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

PedGeneRx - 镰状细胞病 R01 碱基编辑和 Prime 编辑的管理补充

• 批准号: 10594247
• 负责人: DAVID R LIU
• 金额: $ 18.2万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10594247
• 关键词: Academic Medical Centers; Address; Adenovirus Vector; Administrative Supplement; Adverse event; Affect; Age; American; Attitude; Award; Belief; Benefits and Risks; Caring; Child; Childhood; Clinical; Clinical Research; Clinical Trials; Communication; Complex; Data; Decision Aid; Decision Making; Development; Disease; Early treatment; Education; Ensure; Face; Family; Family psychotherapy; Gene therapy trial; Genetic; Health Personnel; Healthcare; Hemoglobinopathies; Hemophilia A; Individual; Informed Consent; International; Interview; Investigational New Drug Application; Knowledge; Long-Term Effects; Mendelian disorder; Methods; Morbidity - disease rate; Multimedia; Needs Assessment; Neuromuscular Diseases; Non-Viral Vector; Online Systems; Parents; Participant; Patients; Prevalence; Quality of life; Rare Diseases; Research; Research Ethics; Research Personnel; Safety; Semantics; Sickle Cell Anemia; Structure; Techniques; Technology; Testing; Trust; Uncertain Risk; Uncertainty; Underrepresented Minority; United States; United States Food and Drug Administration; Viral; Viral Vector; Vulnerable Populations; Work; base editing; bench to bedside; booster vaccine; care delivery; care preference; clinical practice; congenital immunodeficiency; cost; curative treatments; design; early phase clinical trial; evidence base; experience; gene therapy; improved; innovation; mortality; novel; novel therapeutics; patient oriented; patient-clinician communication; pediatric patients; pilot test; pre-clinical; prime editing; programs; prototype; rare genetic disorder; risk benefit ratio; satisfaction; success; support tools; tool; treatment choice; vector; web platform; young adult

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.

摘要： 对于开发用于患有单基因疾病的患者的新疗法存在大量未满足的需求 例如镰状细胞病（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学中的一个重要问题-提高知情同意的质量和建立 与弱势研究参与者群体（儿科）进行基因治疗交流的能力 患者以及代表性不足的少数群体）。由于早期治疗可以降低长期发病率， 生活质量，降低早期死亡率，必须关注儿科患者。考虑到基因 治疗，家庭面临复杂的治疗选择时，考虑他们是否应该追求一种新的治疗方法 长期效果不确定，不同治疗方案的风险效益比难以确定 比较一下我们假设，家庭对这些治疗有独特的信息需求， 具有决策辅助的专门教育平台对于促进以家庭为中心的协作性教育至关重要。 决策和整体满意度时，考虑基因治疗他们的孩子的罕见疾病。根据本 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， 结构化访谈的父母，他们的孩子（a）有（或被提供）基因治疗或（B）有一个障碍， 儿科基因治疗试验即将开始。为了完成对难民的真正全面的需求评估， 我们将采访10-20名有经验的医疗保健提供者， 儿科基因治疗家族然后，我们将开发和完善一个多媒体网络平台， 一个关于基因治疗的信息工具包，其中包括一个儿科基因治疗支持工具， 作为目标的一部分（目标2）。为达致这项以病人为本的质素改善计划的目标， 访谈将录音，逐字转录，并使用语义内容分析进行分析， 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 帮助病人做决定这些工具将通过完善的方法反复开发和完善， Alpha和Beta测试试点内容。我们的研究团队计划与Booster Shot Media公司合作， 在为研究人员和学术医疗中心创建以患者为中心的内容以进行交流方面经验丰富 医疗保健的其他方面。该项目具有创新性，将填补患者-提供者之间的重要空白 关于儿科疾病基因治疗的交流。一旦完成，这将是第一个（据我们所知） 经验证的、基于证据的决策支持工具包，提供给患有罕见疾病的儿童的父母， 适合基因治疗