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.

抽象的： 为单基因疾病患者开发新疗法有很大的未满足 例如镰状细胞疾病（SCD）和基因治疗技术代表了潜在的新解决方案。这 项目解决了研究道德中的一个重要问题 - 提高知情同意和建设的质量 基因疗法与脆弱的研究参与者人群的交流能力（小儿 患者以及代表性不足的少数民族）。由于早期治疗可以降低长期发病率，请改善 生活质量并降低早期死亡率，必须专注于小儿患者。在考虑基因 治疗，家庭在考虑是否应纯化新疗法时面临复杂的治疗选择 在长期效果不确定的情况 比较。我们假设家庭在这些治疗方面有独特的信息需求， 具有决定性辅助工具的专用教育平台对于促进以家庭为中心的协作，至关重要 考虑孩子的罕见疾病基因疗法时，决策和总体满意度。在此 行政补充，我们将进行需求评估（AIM 1），其中大约50个半 与孩子（a）接受过（或提供）基因疗法的父母的结构化访谈，或者（b）有疾病 小儿基因疗法踪迹即将到来。完成真正的全面需求评估 差距和想要基因疗法的差距，我们将采访10-20个医疗保健提供者，并有经验 小儿基因治疗家族。然后，我们将开发和完善一个多媒体网络平台，以提供家庭 借助有关基因疗法的信息包，其中将包括儿科基因治疗支持工具 作为此目标的一部分发展（目标2）。为了实现此患者对焦质量改进项目的目标： 访谈将通过语义分析记录，逐字记录，逐字记录和分析 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 用于患者决策艾滋病。这些工具将通过完善的方法进行开发和完善 Alpha和Beta测试试点含量。我们的研究团队计划与一家公司Booster Shot Media合作 在创建以患者为中心的内容供研究人员和学术医疗中心进行交流的经验 关于医疗保健的其他方面。该项目具有创新性，将填补患者提供者的重要空白 围绕小儿疾病基因治疗的沟通。一旦完成，这将是第一个（据我们所知） 经过验证，证据的决策支持工具包，可用于罕见疾病的父母 有资格接受基因治疗。