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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. Identifier: NCT02595957
Recruitment Status : Recruiting
First Posted : November 4, 2015
Last Update Posted : January 28, 2022
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )

Tracking Information
First Submitted Date November 3, 2015
First Posted Date November 4, 2015
Last Update Posted Date January 28, 2022
Actual Study Start Date December 22, 2015
Estimated Primary Completion Date December 31, 2028   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: January 22, 2020)
  • 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
  • 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
  • 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.
  • 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.
Original Primary Outcome Measures
 (submitted: November 3, 2015)
Participant views of either positive or negative secondary findings analysis [ Time Frame: 3 months ]
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title Genomic Services Research Program
Official Title Genomic Services Research Program
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.

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.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
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.@@@@@@
  • Colon Cancer
  • Breast Cancer
Intervention Not Provided
Study Groups/Cohorts
  • 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
Publications * Sapp JC, Johnston JJ, Driscoll K, Heidlebaugh AR, Miren Sagardia A, Dogbe DN, Umstead KL, Turbitt E, Alevizos I, Baron J, Bönnemann C, Brooks B, Donkervoort S, Jee YH, Linehan WM, McMahon FJ, Moss J, Mullikin JC, Nielsen D, Pelayo E, Remaley AT, Siegel R, Su H, Zarate C; NISC Comparative Sequencing Program, Manolio TA, Biesecker BB, Biesecker LG. Evaluation of Recipients of Positive and Negative Secondary Findings Evaluations in a Hybrid CLIA-Research Sequencing Pilot. Am J Hum Genet. 2018 Sep 6;103(3):358-366. doi: 10.1016/j.ajhg.2018.07.018. Epub 2018 Aug 16.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: October 30, 2020)
Original Estimated Enrollment
 (submitted: November 3, 2015)
Estimated Study Completion Date December 31, 2028
Estimated Primary Completion Date December 31, 2028   (Final data collection date for primary outcome measure)
Eligibility Criteria
  • 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.
Sexes Eligible for Study: All
Ages 1 Month and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contact: Emily W Modlin (301) 496-6639
Listed Location Countries United States
Removed Location Countries  
Administrative Information
NCT Number NCT02595957
Other Study ID Numbers 160017
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )
Study Sponsor National Human Genome Research Institute (NHGRI)
Collaborators Not Provided
Principal Investigator: Leslie G Biesecker, M.D. National Human Genome Research Institute (NHGRI)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date January 25, 2022