Johnson, C D

ABSTRACT Background To explore the prevalence of serious adverse events ( SAEs ) associated with retinal viral gene therapy and to examine trends influencing SAE occurrences in human gene therapy surgeries and pre‐clinical animal trials. Methods Literature review was performed to identify peer‐reviewed human and animal studies relevant to viral gene therapy, subretinal injections, and intravitreal injections. For clinical trials and post‐approval LUXTURNA studies, only those that examined SAEs were included. Results Of included clinical trial studies ( n = 31), SAEs were recorded in 51 out of 438 eyes (11.6%) that received subretinal injections and in 11 out of 348 eyes (3.2%) that received intravitreal injections. There were fewer intravitreal‐related SAEs and less vision loss compared to subretinal gene therapy. Inflammation was the predominant SAE following intravitreal injections, whereas unexplained vision loss was the most common for subretinal injections. Clinical trials utilising subretinal injections met primary or secondary efficacy endpoints more than intravitreal trials. Eighteen studies (429 eyes) of post‐approval LUXTURNA were reviewed, and SAEs were reported in 24.7% of eyes, retinal degeneration being most common (20.7%). For 58 animal studies, SAEs were recorded in 17.3% of eyes that received subretinal injections and 8.7% of eyes that received intravitreal injections. Conclusions Subretinal injections show higher efficacy than intravitreal injections but are associated with more serious adverse events. Consistent adverse event patterns in humans and large animals highlight their predictive value for safety. There is a need for optimised delivery methods, refined dosing protocols, and improved post‐treatment monitoring to improve safety and effectiveness in gene therapy.

Public trust in physicians has declined over the last 50 years. Future physicians will need to mend the patient–physician trust relationship. In conjunction with the American Medical Association’s Accelerating Change in Medical Education initiative, the Mayo Clinic Alix School of Medicine implemented the Science of Health Care Delivery (SHCD) curriculum—a 4-year curriculum that emphasizes interdisciplinary training across population-centered care; person-centered care; team-based care; high-value care; leadership; and health policy, economics, and technology—in 2015. In this medical student perspective, the authors highlight how the SHCD curriculum has the potential to address issues that have eroded patient–physician trust. The curriculum reaches this aim through didactic and/or experiential teachings in health equity, cultural humility and competence, shared decision making, patient advocacy, and safety and quality of care. It is the authors’ hope that novel medical education programs such as the SHCD curriculum will allow the nation’s future physicians to own their role in rebuilding and fostering public trust in physicians and the health care system.