NCGENES: North Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing

Study Overview
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Brief Summary
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This study is part of a larger consortium project investigating the validity and best use of next-generation sequencing (in particular, whole exome sequencing, or WES) in clinical care. This sub-project is investigating benefits and harms of providing WES diagnostic and different types of incidental findings to adult patients and parents of pediatric patients who undergo WES because they have symptoms suggesting genetic disease.

Detailed Description
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This study is part of a larger consortium project investigating the validity and best use of next-generation sequencing (in particular, whole exome sequencing, or WES) in clinical care. Participants are patients who were either seen in the University of North Carolina Cancer and Adult Genetics Clinic or referred to the study by their physician. They will be approached by their physician or a genetic counselor for recruitment. Once enrolled, a clinical geneticist or genetic counselor will obtain consent and collect blood samples to be analyzed using WES. Results may include information related to a diagnosis and incidental information. Medically actionable incidental findings will be CLIA (Clinical Laboratory Improvement Amendments)-certified and returned to participants in a routine genetic counseling session, along with diagnostic findings. Eligible adult participants will be randomized to have the opportunity to choose to get certain types of non-medically actionable incidental findings, as well. Their decisions will be investigated, as will psychosocial and behavioral responses to sequencing and receiving sequencing information. This is a longitudinal, mixed methods study (i.e., multiple assessments pre- and post-return of results, with both quantitative and qualitative methods used to gather data). Because only the quantitative component of the study uses randomization, only measures and procedures associated with that component are described here.

Official Title
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NCGENES: North Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing

Conditions
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Cancer, Cardiovascular Disease, Neurologic Dysfunction, Congenital Abnormalities, Hearing Loss

Intervention / Treatment
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* Behavioral: Experimental


Participation Criteria
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Eligibility Criteria
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- To receive whole exome sequencing in the study, adult or child patients must have a significant chance of having a genetic disorder, as determined by experts on the study team using criteria that depend on the genetic disorder in question. Representative criteria are listed below and will be considered together to determine whether patterns indicate a likely genetic etiology. Cancer Age of diagnosis Presence of bilateral (or multiple) cancers Diagnosis of a rare type of cancer Details of the family history Cardiovascular Conditions Certain clinical findings, such as prolonged QT interval on electrocardiogram. Presence of hypertrophic cardiomyopathy or aortic aneurysm Age of diagnosis Presence of family history Pediatric neurodevelopmental disorders Specific brain structural brain abnormalities Presence of certain seizure types Dysmorphic features
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Option to request non-medically actionable incidental information (after receiving education about them) | Behavioral: Experimental<br>* Option to request non-medically actionable incidental information (after receiving education about them)<br>|
| No Intervention: Control<br>No option to request non-medically actionable incidental information | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extent of test-specific distress 2 weeks after return of results | Measured with an adapted version of the multidimensional impact of testing scale (MICRA) | 2 weeks after return of diagnostic results; for adult patient participants who are eligible and who request them, 2 weeks after return of non-medically actionable incidental results | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in test-specific distress at 3 and 6 months after return of results | Measure is an adapted version of the multidimensional impact of testing scale MICRA) | Adult patient participants: change from 2 weeks after return of diagnostic results to 3 months and 6 months after return of diagnostic results | 
| Extent of communication of test results with other people | Motivations of communications will also be assessed and examined for descriptive analyses. | 2 weeks after return of diagnostic results | 
| Extent of information seeking | Participants will answer questions about the extent to which they sought information about whole exome sequencing and results it produces. Questions also ask about sources of that information (e.g., the Internet, doctors) to provide descriptive data about how participants get information. | 2 weeks after consent (T1) and change from T1 to 2 weeks after return of diagnostic results | 
| Extent of Decision Regret 2 weeks after consent |  | All participants: 2 wks after consent (T1) | 
| Extent of Decision Regret 2 weeks after return of results | Also administered 2 wks after return of non-medically actionable incidental results for eligible adult patient participants who request them. | All participants: 2 wks after return of diagnostic (dx) results and, for eligible adults who request them, return of incidental results | 
| Change in decision regret |  | For all participants: Change from post-consent to post-return of results; Additional for adults: change at 3 and 6 months after return of dx results | 
| Extent of Healthcare Utilization 2 weeks after consent |  | All participants: 2 wks after consent (T1) | 
| Extent of Healthcare Utilization 2 weeks after return of results |  | All participants: 22 wks after return of diagnostic (dx) results | 
| Change in Healthcare Utilization |  | All participants: Change in utilization from post-consent to post-return of results; Additional for adult patients: Change at 3 and 6 months after return of dx results | 
| Enactment of health-related lifestyle behaviors 2 weeks after consent | Behaviors include those related to diet, physical activity, smoking, drinking, and substance use. | Adult participants: 2 wks after consent (T1) | 
| Enactment of health-related lifestyle behaviors 2 weeks after return of results | Behaviors include those related to diet, physical activity, smoking, drinking, and substance use. | Adult participants: 2 wks after return of diagnostic (dx) results | 
| Change in enactment of health-related lifestyle behaviors | Behaviors include those related to diet, physical activity, smoking, drinking, and substance use. | Adult participants: Change in behaviors from 2 wks after consent (T1) to 2 wks, 3 months, and 6 months after return of dx results | 
| Extent of psychological distress 2 weeks after consent | Symptoms of depression and anxiety measured with the Hospital Anxiety and Depression Scale | All participants: 2 wks after consent | 
| Extent of psychological distress 2 weeks after return of results | Symptoms of depression and anxiety measured with the Hospital Anxiety and Depression Scale | All participants: 2 wks after return of diagnostic (dx) results | 
| Change in extent of psychological distress | Symptoms of depression and anxiety measured with the Hospital Anxiety and Depression Scale | All participants: Change from 2 wks after consent (T1) to 2 wks after return of diagnostic (dx) results; Additional for adult patients: Change at 3 and 6 months after return of dx results | 
| Extent of health-related Quality of Life 2 weeks after consent | Measured with the Medical Outcomes Study Short Form-12 | All participants: 2 wks after consent (T1) | 
| Extent of health-related Quality of Life 2 weeks after return of results | Measured with the Medical Outcomes Study Short Form-12 | All participants: 2 wks after return of diagnostic results | 
| Change in extent of health-related Quality of Life | Measured with the Medical Outcomes Study Short Form-12 | All participants: Change from 2 wks after consent to 2 weeks after return of diagnostic results | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Cardiovascular disease, Neurodegenerative disease, Neurodevelopmental disease, Dysmorphology, Hearing loss, Other conditions, including ophthalmic conditions