Incorporating the patient perspective into clinician-reported outcome (ClinRO) content validation and meaningful within-patient change thresholds

Abstract Background Clinician-reported outcome measures (ClinROs) are completed by trained clinical experts, yet the signs and behaviors they capture must reflect meaningful aspects of health to patients. FDA Patient Focused Drug Development (PFDD) Guidance indicates the importance of establishing content validity for ClinROs. Patient and caregiver input can support the conceptual relevance of ClinROs and inform score interpretation such as meaningful change thresholds. Objective To synthesize lessons learned from four qualitative case studies in which patient or caregiver input informed (1) ClinRO content validity and (2) within-patient clinically meaningful change thresholds, and to develop methodological recommendations for future studies. Methods We reviewed four, purposively selected, qualitative studies designed to inform the development or validation of ClinROs. Contexts were varied across neurodegenerative and autoimmune conditions. Across studies, concept elicitation and cognitive debriefing interviews were conducted with patients or caregivers alongside clinical expert interviews. Visual aids and task adaptations were used to support participants’ comprehension of clinical terminology and inform scoring discussions. Results We propose six methodological recommendations for incorporating patient/caregiver input during ClinRO development and validation. When gathering patient/caregiver input to inform content validity, researchers should: (1) frame the purpose; (2) use multimodal supports; (3) simplify scoring for the task; (4) map language. When developing an endpoint hierarchy researchers should align endpoints with patient priorities. When informing meaningful change thresholds, researchers should elicit discussion of patient perspective. The reviewed studies confirmed that patients and caregivers could generally understand and participate in interview tasks using visual aids provided. Conclusions Incorporating patient/caregiver input during ClinRO development/validation strengthens content validity and provides qualitative insights into meaningful change thresholds to inform score interpretation. Practical techniques (advance framing, visual aids, simplified scoring) support patient/caregiver engagement with complex ClinROs. Methodological recommendations are provided for incorporating patient/caregiver input into ClinRO evidence generation to inform patient-focused clinical trial measurement strategies.