Adult Patients With Undiagnosed Conditions and Their Responses to Clinically Uncertain Results From Exome Sequencing
Condition: Undiagnosed Disease
MeSH terms: Undiagnosed Diseases
Study type: Observational

Summary: 
      Background:

      People with conditions that are unknown or hard to diagnose may be helped by a genetic
      technique. It is called exome sequencing. It helps diagnose disease by unlocking all the data
      in a person s genetic code. But the results from it are often unclear. Uncertain results can
      pose problems for doctors and patients. Researchers want to learn more about how people
      respond when they get uncertain results.

      Objective:

      To study the psychological and behavioral effects of getting uncertain results from exome
      sequencing.

      Eligibility:

      Adults who have:

      Had a diagnostic odyssey for at least 6 months. An example is having clinical symptoms but no
      diagnosis.

      And had exome sequencing to try to reach a diagnosis.

      Design:

      Participants will choose a date and time for their interview. They will sign a form to give
      consent and authorization.

      Participants will fill out 2 forms. One is the Intolerance of Uncertainty Short Form Scale.
      The other is the Perceptions of Uncertainties in Genome Sequencing Scale.

      Both scales ask about what it is like to get clinically uncertain results from exome
      sequencing. They focus on coping and other behavioral responses.

      Participants will have a phone interview. It will last for 45-60 minutes. It will be recorded
      and transcribed.

      At the start of the call, the researcher will review the consent form with the participant.
      Participants will give data such as race, education, income, and how long they have been
      looking for a diagnosis.

      Participants will read their responses to the 2 scales during the interview.
    

Detailed description: 
      Patients pursuing exome sequencing in their quest for diagnosis will most often receive a
      clinically uncertain result. A clinically uncertain result is a result that has some level of
      objective uncertainty frequently viewed by clinicians in regard to a patient s diagnosis. A
      clinically uncertain result can be a result that is negative, with no reportable variants, or
      that includes one or more variants deemed uncertain with regard to the cause of a patient s
      illness. Clinically uncertain results present challenges to both providers and patients in
      the forms of disclosing and processing uncertain health information. This exploratory study
      aims to seek insight into the psychological and behavioral impact of receiving clinically
      uncertain results from exome sequencing. Semi-structured phone interviews will be conducted
      with approximately 30-40 adult patients with undiagnosed conditions who have received
      clinically uncertain result from exome sequencing. The interviews will focus on the
      experience of receiving the clinically uncertain result, with emphasis on appraisal of
      uncertainty, coping, and other affective and behavioral responses. Interviews will be
      transcribed and subjected to thematic analysis. Understanding how patients with undiagnosed
      conditions respond to clinically uncertain results from exome sequencing may inform providers
      practices around informed consent for exome sequencing and the disclosure of clinically
      uncertain results through a greater consideration of patient concerns and challenges with
      adaptation. This study may also identify implications for interventions to reduce negative
      effects of receiving uncertain genomic information.
    

Observational model: Other
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Data will be received from up to 250 potential participants, in order to do interviews with
        a sample of approximately 30-40 participants. Participants are adult patients with
        undiagnosed conditions who have received one of the most common types of clinically
        uncertain results (negative result or one or more variants of uncertain significance (VUSs)
        without a known pathogenic result) from exome sequencing. Patients will be recruited from
        Johns Hopkins Hospital Genetics Clinics and Kennedy Krieger Institute.
      
Keywords: Genetic Testing; Variant of Uncertain Significance; Uncertainty; Qualitative