PedGeneRx - Admin Supplement to Base Editing and Prime Editing for Sickle Cell Disease R01

ABSTRACT: There is a substantial unmet need for the development of new treatments for patients with monogenic disorders such as sickle cell disease (SCD) and gene therapy technologies represent a potential novel solution. This project addresses an important issue in research ethics – improving the quality of informed consent and building

capacity for gene therapy communication with a vulnerable population of research participants (pediatric patients, as well as underrepresented minorities). Since early treatment can reduce long-term morbidity, improve quality of life, and reduce early mortality it is imperative to focus on pediatric patients. In considering gene

therapy, families face complex treatment choices when considering whether they should pursue a novel therapy where the long-term effects are uncertain, and the risk-benefit ratios of the different treatment options are difficult to compare. We hypothesize that families have unique informational needs surrounding these treatments and

dedicated educational platforms with decisional aids will be crucial to promoting collaborative, family-centered decision-making and overall satisfaction when considering gene therapy for their child's rare disease. Under this administrative supplement, we will conduct a needs assessment (Aim 1) that includes approximately 50 semi-

structured interviews with parents whose child (a) had (or been offered) gene therapy or (b) has a disorder where pediatric gene therapy trails are on the horizon. To complete a truly comprehensive needs assessment of the gaps and wants around gene therapy, we will interview 10-20 health care providers with experience caring for

pediatric gene therapy families. We will then develop and refine a multimedia web platform that provides families with a toolkit of information about gene therapy, which will include a pediatric gene therapy support tool we develop as part of this aim (Aim 2). To achieve the aims of this patient-focus quality improvement project: the

interviews will be audio recorded, transcribed verbatim, and analyzed using semantic-content analysis by an expert team of mixed-methods researchers. We will use validated tools and follow the international standards for patient decision aids. The tools will be developed and refined iteratively through well-established methods of

alpha and beta testing pilot content. Our research team plans to work with Booster Shot Media, a company experienced in creating patient-centered content for researchers and academic medical centers to communicate about other aspects of healthcare. This project is innovative and will fill an important gap in patient-provider

communication around gene therapy for pediatric disease. Once finalized, this will be the first (to our knowledge) validated, evidenced based decisional-support toolkit available to parents of children with rare disease who are eligible for gene therapy.