We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

Genomic Services Research Program

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02595957
Recruitment Status : Recruiting
First Posted : November 4, 2015
Last Update Posted : January 27, 2023
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )

Brief Summary:


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.


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.


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.


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.


Condition or disease
Colon Cancer Breast Cancer

Detailed Description:
The implementation of genome and exome sequencing creates challenges and opportunities, particularly with respect to the return of medically-actionable secondary findings (SF). This study seeks to investigate the utility and effectiveness of returning SF generated via research or clinical sequencing by studying individuals who have received such findings. Our objectives with this protocol have evolved over time and have been substantially informed by our experiences in returning SF through sequencing initiatives such as the ClinSeq study, the Clinical Center Genomics Opportunity (CCGO), and the Secondary Genomic Findings Service (SGFS). Our work with these studies/initiatives suggests that much remains unknown about how recipients of SF understand these findings, communicate them to their health professionals and families, and whether they adhere to recommended health-preserving actions in both the short and long-term. As well, recipients of SF are an unselected population in which to investigate penetrance of disorders associated with SF genes. Thus, this protocol aims to explore important questions of clinical utility associated with SF return and penetrance of SF-related disorders. Healthcare actions and family communication (clinical utility) are assessed by interviews and surveys with SF recipients. This protocol also includes a pilot program in which selected participants will be invited to the NIH for bespoke phenotyping to uncover the presence of disease and explore avenues to develop interventions to enhance outcomes.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 5000 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Genomic Services Research Program
Actual Study Start Date : September 16, 2014
Estimated Primary Completion Date : December 31, 2028
Estimated Study Completion Date : December 31, 2028

Resource links provided by the National Library of Medicine

Cascade Testing
Family members of individuals who have received secondary genomic findings after exome/genome sequencing
Secondary findings recipients
Individuals who have received secondary genomic findings after exome/genome sequencing

Primary Outcome Measures :
  1. Responses and perceptions [ Time Frame: enrollment and return of results ]
    We will assess affective responses and healthcare and behavioral changes to receiving positive SF results

  2. Family based positive predictive value [ Time Frame: return of results and cascade testing ]
    We will assess penetrance using the family-based positive predictive value metric

  3. Adherence to medical recommendations [ Time Frame: enrollment and return of results ]
    We will assess what individual, community, and systemic factors influence recipients follow through on recommendations and how they communicate SF results with family members.

  4. Health impacts of SF receipt [ Time Frame: enrollment and return of results ]
    We will assess the health impacts of SF receipt and healthcare processes affecting outcomes in SF recipients.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   1 Month and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Individuals who have participated in a sequencing study at the NIH or elsewhere who have have received secondary findings via the involvement of an NIH Investigator are eligible to participate.@@@@@@
  • Any English- or Spanish-speaking recipient of a SF. The circumstances under which SF are generated (either clinically or as part of research studies) indicate that these individuals may represent a wide range of ages of patients, children and


  • 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 may enroll a child in this protocol if he/she is the only person in his/her family who has the SF, is symptomatic of the disease, or is in the age range to receive screening for the disease (e.g., Wilson disease and familial hypercholesterolemia have childhood onset). We will not enroll neonates (less than one month old).
  • We may enroll adults who are unable to consent (i.e., an individual who is impaired at the time of consent) in this protocol if he/she is the only person in his/her family who has the SF, is symptomatic of the disease, or is in the age range to receive screening for the disease.
  • We may enroll women who are pregnant in this protocol and women who become pregnant during the study can continue their participation. We will not perform prenatal genetic testing.
  • NIH staff members are not prohibited from enrollment if they meet the study s eligibility criteria.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02595957

Layout table for location contacts
Contact: Emily W Modlin (240) 408-0447 emily.modlin@nih.gov
Contact: Leslie G Biesecker, M.D. (301) 402-2041 lesb@mail.nih.gov

Layout table for location information
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY dial 711    ccopr@nih.gov   
Sponsors and Collaborators
National Human Genome Research Institute (NHGRI)
Layout table for investigator information
Principal Investigator: Leslie G Biesecker, M.D. National Human Genome Research Institute (NHGRI)
Additional Information:
Layout table for additonal information
Responsible Party: National Human Genome Research Institute (NHGRI)
ClinicalTrials.gov Identifier: NCT02595957    
Other Study ID Numbers: 160017
First Posted: November 4, 2015    Key Record Dates
Last Update Posted: January 27, 2023
Last Verified: January 24, 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) ):
Return of Results
Exome Sequencing
Secondary Findings
Natural History
Additional relevant MeSH terms:
Layout table for MeSH terms
Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases