent with research and theory suggesting that greater adherence to masculine gender norms is associated with greater risk of HD among SMW.⁴⁷

Data collection, management and analysis

Participants complete the baseline and follow-up online surveys via Qualtrics. The DIAMOND and TLFB assessments are administered by RAs over Zoom. Data are entered into a Qualtrics survey or stored on Yale’s secure Box server in a password-protected file, respectively. Participant contact, tracking and scheduling information is recorded in REDCap. Therapy sessions and Zoom assessments are audio-recorded for supervision and quality assurance. These files are stored on Yale’s secure Box server. Therapy recordings are reviewed on a weekly basis by a licensed clinical psychologist. Zoom-administered assessments undergo quality assurance checks performed by the study therapists and other members of the research team.

General statistical considerations

All primary analyses will be performed as intent-to-treat with an overall type I error rate of 5% (two-sided). Parametric distributional assumptions will be checked, and diagnostic and sensitivity analyses will be performed. We will assess the missing mechanism and impact of missing data. Sensitivity analyses under missing at random or missing not at random will be considered, as appropriate. R and Mplus¹⁴¹ will be used to conduct analyses. Baseline descriptives (including demographics and clinical variables) will be presented separately by treatment group. Comparability of continuous variables will be examined graphically and using summary statistics (eg, means, SD). Categorical variables will be examined by calculating frequency distributions.

Sample size justification

Our primary goal is to demonstrate a greater reduction at 12 months in the proportion of heavy drinking days, defined as four or more standard drinks/day, in LGBTQ-affirmative CBT versus TAU supportive counselling. Our sample size is based on a waitlist controlled pilot study of SMW,⁹⁰ in which we saw a 40.2% reduction in HD at 6-month follow-up in the LGBTQ-affirmative CBT arm restricting analyses to participants who reported HD, and on existing meta-analyses of CBT for HD, including remote CBT and CBT for HD and comorbid mental health problems, showing a standardised effect size of d=0.39 compared with other active treatments.¹⁴²,¹⁴⁴ Because our supportive counselling TAU has been previously shown to involve low CBT content,¹⁰⁶ we expect that LGBTQ-affirmative CBT will yield a comparable effect size as in these previous trials. To address the possibility that the effect size may not be as strong as in previous trials, we have designed the trial to find an effect size of d=0.29. With at least 80% power at a 5% type I error rate (two-sided), we need 191 participants per arm to detect this difference between the LGBTQ-affirmative CBT and TAU arms.¹⁴⁵ Based on the retention rate in our pilot study and our other intervention studies with sexual minority individuals, we estimate the retention at 12 months to be 85%. Therefore, we plan to randomise 225 SMW to LGBTQ-affirmative CBT and 225 to TAU. Sample size calculations were carried out using PASS 19 (Kaysville, Utah, USA).

Efficacy analyses

We will employ a linear mixed-effects model to assess change in proportion of heavy drinking days. The model will include fixed effects for time, treatment arm and the interaction between time and treatment. An unstructured covariance pattern will allow for correlation between repeated observations. We will use a contrast statement for the primary comparison of interest: reduction in the proportion of heavy drinking days at the 12-month follow-up. Secondary outcomes of interest include one-level reduction in WHO risk level, the absence of a major depression or anxiety disorder diagnosis and reduction in depression and anxiety symptoms. We will use generalised linear mixed models with a log link for dichotomous outcomes and identity link (linear) for continuous outcomes. If the proportion of heavy drinking days outcome is non-normally distributed, then transformations and other distributions will be considered, including a negative binomial distribution. Sensitivity analyses will adjust for any covariates that are not balanced across arms by the randomisation. To control the false discovery rate and maintain an overall type I error rate of 0.05 for the secondary outcomes, we will use the Benjamini and Hochberg method.¹⁴⁶

Mediation analyses

To examine whether changes in mediators (eg, rejection sensitivity, internalised homophobia, emotion dysregulation, social support) precede and mediate intervention effects consistent with our minority stress conceptual model (figure 1), we will use path analysis/structural equation modelling to model and assess the size of the indirect effect from intervention condition to 12-month outcomes through mediators assessed at 8-month follow-up controlling for baseline effects of these mediators. Using Mplus¹⁴¹ to perform a Monte Carlo simulation power analysis,¹⁴⁷ we estimated that sample sizes of 191 (LGBTQ-affirmative CBT) and 191 (TAU) would provide at least 80% power to detect a small effect size (d=0.2) in the indirect treatment effect with a level of significance of 5%, consistent with effect sizes in our pilot.

Moderation analyses

We will conduct moderation analyses to examine whether the efficacy of LGBTQ-affirmative CBT is moderated by demographic factors (eg, race and ethnicity, sexual identity, gender identity and expression) as well as stigma assessed at the individual (eg, identity concealment), interpersonal (eg, discrimination) and structural (eg, participant perception of their local laws and policies concerning the LGBTQ community) levels. Starting with the linear mixed-effects model (or generalised mixed-effect model) used for the primary efficacy analyses, we will add fixed effects for each of the demographic moderators and stigma moderators and their interaction with time, treatment arm and the interaction between time and treatment arm. Similar to Aim 1, we will control for false discovery using the Benjamini and Hochberg method.¹⁴⁶ Demographic factors¹⁴⁸,¹⁵⁰ and stigma exposures⁹⁰¹⁵¹,¹⁵⁵ are increasingly shown by our team and others to moderate intervention efficacy, which, if also identified in this study, will lead us to direct clinicians to address the relevance of these factors in treatment, consistent with personalised medicine approaches.¹⁵⁶,¹⁵⁸ This will also help identify further adaptations to fine-tune the relevance and fit of this intervention across various groups of SMW.¹⁵⁹

Ethics and dissemination

This study poses no greater than minimal risk to participants. Breach of participant’s confidentiality and experiences of emotional discomfort when completing assessments represent two possible risks. The study team has taken every possible step to minimise such risks and the consent documentation clearly delineates these risks to participants.

Our research protocol informs participants that they may refuse to answer questions, pause and take breaks during interview assessments or psychotherapy sessions, and may discontinue participation at any time. Participants are also welcomed to reach out to the PI or to Yale University’s Human Subjects Committee (HSC) throughout the course of the study. All research staff are thoroughly trained by licensed clinical psychologists to handle situations in which participants become distressed or pose a risk to self or others. Our clinical protocol prioritises participant safety and an immediate referral process.

To minimise the risk of breach of confidentiality, all research team members undergo rigorous training in maintaining participants’ privacy and confidentiality. All team members also undergo Health Insurance Portability and Accountability Act compliance training to protect participants’ protected health information. Further, each participant is assigned a unique study identification number and all study data are kept separately from identifying data. Participants are informed that confidentiality may be compromised in order to provide immediate help if we determine that they are at risk of hurting themselves or another person. We inform participants that they may benefit from participating in this study by learning more about themselves, their mental health and ways of managing stress and negative emotions. Participants may also benefit from 10 weeks of LGBTQ-affirmative therapy that many in our prior studies have found valuable. Benefits to the SMW community are anticipated through the dissemination of RCT findings to inform future trainings and implementation.

To further protect participants, a data and safety monitoring board (DSMB) convenes annually, and as needed, to determine safe and effective study conduct and recommend conclusion of the study if significant risks develop or if the trial is unlikely to be concluded successfully. Members of the DSMB are faculty from the two sponsoring institutions with no competing interests. Every adverse event is evaluated by PI JP within 24 hours and classified as serious (mild, moderate, severe) or non-serious and graded by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. This study follows HSC requirements for reporting adverse events. All serious or unexpected adverse events that are definitely, probably or possibly related to study participation are reported to the HSC within 48 hours of Yale researchers becoming aware of the event. The NIH project officer will be provided copies of these reports and informed of any actions taken by the HSC as a result of such events. PIs JP and TH will promptly inform the NIH and HSC of any changes in recruitment or in the protocol relevant to safety as the study is being performed. They will additionally notify NIH of any actions taken by the HSC during continuing study review and of any major changes in the protocol, which would occur with the HSC’s approval.

