Return of Primary and Secondary Findings From Genome Sequencing: Recipient Attitudes and Health Outcomes
| Status: | Enrolling by invitation |
|---|---|
| Conditions: | Breast Cancer, Colorectal Cancer, Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any - 100 |
| Updated: | 1/30/2019 |
| Start Date: | December 22, 2015 |
| End Date: | December 31, 2025 |
Background:
Genes are the instructions a person s body uses to function. Genome sequencing is a new way
to look at genes that your main research team is using to learn the causes of the condition
they are studying. When a new cause is found this way, it is called a primary variant. Each
person has many variants. Most do not cause disease. Sequencing can also find secondary
variants. These are not related to the condition your main research team is studying, but may
show a person to be at high risk for cancer or another condition. Researchers want to learn
more about what it means to have a secondary variant.
Objectives:
To find new gene changes that lead to certain medical conditions. To better understand the
causes of certain diseases. To learn about how people understand their genetic test results.
Eligibility:
People with rare diseases who have already consented to and enrolled in another protocol run
by a group other than the National Human Genome Research Institute.
Design:
DNA samples that were already collected will be studied.
Participants may be asked to send in a second DNA sample (blood or saliva). These will be
used to verify any findings.
If a primary variant for the participant s health condition is found through genome
sequencing, this will be shared with the participant by their primary research team.
If the participant has a secondary finding, it will be shared by phone call or
videoconference by this research group in the National Human Genome Research Institute. Some
participants may get their results in person at the clinic.
Three months after getting their secondary findings, participants will do an online survey
and phone interview. They will be asked about how they have used the information.
Some people who do not receive a secondary finding from genome sequencing will be asked to do
an online survey three months after the get that result.
Participants who have a secondary finding can get genetic counseling.
Genes are the instructions a person s body uses to function. Genome sequencing is a new way
to look at genes that your main research team is using to learn the causes of the condition
they are studying. When a new cause is found this way, it is called a primary variant. Each
person has many variants. Most do not cause disease. Sequencing can also find secondary
variants. These are not related to the condition your main research team is studying, but may
show a person to be at high risk for cancer or another condition. Researchers want to learn
more about what it means to have a secondary variant.
Objectives:
To find new gene changes that lead to certain medical conditions. To better understand the
causes of certain diseases. To learn about how people understand their genetic test results.
Eligibility:
People with rare diseases who have already consented to and enrolled in another protocol run
by a group other than the National Human Genome Research Institute.
Design:
DNA samples that were already collected will be studied.
Participants may be asked to send in a second DNA sample (blood or saliva). These will be
used to verify any findings.
If a primary variant for the participant s health condition is found through genome
sequencing, this will be shared with the participant by their primary research team.
If the participant has a secondary finding, it will be shared by phone call or
videoconference by this research group in the National Human Genome Research Institute. Some
participants may get their results in person at the clinic.
Three months after getting their secondary findings, participants will do an online survey
and phone interview. They will be asked about how they have used the information.
Some people who do not receive a secondary finding from genome sequencing will be asked to do
an online survey three months after the get that result.
Participants who have a secondary finding can get genetic counseling.
The implementation of genome and exome sequencing creates challenges and opportunities. We
propose to pilot the implementation of exome sequencing for incidental/secondary findings in
the NIHCC and measure its perceived utility. Through the Clinical Center Genomics Opportunity
(CCGO), we have offered to investigators in 10 institutes access to exome sequencing for gene
identification studies of their rare disease patients. We are using this research resource to
increase the research use of genomics outside NHGRI, to begin to build the NIHCC clinical
laboratory infrastructure to support genome scale data, and to familiarize clinicians in the
NIHCC with genomic medicine. To accomplish these clinical goals, we propose to generate exome
data in a CLIA- (NotEqual)compliant environment at NISC and use those data to evaluate
patients for the presence of variants in genes recommended by the American College of Medical
Genetics and Genomics policy on incidental and secondary findings, which is consistent with
the policy recommendations of the Presidential Commission for the Study of Bioethical Issues.
Thus, the exome data will have a dual purpose the entire dataset will be available for
research to the ordering principal investigator and a small subset of those data will be used
to test our ability to identify high risk variants for actionable disorders, coupled to
knowledgeable clinical interpretation, genetic counseling and referral for ongoing care. The
human subjects review and approval of the gene identification research use of the exome data
will be addressed by the approved PIs through their own IRBs. Here, we are requesting review
of the generation of the sequence data by next-gen technology for secondary variants, a
bioinformatic pipeline for filtering those variants, manual curation of the variants, and
behavioral follow up of participants who receive secondary findings results to measure their
utility and perceived value. Additional and critical Specific Aims are to measure the
efficacy by which we communicate 1) to the participants who do not receive a secondary
finding the concept that a secondary findings analysis is not a substitute for an indicated
single gene and 2) explore the interpretation and outcomes of results for those who receive a
secondary finding.
propose to pilot the implementation of exome sequencing for incidental/secondary findings in
the NIHCC and measure its perceived utility. Through the Clinical Center Genomics Opportunity
(CCGO), we have offered to investigators in 10 institutes access to exome sequencing for gene
identification studies of their rare disease patients. We are using this research resource to
increase the research use of genomics outside NHGRI, to begin to build the NIHCC clinical
laboratory infrastructure to support genome scale data, and to familiarize clinicians in the
NIHCC with genomic medicine. To accomplish these clinical goals, we propose to generate exome
data in a CLIA- (NotEqual)compliant environment at NISC and use those data to evaluate
patients for the presence of variants in genes recommended by the American College of Medical
Genetics and Genomics policy on incidental and secondary findings, which is consistent with
the policy recommendations of the Presidential Commission for the Study of Bioethical Issues.
Thus, the exome data will have a dual purpose the entire dataset will be available for
research to the ordering principal investigator and a small subset of those data will be used
to test our ability to identify high risk variants for actionable disorders, coupled to
knowledgeable clinical interpretation, genetic counseling and referral for ongoing care. The
human subjects review and approval of the gene identification research use of the exome data
will be addressed by the approved PIs through their own IRBs. Here, we are requesting review
of the generation of the sequence data by next-gen technology for secondary variants, a
bioinformatic pipeline for filtering those variants, manual curation of the variants, and
behavioral follow up of participants who receive secondary findings results to measure their
utility and perceived value. Additional and critical Specific Aims are to measure the
efficacy by which we communicate 1) to the participants who do not receive a secondary
finding the concept that a secondary findings analysis is not a substitute for an indicated
single gene and 2) explore the interpretation and outcomes of results for those who receive a
secondary finding.
- ELIGIBILITY CRITERIA:
- Any English- (NotEqual)or Spanish-speaking participant whose primary NIH Investigator
is a CCGO PI, who has ordered a CLIA exome from NISC, or who has received a positive
secondary variant result from the SGFS. Participants in a CSER protocol who have
received a positive secondary finding through their CSER study are also eligible for
enrollment in this protocol.
- For minors or decisionally-impaired adults, one parent/guardian, typically the self
designated primary health care support parent, will be enrolled. If the parents claim
equal roles, whichever of the parents selects to participate in the interview/survey
will be enrolled.
- It is important to emphasize that we will not ask minors or decisionally impaired
adults to participate in the social and behavioral components of the study. Because
validated instruments for our surveys largely do not exist in languages other than
English, we cannot administer these measures to non-English speakers.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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