Clinical trial NCT01902901: Clinical Implementation of Carrier Status Using Next Generation Sequencing
Official title: Clinical Implementation of Carrier Status Using Next Generation Sequencing
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Genetic Disorders
Keywords: Whole Genome Sequencing
Carrier status
Genetics
Lead sponsor: Kaiser Permanente
Sponsor class: OTHER
Collaborators: name: National Human Genome Research Institute (NHGRI)
First posted: 2013-07-18
Enrollment: 384
Sex: ALL
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients That Receive Carrier Testing and Have Results to Return
timeFrame: Assessed annually for 4 years, data at the end of the study reported.
Secondary outcomes:
measure: Patient Satisfaction
timeFrame: Assessed annually for 4 years, data at the end of Year 3 reported.
Other outcomes:
measure: Healthcare Utilization
timeFrame: The end of Year 4
Locations:
city: Portland
country: United States
facility: Kaiser Permanente Northwest
state: Oregon
Study officials:
affiliation: Kaiser Permanente
name: Katrina Goddard, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Seattle Children's Hospital
name: Benjamin Wilfond, MD
role: PRINCIPAL_INVESTIGATOR
References: