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Mackenzie's Mission: The Australian Reproductive Carrier Screening Project

Primary Purpose

X-Linked Genetic Diseases, Autosomal Recessive Disorder

Status
Active
Phase
Not Applicable
Locations
Australia
Study Type
Interventional
Intervention
Reproductive Genetic Carrier Screening
Sponsored by
Murdoch Childrens Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional health services research trial for X-Linked Genetic Diseases focused on measuring reproductive genetics, carrier screening, rare disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

In order to take part in the study, couples need to have visited a recruiting HCP who will assess them for eligibility based on the criteria below:

INCLUSION CRITERIA

  • 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.

EXCLUSION CRITERIA

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.

Sites / Locations

  • Forster Community Health Service
  • Liverpool Hospital
  • Hunter Genetics
  • Royal Hospital for Women
  • Sydney Children's Hospital, Randwick
  • Royal Prince Alfred Hospital
  • The Children's Hospital at Westmead
  • Westmead Hospital
  • Campbelltown Hospital
  • Tamworth Communith Health Services
  • Taree Community Health Service
  • Wagga Wagga Base Hospital
  • Royal Darwin Hospital
  • Royal Brisbane and Women's Hospital
  • Cairns Hospital
  • Mareeba Hospital
  • Women's and Children's Hospital
  • Royal Hobart Hospital
  • Victorian Clinical Genetics Services
  • Northern Hospital
  • Mercy Hospital for Women
  • West Gippsland Heath Service (Warragul Hospital)
  • Joondalup Health Campus
  • King Edward Memorial Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Participating Couples

Arm Description

Reproductive Genetic Carrier Screening

Outcomes

Primary Outcome Measures

Screening Uptake (Quantitative)
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
Analysis of carrier frequencies of the genes tested and the frequency of identification of increased-risk couples
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.
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.
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.
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.
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)
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)

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Participant Experience - Health Literacy
Questions to assess health literacy level
Participant Experience - Evaluation of Educational and Decision-Aid Materials
Questions to evaluate resources developed for participating couples e.g. decision aid, website, brochure
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].
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)
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
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)
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.
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.
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.

Full Information

First Posted
October 21, 2019
Last Updated
April 20, 2023
Sponsor
Murdoch Childrens Research Institute
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
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1. Study Identification

Unique Protocol Identification Number
NCT04157595
Brief Title
Mackenzie's Mission: The Australian Reproductive Carrier Screening Project
Official Title
Mackenzie's Mission: The Australian Reproductive Carrier Screening Project
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 21, 2019 (Actual)
Primary Completion Date
March 31, 2022 (Actual)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Murdoch Childrens Research Institute
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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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. - 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
X-Linked Genetic Diseases, Autosomal Recessive Disorder
Keywords
reproductive genetics, carrier screening, rare disease

