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

摘要： 为单基因疾病患者开发新的治疗方法有大量未得到满足的需求 如镰状细胞病(SCD)和基因治疗技术代表了一种潜在的新解决方案。这 该项目解决了研究伦理中的一个重要问题--提高知情同意的质量和建立 与研究参与者中的弱势群体进行基因治疗沟通的能力(儿科 患者，以及代表不足的少数群体)。既然早期治疗可以减少长期发病率，改善 提高生活质量，降低早期死亡率，关注儿科患者势在必行。在考虑基因的时候 治疗，家庭在考虑是否应该寻求新的治疗方法时面临复杂的治疗选择 如果长期效果不确定，不同治疗方案的风险-收益比很难确定 来比较一下。我们假设家庭对这些治疗有独特的信息需求 具有决策辅助的专用教育平台将是促进协作性、以家庭为中心的关键 在考虑对孩子的罕见疾病进行基因治疗时的决策和总体满意度。在这下面 作为行政补充，我们将进行需求评估(目标1)，其中包括大约50个半 对孩子(A)已经(或被提供)基因治疗或(B)患有疾病的父母进行结构化访谈，其中 儿科基因治疗试验即将到来。要完成真正全面的 关于基因治疗的差距和需求，我们将采访10-20名有护理经验的卫生保健提供者 儿科基因治疗家庭。然后，我们将开发和完善一个多媒体网络平台，为家庭提供 有了关于基因治疗的信息工具包，其中将包括我们的儿科基因治疗支持工具 将发展作为这一目标的一部分(目标2)。为了实现这个以患者为中心的质量改进项目的目标： 访谈将被录音，逐字转录，并使用语义内容分析由 混合方法研究人员的专家团队。我们将使用经过验证的工具并遵循国际标准 用来帮助病人做决定。这些工具将通过完善的方法迭代开发和改进 Alpha和Beta测试试点内容。我们的研究团队计划与Booster Sshot Media公司合作 在创建以患者为中心的内容方面经验丰富，便于研究人员和学术医疗中心进行交流 关于医疗保健的其他方面。这个项目是创新的，将填补患者-提供者之间的一个重要空白 围绕儿科疾病的基因治疗进行交流。一旦最终敲定，这将是(据我们所知)第一次 经过验证的、基于证据的决策支持工具包，可供患有罕见疾病的儿童的父母使用 有资格接受基因治疗。

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.