Outcome domains in lichen sclerosus
Authors: C.A. Goodrum, P.A. Leighton, R.C. Simpson
Journal: British Journal of Dermatology (2020)

Dear Editor, Lichen sclerosus (LS) is a chronic inflammatory dermatosis predominantly affecting the genitals. It can affect men, women and children. LS affecting female genitalia typically presents with itchy patches that impact on physical and psychosocial-sexual functioning.1, 2 Symptoms in men include difficulty urinating due to urethral narrowing, difficulty in foreskin retraction due to scarring, and dyspareunia. Complications include loss of anatomy and malignant transformation. Clinical trials are vital for evidence-based practice by providing current supportive evidence to inform clinical decision-making. When results of multiple clinical studies are pooled, a stronger evidence base is obtained than with a single study. However, there is inconsistency in outcomes measured in trials of vulval skin conditions; one systematic review found 28 vulval randomized controlled trials, measuring 25 outcomes using 49 different scales.3 The heterogeneity of these outcomes/scales means they cannot be effectively compared or combined in meta-analyses, which is a source of research wastage.4 Minimizing differences in outcomes collected during trials by developing and using core outcome sets can reduce this research 'waste'. A 'core outcome set' is an agreed standardized minimum collection of outcomes that should be measured and reported across all clinical trials of a specific condition.5 The aim of this study was to inform the development of a core outcome set for genital LS by establishing outcome domains of importance to patients and healthcare professionals. An online survey was disseminated to international stakeholders from September to October 2017 during a James Lind Alliance LS Priority Setting Partnership.6 As this was patient and public involvement into research, ethical approval was not required. Anonymized free-text responses about 'important symptoms or aspects of LS' were collected. Data were analysed using NVivo12 software through an iterative sequence of qualitative analyses.7 Firstly, keywords were identified using word frequency counts. They were subsequently analysed in the wider context of the data in a 'keyword-in-context' analysis. This informed a thematic analysis, where each response was summarized/characterized using a 'code' (a simple label of content). Similar 'codes' were grouped within broader 'themes', with review of themes (and data captured therein) informing the generation of outcome domains. The survey was completed by 653 respondents submitting 1953 responses in total. There were 404 patients/carers (92% female, 5% male) of whom 5% were children/representatives of children, 222 healthcare professionals (64 gynaecologists, 58 dermatologists, 35 sexual health physicians, 23 primary care physicians, 19 urologists and 23 'other health professional') and 27 'other'. Word counts identified that itch was the most commonly used 'keyword' (used 395 times); a contextual review identified variation in how 'keywords' were used (e.g. 'presence of itch' or 'itch ceasing'). Consistent use of keywords informed the creation of 37 distinct 'codes', each code capturing a commonly reported experience/opinion. Codes were organized within six broader 'themes', which drew together closely related or connected codes (Table 1). Each theme points to an outcome domain of importance for LS, the thematic analysis therein provides insight about how to potentially operationalize that domain. Symptoms of LS, such as itching and pain, and their persistent nature cause significant discomfort and psychological distress (Symptoms). As such LS impacts on daily activities and normal functioning (Quality of life). People with LS reported problems with dyspareunia, physical inability to engage in intercourse due to narrowing of the vaginal opening, and lack of sexual drive from loss of sensation. They referred to the emotional impact on relationships as well as their own psychosocial-sexual wellbeing (Sexual dysfunction). Responses placed greater significance on the changes related to anatomical structure (229 responses) than on variations in cosmetic appearance (70 responses) (Appearance). Many participants described fear of potential progression to malignancy and irreversible stenosis (Progression of the condition). The importance of better awareness of LS among the general public and doctors was highlighted to aid earlier diagnosis and prevention of scarring. Many patients called for treatment that quickly resolves symptoms, reduces flare-ups and is easier to use than the standard first-line therapy of topical steroids (Management of the condition). The six key themes/domains identified above will inform the first stage of development for a LS core outcome set through the CORALS (Core Outcomes for ReseArch in LS) initiative.8 The first stage will obtain international consensus on core outcome domains via an electronic-Delphi exercise. Subsequent work to identify appropriate outcome measurement instruments will then be needed to use in the final core outcome set. Although CORALS is intended for use in randomized trials, we believe that understanding these outcomes of importance is valuable for managing LS in the outpatient clinic. Ensuring that these issues are addressed during the consultation will benefit patient experience and overall quality of care.