Clinical Implementation of Carrier Status Using Next Generation Sequencing (NextGen)

Kaiser Permanente

Status: Completed

Conditions: Genetic Disorders

Treatments: Genetic: Whole Genome Sequencing; Genetic: Carrier status testing

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01902901

1UM1HG007292-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 384 patients

Sex: All

Ages: 21 to 50 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Screening

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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384 participants in 2 patient groups

Usual care

Active Comparator group

Description:

Requested carrier status testing.

Treatment:

Genetic: Carrier status testing

Whole Genome Sequencing

Experimental group

Description:

These participants will receive the carrier status testing they requested from their provider, plus whole genome sequencing.

Treatment:

Genetic: Whole Genome Sequencing

Genetic: Carrier status testing