Pediatric Pharmacogenomics and Personalized Medicine

描述（由申请人提供）：临床医生、制药公司和监管机构面临的一个主要挑战是更好地了解个体发育和遗传变异对从早产儿和足月新生儿到婴儿、儿童和青少年的儿科年龄范围内观察到的药物处置和反应变异性的相对贡献。在过去的 25 年里，人们对遗传变异对成人药物处置和反应变异性的影响的认识大幅增加，但药物遗传学和药物基因组学原理在儿科药物治疗中的应用却远远落后。将成人在药物基因组学和个性化医疗方面的经验外推到不同年龄和发育阶段的儿科患者充满了许多挑战。有些儿科疾病与成人没有相关性，或者与成人相比，在儿童中更为常见。同样，一些药物不良反应是儿童所特有的，或者在儿童中发生的频率较高。与成人相比，儿科药物遗传学和药物基因组学涉及额外的复杂性测量，因为发育过程或个体发育引起的变异叠加在遗传变异上。在药物处置和反应的背景下，个体发育带来的额外复杂性表现为剂量要求、药物功效或毒性风险相对于基于成人经验的预期的意外差异。该提案的主要目标是继续由密苏里州堪萨斯城儿童慈善医院和诊所的个性化医疗和治疗创新中心以及临床药理学和医学治疗部组织的“儿科药物基因组学和个性化医疗”系列年会。会议的目标是 1) 将临床医生、基础科学家和转化科学家以及相关医疗保健从业者聚集在一起，进行多学科和跨学科对话，旨在在儿科环境中实施个性化医疗； 2) 提供一个论坛，展示和传播与应用药物基因组策略研究儿童药物分布和反应变异性相关的研究； 3) 探索儿童特有的药物基因组学和个性化医疗的伦理、法律和社会影响； 4) 创造交流机会，促进讨论、合作和协作，制定战略来满足已确定的研究需求。最终，该计划的目标是提高所有年龄段儿童药物的安全性和有效性。 公共健康相关性：一次专门关注儿科药物基因组学和个性化医疗的会议将为拥有提高儿童药物安全性和有效性的共同目标的临床医生和研究人员提供一个论坛，以讨论问题、交流想法并建立对于提高所有年龄段和发育阶段儿童的药物安全性和有效性至关重要的合作和合作协议。

DESCRIPTION (provided by applicant): A major challenge for clinicians, pharmaceutical companies and regulatory agencies is to better understand the relative contributions of ontogeny and genetic variation to observed variability in drug disposition and response across the pediatric age spectrum from pre-term and term newborns, to infants, children and adolescents. Knowledge of the contribution of genetic variation to variability in drug disposition and response in adults has increased substantially over the past 25 years, but the application of pharmacogenetic and pharmacogenomic principles to pediatric drug therapy has lagged well behind. Extrapolation of adult experience with pharmacogenomics and personalized medicine to pediatric patients of different ages and developmental stages is fraught with many challenges. Some pediatric diseases have no adult correlate or are more prevalent in children compared to adults. Likewise, several adverse drug reactions are unique to children or occur at a higher frequency in children. Compared to adults, pediatric pharmacogenetics and pharmacogenomics involves an added measure of complexity as variability due to developmental processes,or ontogeny, is superimposed upon genetic variation. In the context of drug disposition and response, the additional complexity that ontogeny contributes manifests as unanticipated differences in dosing requirements, drug efficacy or risk of toxicity relative to what is expected based on experience in adults. The primary objective of this proposal is to continue an ongoing series of annual conferences on "Pediatric Pharmacogenomics and Personalized Medicine" organized by the Center for Personalized Medicine and Therapeutic Innovation and Division of Clinical Pharmacology and Medical Therapeutics at Children's Mercy Hospitals and Clinics in Kansas City, MO. The goals of the meeting are 1) To bring together clinicians, basic and translational scientists and allied healthcare practitioners, and engage in multi- and cross-disciplinary dialogue aimed at implementing personalized medicine in pediatric settings; 2) To provide a forum for the presentation and dissemination of research related to the application of pharmacogenomic strategies to investigations of variability of drug disposition and response in children; 3) To explore the ethical, legal and societal implications of pharmacogenomics and personalized medicine that are unique to children; and 4) To create networking opportunities for stimulating discussion, cooperation and collaboration to devise strategies to address research needs identified. Ultimately, the goal of this program is to improve the safety and efficacy of medications in children of all ages. PUBLIC HEALTH RELEVANCE: A meeting focused exclusively on Pediatric Pharmacogenomics and Personalized Medicine will provide clinicians and researchers who share a common goal of improving drug safety and efficacy in children a forum to discuss the issues, exchange ideas and establish collaborations and cooperative agreements critical to improving the safety and efficacy of medications in children of all ages and developmental stages.