Mackenzie's Mission: The Australian Reproductive Carrier Screening Project

NCT04157595 | Completed

• 1 other identifier: RCH HREC 2019.097
• Study Type: interventional
• Target: 18,302
• Locations: 1 country
• Sites: 24

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

Conditions

X-Linked Genetic Diseases; Autosomal Recessive Disorder

Keywords

reproductive genetics; carrier screening; rare disease

Outcome Measures

Primary Outcomes (8)

• Screening Uptake (Quantitative)

  Practitioners offering screening will be asked to record the number of couples offered screening which will allow calculation of screening uptake.

  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

  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.

  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.

  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.

  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.

  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)

  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)

  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

  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

  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

  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

Other Outcomes (12)

• Ethical Issues - Assessment of ethical aspects of publicly funded preconception screening

  Throughout study; 3 years

• Implementation Outcomes - Barriers & Enablers to Implementation

  Study investigators; at committee meetings for the duration of the study (3 years); Jan 2019 - Dec 2022

• Implementation Outcomes - Anticipated vs Actual Outcomes

  Study investigators; 1 month before the study begins recruitment

Study Arms (1)

Participating Couples

EXPERIMENTAL

Reproductive Genetic Carrier Screening

Other: Reproductive Genetic Carrier Screening

Interventions

Reproductive Genetic Carrier Screening OTHER

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

Participating Couples

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Murdoch Childrens Research Institute: lead
• Australian Government Department of Health and Ageing: collaborator
• The University of New South Wales: collaborator
• The University of Western Australia: collaborator
• Harry Perkins Institute of Medical Research: collaborator
• University of Sydney: collaborator
• Macquarie University, Australia: collaborator
• Griffith University: collaborator
• Victorian Clinical Genetics Services: collaborator
• NSW Health Pathology: collaborator
• PathWest Laboratory Medicine WA: collaborator
• King Edward Memorial Hospital: collaborator
• Royal Brisbane and Women's Hospital: collaborator
• Women's and Children's Hospital, Australia: collaborator
• Sydney Children's Hospitals Network: collaborator
• Royal Hobart Hospital: collaborator

Study Sites (24)

Forster Community Health Service

Forster, New South Wales, 2428, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Hunter Genetics

Newcastle, New South Wales, 2298, Australia

Location

Royal Hospital for Women

Sydney, New South Wales, 2031, Australia

Location

Sydney Children's Hospital, Randwick

Sydney, New South Wales, 2031, Australia

Location

Royal Prince Alfred Hospital

Sydney, New South Wales, 2050, Australia

Location

The Children's Hospital at Westmead

Sydney, New South Wales, 2145, Australia

Location

Westmead Hospital

Sydney, New South Wales, 2145, Australia

Location

Campbelltown Hospital

Sydney, New South Wales, 2560, Australia

Location

Tamworth Communith Health Services

Tamworth, New South Wales, 2340, Australia

Location

Taree Community Health Service

Taree, New South Wales, 2430, Australia

Location

Wagga Wagga Base Hospital

Wagga Wagga, New South Wales, 2650, Australia

Location

Royal Darwin Hospital

Darwin, Northern Territory, 0810, Australia

Location

Royal Brisbane and Women's Hospital

Brisbane, Queensland, 4029, Australia

Location

Cairns Hospital

Cairns, Queensland, 4870, Australia

Location

Mareeba Hospital

Mareeba, Queensland, 4880, Australia

Location

Women's and Children's Hospital

Adelaide, South Australia, 5006, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

Victorian Clinical Genetics Services

Melbourne, Victoria, 3052, Australia

Location

Northern Hospital

Melbourne, Victoria, 3076, Australia

Location

Mercy Hospital for Women

Melbourne, Victoria, 3084, Australia

Location

West Gippsland Heath Service (Warragul Hospital)

Warragul, Victoria, 3820, Australia

Location

Joondalup Health Campus

Joondalup, Western Australia, 6027, Australia

Location

King Edward Memorial Hospital

Perth, Western Australia, 6008, Australia

Location

Related Publications (1)

• 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.

  PMID: 39565987 DERIVED

MeSH Terms

Conditions

Genetic Diseases, X-Linked; Rare Diseases

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Martin Delatycki

  Murdoch Children's Research Institute/Victorian Clinical Genetics Services

  PRINCIPAL INVESTIGATOR

• Edwin Kirk

  Sydney Children's Hospital Network/NSW Health Pathology/UNSW

  PRINCIPAL INVESTIGATOR

• Nigel Laing

  University of WA/Harry Perkins Institute/PathWest Laboratory Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2019
• First Posted: November 8, 2019
• Study Start: November 21, 2019
• Primary Completion: March 31, 2022
• Study Completion: December 31, 2024
• Last Updated: July 31, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

AU (24)