AIMS: FDA guidance (2019) for the development of treatments for uUTI indicates endpoints should assess ‘resolution of the symptoms of uUTI present at trial entry.’ Symptom resolution endpoints for uUTI are commonly measured using ClinROs due to a lack of availability of well-accepted patient-reported outcome measures (PROs). Whilst there are established methods for exploring the meaningfulness of endpoints defined with PROs with patients, the relevance of endpoints derived from ClinRO measures (when they are used in place of PRO measures due to a lack of PRO availability) is rarely explored with patients. This study utilized established PRO methodology and applied it to a ClinRO-based endpoint in uUTI.
METHODS: Thirty adolescents and adults based in the US, with a clinician-confirmed diagnosis of a uUTI infection within 14 days of screening, were interviewed. Participants were English or US-Spanish speaking. Interviews were 60-min in length and conducted in the participants’ native language. They were recorded, transcribed, and analyzed using best-practice qualitative methods. Participants were asked to provide their interpretations of the ClinRO response options and how they would define symptom resolution and treatment success. Participants were also asked if the content of the ClinRO measure adequately captured their experiences with UTI and what change in score would be meaningful to them and why.
RESULTS: Participants were able to partake in the interview and understood what was asked of them. They were able to provide interpretations of the meanings of and differences between each ClinRO response option and the smallest amount of improvement they would consider meaningful and how this translated into a treatment success. Participants’ definition of symptom resolution on the ClinRO supported the regulatory definition and clinical study endpoints, specifically that achieving symptom resolution was an important and expected outcome for treatment of uUTI.
CONCLUSION: Until well-defined and reliable PRO instruments that measure clinically important symptoms of uUTI are available and accepted for regulatory use, patients should be involved in the definition of clinical study endpoints that use ClinROs to rate symptoms, in the place of PROs. This can be applied similar conditions without well-accepted PRO symptom assessments.
