ANZCTR - Registration

Registration number

ACTRN12623000053628

Ethics application status

Approved

Date submitted

19/12/2022

Date registered

17/01/2023

Date last updated

21/07/2024

Date data sharing statement initially provided

17/01/2023

Type of registration

Prospectively registered

Titles & IDs

Public title

The MAGPIE Study: Multi-cancer genomic risk assessment to target screening in general practice

Scientific title

The MAGPIE Study: Multi-cancer genomic risk assessment to target screening in general practice patients aged 45-59.

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

The MAGPIE Study (Multi-cAncer Genomic risk assessment to target screening in general PractIcE)

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Breast Cancer

Bowel Cancer

Prostate Cancer

Melanoma

Breast cancer screening

Bowel cancer screening

Prostate cancer screening

Skin cancer screening

Condition category

Condition code

Cancer

Breast

Cancer

Malignant melanoma

Cancer

Prostate

Cancer

Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

This study is testing the behavioural impact of a ‘complex intervention’ which comprises several parts. The main part is a genomic test - (i.e., a personalised risk estimate determined from the participant’s polygenic risk score - which will be collected via a single saliva collection kit; participants self-reported family history of cancer, age and sex) with personalised screening recommendations derived from this risk. The initial consult whereby the genomic risk will be determined will be followed up 2-3 weeks later, whereby participants will be invited to attend a 20-minute one-on-one visit with a researcher to go through their personal risk report, participants will receive their personal risk score report and be given recommendations for screening for each cancer type.

These reports have been developed specifically to inform about risk but also to impact cancer screening behaviour. The risk reports will include clear and succinct written detail about cancer screening recommendations for the four cancers as well as infographics depicting the participants specific risk scores and diagrams that depict the differences in mortality for populations that do and don't screen for the four cancers. All these diagrams and infographics will be discussed during the results meeting with the researcher.
Reports will be given to both participants and GPs by the researcher conducting the results appointments, these will be given to participants and GPs either by hardcopy or provided electronically via email or secure password protected hyperlink

The follow-up consultation between participant and researcher will be conducted in person or via telehealth method - whichever is preferrable to the participant, where a discussion around personal risk and screening pathways for each of the three gender-specific cancers with a risk report for the participant and their GP will be conducted. Participants will then be encouraged to book in to see their GP in order to action any screening recommendations as a result of the risk score report. Over the study period, participants will be required to meet with the researcher twice within an approximate one-month period and will be required to see their GP once during the study period and encouraged to see their GP at least once in order to follow-up and action any screening recommendations. The overall period of the study for participants will be 6-7 months from recruitment.

Calculation of cancer risk from the polygenic risk score: A polygenic risk score will be generated by determining how many risk alleles are present at each of the single nucleotide polymorphisms (SNPs) associated with risk of each cancer. This list of SNPs and relative risks of cancer for each SNP will be determined using the most up-to-date literature: breast cancer (BrCa) 313 SNPs, colorectal cancer (CRC) 140 SNPs, prostate cancer (PrCa) 269 SNPs, melanoma 85 SNPs. Increased risks from a family history of any of the cancers will also be accounted for. This will be calculated using the number and age of diagnosis of any first- or second-degree relatives with the cancer in question. Familial aggregation studies provide published estimates of the relative risk conferred by the presence of the most common combinations of family history for each cancer.

Determination of cancer screening recommendations, incorporating the polygenic risk score-derived ten-year-risks and/or relative risks: Screening for these four cancers is recommended in Australia by determining an individual's risk category (mainly using the presence and strength of a family history of cancer), which in turn has attached screening recommendations. These risk categories have defined risk thresholds. Our intervention uses the same principles and risk thresholds as in the approved guidelines but uses the genomic test (including family history) to determining risk level.

Recommended screening for those at lower-than-average risk: For all cancers, screening recommendations will not be downgraded from what would otherwise be recommended according to the respective Australian guidelines.
- For those without increased risk of CRC: 2-yearly iFOBT will be recommended from 50 years.
- For those without increased risk of BrCa: 2-yearly mammogram will be recommended from 50 years.
- For those without increased risk of PrCa: A consideration of 2-yearly PSA from 50 years will be recommended.
- For those without increased risk of melanoma: SunSmart measures and self-monitoring of any skin changes will be recommended but no screening will be advised.

The guidelines followed for the recommended screening pathways are based off the Revised Australian national guidelines for colorectal cancer screening: family history (2018), Cancer Council Australia Colorectal Cancer Guidelines Working Party. Clinical practice guidelines for the prevention, early detection and management of colorectal cancer (2017), Prostate Cancer Foundation of Australia and Cancer Council Australia PSA Testing Guidelines Expert Advisory Panel. Clinical practice guidelines PSA Testing and Early Management of Test-Detected Prostate Cancer (2016) and The Royal Australian College of General Practitioners. Guidelines for preventive activities in general practice (2016)

Recommended screening for those whose family history meets genetics referral guidelines: Those who meet the referral guidelines due to their family history of cancer will be recommended as part of their personalised screening report to discuss referral to a genetics service with their GP.

Colorectal cancer:
Those who are due an Immunochemical Fecal Occult Blood Test (iFOBT) will be given one by the researcher to discuss with their GP, by their GP directly or by their GP via the National Bowel Cancer Screening Program (NBCSP). All participants who are in the iFOBT screening group will be given a brief demonstration on its use to increase their self-efficacy to perform the test. For those who have reported having polyps found on their last colonoscopy, an information sheet regarding the guidelines on surveillance colonoscopy after polypectomy will be given to participants’ GPs to assist their clinical discussion. For those at increased risk of Colorectal Cancer (CRC), they are recommended to discuss with their GP referral for screening colonoscopy.

