Expert clinicians and patients with alopecia areata were interviewed to develop a new outcome measure called the Alopecia Areata Investigator Global Assessment (AA-IGATM) to evaluate treatment success in clinical trials. Through iterative development and feedback, the measure was refined to a 5-grade scale assessing scalp hair loss from 0-100%. Both clinicians and patients agreed that regrowing hair to the 21-49% range defined as the 'Limited' category would be considered a clinically meaningful treatment success for patients originally having ≥50% scalp hair loss. The finalized AA-IGATM incorporates input from experienced clinicians and patients to capture what constitutes meaningful improvement from both perspectives.

1. The Role of Patients in the Development of the
Alopecia Areata Investigator Global Assessment (AA-
IGA™), a Clinician-Reported Measure Evaluating
Clinically Meaningful Success in Clinical Trials
Kathleen W. Wyrwich1, Helen Kitchen2, Sarah Knight2,
Natalie V. J. Aldhouse2, Jake Macey2, Fabio P. Nunes1,
Yves Dutronc1, Natasha A. Mesinkovska3, Justin M. Ko4,
Brett A. King5
1Eli Lilly and Company
2DRG Abacus
3University of California; Irvine School of Medicine
4Stanford University School of Medicine
5Yale School of Medicine

2. Introduction and Objective
• To evaluate new alopecia areata (AA) treatments, AA outcome measures
must incorporate input from both experienced clinicians and patients with
AA to understand clinically meaningful success
• Through in-depth interviews of key informant groups, we developed a five-
grade investigator global assessment (IGA) scale to measure clinically
meaningful treatment response to AA treatment for patients with ≥ 50%
scalp hair loss
• Patient input was essential to the development of this content valid measure
Company Confidential ©2018 Eli Lilly and Company

3. Methods and Samples
Methods
• 10 US dermatologists expert in the treatment of AA
– Interviews investigated treatment benefit and clinical
gradations
• 30 US patients with AA history of ≥ 50% scalp hair loss
(Group 1)
– Patients who had been successfully treated with oral
Janus kinase inhibitors (JAKi) were included to
understand their perception of scalp hair growth success
– The patient interviews explored perspectives and
expectations of AA treatment
• Data from clinicians and Group 1 patients were
analyzed using thematic methods
– Identified key treatment outcome and the content validity
of the newly developed IGA
• 40 US patient interviews conducted by NAAF PRO
Consortium Partnership (Group 2)
– Transcripts reviewed and coded to summarize key
concepts and provided insights on patients’ aspirations
for an ideal AA treatment
Characteristic Patients (N=30)
Female, n (%) 17 (57)
Age
Mean [range]
Adults aged ≥18, n (%)
Adolescents aged 15-17, n (%)
35.3 [15-72]
25 (83)
5 (17)
Successfully treated with JAKi, n (%) 18 (60)
Most recent SALT score, mean [range] 57.9 (0.0-100.0)
Table 2: Patient Interviews - Group 1
Characteristic Clinicians (N=10)
Years experience treating patients with AA, mean [range] 23.2 [9-45]
Type of practice, n (%)
University hospital
Specialist dermatology center
9 (90)
1 (10)
Table 1: Clinician Interviews
Table 3: Patient Interviews - Group 2
Characteristic Patients (N=40)
Female, n (%) 27 (68)
Age
Adults aged ≥18, n (%)
Adolescents aged 12-17, n (%)
30 (75)
10 (25)
Currently receiving treatment, n (%) 17 (43)
Patient-estimated percentage of scalp hair loss
25-49%
50-75%
75-100%
5 (13)
12 (30)
23 (58)

4. • Expert clinicians (n=10) judged overall AA treatment success by whether scalp hair had regrown
• Most considered 80% (n=5) or 75% (n=3) scalp hair as a treatment success threshold (Figure 1)
• Scalp hair loss was the most bothersome AA sign/symptom for 77% (n=23) of the sample in Group 1
• 73% of the adults and 87% of the adolescents noted some aspect of scalp hair regrowth when describing an
ideal treatment/meaningful improvement in Group 2
Important signs/symptoms of AA
Results: Key Concept
Figure 1. Clinician
Treatment Success
Thresholds

5. Results: Initial AA-IGA Development
Iterative development of the AA-IGA
None Limited Moderate Severe Complete
Please rate the patient’s scalp
hair loss, as it looks today.
____% ____% ____% ____% ____%
• Clinicians were shown the draft AA-IGA in Figure 2
and asked to suggest percentage ranges of scalp
hair loss for each response category (Figure 3)
Figure 2. Draft AA-IGA shown to clinicians
: Initial clinician-proposed descriptions of the draft IGA category percent ranges*1
2
Figure 3. Draft AA-IGA
category percentages
suggested by
clinicians

6. Results: Additional Iteration in the AA-IGA Development
Iterative development of the AA-IGA
None Limited Moderate Severe Complete
Please rate the patient’s scalp
hair loss, as it looks today.
0% 1-20% 21-49% 50-99% 100%
• Clinicians were then shown proposed ranges in
Figure 4 and asked their opinions (Figure 5)
Figure 4. AA-IGA Category percentages suggested to clinicians
Figure 5. Draft AA-IGA
category percentages
suggested by
clinicians

7. Results: Small Panel Review
• Two expert clinicians reviewed the clinician data on the gradations and associated
percentages, with a focus on observed inconsistencies
• They concluded that the fifth category of the IGA should be named ‘Very Severe’ and
include patients with 95–100% hair loss due to these patients:
– Being clinically very similar to those with 100% hair loss, with few terminal hairs on the scalp, and
– Clinically differentiated from patients with 50–94% (‘Severe’) scalp hair loss
Iterative development of the AA-IGA: Small Panel Review
Draft full version of the AA-IGA™ for review in patient interviews1
2
None Limited Moderate Severe Very Severe
Please rate the patient’s scalp hair
loss, as it looks today. 0% 1-20% 21-49% 50-94% 95-100%
Figure 6. Draft
version of AA-IGA
used in patient
interviews (Group 1)

8. Results: Group 1 Input on Treatment Success and AA-IGA™
Figure 7. What amount of scalp hair -- short of 100% -- would
you consider a treatment success?
Most patients
perceived treatment
success as
achieving
~70 - 90% scalp hair
(median = 80%)
Iterative development of the AA-IGA: Patient (Group 1) Review
• All 30 patients confirmed the appropriateness of the AA-IGA and the specific gradations
• All queried patients stated that reaching the ‘Limited’ AA-IGA category after treatment
would be a success

9. • The AA-IGA™ is a robust ordinal measure
- Each category represents a distinct and clinically meaningful gradation of the SALT 0-100%
scores that reflects clinicians’ and patients’ perspectives and treatment expectations
• Nearly all queried clinicians and patients confirmed that achieving 0-20% scalp affected
was an appropriate treatment success threshold for patients with ≥ 50% scalp hair loss
• When reviewed with patients and clinicians, the AA-IGA was supported as a meaningful
clinician-reported measure of scalp hair loss
Figure 8. Alopecia Areata Investigator Global Assessment (AA-IGA™)
Conclusions