Development of Clinician-Reported Outcome (ClinRO) and Patient-Reported Outcome (PRO) Measures for Eyebrow, Eyelash and Nail Assessment in Alopecia Areata

Expert dermatologists practicing in the USA were identified by their involvement in contemporary research and treatment of patients with AA. Eligible patients in North America were identified by dermatologists at the University of California Irvine, Yale University, Northwest Dermatology Research Center, SKiN Centre for Dermatology and Dawes Fretzin Dermatology. Patients were eligible for inclusion if they had severe AA, determined by present or recent experience of ≥ 50% scalp hair loss. Purposive sampling targeted the inclusion of patients with current or previous eyebrow, eyelash and/or nail involvement to ensure that the PRO measures and accompanying photoguides were reviewed by patients with relevant AA experience. Full eligibility criteria for each round of the study are provided in the Online Resource 1.

Ten expert dermatologists, with 6–38 years (mean 21.2) of experience in managing patients with AA, and 45 patients with AA, aged 15–72 years (mean 33.5), participated in these interviews (round 1 [n = 30]; round 2 [n = 15]). A diverse patient sample was recruited: 58% (n = 26) of participants were female, 44% (n = 20) were non-Caucasian, 53% (n = 24) reported a high school diploma or lower education level and 78% (n = 35) had partial/full eyebrow and/or eyelash hair loss. Full clinical and demographic characteristics are provided in Online Resource 2.

Dermatologists described eyebrow and eyelash hair loss as facial defining features that changed patients’ appearance and were difficult to conceal. In clinical practice, dermatologists assessed eyebrow hair loss primarily through consideration of coverage/continuity (i.e., absence of gaps), although some dermatologists considered density (fullness/thickness) and symmetry (across both eyes). Similarly, dermatologists assessed eyelash hair loss through consideration of continuity and symmetry.

Patients reported eyebrow hair loss (n = 28/35 [80%]) and/or eyelash hair loss (n = 25/35 [71%]) among their three most bothersome signs/symptoms of AA. Patients described feeling embarrassed and self-conscious about their eyebrow hair loss and/or eyelash hair loss, expressing a desire to look “normal” or cosmetically acceptable. Some described concealing their eyebrow loss using makeup or hats/glasses. Patients who experienced eyebrow hair loss (n = 38) primarily described their eyebrow hair loss in terms of gaps/patches, thinness, density and/or symmetry. Patients who experienced eyelash hair loss (n = 32) described the gaps as the most important aspect of their eyelashes to consider in evaluation.

Many (n = 22) patients also described functional impacts of eyebrow and/or eyelash hair loss, including problems with sweat (n = 6) or debris (n = 13) getting into their eyes, irritation from the wind (n = 2) or difficulty seeing because of glare or sunlight (n = 4). These patients described the sensation as “itching,” “burning,” “dry,” or “like something being stuck in the eye.”

All dermatologists described AA-related nail involvement as “pitting/pits” (n = 6), “breaking”/“splitting”/“brittleness” (n = 4), “dystrophy” (n = 2), “roughness” (n = 2), and “shedding” (n = 1). Patients with nail damage (n = 14) described their nails as pitted, split, bumpy, grainy, indented and/or feeling brittle, thin and/or weak. For some participants, nail damage was an aesthetic issue, whereas for others it caused functional problems (most did not experience any nail pain). The SPM identified that the severity of nail damage was more important than the number of nails that were damaged.

From these insights, it was identified that PRO and ClinRO measures to assess eyebrow hair loss, eyelash hair loss, eye irritation and nail appearance should be developed as both dermatologists and patients considered these to be important signs/symptoms of AA. Patient and dermatologist quotes that support measurement concepts are presented in ESM 3.

The ClinRO measures for eyebrow hair loss and eyelash hair loss underwent three iterative revisions based on feedback provided in the dermatologist interviews (ESM 4 and 5). A four-option response scale was confirmed by dermatologists as appropriate to allow assessment of incremental severity on each ClinRO measure. The final version of each ClinRO measure was confirmed during the SPM and is presented in Table 1. These measures were also reviewed by patients, time permitting. In round 2, almost all patients who were consulted considered the final ClinRO Measure for Eyebrow Hair Loss™ (n = 9/11) and the final ClinRO Measure for Eyelash Hair Loss™ (n = 9/11) to be important for evaluating treatment outcomes.

The PRO measures were reviewed in dermatologist interviews and in the SPM; several changes were suggested to more closely align PRO measure wording with that of the ClinRO measures. Versions of the PRO measures were then tested with patients over two rounds of interviews with interim revision between rounds. The changes resulting from patients’ feedback are reported in ESM 4 and 5. In round 2 interviews, all patients could provide responses to each PRO measure and generally understood the item wording and severity gradations within the response scale options. Therefore, no further changes or testing were required. The final version of each PRO measure is presented in Table 1.

A PRO measure to assess eye irritation was developed; a ClinRO measure was not developed because only a patient can report on the sensation of eye irritation. Dermatologist and patient feedback on the PRO measure to assess eye irritation is summarized in ESM 6. The final version of the PRO measure (Table 2) was confirmed by patients following round 2 interviews; all 15 patients could understand and interpret the item consistently with its intended meaning, and a few commented that the example descriptors provided in parentheses (itching, stinging, burning, dry) had helped them interpret the concept of eye irritation.

Dermatologist and patient feedback on the ClinRO and PRO measures to assess nail involvement is summarized in ESM 7. The final version of the PRO measure (Table 3) was confirmed by patients following round 2 interviews; all patients could understand and interpret the item consistently with its intended meaning, and the response options were generally understood and used appropriately. Patients consulted (n = 10/11) also confirmed the relevance of the PRO and ClinRO measure, reporting that it was important for clinicians and patients to rate nail appearance.

Five of the expert dermatologists who participated in the COA development interviews (AA experience range 8–30 years [mean 17.7]) participated in interviews to develop and confirm the photoguides. Ten patients with AA with current eyebrow hair loss (n = 9 [90%]), eyelash hair loss (n = 8 [80%]) and/or nail damage (n = 3 [30%]), aged 21–54 years (mean 37.0) were also interviewed (see ESM 8).

The photoguides were developed to help raters derive their score, standardize ratings across raters and provide clear visual instructions for assessment of the observable signs of AA (eyebrow hair loss, eyelash hair loss and nail damage). A photoguide to accompany the PRO Measure for Eye Irritation™ symptom measure was not developed.

High-resolution photographs of patients’ eyebrows, eyelashes and nails were obtained, with patient consent, from a specialist dermatology clinic. The eyebrow, eyelash and/or nail damage of these patients were rated by their dermatologists using the relevant ClinRO measure. Selected photographs were then edited using Adobe^® Photoshop^® software to depict greater or lesser severity (i.e., more or less hair loss/nail damage) corresponding to each measures’ response options. The edited images were reviewed by dermatologists and iteratively modified throughout the dermatologist interview process to incorporate their feedback. Images were then approved by the lead AA expert and included in the photoguides, resulting in a final set of four severity images depicting three different patients/presentations for eyebrow loss and two different patients/presentations for eyelash hair loss and nail damage (photographs for eyelash hair loss and nail damage required enlargement for raters to be able to clearly view the detail presented). See ESM 9 for an illustrative figure of the development methodology and ESM 10 for the final photoguides.

The final images received a 98% approval rating from the dermatologists and patients who reviewed them, confirming that the images appropriately depicted the severity levels they represented and that the photoguides provided a clear visual instruction for assessment. Nearly all dermatologists and patients felt that the photoguides helped them to derive ratings and would help to standardize ratings.