Ending the Diagnostic Odyssey: Whole Genome Sequencing (WGS) to Identify Genetic Determinants of Previously Undiagnosed Disease in Children
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 1,000
- 试验地点
- 2
- 主要终点
- Number of patients enrolled per year
研究概览
简要总结
The goal of this collaborative research is to study human genomes in children with suspected congenital disease, multiple-congenital anomalies and/or multi-organ disease of unknown etiology by understanding the potential value of Whole Genome Sequencing (WGS) in establishing genetic diagnosis. The study will examine diagnosis rates, changes in clinical care as a result of a genetic diagnosis, health economics including potential cost-effectiveness of WGS and patient and provider experience with genomic medicine.
详细描述
The goal of this collaborative research is to study human genomes in children with suspected congenital disease, multiple-congenital anomalies and/or multi-organ disease of unknown etiology, in order to understand the potential value of WGS in establishing a genetic diagnosis. The study will examine diagnosis rates, changes in clinical care as a result of a genetic diagnosis, health economics including potential cost-effectiveness of WGS, and patient and provider experience with genomic medicine. Other clinical information of the type collected by treating physicians and stored in electronic medical records will also be collected to aid in the interpretation of laboratory data. Participants will also be asked to consent for future access of the medical record, future research on biospecimens and data generated from genomic sequencing, and for the ability to re-contact.
As part of this effort, Nicklaus Children's Hospital plans to create a large integrated database that contains the DNA sequences of the participants' whole human genomes and additional health information regarding characteristics and health of the persons whose samples have been sequenced. Scientists can then use the database to try to link those traits, diseases, and other conditions to changes in the sequence of the genome. Nicklaus Children's Hospital plans to make the database available to its collaborators, such as RCIGM, pharmaceutical and biotechnology companies, and other academic institutions which will use the database to find better, innovative ways to prevent, diagnose, and treat cancer and other diseases. De-identified data from this study will be shared with the community at-large, including publications and public databases. In addition, participants will be given the option to allow biospecimens (i.e., residual blood, saliva, CSF, etc.) to be included in biorepositories at Nicklaus Children's Hospital and Rady Pediatric Genomics & Systems Medicine Institute (RCIGM).
The study will provide clinical laboratory-confirmed results related to the affected patient's phenotype, including optional incidental findings unless subjects opt-out for these additional results, to allow for these research findings to be used in clinical care. Furthermore, this study will aggregate data regarding standard clinical genetic testing as well as cost measures to not only identify differences in diagnostic rates, diagnostic accuracy, and times to diagnoses, but to determine the cost-effectiveness of this testing and subsequent changes in care management. Clinical utility will be defined as changes in care that follow directly from results of genetic testing (both positive and negative), including standard clinical tests and WGS. This data will be used to further examine the analytic, diagnostic, and clinical utility and cost-effectiveness of this testing.
WGS methods continue to improve and pediatric genomic medicine is a very new field of medical practice. This study will also inform investigators regarding best practices, both in terms of traditional medical outcomes and patient-centered outcomes. Consequently, this study will also act as a biorepository for samples and data as the ability to share genomic and phenotypic data amongst researchers is critical to progressing our understanding of the nascent field of pediatric genomic medicine.
Specific Aims:
研究设计
- 研究类型
- Observational
- 观察模型
- Family Based
- 时间视角
- Prospective
入排标准
- 年龄范围
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Symptomatic male or female children ages 0-21 who have un unknown medical condition thought to have an underlying genetic cause after parental consent has been obtained.
- •Willingness of referring provider or other qualified medical staff member to participate in this study by facilitating collection of biologic specimens and clinical information.
- •Patient whose medical condition can be reasonably attributed to a possible genetic etiology.
- •Patient have had at least one diagnostic test without a definite diagnosis.
排除标准
- •Unwillingness to consent to research.
- •Affected adults (>21 years of age), unless they are a biological relative of the affected child.
- •Any patient whose medical condition cannot be reasonably attributed to a possible genetic etiology or there is a prior diagnosis that explains the child's clinical presentation.
结局指标
主要结局
Number of patients enrolled per year
时间窗: Yearly throughout study completion up to 50 years
Total number of enrolled patients who will undergo WGS testing
次要结局
- Clinical Utility(Throughout study completion up to 50 years)
- Phenome(Throughout study completion up to 50 years)
- Clinically-confirmed diagnoses(Throughout study completion up to 50 years)
- Diagnosis Rate of genetic diseases(Throughout study completion up to 50 years)