Developing patient-reported outcome measures for children and teenagers for clinical trials of sight-restoring interventions in very low and ultra-low vision

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Sight-restoring new technologies and treatments are rapidly evolving, including pharmaceutical treatments, gene therapy, stem cells and retinal visual prostheses. As many of the causes addressed by these interventions lead to early onset visual loss, children and teenagers participate in the respective clinical trials. At this stage, interventional trials are often limited to persons who have little or no vision, and any improvements in visual function are expected to be small and unlikely to be captured in conventional clinical measurements. Thus, the evaluation of therapeutic efficacy should include patient-reported outcome measures (PROMs) such as vision-related quality of life (VRQoL) and visual functioning. We know that PROMs for children and teenagers need to be age-appropriate in content and display, and that children below the age of eight years should be excluded from self-report for a number of reasons such need for proxy report. Thus, we will concentrate on children aged 8 to 18 in this project. Recently, robust PROM instruments targeting children and teenagers with severe visual impairment or blindness were developed by Prof. Jugnoo Rahi (collaborator in this project). To be age-appropriate two versions (children 8-12 and teenagers 13-18 years) were created for both the Functional Vision Questionnaire for Children and Young People (FVQ_CYP) and the Vision related Quality of Life instrument for Children and Young People (VQol_CYP). Both PROMs are theoretically suited as endpoints for clinical trials pending several hurdles being addressed:1. Additional language versions are needed: Any trials will be multi-national as only rare diseases cause visual impairment in these age groups. Thus we will create German PROM versions.2. PROM instruments must yield high-quality data, be psychometrically robust and allow for comparison across different language versions: We will assess psychometric performance for the UK English and German version including any calibration needed to allow for sample-independent comparisons using modern psychometric theory e.g. the Rasch model.3. Allow for continuous measurement across age-appropriate versions:As respondents naturally age whilst participating in clinical trials they may start with the child version but continue with the version for teenagers which requires calibration across both versions. This calibration has not been done for the FVQ_CYP nor the VQoL_CYP.This project will deliver ready to use PROMs for children and teenagers with visual impairment for use in clinical trials, allowing children and teenagers participating in the evaluation of tested interventions as well as enabling them to voice their preferences and share in the medical decision making.