North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 548
- 试验地点
- 6
- 主要终点
- Initial Patient Pediatric Quality of Life (Peds QL) Score
研究概览
简要总结
The "North Carolina Clinical Genomic Evaluation by Next-gen Exome Sequencing, 2 (NCGENES 2)" study is part of a larger consortium project investigating the clinical utility, or net benefit of an intervention on patient and family well-being as well as diagnostic efficacy, management planning, and medical outcomes. A clinical trial will be implemented to compare (1) first-line exome sequencing to usual care and (2) participant pre-visit preparation to no pre-visit preparation. The study will use a randomized controlled design, with 2x2 factorial design, coupled with patient-reported outcomes and comprehensive clinical data collection addressing key outcomes, to determine the net impact of diagnostic results and secondary findings.
详细描述
The NCGENES 2 study is part of the "Clinical Sequencing Evidence-Generating Research (CSER2)" - Clinical Sites with Enhanced Diversity (U01), and brings together interdisciplinary experts from across North Carolina to address questions critical to the translation of genomic medicine to the care of patients with suspected genetic disorders.
In this renewal of the initial NCGENES study, NCGENES 2 will carry out a clinical trial of exome sequencing as a diagnostic test to answer the next set of questions vital to making genome-scale sequencing a routine clinical tool. The study population will be drawn from a state-wide network of Clinical Genetics and Pediatric Neurology clinics -- clinical domains in which patients are enriched for phenotypes caused by heterogeneous genetic conditions. Exome sequencing and genome sequencing (ES/GS) are efficient means of establishing a molecular diagnosis in these populations, with yields of positive or possible diagnostic results in at least 30% of patients examined based on findings from NCGENES and other work. Evidence will be generated regarding the clinical utility of ES/GS using a prospective randomized controlled trial that compares usual care plus exome sequencing to usual care. Patient-reported data, electronic health records data, and administrative claims data will be used to evaluate defined health outcomes, in collaboration with experts in health economics and health services research, to address pressing questions about the utility of exome sequencing. Furthermore, an examination of communication between patients and physicians, and between physicians and laboratories, and how these critical interactions affect the utility of genomic sequencing will be conducted. A second, nested randomized trial (crossed with exome sequencing in a full-factorial design) will be incorporated to test the hypothesis that a theory-based, multi-component pre-clinic preparation intervention for patients will improve patient-centered outcomes. An "embedded Ethical, Legal, and Social Implications (ELSI)" component will provide feedback to providers regarding communication discrepancies to iteratively improve care. Finally, the challenges of integrating clinical data and genomic information across a state-wide network of sites and examining different models of interaction between genomic clinicians and molecular diagnostic laboratorians will be explored.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Double (Care Provider, Outcomes Assessor)
盲法说明
The study coordinator will assign the first randomization to pre-visit preparation arm and care providers will not be told of the patient's pre-visit preparatory randomization arm prior to the first usual care visit. Randomization to exome sequencing will be performed after the first usual care visit by the study coordinator.
Investigators will receive de-identified coded data and thus will not be able to link a patient name to an intervention arm. Some analyses will require individual-level randomization arm status to allow for comparison of parent questionnaire responses or health outcomes by arm - a major focus of this study.
All interviewers and medical records staff conducting telephone surveys and/or medical records abstraction for clinical data will be blinded to the participants randomization status. Access to this information will be blocked in the electronic patient tracking status by study role.
入排标准
- 年龄范围
- 0 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Parents meeting the following criteria:
- •Parent of a child who meets the criteria below
- •At least 18 years old.
- •Must be able to provide informed consent for child and self.
- •Must be fluent in English or Spanish.
- •Children meeting the following criteria:
- •Infants and children 15 years old or less.
- •Referred for initial evaluation of a possible monogenic disorder OR
- •Seen for evaluation of an undiagnosed disorder in a study-associated clinic.
排除标准
- •Younger than 18 years old.
- •Unwilling to complete study surveys and other procedures.
- •Have cognitive or other impairments precluding ability to provide giving informed consent.
- •Not fluent in English or Spanish.
- •Unable to attend all clinic visits
- •Have a known genetic or non-genetic diagnosis (only referred for counseling or management).
- •Medically unstable.
