Report on the progress of NAAF’s Patient-Reported Outcome (PRO) Consortium to develop a single, consensus-defined PRO instrument that can be shared across industry partners and other ongoing initiatives to incorporate the voice of the patient in alopecia areata research.

1. NAAF PATIENT-REPORTED
OUTCOMES CONSORTIUM
Bringing the voice of the patient into
the drug development process 

2. OBJECTIVE 
develop a single, evidence-based
patient-reported outcome measure
for alopecia areata for qualification as
a Drug Development Tool to support:
• medical product approval
• labeling claims
• and real world evidence
• Comparative Effectiveness Research
• Precision Medicine

3. AA PRO CONSORTIUM PARTNERS
Biopharmaceutical
Industry Partners
Alopecia Areata
KOLs

4. AA PRO Industry Partners

5. INITIATIVE RATIONALE 
• Shared investment and value
• Third-party neutrality
• Recognition and reach with patient community
• Patient engagement credibility with FDA
• Industry expertise navigating FDA
• Single standardized approach for eventual CER

6. GAP ANALYSIS 
• Three existing AA-specific PRO instruments
• Significant gaps in development per FDA PRO Guidance
• Available generic instruments
• Insufficient to support product labeling claims
• PDUFA VI and 21st Century Cures require enhanced inclusion of patients
• Patient input throughout instrument development
• Real World Evidence
• CER
• Precision Medicine
• Shared Decision Making

7. Q1/2 2017 Q3/4 2017 Q1/2 2018 Q3/4 2018 2019
Literature review
Develop Qualitative Study Protocol
Assemble Consortium Partners and
select Working & Observer Groups
Conduct 15 adult and 10
adolescent in-person Interviews
during NAAF Conference to elicit
concepts of meaningful
treatment benefit
Content and Conceptual
Framework including
Preliminary PRO Instrument
with instructions
Conduct 30 Interviews with
Draft AA PRO Instrument
Review Protocol for PRO
Validation – Test scoring,
reliability and validity in
current or recent clinical trial
(timing depends on whether
we can slot into an existing
trial or do a stand-alone
validation)
Prepare Abstract and manuscript
for publishing
PHASE I
PHASE II
Laying the groundwork & Ongoing Communication
Qualitative Study - Conceptualizing treatment benefit, Develop Draft AA PRO Instrument
Quantitative Study – Test, Validate and publish AA PRO Instrument
DDT Tracking #
FDA letter of intent
CPIM Meeting 4/19
Initial briefing package to FDA
Follow-up briefing package to FDA
Develop Psychometric
Statistical Analysis Plan (SAP)
Kick-off Meeting – elicit constructs
of interest to PRO Consortium
IRB Approval of Study Protocol (6/20/17)
Transcribe and Analyze data
IRB Approval of Amended
Protocol
Protocol Amendment
with study procedures
and interview guide
Transcribe and Analyze data
Propose changes to PRO
Instrument based on findings
Prepare Qualitative Report
Prepare Initial briefing package
Consortium Progress Meeting
Conduct Psychometric analyses
Prepare Final Validation Report
Prepare Follow-up briefing
package for FDA Submission
Consortium Progress Meeting
Consortium Progress Meeting
Conduct 15 phone Interviews
with adults recruited from
clinical sites to elicit concepts
of meaningful treatment
benefit
Consortium Progress
Meeting
TIMELINE AND MILESTONES 
Concept Elicitation
Cognitive
Debriefing
Validation

8. PROCESS OVERVIEW 
• Phase I (Concept Elicitation Interviews):
• Identify important concepts related to AA and inform measure
development.
• Phase II (Cognitive Interviews):
• Assess content validity of the measure.
• Phase III (Validation):
• Examine scoring structure, reliability and validity of the AA PRO.

9. Q1/2 2017 Q3/4 2017 Q1/2 2018 Q3/4 2018 2019
Literature review
Develop Qualitative Study Protocol
Assemble Consortium Partners and
select Working & Observer Groups
Conduct 15 adult and 10
adolescent in-person Interviews
during NAAF Conference to elicit
concepts of meaningful
treatment benefit
Content and Conceptual
Framework including
Preliminary PRO Instrument
with instructions
Conduct 30 Interviews with
Draft AA PRO Instrument
Review Protocol for PRO
Validation – Test scoring,
reliability and validity in
current or recent clinical trial
(timing depends on whether
we can slot into an existing
trial or do a stand-alone
validation)
Prepare Abstract and manuscript
for publishing
PHASE I
PHASE II
Laying the groundwork & Ongoing Communication
Qualitative Study - Conceptualizing treatment benefit, Develop Draft AA PRO Instrument
Quantitative Study – Test, Validate and publish AA PRO Instrument
DDT Tracking #
FDA letter of intent
CPIM Meeting 4/19
Initial briefing package to FDA
Follow-up briefing package to FDA
Develop Psychometric
Statistical Analysis Plan (SAP)
Kick-off Meeting – elicit constructs
of interest to PRO Consortium
IRB Approval of Study Protocol (6/20/17)
Transcribe and Analyze data
IRB Approval of Amended
Protocol
Protocol Amendment
with study procedures
and interview guide
Transcribe and Analyze data
Propose changes to PRO
Instrument based on findings
Prepare Qualitative Report
Prepare Initial briefing package
Consortium Progress Meeting
Conduct Psychometric analyses
Prepare Final Validation Report
Prepare Follow-up briefing
package for FDA Submission
Consortium Progress Meeting
Consortium Progress Meeting
Conduct 15 phone Interviews
with adults recruited from
clinical sites to elicit concepts
of meaningful treatment
benefit
Consortium Progress
Meeting
TIMELINE AND MILESTONES 
Concept Elicitation
Cognitive
Debriefing
Validation

