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NIH

Information for Clinical Research Staff and Protocol Coordinators

The SGFS will annotate new and existing exome and genome sequencing data for the presence of "actionable secondary findings." Participants with confirmed secondary findings will be offered genetic counseling to disclose these results with the SGFS genetic counselor. The complete Guidance Memo describing the SGFS in detail can be found here.

How does it work?

We review your research sequence data to look for possible secondary findings
  • We will review your de-identified data. All findings are considered preliminary until confirmed with a second sample.
  • We will call you if we find possible secondary variants for return.

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We need to know who the best point of contact is for us to work with.
  • We will also want to talk with someone in your group who is familiar with the participant and can give us some basic information, like the participant's name and what language they speak, etc.

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SGFS staff will coordinate getting a second sample from your participant
  • PLEASE REVIEW THE SECTION ON CONSENT FOR INFORMATION ABOUT HOW TO TALK WITH PARTICIPANTS ABOUT THIS POSSIBILITY
  • You will need to register your patient at the NIHCC (if he/she is not already registered) and enter an order in NHGRI Genomic Variant Confirmation (CRIS) for confirmation of research findings

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We will confirm the preliminary finding and provide genetic counseling to your participant
  • We will send your participant a counseling letter, file the result in the NIH medical record, and complete a genetics consult

What's an actionable secondary finding and why return it?

  • Actionable secondary findings are generally unrelated to your primary research questions, but should be returned to participants
  • Currently, the American College of Medical Genetics recommends that variants in 59 genes be returned to people undergoing clinical sequencing - this is frequently referred to as the "ACMG list."
  • Secondary findings are genetic predispositions to treatable or preventable diseases that participants may not have been aware of - they have the potential to improve health outcomes for your participants and their families
  • Most participants, when asked, say that they would like to receive this kind of information.

What does genetic counseling for secondary findings look like?

A very brief outline of the results return counseling session is:

  • Disclosure of result
  • Communication of recommendations for healthcare
  • Family history and risk assessment
  • Psychosocial assessment
  • Referral to appropriate provider near the patient's home
  • A genetic counseling letter and the result will be sent to the patient and a genetics consult will be entered into CRIS.

Key points to consider when submitting an application to the SGFS

  • Don't give participants a choice about receiving secondary findings if you intend to submit your exome data to us for annotation; we assume that every patient's data we review has consented to have their exome analyzed for these variants
  • Consider characteristics about your cohort or an individual participant that might complicate the return of secondary variants and be honest about these complications when consenting participants (e.g., your cohort/participant is not English-speaking, lives outside the US, has little access to healthcare, or all three)

Confirmation of Secondary Variants 

  • If a pathogenic or likely pathogenic variant is identified in one of the SGFS genes then confirmation by Sanger sequencing will be offered.
  • A new DNA sample will be required. Saliva is strongly preferred; in rare instances a blood sample can be accepted. Saliva can be which can be collected via a saliva sample kit mailed to the patient by SGFS staff. or a blood draw performed at the NIH Clinical Center.
  • Direct submission of previously isolated DNA may be acceptable but submission of a saliva sample is strongly preferred. 
  • Direct submission of previously isolated DNA can only be accepted for confirmation of secondary findings if:
    1. There is documentation that the new sample and the original sample were collected at a different times (i.e. independently of one another)
    2. The new sample was processed in a CLIA certified lab. DNA from any other source cannot be processed for confirmation of secondary findings 

Consent

How do I explain this to our participants? What about consent?

The SGFS staff has some suggestions based our experience working with research participants who will receive secondary findings as part of their participation in an NIH research study. Suggested language to incorporate into protocols and consent forms can be found here and you can view some brief training videos here.

In our experience, the wait between told that there is a possible secondary finding and actually getting that finding confirmed can be very anxiety provoking. To mitigate this, the SGFS staff member who will contact your participant to coordinate getting a confirmatory sample will not know the participant's possible finding and will simply state that there is a potential genetic finding that your team would like to learn more about and that this will require submission of a new sample. When consenting participants, it may be helpful to emphasize that the participant may be re-contacted in the future to provide another sample for any number of reasons, not solely to confirm a potential secondary finding.

Practical points to emphasize during consent
  • The purpose of annotating for and returning secondary findings is to improve outcomes for participants - most participants are very comfortable with this idea, even if seems like initially unwelcome information
  • Secondary variants will only be present in a small fraction of your participants
  • Not having any secondary findings present does not mean that a person has a "clean genetic bill of health" - they can still get any of the diseases associated with the genes we look at in our analysis
  • Participants who have secondary findings will receive genetic counseling about what the finding means for them and their family members and what next steps to take.


Last Updated: December 4, 2017