7. Study Design

Primary Purpose
Health Services Research
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18302 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Participating Couples
Arm Type
Experimental
Arm Description
Reproductive Genetic Carrier Screening
Intervention Type
Other
Intervention Name(s)
Reproductive Genetic Carrier Screening
Intervention Description
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
Primary Outcome Measure Information:
Title
Screening Uptake (Quantitative)
Description
Practitioners offering screening will be asked to record the number of couples offered screening which will allow calculation of screening uptake.
Time Frame
At offer of screening
Title
Frequency of Increased-Risk Couples
Description
Analysis of carrier frequencies of the genes tested and the frequency of identification of increased-risk couples
Time Frame
At reporting of results (~Weeks 5-6 since enrolment)
Title
Reproductive Choices made by Increased-Risk Couples
Description
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.
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.
Title
Cohort Characteristics of those who decline and those who accept RGCS
Description
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.
Time Frame
Couples who decline screening;at offer or at enrolment (Day 0); optional. Couples who accept screening; at enrolment (Day 0); compulsory.
Title
Predictors of Uptake - Decliners
Description
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.
Time Frame
Couples who decline screening; at offer or enrolment (Day 0); optional
Title
Predictors of Uptake - Decliners
Description
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.
Time Frame
At decision not to provide samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Title
Predictors of Uptake - Acceptors
Description
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)
Time Frame
Couples who accept screening; at offer or enrolment (Day 0); compulsory.
Title
Predictors of Uptake - Acceptors
Description
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)
Time Frame
At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Secondary Outcome Measure Information:
Title
Participant Experience - Attitudes/Perceptions
Description
Survey assessing attitudes towards carrier screening in the general population, and the attitudes of the couple towards carrier screening for themselves.
Time Frame
Couples who decline screening;at offer or at enrolment (Day 0); optional. Couples who accept screening; at enrolment (Day 0); compulsory.
Title
Participant Experience - State-Anxiety - pre-screening
Description
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.
Time Frame
Couples who decline screening; at enrolment (Day 0); optional. Couples who accept screening; at enrolment (Day 0); compulsory.
Title
Participant Experience - State-Anxiety - pre-screening II
Description
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.
Time Frame
At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Title
Participant Experience - State-Anxiety - post-result
Description
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.
Time Frame
Low-risk and increased-risk couples; post-result (~Weeks 17-18 since enrolment); optional
Title
Participant Experience - State-Anxiety - long-term follow-up
Description
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.
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
Title
Participant Experience - Trait-Anxiety - pre-screening
Description
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.
Time Frame
Couples who decline screening; at enrolment (Day 0); optional. Couples who accept screening; at enrolment (Day 0); compulsory.
Title
Participant Experience - Trait-Anxiety - pre-screening II
Description
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.
Time Frame
At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Title
Participant Experience - Trait-Anxiety - post-result
Description
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.
Time Frame
Low-risk and increased-risk couples; post-result (~Weeks 17-18 since enrolment); optional
Title
Participant Experience - Trait-Anxiety - long-term follow-up
Description
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.
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
Title
Health Economic Impact - Assessment of Quality of Life - pre-screening
Description
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.
Time Frame
Couples who decline testing, at enrolment (Day 0); optional. Couples who accept testing, at enrolment (Day 0); compulsory
Title
Health Economic Impact - Assessment of Quality of Life - post-result
Description
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.
Time Frame
Low-risk and increased-risk couples; post-result (~Weeks 17-18 since enrolment); optional
Title
Health Economic Impact - Assessment of Quality of Life - long-term follow-up
Description
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.
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
Title
Health Economic Impact - Participants' willingness to pay
Description
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.
Time Frame
Couples who decline screening, at enrolment (Day 0); optional. Couples who accept screening, at enrolment (Day 0); compulsory
Title
Participant Experience - Health Literacy
Description
Questions to assess health literacy level
Time Frame
At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Title
Participant Experience - Evaluation of Educational and Decision-Aid Materials
Description
Questions to evaluate resources developed for participating couples e.g. decision aid, website, brochure
Time Frame
At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Title
Participant Experience - Decisional Conflict
Description
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].
Time Frame
At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Title
Participant Experience - Deliberation
Description
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)
Time Frame
At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Title
Participant Experience - Decision-Making Approach
Description
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
Time Frame
At provision of samples for screening, anticipated to be within ten days of enrolment (Days 2-10); optional
Title
Participant Experience - Genomics Outcome Scale (GOS-6)
Description
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)
Time Frame
Increased-risk couples, before and after genetic counselling session (~Weeks 5-6 since enrolment)
Title
Participant Experience - Decisional Regret - post-result
Description
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.
Time Frame
Low-risk and increased-risk couples; post-result (~Weeks 17-18 since enrolment); optional
Title
Participant Experience - Decisional Regret - long-term follow-up
Description
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.
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
Title
Participant Experience - Qualitative Interviews
Description
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.
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
Other Pre-specified Outcome Measures:
Title
Ethical Issues - Assessment of ethical aspects of publicly funded preconception screening
Description
