The FDA-labeled dermatology endpoint review concluded that in general, ordinal, static investigator global assessment (IGA) scales informed the interpretation of clinical trial results in approved dermatologic conditions (2015–2017). Nearly all of the IGAs used in recent dermatology product labeling had 4 or 5 levels; the IGA levels demonstrated a distinct, non-overlapping and clinically relevant gradations of the specific disease/condition, with the highest level (0 or none) representing true clinical absence of the disease/condition. A static (versus dynamic) IGA assesses the clinician’s current impression of disease severity and does not depend on the clinician’s recollection of baseline disease severity, which could introduce recall bias . Interestingly, an assessment at one of the top two levels (0 or 1) with at least a 2-level change from baseline was often required to establish individual patient treatment success.
Ten dermatologists, expert in the diagnosis and treatment of AA from across the US of participated in the qualitative telephone interviews in July 2017. On average, these clinicians had been treating or managing patients with AA for 21.2 years (range: 6–38 years).
The clinicians overwhelmingly described scalp hair loss as the most presenting complaint for patients with AA and the primary sign of AA. All interviewed clinicians assessed patients’ scalp hair loss in clinical practice, and used either the SALT to evaluate a patient’s change over time or made a visual assessment of whether significant improvement had been achieved since a prior visit. Additionally, two of the clinicians made use of photography to monitor the progress of their patients with AA. All clinicians were familiar with the SALT, and nine of the 10 clinicians had used the SALT in AA clinical studies. All clinician agreed that assessments of regrown hair should include only terminal hair (not vellus hair), although the latter may be an early indicator of eventual terminal hair growth.
When queried about their perspectives on AA “treatment success,” clinicians noted several factors influencing their judgment of this goal. The quantity of scalp hair growth was described as the primary aim for treatment by all clinicians, with other factors were noted by a smaller number of clinicians, including location/pattern of regrowth and hair density.
When asked to describe the amount/percentage of scalp hair they would consider a treatment success, the predominant response was 80% of the scalp hair (n = 5), followed by 75% (n = 3) and 90% (n = 1) (Fig. 1). The remaining clinician did not report a static scalp hair amount, choosing “at least 50% improvement” as the treatment success response.
Figure 1. Clinician Treatment Success Thresholds
Although patient input on the key construct and the appropriate level for that construct to indicate a treatment success/clinical benefit was still needed, clinicians are the primary reporter of scalp hair loss in clinical practice and research. Therefore, clinicians reviewed and iteratively developed the IGA for AA scalp hair loss, with a focus on ensuring distinct and clinically relevant gradations of scalp hair loss. The iterative process used in these IGA discussion is detailed elsewhere , and summarized here. Using a top level of 0 (None) representing the absence of scalp hair loss (SALT score 0), the next level (1 = Limited) included SALT score 1–20, with the SALT score 20 upper bound representing the clinician’s most commonly-reported treatment success level (Fig. 1). The fourth level (3 = Severe) of the proposed IGA initiated at SALT score 50, and aligned with the lower limit for extensive scalp hair loss [7, 28]. Consequently, the third level (2 = Moderate; SALT score 21–49) was sandwiched between Limited and Severe. Achieving clinician consensus on the draft IGA’s fifth level at the highest end of the extensive scalp hair loss spectrum was a challenge; nonetheless, with careful review of all de-identified Clinician Interview responses by the Small Panel members, a relevant description of the 5th level reflecting the clinicians’ learnings from patients in this scalp hair loss category (4 = Very Severe; SALT score 95–100) was created to capture patients with nearly complete or complete scalp hair loss. In due course, the draft IGA was reviewed during the Patient Interviews.
The Clinician Interviews also provided insights into other hair loss locations, such as eyebrow and eyelash hair loss. These insights and newly developed sign/symptom COAs are presented elsewhere .
Thirty patients with a history of ≥ 50% scalp hair loss were interviewed in October 2017. The patients’ demographic and clinical characteristics at the time of the interviews are detailed elsewhere , and synopsized here. Five of the patient interviewees were adolescents (ages 15–17 years old; 3 females/2 males) and 25 of the patient interviewees were adults (ages 18–72 years old; 14 females/11 males). Nine patients were non-Caucasian (Asian, Black, Other). Sixty percent of the adolescents and 84% of the adult patient interviewees had experienced some eyebrow and/or eyelash hair loss, meeting the recruitment goal (80% overall) to oversample these patients with AA. On average, these patients had been diagnosed with AA for 11.4 years (range: 1–46 years). The most recent clinician-assess SALT scores for these patients ranged of 0-100 (mean = 57.9), reflecting the inclusion of patients who had experienced improvements with treatment (60% were currently or previously treated with JAK inhibitors), and the opportunity to obtain recently-informed understandings hair growth changes related to treatment to further understand clinically meaningful change/clinical benefit.