结局指标
主要结局
Initial Patient Pediatric Quality of Life (Peds QL) Score
时间窗: 4-6 weeks prior to clinic visit 1
The Peds QL Measurement Model for the Pediatric Quality of Inventory measures the core dimensions of health as delineated by the World Health Organization as well as role (school) functioning. The 23-item PedsQL Core Scales (Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning) are developmentally appropriate surveys (Ages 2-4, 5-7, 8-12, 13-18) designed for parent proxy report. The 23 items are grouped together on the questionnaire, and are answered on a scale of 0-4. Items are reversed scored and linearly transformed to a 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0), so that higher scores indicate better Health-Related Quality of Life (HRQOL). This questionnaire will be self-administered at home.
Final Patient Pediatric Quality of Life (Peds QL) Score
时间窗: 6 months after return of results
The Peds QL Measurement Model for the Pediatric Quality of Inventory measures the core dimensions of health as delineated by the World Health Organization as well as role (school) functioning. The 23-item PedsQL Core Scales (Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning) are developmentally appropriate surveys (Ages 2-4, 5-7, 8-12, 13-18) designed for parent proxy report. The 23 items are grouped together on the questionnaire, and are answered on a scale of 0-4. Items are reversed scored and linearly transformed to a 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0), so that higher scores indicate better HRQOL. This questionnaire will be interviewer administered by telephone.
Initial Caregiver QoL Score
时间窗: 4-6 weeks prior to clinic visit 1
The Short-Form Health Survey (SF-12) questionnaire is a reliable measure of perceived health that describes the degree of general physical health status and mental health distress. It consists of 12 items, derived from the physical and mental domains. Scores have a range of 0 to 100 and were designed to have a mean score of 50 and a standard deviation of 10 in a representative sample of the US population, with higher scores indicating greater functioning. This questionnaire will be self-administered at home.
Intermediate Caregiver QoL Score
时间窗: 2 weeks after return of results
The SF-12 questionnaire is a reliable measure of perceived health that describes the degree of general physical health status and mental health distress. It consists of 12 items, derived from the physical and mental domains. Scores have a range of 0 to 100 and were designed to have a mean score of 50 and a standard deviation of 10 in a representative sample of the US population, with higher scores indicating greater functioning. This questionnaire will be interviewer administered by telephone.
Final Caregiver QoL Score
时间窗: 6 months after return of results
The SF-12 questionnaire is a reliable measure of perceived health that describes the degree of general physical health status and mental health distress. It consists of 12 items, derived from the physical and mental domains. Scores have a range of 0 to 100 and were designed to have a mean score of 50 and a standard deviation of 10 in a representative sample of the US population, with higher scores indicating greater functioning. This questionnaire will be interviewer administered by telephone.
Post-Clinic Visit 1 Mean Patient Centeredness Score
时间窗: Immediately after clinic 1 day of visit 1
Patient centeredness scale, which measures the caregiver's perception of the level of patient centeredness of their visit with their child's provider (developed by Little et al., 2001). Self-administered in the clinic, immediately after clinic visit 1. Item responses will be coded as: 1=Very strongly disagree; 2=Strongly disagree; 3=Moderately disagree; 4=Neither agree nor disagree; 5=Moderately agree; 6=Strongly agree; 7=Very strongly agree. Response values will be summed and divided by the total number of items (21) to obtain mean scores ranging from 0-7 where higher values indicate stronger perceptions of patient centeredness.
Post-Return of Results Mean Patient Centeredness Score
时间窗: 2 weeks after return of results
Patient centeredness scale, which measures the caregiver's perception of the level of patient centeredness of their visit with their child's provider (developed by Little et al., 2001). Self-administered in the clinic, immediately after clinic visit 1. Item responses will be coded as: 1=Very strongly disagree; 2=Strongly disagree; 3=Moderately disagree; 4=Neither agree nor disagree; 5=Moderately agree; 6=Strongly agree; 7=Very strongly agree. Response values will be summed and divided by the total number of items (21) to obtain mean scores ranging from 0-7 where higher values indicate stronger perceptions of patient centeredness.
Number of Questions Caregiver Asks in Clinic Visit 1
时间窗: During clinic 1 day of visit 1
Count of number of questions caregiver asks provider in the audio recording of clinic visit 1. Coded by trained study staff.
