ABSTRACT
Purpose : R-shiny apps can be useful in maintaining and analyzing data collected in clinical trials of rare diseases, where a suite of measures is used to characterize retinal and visual function, functional vision, and safety courses over time following the treatment. In a phase 3 trial, participants with biallelic RPE65 mutation-associated inherited retinal dystrophy (IRD), an ultra-rare genetic disorder, received bilateral, subretinal injections of gene augmentation therapy, voretigene neparvovec and followed-up annually. We explored the development of a novel data visualization tool, VNEAN (R-shiny application), to help in maintenance and analyses of complex trial data into a visual storytelling form that is easier to understand for healthcare audience. Methods : We developed an interactive and dynamic application using Shiny package for R programming language. This app improves the ability to explore the longitudinal trajectory of main efficacy outcomes (mobility testing and full-field light sensitivity) in concert with other data, including visual function and safety that can be visualized overall and in subsets. Results : This app has 11 modules of data analyses (Figure 1), including longitudinal visualization, analyses of correlation between changes, and timeline of adverse events. It presents the durability in improvement of functional vision, retinal and visual function, and the safety data at the group, subset and participant levels. The dynamic interface allows the user to define a subset based on the measures at baseline and/or their changes and select measures and/or timepoints. Conclusions : COVID-19 demonstrated digital engagement at its peak. The R shiny app has the potential to provide alternative data visualization and interpretations of analyses that offer a comprehensive representation of the data generated in rare diseases, not easily achievable via traditional didactic lectures and static data methods. This patient-centric and enduring visualization approach enables health care professionals to learn and retain information for the management and engagement of IRD patients in their clinical practice. Additionally, this application can progress the knowledge and understanding of treatment effects of rare diseases and help inform the design of future small- or largescale trials.
ABSTRACT
Purpose : Voretigene neparvovec (VN) is the first ocular gene therapy approved in multiple countries including the USA and Europe for treating patients (pts) with visual impairment due to confirmed biallelic RPE65 mutation-associated inherited retinal dystrophy having sufficient viable retinal cells. PERCEIVE, a registry-based post-authorization safety study, is designed to assess long-term safety of VN in a real-world (RW) setting. Here, baseline characteristics of participating pts treated with VN up to August 2020 are reported. Methods : PERCEIVE is an ongoing, prospective, longitudinal, multicenter (ex-US), observational, safety study, which commenced December 2019 with the aim to enroll a minimum of 40 pts. All VN-treated pts are encouraged to participate in the study to maximize data collection, including those treated prior to study inception. After receiving VN as per local prescribing information, pts are followed-up as per the routine medical care for 5 years. The objectives are to characterize the long-term safety profile of VN via systematic collection of adverse event data, to follow pregnancy outcomes and assess visual function over time. Results : Until data cut-off (Aug 2020), of the 15 pts enrolled, 10 pts (16 eyes) have received VN (6 bilateral;4 unilateral). All treated pts are from Europe (Germany: 6;France: 3;Austria: 1). At the time of enrollment, the mean (standard deviation [SD]) age was 27.6 (9.81) years with a range of 15-51 years (1 adolescent;9 adults). The majority of treated pts are female (n=7;70%). For the treated eyes (n=16), baseline mean (SD) visual acuity was 0.96 (0.37) logMAR (n=14;range: 0.5-1.6 logMAR) and full-field stimulus threshold (white light) was -4.32 (9.40) dB (n=15;range: -34.9 to 3.2 dB). Optical coherence tomography (OCT) revealed a mean foveal thickness of 150.5 (41.07) μm (n=15;range: 76- 216 μm). Central OCT showed that 11 eyes had an outer nuclear layer with a thickness range of 36-74 μm (n=9), while it was absent in 4 eyes. The ellipsoid zone line was disrupted in 9 eyes and was undetected in 6. Conclusions : While enrollment and in person follow-up of VN-treated pts has been impacted due to COVID-19, PERCEIVE has started to provide valuable information on baseline characteristics of this vision-impaired population, and effect of VN therapy in a RW setting.