X-Linked Genetic DiseasesNCT04157595
Mackenzie's Mission: The Australian Reproductive Carrier Screening Project
A study testing Reproductive Genetic Carrier Screening in people with X-Linked Genetic Diseases and Autosomal Recessive Disorder, run by Murdoch Childrens Research Institute at 24 sites in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- X-Linked Genetic Diseases, Autosomal Recessive Disorder
- What is being tested?
- Reproductive Genetic Carrier Screening
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18,302 participants
- Where
- 24 sitesAustralia
- Study dates
- 21 Nov 2019to 31 Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Planning to become pregnant or in early pregnancy (less than 10 weeks gestation at enrolment and less than 11 weeks gestation at sample receipt by the laboratory)
- Both members of the couple available to participate in the study and available to provide a sample for testing at the same time.
- If the couples are using an egg/sperm donor/s, the donor/s need to be available to provide a DNA sample for testing and consent to having carrier screening.
- NB: If both members of the couple are known carriers of the same autosomal recessive condition, or the female is a known carrier of an X-linked recessive condition, they will still be eligible to have RGCS through the study, but will only be considered an 'increased-risk' couple for the purposes of this study if they are identified through the study testing to be carriers of pathogenic variants in a different gene.
Who cannot join
- Participating couples meeting any of the following requirements will be excluded from this study:
- Pregnant and greater than 10 weeks gestation at enrolment.
- Only one member of the couple agrees to participate in the study.
- One or both members of the couple are less than 18 years old.
- Both members of the couple are not available to be tested at the same time.
- The couple are using an egg/sperm donor/s and the donor/s are not available for testing or the couple are using an anonymous donor.
- One member of the couple has already been screened as part of the study.
Trial locations and contacts
24 sites in 1 country.
24 sites in 1 country
Australia24 sites
Women's and Children's Hospital
Adelaide, South Australia, 5006
Royal Brisbane and Women's Hospital
Brisbane, Queensland, 4029
Cairns Hospital
Cairns, Queensland, 4870
Royal Darwin Hospital
Darwin, Northern Territory, 0810
Forster Community Health Service
Forster, New South Wales, 2428
Royal Hobart Hospital
Hobart, Tasmania, 7000
Joondalup Health Campus
Joondalup, Western Australia, 6027
Liverpool Hospital
Liverpool, New South Wales, 2170
Mareeba Hospital
Mareeba, Queensland, 4880
Victorian Clinical Genetics Services
Melbourne, Victoria, 3052
Northern Hospital
Melbourne, Victoria, 3076
Mercy Hospital for Women
Melbourne, Victoria, 3084
Hunter Genetics
Newcastle, New South Wales, 2298
King Edward Memorial Hospital
Perth, Western Australia, 6008
Royal Hospital for Women
Sydney, New South Wales, 2031
Sydney Children's Hospital, Randwick
Sydney, New South Wales, 2031
Royal Prince Alfred Hospital
Sydney, New South Wales, 2050
The Children's Hospital at Westmead
Sydney, New South Wales, 2145
Westmead Hospital
Sydney, New South Wales, 2145
Campbelltown Hospital
Sydney, New South Wales, 2560
Tamworth Communith Health Services
Tamworth, New South Wales, 2340
Taree Community Health Service
Taree, New South Wales, 2430
Wagga Wagga Base Hospital
Wagga Wagga, New South Wales, 2650
West Gippsland Heath Service (Warragul Hospital)
Warragul, Victoria, 3820
About this study
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
Read the 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.
- This includes conditions with significant negative impact on quality of life for the child, the condition being lethal in childhood, and a significant impact on the family.
- AND/OR: There is a potential benefit for knowing about the condition to inform management in the neonatal period. This criterion was particularly important if the condition was either not included on a newborn screening panel, and/or intervention would be required prior to results from newborn screening being known.
- AND there is strong evidence for mutations in the gene being causative of the condition in question, with enough variants reported to allow confidence in informing couples of their chance of having a child with the condition in question.