Breast cancer:
Those who are due a mammogram will be given the phone number to book a mammogram through BreastScreen Victoria and the website address to book one online. Providing the website and phone number to book a mammogram aims to remove practical barriers to complete the screening.
Mammograms are available through the national screening program for all over 40, with the caveat that those in their 40s should discuss their individual risk factors with their doctor.

Prostate Cancer:
Prostate Specific Antigen (PSA) screening is not universally recommended as a screening test in Australia. Instead, Australian guidelines recommend that for those who request it, GPs should discuss the request with patients and use a decision aid developed to facilitate informed decision making about this test.

Melanoma:
GPs can conduct clinical skin examinations to screen for melanoma. As this is likely to require a dedicated GP appointment, the researcher will offer to assist participants in making an additional appointment at their practice for this purpose.

All final decisions on screening path are made by the participant and their GP together.

In order to monitor adherence to the intervention and effectiveness of the method of intervention, a risk report session attendance checklist will be available within the researcher's secure study redcap database and an audit of GP medical records will be conducted to determine follow-up visits and screening attendance etc.

Intervention code [1]

Early detection / Screening

Intervention code [2]

Prevention

Intervention code [3]

Behaviour

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

To measure the effect on screening behaviour of a personalised cancer risk estimate for breast cancer (derived from a polygenic risk score) for primary care patients aged 45-59. The primary outcome is the proportion, for breast cancer, who complete risk-appropriate screening of those who require screening within six months follow up post the genomic risk results.
Screening behaviour will be determined from participant self-report (from the study-specific follow-up questionnaires) and GP record audit. Risk-appropriate screening is defined as being concordant with the screening recommended as part of the intervention. How the risk-appropriate screening recommendations will be derived from the Australian National Screening Guidelines.
Screening behaviour will be obtained from the following sources:
1. Participant self-report;
2. Data from their GP records (results of screening tests for breast cancer e.g. mammogram, breast ultrasound etc.); Processes to obtain consent to access these data will already be established.

Timepoint [1]

Baseline (participant recruitment/DNA test) and 6 months (post-recruitment).
1 month, 2 month and 6 month post recruitment questionnaires.

Primary outcome [2]

To measure the effect on screening behaviour of a personalised cancer risk estimate for bowel cancer (derived from a polygenic risk score) for primary care patients aged 45-59. The primary outcome is the proportion, for bowel cancer, who complete risk-appropriate screening of those who require screening within six months follow up post the genomic risk results.
Screening behaviour will be determined from participant self-report (from the study-specific follow-up questionnaires) and GP record audit. Risk-appropriate screening is defined as being concordant with the screening recommended as part of the intervention. How the risk-appropriate screening recommendations will be derived from the Australian National Screening Guidelines.
Screening behaviour will be obtained from the following sources:
1. Participant self-report;
2. Data from their GP records (results of screening tests for bowel cancer e.g. iFOBT, colonoscopy etc.); Processes to obtain consent to access these data will already be established.

Timepoint [2]

Baseline (participant recruitment/DNA test) and 6 months (post-recruitment).
1 month, 2 month and 6 month post recruitment questionnaires.

Primary outcome [3]

To measure the effect on screening behaviour of a personalised cancer risk estimate for prostate cancer (derived from a polygenic risk score) for primary care patients aged 45-59. The primary outcome is the proportion, for prostate cancer, who complete risk-appropriate screening of those who require screening within six months follow up post the genomic risk results.
Screening behaviour will be determined from participant self-report (from the study-specific follow-up questionnaires) and GP record audit. Risk-appropriate screening is defined as being concordant with the screening recommended as part of the intervention. How the risk-appropriate screening recommendations will be derived from the Australian National Screening Guidelines.
Screening behaviour will be obtained from the following sources:
1. Participant self-report;
2. Data from their GP records (results of screening tests for prostate cancer e.g. PSA test, prostate biopsy, discussion about consideration of PSA testing etc.); Processes to obtain consent to access these data will already be established.

Timepoint [3]

Baseline (participant recruitment/DNA test) and 6 months (post-recruitment).
1 month, 2 month and 6 month post recruitment questionnaires.

Secondary outcome [1]

*PLEASE NOTE THIS IS A FOURTH PRIMARY OUTCOME OF THE STUDY*
To measure the effect on screening behaviour of a personalised cancer risk estimate for melanoma (derived from a polygenic risk score) for primary care patients aged 45-59. The primary outcome is the proportion, for melanoma, who complete risk-appropriate screening of those who require screening within six months follow up post the genomic risk results.
Screening behaviour will be determined from participant self-report (from the follow-up questionnaires) and GP record audit. Risk-appropriate screening is defined as being concordant with the screening recommended as part of the intervention. How the risk-appropriate screening recommendations will be derived from the Australian National Screening Guidelines.
Screening behaviour will be obtained from the following sources:
1. Participant self-report;
2. Data from their GP records (results of screening tests for melanoma e.g. a full body skin check etc.); Processes to obtain consent to access these data will already be established.

Timepoint [1]

Baseline (participant recruitment/DNA test) and 6 months (post-recruitment).
1 month, 2 month and 6 month post recruitment questionnaires.

Secondary outcome [2]

The secondary objectives of this study are to evaluate the feasibility of implementation of this test in primary care, and the impact on elements known to influence screening behaviour within six months after genomic risk results, compared over time to baseline measures, including:
1. salience and coherence, based on the Preventative Health Model (validated questionnaire)

Semi-structured, one-on-one face-to-face/teletrial interviews with a member of the research team will be conducted to obtain these survey answers.

Timepoint [2]