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NAAF Patient-Reported Outcomes Consortium
The document outlines the goals of the NAAF Patient-Reported Outcomes Consortium, aiming to develop a standardized, evidence-based patient-reported outcome measure for alopecia areata that can support drug development and regulatory approval. It discusses the consortium's phases, including qualitative studies, cognitive debriefing, and psychometric validation, while highlighting challenges and benefits of collaboration with the FDA and industry partners. The initiative addresses the significant unmet medical need for effective treatment options for alopecia areata by integrating patient voices in the drug development process.
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NAAF Patient-Reported Outcomes Consortium
- 1. NAAF PATIENT-REPORTED OUTCOMES CONSORTIUM Bringingthe voice of the patient into the drug development process
- 2. OBJECTIVE develop asingle, 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 CONSORTIUMPARTNERS Biopharmaceutical Industry Partners Alopecia Areata KOLs
- 4. AA PRO IndustryPartners
- 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 Q3/42017 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 Q3/42017 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.
- 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 Q3/42017 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 • EducateFDA 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 EntersPRO 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 Meeting4/19/17 • 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 CallAttendees
- 23. IDEOM Meeting May2017 • 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 Meetingon 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 ReportMay 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 THERAPEUTICAREAS 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-PathAdvisory 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 IndustryPartners
- 31. PRO Consortium Benefits “AboveBrand” industry collaboration to benefit patients Consistent instrument across trials for eventual CER Build relationships with FDA and educate them about aa
- 32. Next Opportunity • DATAFOR 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