Number of In-patient Hospital Admissions Among Child Participants 1 Year Prior to Return of Results
时间窗: 1 year prior to return of results
Count of number of in-patient hospital admissions among child participants during 1 year prior to return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Admissions were summed across all participants.
Number of In-patient Hospital Admissions Among Child Participants 1 Year After Return of Results
时间窗: 1 year after return of results
Count of number of in-patient hospital admissions among child participants during 1 year after return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Admissions were summed across all participants.
Number of In-patient Hospital Days Among Child Participants 1 Year Prior to Return of Results
时间窗: 1 year prior to return of results
Count of number of in-patient hospital days among child participants during 1 year prior to return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Days were summed across all participants.
Number of In-patient Hospital Days Among Child Participants 1 Year After Return of Results
时间窗: 1 year after return of results
Count of number of in-patient hospital days among child participants during 1 year after return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Days were summed across all participants.
Number of Long-term Care Admissions Among Child Participants 1 Year Prior to Return of Results
时间窗: 1 year prior to return of results
Count of number of long-term care admissions among child participants during 1 year prior to return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Admissions were summed across all participants.
Number of Long-term Care Admissions Among Child Participants 1 Year After Return of Results
时间窗: 1 year after return of results
Count of number of long-term care admissions among child participants during 1 year after return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Admissions were summed across all participants.
Number of Long-term Care Days Among Child Participants 1 Year Prior to Return of Results
时间窗: 1 year prior to return of results
Count of number of long-term care days among child participants during 1 year prior to return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Days were summed across all participants.
Number of Long-term Care Days Among Child Participants 1 Year After Return of Results
时间窗: 1 year after return of results
Count of number of long-term care days during 1 year after return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Days were summed across all participants.
Number of ER Visits Among Child Participants 1 Year Prior to Return of Results
时间窗: 1 year prior to return of results
Count of number of ER visits during 1 year prior to return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Visits were summed across all participants.
Number of ER Visits Among Child Participants 1 Year After Return of Results
时间窗: 1 year after return of results
Count of number of ER visits during 1 year after return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Visits were summed across all participants.
Number of Specialists Visits Among Child Participants 1 Year Prior to Return of Results
时间窗: 1 year prior to return of results
Count of number of specialists visits during 1 year prior to return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Visits were summed across all participants.
Number of Specialists Visits Among Child Participants 1 Year After Return of Results
时间窗: 1 year after return of results
Count of number of specialists visits during 1 year after return of results using data obtained from the Electronic Medical Record. Coded by trained study staff. Visits were summed across all participants.
次要结局
- Initial Average Peds QL Score for "Missing School for Not Feeling Well"(4-6 weeks prior to clinic visit 1)
- Final Average Peds QL Score for "Missing School for Not Feeling Well"(6 months after return of results)
- Initial Average Peds QL Score for "Missing School for Doctors Visit"(4-6 weeks prior to clinic visit 1)
- Final Average Peds QL Score for "Missing School for Doctors Visit"(6 months after return of results)
- Initial Amount of Work Missed Because of Child's Condition or Treatments Score(4-6 weeks prior to clinic visit 1)
- Final Amount of Work Missed Because of Child's Condition or Treatments Score(6 months after return of results)
- Initial Difficulty With Finishing Normal Work (Including Both Work Outside of the Home and Housework) Because of Child's Condition or Treatments Score(4-6 weeks prior to clinic visit 1)
- Intermediate Difficulty With Finishing Normal Work (Including Both Work Outside of the Home and Housework) Because of Child's Condition or Treatments Score(2 weeks after return of results)
- Final Difficulty With Finishing Normal Work (Including Both Work Outside of the Home and Housework) Because of Child's Condition or Treatments Score(6 months after return of results)
- Percent Concordance of Caregiver and Provider Reports of Genetic or Genomic Test Results(2 weeks after return of results)
- Mean Baseline Self Efficacy Score(4-6 weeks prior to clinic visit 1)
- Mean Pre-Clinic Visit 1 Self Efficacy Score(Immediately before Clinic Visit 1)
- Post-Return of Results Mean FACToR Uncertainty Subscale Score(2 weeks after return of results)
- Vital Status at Final f/u(Final follow-up, up to approximately three years after clinic visit 1)
- Number of Child Participants With Causes of Death Unrelated to the Study(Final follow-up, up to approximately three years after clinic visit 1)