A series of scholarly outputs (e.g. journal articles) critically considering ethical issues in publicly funded preconception screening programs. The issues being identified include (but are not limited to) reproductive autonomy, public health ethics frameworks, eugenics, secondary findings. Additional ethical issues will be considered as they arise in the trial. The method to be used is applied ethics, which is non-empirical.
Time Frame
Throughout study; 3 years
Title
Implementation Outcomes - Barriers & Enablers to Implementation
Description
Barriers and enablers to implementation will be identified and recorded at study committee meetings via responses to the following questions: What has changed over the last month or so? What has gone well/not so well? Has anything surprised you?
Time Frame
Study investigators; at committee meetings for the duration of the study (3 years); Jan 2019 - Dec 2022
Title
Implementation Outcomes - Anticipated vs Actual Outcomes
Description
To assess whether planned and anticipated outcomes are realised, study investigators will be asked to complete a time-capsule survey predicting the outcomes of the study. Following the completion of the study, the responses will be matched to the final outcomes.
Time Frame
Study investigators; 1 month before the study begins recruitment
Title
Implementation Outcomes - Patient Safety Behaviour Questionnaire
Description
Questionnaire assessing what HCPs in the wider community think about carrier screening, and what the barriers/enablers are to offering carrier screening to patients in usual care.
Time Frame
HCPs; at HCP conferences or professional meetings; for the duration of the study (3 years).
Title
Implementation Outcomes - Uptake by HCPs
Description
Survey of HCPs invited to recruit to the study, including those who agree to recruit couples and those who decline to recruit couples. The survey will explore potential barriers to RGCS, factors that might influence confidence/ability to refer appropriate couples for RGCS and readiness to change. HCPs can opt-in to be contacted for interview to provide further information about implementation.
Time Frame
HCPs; at invitation to become a recruiting HCP; for the duration of the study (3 years)
Title
Implementation Outcomes - Factors influencing Recruitment by HCPs - post-education
Description
Survey of HCPs who agree to recruit to the study, measuring factors influencing recruitment such as knowledge, ability and confidence.
Time Frame
Recruiting HCPs; 3 months after education
Title
Implementation Outcomes - Factors influencing Recruitment by HCPs - post-recruitment
Description
Survey of HCPs who have recruited to the study, measuring factors influencing recruitment. Opt-in to be contacted for interview to further explore the experience of offering RGCS to patients and any barriers/enablers of implementation.
Time Frame
Recruiting HCPs; 6 weeks after recruitment of first participant
Title
Implementation Outcomes - HCP Experience - post-implementation
Description
Survey of HCPs who have recruited to the study, examining their experience of offering reproductive genetic carrier screening.
Time Frame
Recruiting HCPs; 3 months after end of recruitment
Title
Health Economic Impact - Costs per increased-risk couple identified
Description
Cost in Australian dollars of identifying one increased-risk couple
Time Frame
3 months after enrolment
Title
Health Economic Impact - Costs per affected pregnancy identified
Description
Cost in Australian dollars of identifying one affected pregnancy
Time Frame
6 months after enrolment
Title
Health Economic Impact - Costs per affected birth averted
Description
Average cost in Australian dollars of taking reproductive measures to avoid having an affected live birth (e.g. pre-implantation genetic diagnosis, prenatal diagnosis, termination etc.)
Time Frame
Throughout study; 3 years
Title
Health Economic Impact - Costs of the carrier screening program
Description
Total costs of the carrier screening program
Time Frame
Throughout study; 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
In order to take part in the study, couples need to have visited a recruiting HCP who will assess them for eligibility based on the criteria below: INCLUSION CRITERIA 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. EXCLUSION CRITERIA 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Martin Delatycki
Organizational Affiliation
Murdoch Children's Research Institute/Victorian Clinical Genetics Services
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Edwin Kirk
Organizational Affiliation
Sydney Children's Hospital Network/NSW Health Pathology/UNSW
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nigel Laing
Organizational Affiliation
University of WA/Harry Perkins Institute/PathWest Laboratory Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Forster Community Health Service
City
Forster
State/Province
New South Wales
ZIP/Postal Code
2428
Country
Australia
Facility Name
Liverpool Hospital
City
Liverpool
State/Province
New South Wales
ZIP/Postal Code
2170
Country
Australia
Facility Name
Hunter Genetics
City
Newcastle
State/Province
New South Wales
ZIP/Postal Code
2298
Country
Australia
Facility Name
Royal Hospital for Women
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
Sydney Children's Hospital, Randwick
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
Royal Prince Alfred Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
The Children's Hospital at Westmead
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Westmead Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Campbelltown Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2560
Country
Australia
Facility Name
Tamworth Communith Health Services
City
Tamworth
State/Province
New South Wales
ZIP/Postal Code
2340
Country
Australia
Facility Name
Taree Community Health Service
City
Taree
State/Province
New South Wales
ZIP/Postal Code
2430
Country
Australia
Facility Name
Wagga Wagga Base Hospital
City
Wagga Wagga
State/Province
New South Wales
ZIP/Postal Code
2650
Country
Australia
Facility Name
Royal Darwin Hospital
City
Darwin
State/Province
Northern Territory
ZIP/Postal Code
0810
Country
Australia
Facility Name
Royal Brisbane and Women's Hospital
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Cairns Hospital
City
Cairns
State/Province
Queensland
ZIP/Postal Code
4870
Country
Australia
Facility Name
Mareeba Hospital
City
Mareeba
State/Province
Queensland
ZIP/Postal Code
4880
Country
Australia
Facility Name
Women's and Children's Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5006
Country
Australia
Facility Name
Royal Hobart Hospital
City
Hobart
State/Province
Tasmania
ZIP/Postal Code
7000
Country
Australia
Facility Name
Victorian Clinical Genetics Services
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Northern Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3076
Country
Australia
Facility Name
Mercy Hospital for Women
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
West Gippsland Heath Service (Warragul Hospital)
City
Warragul
State/Province
Victoria
ZIP/Postal Code
3820
Country
Australia
Facility Name
Joondalup Health Campus
City
Joondalup
State/Province
Western Australia
ZIP/Postal Code
6027
Country
Australia
Facility Name
King Edward Memorial Hospital
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6008
Country
Australia

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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.

Learn more about this trial

Mackenzie's Mission: The Australian Reproductive Carrier Screening Project

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