Mackenzie's Mission: The Australian Reproductive Carrier Screening Project
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 18,302
- Locations
- 48
- Primary Endpoint
- Reproductive Choices made by Increased-Risk Couples
Study Overview
Brief Summary
This study will investigate reproductive genetic carrier screening (RGCS) in 10,000 couples across Australia. Carrier screening for approximately 1300 genes associated with severe, childhood-onset, X-linked and autosomal recessive conditions will be performed on each member of the couple. A combined result will be issued indicating whether the couple has a 'low' or 'increased' risk of having a child with a genetic condition. It is anticipated that 1-2% of couples will be at an increased risk of having an affected child.
The study will evaluate all aspects of the RGCS program to assess the feasibility and acceptability of a publicly-funded population-wide RGCS program, including:
- education of recruiting healthcare providers
- education of participating couples
- implementation and uptake of RGCS
- frequency of increased-risk couples and their reproductive decisions
- psychosocial impacts
- ethical issues
- health economic implications
- health implementation research
Detailed Description
PROTOCOL SYNOPSIS
Couples will be invited to take part in the study by their healthcare provider (HCP). The couple will enrol via an online portal, complete an education module, provide consent and complete a questionnaire. Those who consent to carrier screening will be sent mouth swab kits with samples returned by mail.The carrier screening performed will be done via accredited testing laboratories in partnership with clinical genetics services. Genetic counselling will be available to study participants throughout the process. Couples at increased risk will be offered a genetic counselling consultation and offered support to access reproductive options (i.e. prenatal diagnosis, preimplantation genetic diagnosis (PGD) which will be funded by the study for one cycle of IVF with PGD). All participants will be asked to complete an initial survey at study enrolment and invited to complete optional surveys at the time of screening, after return of screening results, and approximately 13 to 19 months after results. Subsets of participants will also be invited to take part in interviews.
GENE LIST FOR CARRIER SCREENING
The approximately 1300 genes tested in the Mackenzie's Mission carrier screening panel meet the following criteria:
- The associated condition is one where an 'average' couple would take steps to prevent the birth of a child with that condition.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Health Services Research
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Reproductive Choices made by Increased-Risk Couples
Time Frame: Reproductive choices made by couples will be tracked from the date an increased-risk result is received until study closure on 31 December 2022. A subset of couples will be interviewed ~19 months after receiving an increased-risk result.
For pregnant couples, the investigators will ascertain how many have prenatal diagnosis (PND), and of those who have PND and an affected fetus is identified, how many terminate the pregnancy. For those who are not pregnant at the time of screening, the investigators will ascertain choices for future pregnancies that occur during the timeframe of the study, including how many choose preimplantation genetic diagnosis (PGD), how many choose a naturally conceived pregnancy with PND and how many choose a naturally conceived pregnancy without any testing.
Screening Uptake (Quantitative)
Time Frame: At offer of screening
Practitioners offering screening will be asked to record the number of couples offered screening which will allow calculation of screening uptake.
Frequency of Increased-Risk Couples
Time Frame: At reporting of results (~Weeks 5-6 since enrolment)
Analysis of carrier frequencies of the genes tested and the frequency of identification of increased-risk couples
Cohort Characteristics of those who decline and those who accept RGCS
Time Frame: Couples who decline screening;at offer or at enrolment (Day 0); optional. Couples who accept screening; at enrolment (Day 0); compulsory.
Short survey capturing personal information: age, country of birth, language spoken at home, ethnicity, religion and religiosity, education level, employment status, household income, marital status, pregnancy history and family/genetic history information.
Predictors of Uptake - Decliners
Time Frame: At decision not to provide samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Survey asking main reason(s) for declining to participate informed by the Health Belief Model (HBM). The HBM is used to predict and explain uptake of a health behaviour. It includes four components: perceived benefits, perceived susceptibility, perceived severity and perceived barriers (Janz and Becker 1984). A subset of declining couples will be invited for interview to explore the decision-making process and their reasons for declining testing.
Predictors of Uptake - Acceptors
Time Frame: At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Survey asking main reason(s) for choosing to participate informed by the Health Belief Model (HBM). The HBM is used to predict and explain uptake of a health behaviour. It includes four components: perceived benefits, perceived susceptibility, perceived severity and perceived barriers (Janz and Becker 1984)
Secondary Outcomes
- Participant Experience - State-Anxiety - pre-screening II(At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional)
- Participant Experience - State-Anxiety - post-result(Low-risk and increased-risk couples; post-result (~Weeks 17-18 since enrolment); optional)
- Participant Experience - State-Anxiety - long-term follow-up(Low-risk couples; long-term follow-up (~13 months since enrolment); optional. Increased-risk couples; long-term follow-up (~19 months since enrolment); optional)
- Participant Experience - Trait-Anxiety - post-result(Low-risk and increased-risk couples; post-result (~Weeks 17-18 since enrolment); optional)
- Participant Experience - Trait-Anxiety - long-term follow-up(Low-risk couples; long-term follow-up (~13 months since enrolment); optional. Increased-risk couples; long-term follow-up (~19 months since enrolment); optional)
- Health Economic Impact - Assessment of Quality of Life - post-result(Low-risk and increased-risk couples; post-result (~Weeks 17-18 since enrolment); optional)
- Health Economic Impact - Assessment of Quality of Life - long-term follow-up(Low-risk couples; long-term follow-up (~13 months since enrolment); optional. Increased-risk couples; long-term follow-up (~19 months since enrolment); optional)
- Participant Experience - Attitudes/Perceptions(Couples who decline screening;at offer or at enrolment (Day 0); optional. Couples who accept screening; at enrolment (Day 0); compulsory.)
- Participant Experience - Trait-Anxiety - pre-screening(Couples who decline screening; at enrolment (Day 0); optional. Couples who accept screening; at enrolment (Day 0); compulsory.)
- Participant Experience - Trait-Anxiety - pre-screening II(At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional)
- Health Economic Impact - Assessment of Quality of Life - pre-screening(Couples who decline testing, at enrolment (Day 0); optional. Couples who accept testing, at enrolment (Day 0); compulsory)
- Participant Experience - State-Anxiety - pre-screening(Couples who decline screening; at enrolment (Day 0); optional. Couples who accept screening; at enrolment (Day 0); compulsory.)
- Participant Experience - Decisional Conflict(At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional)
- Participant Experience - Genomics Outcome Scale (GOS-6)(Increased-risk couples, before and after genetic counselling session (~Weeks 5-6 since enrolment))
- Participant Experience - Evaluation of Educational and Decision-Aid Materials(At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional)
- Participant Experience - Decisional Regret - long-term follow-up(Low-risk couples; long-term follow-up (~13 months since enrolment); optional. Increased-risk couples; long-term follow-up (~19 months since enrolment); optional)
- Health Economic Impact - Participants' willingness to pay(Couples who decline screening, at enrolment (Day 0); optional. Couples who accept screening, at enrolment (Day 0); compulsory)
- Participant Experience - Deliberation(At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional)
- Participant Experience - Decision-Making Approach(At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional)
- Participant Experience - Qualitative Interviews(Low-risk couples; long-term follow-up (~13 months since enrolment); optional. Increased-risk couples; long-term follow-up (~19 months since enrolment); optional)
- Participant Experience - Health Literacy(At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional)
- Participant Experience - Decisional Regret - post-result(Low-risk and increased-risk couples; post-result (~Weeks 17-18 since enrolment); optional)