- Being tested
- Reproductive Genetic Carrier Screening
- Keywords
- reproductive genetics, carrier screening, rare disease
- Medical subject headings
- Genetic Diseases, X-Linked, Rare Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Reproductive Genetic Carrier ScreeningOther
Carrier screening for approximately 1300 genes associated with severe autosomal recessive and X-linked recessive conditions affecting children 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
| Study group | Role | What they receive |
|---|---|---|
| Participating Couples | Experimental | Reproductive Genetic Carrier Screening Receives: Other: Reproductive Genetic Carrier Screening |
What is being measured
The primary outcome is the main question the study is designed to answer.
Screening Uptake (Quantitative)
Practitioners offering screening will be asked to record the number of couples offered screening which will allow calculation of screening uptake.
Measured: At offer of screening
Frequency of Increased-Risk Couples
Analysis of carrier frequencies of the genes tested and the frequency of identification of increased-risk couples
Measured: At reporting of results (~Weeks 5-6 since enrolment)
Reproductive Choices made by Increased-Risk Couples
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.
Measured: 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.
Cohort Characteristics of those who decline and those who accept RGCS
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.
Measured: Couples who decline screening;at offer or at enrolment (Day 0); optional. Couples who accept screening; at enrolment (Day 0); compulsory.
Predictors of Uptake - Decliners
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.
Measured: Couples who decline screening; at offer or enrolment (Day 0); optional
Predictors of Uptake - Decliners
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.
Measured: At decision not to provide samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Predictors of Uptake - Acceptors
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)
Measured: Couples who accept screening; at offer or enrolment (Day 0); compulsory.
Predictors of Uptake - Acceptors
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)
Measured: At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Secondary outcomes (22)
Participant Experience - Attitudes/Perceptions
Survey assessing attitudes towards carrier screening in the general population, and the attitudes of the couple towards carrier screening for themselves.
Measured: Couples who decline screening;at offer or at enrolment (Day 0); optional. Couples who accept screening; at enrolment (Day 0); compulsory.
Participant Experience - State-Anxiety - pre-screening
Six-item short-form of the state-anxiety scale of the Spielberger State-Trait Anxiety Inventory (STAI) (Marteau and Bekker 1992). This scale measures how the respondent feels "right now, at this moment". Scores range from 20 to 80. A high score indicates the presence of high levels of anxiety.
Measured: Couples who decline screening; at enrolment (Day 0); optional. Couples who accept screening; at enrolment (Day 0); compulsory.
Participant Experience - State-Anxiety - pre-screening II
Six-item short-form of the state-anxiety scale of the Spielberger State-Trait Anxiety Inventory (STAI) (Marteau and Bekker 1992). This scale measures how the respondent feels "right now, at this moment". Scores range from 20 to 80. A high score indicates the presence of high levels of anxiety.
Measured: At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Participant Experience - State-Anxiety - post-result
Six-item short-form of the state-anxiety scale of the Spielberger State-Trait Anxiety Inventory (STAI) (Marteau and Bekker 1992). This scale measures how the respondent feels "right now, at this moment". Scores range from 20 to 80. A high score indicates the presence of high levels of anxiety.
Measured: Low-risk and increased-risk couples; post-result (~Weeks 17-18 since enrolment); optional
Participant Experience - State-Anxiety - long-term follow-up
Six-item short-form of the state-anxiety scale of the Spielberger State-Trait Anxiety Inventory (STAI) (Marteau and Bekker 1992). This scale measures how the respondent feels "right now, at this moment". Scores range from 20 to 80. A high score indicates the presence of high levels of anxiety.
Measured: 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 - pre-screening
20-item trait-anxiety scale (Form Y2) of the Spielberger State-Trait Anxiety Inventory (STAI). This scale measures how the respondent "generally" feels. Scores range from 20 to 80. A high score indicates the presence of high levels of anxiety.
Measured: 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
20-item trait-anxiety scale (Form Y2) of the Spielberger State-Trait Anxiety Inventory (STAI). This scale measures how the respondent "generally" feels. Scores range from 20 to 80. A high score indicates the presence of high levels of anxiety.
