OPTIMIZING ENDPOINTS FOR CRSWNP BIOLOGIC TRIALS: REGULATORY, HTA, AND PATIENT-CENTERED EVIDENCE REQUIREMENTS
Author(s)
Setareh A. Williams, PhD1, Russell V. Becker, MS2, Catherine E. Hueston, PhD3, Charles D. Williams, BS1;
1Star Biopharma Consulting, LLC., Health Economics and Outcomes Research, Malvern, PA, USA, 2Star Biopharma Consulting, LLC., Health Economics and Outcomes Research, Mobile, AL, USA, 3Star Biopharma Consulting, LLC., Regulatory Science, Malvern, PA, USA
1Star Biopharma Consulting, LLC., Health Economics and Outcomes Research, Malvern, PA, USA, 2Star Biopharma Consulting, LLC., Health Economics and Outcomes Research, Mobile, AL, USA, 3Star Biopharma Consulting, LLC., Regulatory Science, Malvern, PA, USA
OBJECTIVES: Define patient-centered endpoint strategy for biologic trials in chronic rhinosinusitis with nasal polyps (CRSwNP) aligned with regulatory expectations, Health Technology Assessment (HTA) review, and patients prioritized endpoints.
METHODS: We conducted a targeted landscape review with evidence from phase III CRSwNP trials and endpoint schedules (ClinicalTrials.gov; US Food and Drug Administration [FDA] materials), HTA reports and economic models, guidelines/consensus statements (American Rhinologic Society [ARS], European Position Paper on Rhinosinusitis and Nasal Polyps [EPOS], Delphi panels), biomedical and psychometric literature (PubMed, Embase, PsycINFO), and global patient reported outcome (PRO) expert input.
RESULTS: Co-primary endpoints typically pair clinician-assessed nasal polyp score with a PRO nasal congestion/obstruction score. Sino-Nasal Outcome Test-22 (SNOT-22), more responsive to symptom change than EuroQol-5D (EQ-5D), is frequently used; HTA familiarity supports inclusion with prespecified total and domain analyses despite lack of FDA qualification. Clinical practice guidelines recommend SNOT-22 alongside objective assessment and indicators of worsening (systemic corticosteroid use and progression to surgery). EQ-5D is recommended for utility estimation in economic modeling. Olfaction is patient-salient; include University of Pennsylvania Smell Identification Test (UPSIT) or another validated smell test with cultural adaptation. For comorbid asthma, Asthma Control Questionnaire (ACQ) is recommended. Symptom scales vary (visual analogue scale [VAS], numerical rating, categorical); standardize a priori. To capture patient perspective, assess Treatment Satisfaction Questionnaire Measure (TSQM) and concise resource utilization (oral corticosteroid bursts/cumulative exposure; unplanned visits/urgent care/emergency department [ED]; imaging; sinus surgery), with exploratory subgroups by biomarkers (eosinophils, fractional exhaled nitric oxide [FeNO], immunoglobulin E [IgE]) and comorbidities (obstructive sleep apnea, migraine, depression/anxiety) associated with higher burden and lower response.
CONCLUSIONS: A stakeholder-aligned endpoint battery spanning symptoms, disease-specific PRO, utilities, olfaction, disease control, treatment experience, and resource utilization improves interpretability of clinical findings, strengthens HTA readiness, and reflects patients’ perspective of treatment.
METHODS: We conducted a targeted landscape review with evidence from phase III CRSwNP trials and endpoint schedules (ClinicalTrials.gov; US Food and Drug Administration [FDA] materials), HTA reports and economic models, guidelines/consensus statements (American Rhinologic Society [ARS], European Position Paper on Rhinosinusitis and Nasal Polyps [EPOS], Delphi panels), biomedical and psychometric literature (PubMed, Embase, PsycINFO), and global patient reported outcome (PRO) expert input.
RESULTS: Co-primary endpoints typically pair clinician-assessed nasal polyp score with a PRO nasal congestion/obstruction score. Sino-Nasal Outcome Test-22 (SNOT-22), more responsive to symptom change than EuroQol-5D (EQ-5D), is frequently used; HTA familiarity supports inclusion with prespecified total and domain analyses despite lack of FDA qualification. Clinical practice guidelines recommend SNOT-22 alongside objective assessment and indicators of worsening (systemic corticosteroid use and progression to surgery). EQ-5D is recommended for utility estimation in economic modeling. Olfaction is patient-salient; include University of Pennsylvania Smell Identification Test (UPSIT) or another validated smell test with cultural adaptation. For comorbid asthma, Asthma Control Questionnaire (ACQ) is recommended. Symptom scales vary (visual analogue scale [VAS], numerical rating, categorical); standardize a priori. To capture patient perspective, assess Treatment Satisfaction Questionnaire Measure (TSQM) and concise resource utilization (oral corticosteroid bursts/cumulative exposure; unplanned visits/urgent care/emergency department [ED]; imaging; sinus surgery), with exploratory subgroups by biomarkers (eosinophils, fractional exhaled nitric oxide [FeNO], immunoglobulin E [IgE]) and comorbidities (obstructive sleep apnea, migraine, depression/anxiety) associated with higher burden and lower response.
CONCLUSIONS: A stakeholder-aligned endpoint battery spanning symptoms, disease-specific PRO, utilities, olfaction, disease control, treatment experience, and resource utilization improves interpretability of clinical findings, strengthens HTA readiness, and reflects patients’ perspective of treatment.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
HTA69
Topic
Health Technology Assessment
Topic Subcategory
Decision & Deliberative Processes
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Respiratory-Related Disorders (Allergy, Asthma, Smoking, Other Respiratory), STA: Biologics & Biosimilars