10. PHASE I: RESULTS 
• Interviewed 30 adults and 12 adolescents
• Recruited through NAAF as well as five clinical sites
• Results
• Single measure is appropriate for adults (≥ 18 years) and adolescents (12-17 years)
• FDA Engagement –
• 2 CPIM calls with deep FDA bench.
• Buy-in to concept of Kybella-like primary satisfaction question with additional clarifying questions.
• Key concepts identified:
• Hair coverage, hair quality and impacts related daily activities, coping and emotions
• Draft PRO Developed
• FDA Informal Feedback
• Submission 6/7/2018
• FDA Comments 8/30/2018

11. Concepts

12. Example PRO – Chin Fat
• Co-Primary Endpoints – ClinRO and PRO
• Submental convexity or fullness
• Visual and Emotional impacts
• Happy
• Bothered
• Self-conscious
• Embarrassed
• Looking older
• Looking overweight
• KYBELLA Label Claim included:
• The overall patient-reported satisfaction and self-perceived visual attributes showed
greater improvement in the KYBELLA group than in the placebo group

13. AA PRO Concepts
• Coverage
• Satisfaction
• Scalp
• Other body areas
• Impacts
• Daily activities
• Coping
• Emotional/Psychological

14. Q1/2 2017 Q3/4 2017 Q1/2 2018 Q3/4 2018 2019
Literature review
Develop Qualitative Study Protocol
Assemble Consortium Partners and
select Working & Observer Groups
Conduct 15 adult and 10
adolescent in-person Interviews
during NAAF Conference to elicit
concepts of meaningful
treatment benefit
Content and Conceptual
Framework including
Preliminary PRO Instrument
with instructions
Conduct 30 Interviews with
Draft AA PRO Instrument
Review Protocol for PRO
Validation – Test scoring,
reliability and validity in
current or recent clinical trial
(timing depends on whether
we can slot into an existing
trial or do a stand-alone
validation)
Prepare Abstract and manuscript
for publishing
PHASE I
PHASE II
Laying the groundwork & Ongoing Communication
Qualitative Study - Conceptualizing treatment benefit, Develop Draft AA PRO Instrument
Quantitative Study – Test, Validate and publish AA PRO Instrument
DDT Tracking #
FDA letter of intent
CPIM Meeting 4/19
Initial briefing package to FDA
Follow-up briefing package to FDA
Develop Psychometric
Statistical Analysis Plan (SAP)
Kick-off Meeting – elicit constructs
of interest to PRO Consortium
IRB Approval of Study Protocol (6/20/17)
Transcribe and Analyze data
IRB Approval of Amended
Protocol
Protocol Amendment
with study procedures
and interview guide
Transcribe and Analyze data
Propose changes to PRO
Instrument based on findings
Prepare Qualitative Report
Prepare Initial briefing package
Consortium Progress Meeting
Conduct Psychometric analyses
Prepare Final Validation Report
Prepare Follow-up briefing
package for FDA Submission
Consortium Progress Meeting
Consortium Progress Meeting
Conduct 15 phone Interviews
with adults recruited from
clinical sites to elicit concepts
of meaningful treatment
benefit
Consortium Progress
Meeting
TIMELINE AND MILESTONES 
Cognitive
Debriefing
Validation
Concept Elicitation

15. PHASE II: PROGRESS 
• Cognitive interviews in 20 adults and 10 adolescents
• Address quantitative properties of draft PRO, including:
• Clarity of the items
• Interpretation of the items
• Ease of completion
• Comprehensiveness of the instrument
• Format, response scales, and recall period
• FDA Submission
• Submission and request for call on 10/30/2018
• Call scheduled for 1/29/2019
• Refine PRO measure based on cognitive interviews

16. PHASE III: VALIDATION 
• Psychometric evaluation of new PRO (scoring, reliability, validity) in
planned clinical trial
• Slot into clinical trials in Q1/Q2 of 2019
• Review clinical protocol
• recommend additional PROs to support construct validity
• recommend assessment time points to document test-retest reliability
• inform development of Psychometric Statistical Analysis Plan (SAP)
• Potential to submit for DDT qualification of PRO in adults and
adolescents if validation includes both age groups