Measured: At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Participant Experience - Trait-Anxiety - post-result
20-item trait-anxiety scale (Form Y2) of the Spielberger State-Trait Anxiety Inventory (STAI). This scale measures how the respondent "generally" feels. Scores range from 20 to 80. A high score indicates the presence of high levels of anxiety.
Measured: Low-risk and increased-risk couples; post-result (~Weeks 17-18 since enrolment); optional
Participant Experience - Trait-Anxiety - long-term follow-up
20-item trait-anxiety scale (Form Y2) of the Spielberger State-Trait Anxiety Inventory (STAI). This scale measures how the respondent "generally" feels. Scores range from 20 to 80. A high score indicates the presence of high levels of anxiety.
Measured: 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 - pre-screening
12-item Assessment of Quality of Life-4D (AQoL-4D) questionnaire (Hawthorne, Richardson and Osbourne 1999; Richardson and Hawthorne 1998). This questionnaire measures health-related quality of life in four dimensions: Independent Living, Relationships, Mental Health and Senses. Total scores range from a minimum of 12 to a maximum of 48. Higher scores indicate a lower health-related quality of life.
Measured: Couples who decline testing, at enrolment (Day 0); optional. Couples who accept testing, at enrolment (Day 0); compulsory
Health Economic Impact - Assessment of Quality of Life - post-result
12-item Assessment of Quality of Life-4D (AQoL-4D) questionnaire (Hawthorne, Richardson and Osbourne 1999; Richardson and Hawthorne 1998). This questionnaire measures health-related quality of life in four dimensions: Independent Living, Relationships, Mental Health and Senses. Total scores range from a minimum of 12 to a maximum of 48. Higher scores indicate a lower health-related quality of life.
Measured: 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
12-item Assessment of Quality of Life-4D (AQoL-4D) questionnaire (Hawthorne, Richardson and Osbourne 1999; Richardson and Hawthorne 1998). This questionnaire measures health-related quality of life in four dimensions: Independent Living, Relationships, Mental Health and Senses. Total scores range from a minimum of 12 to a maximum of 48. Higher scores indicate a lower health-related quality of life.
Measured: 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
Questions with randomised monetary values to assess maximum amount participants would be willing to pay, and whether the test should be government, privately or Medicare funded.
Measured: Couples who decline screening, at enrolment (Day 0); optional. Couples who accept screening, at enrolment (Day 0); compulsory
Participant Experience - Health Literacy
Questions to assess health literacy level
Measured: At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Participant Experience - Evaluation of Educational and Decision-Aid Materials
Questions to evaluate resources developed for participating couples e.g. decision aid, website, brochure
Measured: At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Participant Experience - Decisional Conflict
16-item scale measuring personal perception of uncertainty, factors contributing to uncertainty, and effective decision making. Includes five subscores: uncertainty, informed, values clarity, support, effective decision making (O'Conner 1993 (updated 2010)). Total scores range from 0 [no decisional conflict] to 100 [very high decisional conflict].
Measured: At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Participant Experience - Deliberation
6-item scale measuring decision deliberation. Dichotomous scale: responses below the midpoint (11 or under) classified as not deliberated and those at or above the midpoint as deliberated (Van den Berg, Timmermans, Ten et al 2006)
Measured: At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Participant Experience - Decision-Making Approach
Survey evaluating decision-making approach i.e. whether it was an individual or shared decision and who was involved in the decision-making process, e.g. couples, family, health-professional
Measured: 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)
6-item scale measuring empowerment as an outcome of clinical genetics services. Total scores range from a minimum of 6 to a maximum of 30. Higher scores indicate higher levels of empowerment (Grant et al. 2018)
Measured: Increased-risk couples, before and after genetic counselling session (~Weeks 5-6 since enrolment)
Participant Experience - Decisional Regret - post-result
A 5-item scale measuring distress and remorse after a health care decision. Scores range from 0 [no regret] to 100 [high regret]. Subset of low-risk couples to be contacted for interview to explore experience of having testing and receiving a low-risk result.
Measured: Low-risk and increased-risk couples; post-result (~Weeks 17-18 since enrolment); optional
Participant Experience - Decisional Regret - long-term follow-up
A 5-item scale measuring distress and remorse after a health care decision. Scores range from 0 [no regret] to 100 [high regret]. Subset of low-risk couples to be contacted for interview to explore experience of having testing and receiving a low-risk result.
Measured: 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 - Qualitative Interviews
Subset of low-risk couples to be contacted for interview to explore longer-term experience of having testing and receiving a low-risk result. Subset of increased-risk couples to be contacted for interview to explore the experience of receiving a increased-risk result, the use of this information in reproductive decision-making, and the communication of genetic information within families.
Measured: Low-risk couples; long-term follow-up (~13 months since enrolment); optional. Increased-risk couples; long-term follow-up (~19 months since enrolment); optional
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2019
- Study start21 Nov 2019
- Primary completion31 Mar 2022
- Study completion31 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for X-Linked Genetic DiseasesStudies of the same condition, open and under way.
- More trials run by Murdoch Childrens Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Health services research
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18,302 participants (actual)
Sponsor and investigators
- Lead sponsor
- Murdoch Childrens Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Australian Government Department of Health and Ageing, The University of New South Wales, The University of Western Australia, Harry Perkins Institute of Medical Research, University of Sydney, Macquarie University, Australia, Griffith University, Victorian Clinical Genetics Services, NSW Health Pathology, PathWest Laboratory Medicine WA, King Edward Memorial Hospital, Royal Brisbane and Women's Hospital, Women's and Children's Hospital, Australia, Sydney Children's Hospitals Network, Royal Hobart Hospital
- Responsible party
- Sponsor
- Investigators
- Martin Delatycki, Principal investigator, Murdoch Children's Research Institute/Victorian Clinical Genetics ServicesEdwin Kirk, Principal investigator, Sydney Children's Hospital Network/NSW Health Pathology/UNSWNigel Laing, Principal investigator, University of WA/Harry Perkins Institute/PathWest Laboratory Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04157595
- Sponsor's protocol ID
- RCH HREC 2019.097
- Status last verified
- Jul 2025
- First submitted
- 21 Oct 2019
- Last updated
- 31 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified samples, genomic data and associated clinical information may be shared with researchers for other Human Research Ethics Committee approved research studies and with recognised national and international databases to advance scientific knowledge.
Publications
Kirk EP, Delatycki MB, Archibald AD, Tutty E, Caruana J, Halliday JL, Lewis S, McClaren BJ, Newson AJ, Dive L, Best S, Long JC, Braithwaite J, Downes MJ, Scuffham PA, Massie J, Barlow-Stewart K, Kulkarni A, Ruscigno A, Kanga-Parabia A, Rodrigues B, Bennetts BH, Ebzery C, Hunt C, Cliffe CC, Lee C, Azmanov D, King EA, Madelli EO, Zhang F, Ho G, Danos I, Liebelt J, Fletcher J, Kennedy J, Beilby J, Emery JD, McGaughran J, Marum JE, Scarff K, Fisk K, Harrison K, Boggs K, Giameos L, Fitzgerald L, Thomas L, Burnett L, Freeman L, Harris M, Berbic M, Davis MR, Cifuentes Ochoa M, Wallis M, Wall M, Chow MTM, Ferrie MM, Pachter N, Quayum N, Lang N, Kasi Pandy P, Casella R, Allcock RJN, Ong R, Edwards S, Sundercombe S, Jelenich S, Righetti S, Lunke S, Kaur S, Stock-Myer S, Eggers S, Walker SP, Theodorou T, Catchpool T, Clinch T, Roscioli T, Hardy T, Zhu Y, Fehlberg Z, Boughtwood TF, Laing NG; Mackenzie's Mission Investigators; Mackenzie's Mission Investigators. Nationwide, Couple-Based Genetic Carrier Screening. N Engl J Med. 2024 Nov 21;391(20):1877-1889. doi: 10.1056/NEJMoa2314768.
PubMed 39565987
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mackenzie's Mission: The Australian Reproductive Carrier Screening Project
- ClinicalTrials.gov ID
- NCT04157595
- Acronym / sponsor ID
- RCH HREC 2019.097
- Keywords
- reproductive genetics, carrier screening, rare disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18,302 participants (actual)
- Lead sponsor
- Murdoch Childrens Research InstituteUniversity, hospital or other
- Collaborators
- Australian Government Department of Health and Ageing, The University of New South Wales, The University of Western Australia, Harry Perkins Institute of Medical Research, University of Sydney, Macquarie University, Australia, Griffith University, Victorian Clinical Genetics Services, NSW Health Pathology, PathWest Laboratory Medicine WA, King Edward Memorial Hospital, Royal Brisbane and Women's Hospital, Women's and Children's Hospital, Australia, Sydney Children's Hospitals Network, Royal Hobart Hospital
- Study start
- 21 Nov 2019 (actual)
- Primary completion
- 31 Mar 2022 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 8 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- This includes conditions with significant negative impact on quality of life for the child, the condition being lethal in childhood, and a significant impact on the family.
- AND/OR: There is a potential benefit for knowing about the condition to inform management in the neonatal period. This criterion was particularly important if the condition was either not included on a newborn screening panel, and/or intervention would be required prior to results from newborn screening being known.
- AND there is strong evidence for mutations in the gene being causative of the condition in question, with enough variants reported to allow confidence in informing couples of their chance of having a child with the condition in question.
Study design
- Primary purpose
- Health services research
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participating Couples | Experimental | Other: Reproductive Genetic Carrier ScreeningReproductive Genetic Carrier Screening |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Planning to become pregnant or in early pregnancy (less than 10 weeks gestation at enrolment and less than 11 weeks gestation at sample receipt by the laboratory)
- Both members of the couple available to participate in the study and available to provide a sample for testing at the same time.
- If the couples are using an egg/sperm donor/s, the donor/s need to be available to provide a DNA sample for testing and consent to having carrier screening.
- NB: If both members of the couple are known carriers of the same autosomal recessive condition, or the female is a known carrier of an X-linked recessive condition, they will still be eligible to have RGCS through the study, but will only be considered an 'increased-risk' couple for the purposes of this study if they are identified through the study testing to be carriers of pathogenic variants in a different gene.
Key exclusion criteria (7 listed)
- Participating couples meeting any of the following requirements will be excluded from this study:
- Pregnant and greater than 10 weeks gestation at enrolment.
- Only one member of the couple agrees to participate in the study.
- One or both members of the couple are less than 18 years old.
- Both members of the couple are not available to be tested at the same time.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Reproductive Genetic Carrier ScreeningCarrier screening for approximately 1300 genes associated with severe autosomal recessive and X-linked recessive conditions affecting children 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 | Other | Participating Couples |
Primary outcome
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
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.
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: Couples who decline screening; at offer or enrolment (Day 0); 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 - 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: Couples who accept screening; at offer or enrolment (Day 0); compulsory.
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)
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)
22 secondary outcomes
Participant Experience - Attitudes/Perceptions
Time frame: Couples who decline screening;at offer or at enrolment (Day 0); optional. Couples who accept screening; at enrolment (Day 0); compulsory.
Participant Experience - State-Anxiety - pre-screening
Time frame: Couples who decline screening; at enrolment (Day 0); optional. Couples who accept screening; at enrolment (Day 0); compulsory.
Participant Experience - State-Anxiety - pre-screening II
Time frame: At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Participant Experience - State-Anxiety - post-result
Time frame: Low-risk and increased-risk couples; post-result (~Weeks 17-18 since enrolment); optional
Participant Experience - State-Anxiety - long-term follow-up
Time frame: 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 - pre-screening
Time frame: 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
Time frame: At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Participant Experience - Trait-Anxiety - post-result
Time frame: Low-risk and increased-risk couples; post-result (~Weeks 17-18 since enrolment); optional
Participant Experience - Trait-Anxiety - long-term follow-up
Time frame: 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 - pre-screening
Time frame: Couples who decline testing, at enrolment (Day 0); optional. Couples who accept testing, at enrolment (Day 0); compulsory
Health Economic Impact - Assessment of Quality of Life - post-result
Time frame: 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
Time frame: 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
Time frame: Couples who decline screening, at enrolment (Day 0); optional. Couples who accept screening, at enrolment (Day 0); compulsory
Participant Experience - Health Literacy
Time frame: At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Participant Experience - Evaluation of Educational and Decision-Aid Materials
Time frame: At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Participant Experience - Decisional Conflict
Time frame: At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Participant Experience - Deliberation
Time frame: At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Participant Experience - Decision-Making Approach
Time frame: 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)
Time frame: Increased-risk couples, before and after genetic counselling session (~Weeks 5-6 since enrolment)
Participant Experience - Decisional Regret - post-result
Time frame: Low-risk and increased-risk couples; post-result (~Weeks 17-18 since enrolment); optional
Participant Experience - Decisional Regret - long-term follow-up
Time frame: 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 - Qualitative Interviews
Time frame: Low-risk couples; long-term follow-up (~13 months since enrolment); optional. Increased-risk couples; long-term follow-up (~19 months since enrolment); optional
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2025.
- Derived from this study: PubMed 39565987Kirk EP, Delatycki MB, Archibald AD, Tutty E, Caruana J, Halliday JL, Lewis S, McClaren BJ, Newson AJ, Dive L, Best S, Long JC, Braithwaite J, Downes MJ, Scuffham PA, Massie J, Barlow-Stewart K, Kulkarni A, Ruscigno A, Kanga-Parabia A, Rodrigues B, Bennetts BH, Ebzery C, Hunt C, Cliffe CC, Lee C, Azmanov D, King EA, Madelli EO, Zhang F, Ho G, Danos I, Liebelt J, Fletcher J, Kennedy J, Beilby J, Emery JD, McGaughran J, Marum JE, Scarff K, Fisk K, Harrison K, Boggs K, Giameos L, Fitzgerald L, Thomas L, Burnett L, Freeman L, Harris M, Berbic M, Davis MR, Cifuentes Ochoa M, Wallis M, Wall M, Chow MTM, Ferrie MM, Pachter N, Quayum N, Lang N, Kasi Pandy P, Casella R, Allcock RJN, Ong R, Edwards S, Sundercombe S, Jelenich S, Righetti S, Lunke S, Kaur S, Stock-Myer S, Eggers S, Walker SP, Theodorou T, Catchpool T, Clinch T, Roscioli T, Hardy T, Zhu Y, Fehlberg Z, Boughtwood TF, Laing NG; Mackenzie's Mission Investigators; Mackenzie's Mission Investigators. Nationwide, Couple-Based Genetic Carrier Screening. N Engl J Med. 2024 Nov 21;391(20):1877-1889. doi: 10.1056/NEJMoa2314768.
- Individual participant dataSharing planned: Yes. De-identified samples, genomic data and associated clinical information may be shared with researchers for other Human Research Ethics Committee approved research studies and with recognised national and international databases to advance scientific knowledge.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin Delatycki principal investigator
Murdoch Children's Research Institute/Victorian Clinical Genetics Services
Edwin Kirk principal investigator
Sydney Children's Hospital Network/NSW Health Pathology/UNSW
Nigel Laing principal investigator
University of WA/Harry Perkins Institute/PathWest Laboratory Medicine
24 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Reproductive Genetic Carrier Screening in people with X-Linked Genetic Diseases and Autosomal Recessive Disorder, run by Murdoch Childrens Research Institute at 24 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Screening Uptake (Quantitative) (time frame: At offer of screening). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04157595, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2025.