Clinical Implementation of Carrier Status Using Next Generation Sequencing

Study Overview
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Brief Summary
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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). The investigators hypothesize that whole genome sequencing will increase the detection of carrier status for Mendelian recessive and x-linked conditions. 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. 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
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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: Patient reported outcomes (PRO) on the impact on quality of life, satisfaction with care, timeliness of reporting, and use of the genomic information. 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. To perform whole genome sequencing, assembly, and variant detection for each sample. To provide variant data on each sample with annotation and ranking of clinical significance. 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.

Official Title
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Clinical Implementation of Carrier Status Using Next Generation Sequencing

Conditions
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Genetic Disorders

Intervention / Treatment
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* Genetic: Whole Genome Sequencing
* Genetic: Carrier status testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Seeking pre-conception carrier status testing or had carrier testing during pregnancy Women with a male partner that can be contacted Kaiser Permanente Northwest members English speaking Not currently pregnant Exclusion Criteria: Currently pregnant No known or accessible male partner Not an English speaker Not a Kaiser Permanente member

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Usual care<br>Requested carrier status testing. | Genetic: Carrier status testing<br>* Carrier status testing<br>|
| Experimental: Whole Genome Sequencing<br>These participants will receive the carrier status testing they requested from their provider, plus whole genome sequencing. | Genetic: Whole Genome Sequencing<br>* Participants will receive Whole Genome Sequencing<br>Genetic: Carrier status testing<br>* Carrier status testing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients That Receive Carrier Testing and Have Results to Return | The investigators will record the number of patients that have both single carrier status testing (usual care) and WGS testing and track how many patients have results to return. | Assessed annually for 4 years, data at the end of the study reported. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Satisfaction | Through surveys, interviews, and observations with patients, the investigators will assess their satisfaction with the testing and return of results process. | Assessed annually for 4 years, data at the end of Year 3 reported. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Whole Genome Sequencing, Carrier status, Genetics