Genetic Disorders
Conditions
Keywords
Whole Genome Sequencing, Carrier status, Genetics
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.
Interventions
GENETICWhole Genome Sequencing
Participants will receive Whole Genome Sequencing
GENETICCarrier status testing
Carrier status testing
Sponsors
National Human Genome Research Institute (NHGRI)
Kaiser Permanente
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients That Receive Carrier Testing and Have Results to Return | Assessed annually for 4 years, data at the end of the study reported. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Satisfaction | Assessed annually for 4 years, data at the end of Year 3 reported. | Through surveys, interviews, and observations with patients, the investigators will assess their satisfaction with the testing and return of results process. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Healthcare Utilization | The end of Year 4 | The investigators will evaluate if expanded carrier testing using WGS causes an increase in subsequent health care utilization compared to usual care (typically just cystic fibrosis carrier testing). |
Countries
United States
Participant flow
Pre-assignment details
One person consented, but then immediately declined while doing the baseline survey, so she was never randomized.
Participants by arm
| Arm | Count |
|---|---|
| Usual Care Requested carrier status testing.
Carrier status testing: Carrier status testing | 179 |
| Whole Genome Sequencing These participants will receive the carrier status testing they requested from their provider, plus whole genome sequencing.
Whole Genome Sequencing: Participants will receive Whole Genome Sequencing
Carrier status testing: Carrier status testing | 202 |
| Total | 381 |
Baseline characteristics
| Characteristic | Usual Care | Whole Genome Sequencing | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 179 Participants | 202 Participants | 381 Participants |
| Age, Continuous | 32 years STANDARD_DEVIATION 4.2 | 33 years STANDARD_DEVIATION 4.6 | 32 years STANDARD_DEVIATION 4.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 13 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 166 Participants | 188 Participants | 354 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 10 Participants | 15 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 26 Participants | 21 Participants | 47 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) White | 143 Participants | 163 Participants | 306 Participants |
| Region of Enrollment United States | 159 participants | 153 participants | 312 participants |
| Sex: Female, Male Female | 179 Participants | 131 Participants | 310 Participants |
| Sex: Female, Male Male | 0 Participants | 71 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 180 | 0 / 203 |
| other Total, other adverse events | 0 / 180 | 0 / 203 |
| serious Total, serious adverse events | 0 / 180 | 0 / 203 |
Outcome results
Primary
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.
Time frame: Assessed annually for 4 years, data at the end of the study reported.
Population: All consented participants, including male partners.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Number of Patients That Receive Carrier Testing and Have Results to Return | 9 Participants |
| Whole Genome Sequencing | Number of Patients That Receive Carrier Testing and Have Results to Return | 155 Participants |
Secondary
Patient Satisfaction
Through surveys, interviews, and observations with patients, the investigators will assess their satisfaction with the testing and return of results process.
Time frame: Assessed annually for 4 years, data at the end of Year 3 reported.
Population: Participants in the usual care arm don't complete satisfaction surveys. Results are WGS arm participants who received genetic testing carrier results in person and reported understanding the information
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Usual Care | Patient Satisfaction | 0 Participants |
| Whole Genome Sequencing | Patient Satisfaction | 141 Participants |
Other Pre-specified
Healthcare Utilization
The investigators will evaluate if expanded carrier testing using WGS causes an increase in subsequent health care utilization compared to usual care (typically just cystic fibrosis carrier testing).
Time frame: The end of Year 4
Population: This data was reported at the end of year 4 for all participants that had at least 6 months of follow-up data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Healthcare Utilization | 10 Face to face medical encounters | Standard Deviation 10 |
| Whole Genome Sequencing | Healthcare Utilization | 10 Face to face medical encounters | Standard Deviation 9 |