The Patient Interviews commenced with discussions of the signs and symptoms experiences with AA, previous treatments and the impacts that AA had on each patient’s everyday life and well-being. These discussions were powerful and informative, and the results directly informed a new conceptual model for AA detailing the sign and symptoms AA, and the physical, emotional, and functional impacts of AA, including stigmatization, relationship and social impacts .
During concept elicitation discussions, the interviewer noted the signs and symptoms mentioned by the patients, and saturation of physical signs and symptoms was achieved . All 30 patients named scalp hair loss as a key sign/symptom. After elicitation of the signs and symptoms experienced, each patient was asked to rank (first/most, second, third) their most bothersome signs and symptoms of AA. Scalp hair loss was named as the most bothersome sign/symptom by 77% of the sample (100% of adolescents/72% of adults). Four adults (16%) named eyebrow hair loss as the most bothersome sign/symptom; eyelash, nose and body hair loss each received the most bothersome ranking from one adult patient . The results from this patient ranking exercise confirmed scalp hair loss as the key concept, despite oversampling patients with eyebrow/eyelash hair loss.
Meaningful treatment success
All 30 patients were asked to discuss their ideal treatment experience, including both the amount, quality and the time to achieve the hair growth that they would deem clinically meaningful. When patients were asked to propose the percentage (amount) of scalp hair coverage -- short of 100% -- that they would need for a treatment to be considered successful, 4 patients were initially unable to answer this question, as they experienced some difficulty in discussing scalp hair coverage in terms of percentages. Of the 26 patients (4 adolescents and 22 adults) who were comfortable answering the question, the majority (n = 20) provided answers within the range of 70–90% scalp hair (median = 80% of scalp hair) (Fig. 2), which was generally similar to the Clinician Interviews results (Fig. 1). Moreover, these results were similar for patients with and without JAK inhibitor treatment experience (median = 75% and 85%, respectively). To understand the ‘why’ behind the treatment success metric, patients were asked how they perceived achievement of their desired threshold could impact them. Patients explained how achieving the reported amount of scalp hair would help to improve their emotional/psychological wellbeing such as increasing their confidence levels, reducing stress, and feeling more comfortable around other people. Some improvements to daily life were also predicted as a result of feeling more comfortable around others, such as being able to work more sociable hours and live a more active lifestyle by attending the gym/swimming pool (Table 1).
Example Patient Interview Quotes Describing the Meaningful Impact of Achieving the Desired Scalp Hair Amount
I would say 80–90%, because then you could still wear a hat and go swimming and do things like that and cover it up a little bit. (27-F-A-100-N)
It would probably be more of a confidence booster. (28-M-A-100-N)
Well, it's kind of hard to say. I mean, for the most part, I guess I would change my hours of operation. Instead of working at nighttime, I'd work in the daytime. That’s what would change my life at least….being around people, yeah. (01-M-A-100-N)
I think just like not being stressed about it because like right now I feel like I can cover it. I don’t have to wear a wig or anything like that but and it still is stressful to like worry about like oh it’s like exposed or something like that. […] I’m guessing if it was 80 percent I would be able to do like different hairstyles […] Also between the two that would be nice and then just generally like not worrying about it as much. I feel like 80 percent I wouldn’t like worry about oh exposed or like my hair what is that going to be like? So I think just in terms of like stress and like variety that would be nice. (20-F-P-60-JAK)
Because it's difficult [currently] to, like I said, go swimming, and you can't—the hardest thing for me is like I mean I used to live such an active lifestyle. So I don't like to go to the gym in a scarf, because it's just so hot and sweaty. And I don't like to go to the pool with a bald head, because everyone like stares at you and then the sun. So I would say that however long it took I would be happy with that to get my regular life back. (27-F-A-100-N)
|Patient IDs: Order of interview – Sex – Adult/Pediatric – SALT score – Previous JAKi treatment. For example, patient 28-M-A-100-N was interviewed 28th, is a male adult with 100% hair loss and not previously treated with JAKi.
Figure 2. Patient Treatment Success Thresholds
Patients noted that a treatment would be successful even if the scalp hair grown was not the exact same color, quality or thickness as their hair before AA. In fact, most patients expected their hair may grow back differently.
During the cognitive debriefing, input from patients was solicited on the relevance, appropriateness and importance of the draft IGA developed during the Clinician Interviews. All 30 patients confirmed agreement with the proposed IGA measure, and none of the patients suggested any further changes to the IGA wording or response levels. Nine patients were asked about their perception of meaningful change as measured by the draft IGA. All nine respondents noted that achieving the Limited (SALT score 1–20) level after nine months would indicate the treatment was successful with affirming quotes including: “That would be great. That would be fantastic.” and “I think that would be a win if you got to Limited.”
These results confirmed the content validity of the AA-IGA™ as a ClinRO conceptualizing of the most important clinical need that can reflect and detect clinically meaningful improvement for patients with extensive AA. The final AA-IGA™ is published elsewhere . As noted for the Clinician Interviews, patients also provided reviews and insights on the clinical relevance and appropriateness of other newly developed AA COAs [24, 30].