Aneuploidy, Prenatal Disorder
Conditions
Keywords
Real life comparative effectiveness, Non-invasive prenatal screening, Fetal aneuploidy, Randomized controlled trial
Brief summary
This project aims to provide high- quality evidence to inform decisions by health care organisations about using first-tier non-invasive prenatal screening (NIPS) to replace traditional screening tests for trisomy 21, and potentially to screen for other fetal chromosome anomalies. We will compare the current screening approach of second-tier NIPS with the use of first-tier NIPS in a large cohort of pregnant women.
Detailed description
There is some data on the performance of NIPS as a first tier screening test but our systematic review has shown that no trial comparing the effectiveness (utility) of 2nd-tier NIPS with that of first-tier NIPS has been published . Further it is important for health care decision makers to have evidence produced in Canada since the geographical context of healthcare can affect uptake as well as patient decision and thus their healthcare trajectories. There is a need for a trial that is between an explanatory trial and a pragmatic trial to provide the types of answer that we aim to document in the present state of knowledge on NIPS-based screening strategies in Canada. Our Objective is to perform a pan-Canadian large-scale comparative utility (clinical outcomes) study of first-tier NIPS (expanded or not) as compared to the new standard of care (NIPS as a 2nd tier test performed much later during pregnancy and only in high risk pregnancies).
Interventions
DIAGNOSTIC_TESTTraditional integrated prenatal screening
biochemical prenatal screening with or without nuchal translucency by US
DIAGNOSTIC_TESTSecond-tier Non-invasive prenatal screening (NIPS)
genomics based NIPS after a positive traditional prenatal screen
DIAGNOSTIC_TESTFirst-tier Non-invasive prenatal screening (NIPS)
genomics based NIPS at first trimester
DIAGNOSTIC_TESTInvasive prenatal testing for fetal aneuploidy
amniocentesis or chorionic villi sampling (CVS)
Sponsors
Genome Quebec
Genome British Columbia
Genome Alberta
Ontario Research Fund
Laval University
St. Justine's Hospital
Ottawa Hospital Research Institute
McGill University
University of British Columbia
University of Alberta
Genome Canada
Canadian Institutes of Health Research (CIHR)
CHU de Quebec-Universite Laval
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
NONE
Intervention model description
Open-label prospective comparative-effectiveness (utility) randomised trial between first-tier NIPS and the standard of care (2nd-tier NIPS).
Eligibility
Sex/Gender
FEMALE
Age
19 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Pregnant women 19 years or older wanting prenatal screening * 10-13+6 wks determined by dating ultrasound or last menstrual period. * Not intending to pursue self pay NIPT
Exclusion criteria
* Known fetal anomaly at the time of recruitment * Multiple gestation * Known twin demise * Planned CVS or amnio for known genetic condition.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gestational age at diagnosis | Up to 24 weeks of gestational age | gestational age at final result in the sub-set of participants that have received a positive NIPS result and that have been offered diagnostic testing |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gestational age at positive screening result | Up to 24 weeks of gestational age | gestational age at final result in the sub-set of participants that have received a positive screening result |
| proportion of women with no results | Up to 24 weeks of gestational age | proportion of women with no NIPS result at first and second attempt |
| numbers of days for women with false positive result of screen to wait for result of definite test | Up to 24 weeks of gestational age | Difference between gestational age (in days) at first positive prenatal screening result and final negative screening result |
| Change in PROMIS-29 Score | At weeks of gestation 10-13, week 16 and week 22 | The PROMIS-29 assesses seven health domains: physical function, anxiety, depression, fatigue, sleep disturbance, pain interference, and ability to participate in social roles and activities. Each of the seven domains has four questions which are scored on a five-point Likert scale. The PROMIS-29 scales will be scored using a T-score metric method available at the Assessment Center website (http://assessmentcenter.net). A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores mean more of the specific scale's construct, which may indicate a desirable or an undesirable outcome. The assessment will be done at recruitment (10-13 weeks of gestation) and at week 16 and week 22 of gestation. |
| Gestational age at negative screening result | Up to 24 weeks of gestational age | gestational age at final result in the sub-set of participants that have received a negative screening result |
| Patient-Reported Experience Measure (PREM) - Score | At 22 weeks of gestation | A 17-questions validated PREM questionnaire on pregnancy experience that measures three dimensions - type of prenatal care received and test results (seven questions), pregnancy visits (four questions (scales 1-5) and prenatal screening experience (six questions). A profile score by looking at frequencies of responses for each item will be used. |
| gestational age at termination of pregnancy | Up to 24 weeks of gestational age | Gestational age at termination of pregnancy for participants having volountary termination |
| percentage of women undergoing invasive diagnostic testing | Up to 24 weeks of gestational age | see outcome title |
| Change in PROMIS Emotional Distress - Anxiety - Short Form 8a Score | At weeks of gestation 10-13, 16 and 22 | The PROMIS-Anxiety short form assesses anxiety with 8 questions. The form includes 8 items and uses a scale of 1-5 (1=Never, 2=Almost never, 3= Sometimes, 4=Often, 5=Almost always). The raw score is the sum of the points for each response. A higher than average raw score indicates higher than average anxiety. A higher score represents higher levels of anxiety. The assessment will be done at recruitment (10-13 weeks of gestation) and at week 16 and week 22 of gestation. |
Countries
Canada
Outcome results
None listed