17. CHALLENGES & BENEFITS
CHALLENGES:
• BioPharma bureaucracy challenging and slow to navigate
• FDA months to schedule meetings or provide feedback
BENEFITS:
“Above Brand” industry collaboration to benefit patients
Consistent instrument across trials for eventual CER
Build relationships with FDA and educate them about aa

18. System-Wide Benefits
• Educate FDA on Alopecia Areata
• 2 CPIM Meetings
• LOI
• 2 PRO progress submissions
• PFDD Meeting
• C-Path Advisory Team
• IDEOM AA Working Group
• PeDRA AA Working Group

19. FDA Acknowledges Need
Enters PRO into COA DDT Qualification Program
"We agree to enter this LOI into the CDER
COA DDT Qualification Program given the
unmet medial need and lack of fit-for-
purpose patient-reported outcome (PRO)
instruments in alopecia areata“
DDT #101

20. PRO CPIM Meeting 4/19/17
• Center for Drug Evaluation and Research
• Office of Translational Sciences – 5
• Office of New Drugs
• Clinical Outcome Assessments – 3
• Office of Drug Evaluation III: Division of Dermatology and Dental Products – 3
• Office of the Center Director: Professional Affairs and Stakeholder Engagement - 1
• Industry – 7 biopharmaceutical companies represented
• Clinical Researchers – 1
• NAAF Patient Advocacy - 3
• Outcomes Research Scientist - 1

21. ClinRO CPIM Meeting – 12/14/17
• FDA CDER – 10 from 3 offices
• Office of Translational Sciences – 3
• Office of New Drugs
• Clinical Outcome Assessments – 3
• Office of Drug Evaluation III: Division of Dermatology and Dental Products – 4
• Industry – 10 from 3 countries
• Clinical Researchers – 3
• NAAF Patient Advocacy - 3
• Outcomes Research Scientist - 1

22. FDA CPIM Call Attendees

23. IDEOM Meeting May 2017
• Present on PRO Consortium
• Informal discussions with FDA COA and OND staff
• Support of PRO Consortium
• Recommend second CPIM call with broader focus
• Advice about developing single instrument or
harmonizing multiple instruments early
• Alopecia Areata Working Group at IDEOM 2019

24. FDA PFDD Meeting on AA
September 2017
• Survey Patients on FDA questions
• Impact and Desired treatment data from 641 patients
• Still opportunity to educate FDA on alopecia areata
• Moving hearts and minds of FDA
• Teresa Mullin on NHC Panel together
• VoP Report acknowledges
• Significant burden
• Unmet need for treatments

25. PFDD VoP Report May 2018
• Appendix 4 Findings to Celebrate:
• Alopecia areata is a chronic disease that places a significant burden on
daily life and has a severe impact on how patients feel and function.
• Symptoms can have considerable detrimental effects on a patient’s quality
of life, emotional wellbeing, social interactions, and ability to live a normal
life.
• There is a significant unmet medical need for treatments for patients with
alopecia areata. No approved therapies exist, and existing off-label
therapies do not adequately manage the condition for most patients.
• Participants at the public meeting highlighted the lack of approved and
effective therapies for alopecia areata, describing their condition as poorly
managed by existing off-label therapies.

26. Critical Path Institute (C-Path)
• Nonprofit organization
• brings together biopharmaceutical
firms, universities, patient groups,
and regulatory agencies from
around the world
• Pre-Competitive Neutral Ground
• to improve public health.
• to identify or create tools that can
accelerate the drug development
and regulatory review process.

27. Critical Path Institute (C-Path)
Alopecia Areata PRO Team
Stephen J. Coons, PhD
Executive Director, PRO Consortium
Sonya Eremenco, MA
Associate Director, PRO Consortium
ePRO specialist previously with Evidera
Maria Mattera, MPH
Assistant Director, PRO Consortium
previously with Evidera
Stephen Karpen
Scientific Director, Regulatory Science
Sarah Mann
Sr. Project Manager, PRO Consortium

28. C-Path PRO Consortium
THERAPEUTIC AREAS
Asthma
Mild Cognitive Impairment Due to Alzheimer’s Disease
Depression
Depression 2.0
Functional Dyspepsia
Irritable Bowel Syndrome
Multiple Sclerosis
Myelofibrosis
Non-Small Cell Lung Cancer
Pediatric Asthma
Rheumatoid Arthritis
Not yet alopecia areataa, autoimmune disease or skin disease…

29. Next Steps
• C-Path Advisory Team
• Call December 12, 2018
• FDA Advisory Call for Phase II Progress
• January 29, 2019
• Validate PRO in Clinical trial
• Adults and adolescents
• Ready to go in 2019
• IDEOM AA Working Group 2019

30. AA PRO Industry Partners

31. PRO Consortium Benefits
“Above Brand” industry collaboration to benefit patients
Consistent instrument across trials for eventual CER
Build relationships with FDA and educate them about aa

32. Next Opportunity
• DATA FOR PAYERS
• Treatments are covered
• Patients have access
• Industry has viable market
• “ABOVE BRAND” COLLABORATION
• Gather data we all need together
• Patient advocacy driven and published