Clinical Implementation of Carrier Status Using Next Generation Sequencing
Condition: Genetic Disorders
MeSH terms: Genetic Diseases, Inborn
Study type: Interventional

Summary: 
      This study is conducting a randomized controlled trial (RCT) with up to 400 subjects (women &
      partners) seeking pre-conception carrier testing to assess the impact of the program using
      Whole Genome Sequencing (WGS).

        1. The investigators hypothesize that whole genome sequencing will increase the detection
           of carrier status for Mendelian recessive and x-linked conditions.

        2. The investigators hypothesize that parents will act on the knowledge of their carrier
           status by making different reproductive choices than parents who do not receive this
           information.

        3. The investigators hypothesize that the psychosocial risks are increased among parents
           who receive expanded carrier screening using Next Generation Sequencing (NGS) compared
           with usual care.
    

Detailed description: 
      Project 1-Clinical Intervention and Outcomes Aim 1: To conduct a randomized controlled trial
      (RCT) with up to 400 subjects (women & partners) seeking pre-conception carrier testing to
      assess the impact of the program using Whole Genome Sequencing (WGS).

      Aim 2: To develop processes for delivering information from WGS directly into the patient's
      electronic medical record, and establish innovative reporting strategies that are informative
      for clinicians and couples acting on this information.

      Aim 3: To measure for the integration of sequence information in clinical care for both
      carrier status and secondary findings including:

        1. Patient reported outcomes (PRO) on the impact on quality of life, satisfaction with
           care, timeliness of reporting, and use of the genomic information.

        2. Process outcomes such as timeliness, number of reportable findings, and time of
           interpretation.

      Project 2 -WGS technology, informatics, and Return of Results Committee (RORC)

      Aim 1: To generate whole genome sequence and interpret variants on samples randomized from
      the Kaiser Permanente Northwest (KPNW) preconception carrier screening cohort.

        1. To perform whole genome sequencing, assembly, and variant detection for each sample.

        2. To provide variant data on each sample with annotation and ranking of clinical
           significance.

        3. To validate data using an orthogonal platform for findings relevant to carrier status
           and actionable secondary findings.

      Aim 2: To develop and implement a return of results committee (RORC) that incorporates
      evidence to assess criteria for reporting carrier status for reproductive decision making and
      secondary findings.

      Project 3 - Ethical and Psychosocial Implications

      Aim 1: To evaluate, patient and clinical perspectives on informational needs, satisfaction,
      knowledge, and decision-making relating to the choice to obtain results of carrier status
      from WGS in four categories of genetic conditions.

      Aim 2: To evaluate, from patient and clinician perspectives, the immediate and downstream
      ethical, psychosocial, and behavioral consequences of expanded carrier screening using WGS.

      Aim 3: To evaluate the impact of expanded carrier test using WGS on subsequent health care
      utilization, and to compare the cost of delivery WGS to usual care.
    

Intervention name(s): Whole Genome Sequencing; Carrier status testing
Intervention type(s): Genetic; Genetic
Intervention description(s): Participants will receive Whole Genome Sequencing; Carrier status testing
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Screening
Keywords: Whole Genome Sequencing; Carrier status; Genetics