Research resources generated by this research will be freely distributed, as available, to qualified academic investigators for non-commercial research. The study investigators as well as their institutions—Yale University, Columbia University, San José State University, Syracuse University and University of New Mexico—will adhere to the NIH Grants Policy on Sharing of Unique Research Resources, including the ‘Sharing of Biomedical Research Resources: Principles and Guidelines for Recipients of NIH Grants and Contracts’ issued in December 1999.¹⁶⁰ The data, codes and study protocols are available by request to qualified researchers on completion of this study. To access the data, codes and study protocols, a proposal should be submitted by an applicant with a PhD or an equivalent degree. Proposals will be reviewed and granted according to principles of ethical and scientific soundness.

Authorship for manuscripts will be determined using the four criteria established by the International Committee of Medical Journal Editors¹⁶¹: significant contribution to the study conceptualisation, study design, or data collection, analysis or interpretation; drafting or critically reviewing the manuscript; approval of the final version of the manuscript; and the agreement to be held responsible for all aspects of the study and to assist in investigating any concerns about the study’s accuracy or integrity. An individual must meet each of these criteria to be considered as an author. We do not intend to use professional writers for manuscripts.

Results of this study will be disseminated to researchers and practitioners through peer-review publications and conference presentations, and directly to study participants. The study sponsor will have no role in the interpretation of data, writing of the resulting reports or the decision to submit the report for publication or presentation.

Patient and public involvement

Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Discussion

This article describes the protocol for Project EQuIP, a two-arm RCT testing the efficacy of LGBTQ-affirmative CBT, a transdiagnostic psychotherapy intervention targeting the pathways through which minority stress compromises LGBTQ individuals’ mental and behavioural health. SMW represent one of the highest-risk groups for HD, which frequently co-occurs with depression and anxiety.^{1 4 16 17} Responding to the near-complete lack of interventions for SMW’s mental and behavioural health, our team developed and pilot tested LGBTQ-affirmative CBT with 60 SMW in a waitlist-controlled trial.⁹⁰ Findings demonstrated preliminary efficacy of LGBTQ-affirmative CBT to improve minority stress coping and reduce SMW’s HD and mental health comorbidities. Further, SMW indicated that LGBTQ-affirmative CBT was acceptable when delivered in-person and when delivered remotely in a second small open trial. The present study now tests the efficacy of LGBTQ-affirmative CBT delivered remotely to SMW across New York, New Jersey and Pennsylvania compared with TAU (ie, supportive counselling) also delivered remotely.

This study represents the first RCT of a psychotherapy intervention specifically developed to address mental and behavioural health among SMW. The intervention being tested here is grounded in minority stress theory and focuses on raising awareness of the harms of minority stress, reducing internalised stigma and rejection schemas, reducing avoidant coping behaviours and validating SMW’s strengths. The intervention is informed by the Unified Protocol for the Transdiagnostic Treatment of Emotional Disorders,⁸⁶,⁸⁹ a flexible protocol that distils CBT into its core components (eg, motivational interviewing for treatment engagement, mindfulness, cognitive restructuring, behavioural exposures). The Unified Protocol shows strong efficacy across several RCTs for reducing depression, anxiety and HD^{89 91 92} in non-SMW samples and is transdiagnostic by targeting the maladaptive cognitive, affective and behavioural processes (eg, emotion dysregulation, impulsivity) shared across disorders involving emotion dysregulation (eg, depression, anxiety and HD). Given that SMW’s HD often co-occurs with depression and anxiety and given the association of these conditions with minority stress, a transdiagnostic treatment targeting the underlying role of minority stress can synergistically reduce SMW’s HD and comorbid depression and anxiety. Results from this RCT can support implementation in frontline settings in need of evidence-based interventions and ways to expand access for SMW.