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Trial registered on ANZCTR


Registration number
ACTRN12615000356561
Ethics application status
Approved
Date submitted
31/03/2015
Date registered
20/04/2015
Date last updated
27/02/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
A research study about personal genetic risk of melanoma among the general population
Scientific title
Does knowledge of personal genetic risk of melanoma, compared to standard prevention advice, motivate behaviour change among the general population? A pilot randomised controlled trial (RCT)

Secondary ID [1] 286423 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
melanoma 294634 0
Condition category
Condition code
Cancer 294892 294892 0 0
Malignant melanoma
Human Genetics and Inherited Disorders 295046 295046 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants randomised to the intervention arm will receive:
1) Personal information about their melanoma genetic risk.
2) Telephone access to a genetic counsellor;
3) Printed and electronic general educational materials on melanoma preventive behaviours including sun exposure, sun protection and skin examinations.

Determination of genetic risk: From participants’ saliva samples, we will genotype specific variants in 20 genes that have a confirmed association with melanoma risk. All variants will have been identified through adequately powered and replicated large, international studies. Genetic risk estimates for melanoma will be presented both as: 1) an absolute-risk and relative-risk estimate of the participant’s lifetime risk of developing melanoma; and 2) a broad genetic risk level – low, average, high. Participants will not be given their individual genotypes, only the risk estimates derived from them. A person’s lifetime risk of melanoma based on the 20 selected genomic variants will be estimated using published statistical methodology. The calculation assumes a multiplicative model and is based on the person’s genomic variation, the odds ratio for melanoma associated with each variant’s risk allele from replication studies or meta-analyses, the corresponding population frequency of each risk allele, and age- and sex-specific melanoma residual lifetime risk estimates from NSW cancer incidence data.

Communication of information on personal melanoma genetic risk: When it is time to give the participant the information on their personal genetic risk of melanoma, they will be contacted by telephone by the study’s genetic counsellor. At this time, the genetic counsellor will ask whether or not the participant has any questions or concerns and will check that they still wish to receive this information (verbal consent) before talking to them about their personal melanoma genetic risk derived from their saliva sample. When speaking to the genetic counsellor, participants can decide whether they would like to 1) receive their risk information from the genetic counsellor over the telephone, followed by receiving the same information in a written format; or 2) whether they would prefer not to speak to the genetic counsellor at that time, but would prefer to first receive their risk information in a written format. Regardless of whether or not participants elect to receive their risk information first over the telephone from the genetic counsellor, all participants will receive written communication of their personal melanoma genetic risk either via mailed letter or emailed letter (according to personal preference as indicated on the Consent Form). If the participant has any further questions about the information we send them, they can contact the study’s genetic counsellor by telephone to discuss further. The genetic counsellor will provide a mandatory follow up call to all those participants who elect to wait to receive their risk information via letter where the results indicate a high risk. There is no limit on the number and duration of telephone-based counselling sessions. A qualified genetic counsellor will administer the sessions.
Intervention code [1] 291499 0
Prevention
Intervention code [2] 291629 0
Behaviour
Comparator / control treatment
All participants randomised to the study (both intervention and control groups) will receive written educational materials on melanoma preventive behaviours including sun exposure, sun protection and skin examinations.

The control group will also provide a saliva sample for DNA testing and genetic risk determination at the same time as those in the intervention group. The control group are offered their personal genetic risk information at the end of the study (about 8 months after the saliva sample). All participants will have access to a study-dedicated genetic counsellor by telephone at the time of consent and when they receive their results.
Control group
Active

Outcomes
Primary outcome [1] 294650 0
Sun exposure. Measured using time (mins) spent outdoors during peak UV hours (10am-2pm/11am-3pm [depending on daylight savings]) on weekdays and weekends during the past month: "Thinking about the past month, we would like to know the times of day as well as the usual length of time that you spent outside between 9am and 5pm on a typical weekday/Saturday/Sunday. (Participants tick one response: 0,<15,15-29,30-44,45–60 mins; for each 1-hour time period between 9am and 5pm)."

In a 10% random sample of participants, we will objectively measure UV exposure using polysulfone film time-stamped UV dosimeter badges – the gold standard for assessing cumulative and daily personal UV exposure. They will be mounted in custom-made wristbands attached to the left wrist, and worn over 2 weekdays and 2 week-end days, which is sufficient for estimating habitual weekly behaviour.
Timepoint [1] 294650 0
3-months after delivery of the genetic risk information
Primary outcome [2] 294811 0
Sun protection. Measured using the sun protection habits index, calculated as the mean of five protective behaviours on a 4-point Likert scale (1=never or rarely, 4=always): "During the past month, when outside, how often did you..... wear sunscreen? wear a shirt with sleeves that covered your shoulders? wear a hat? stay in the shade? wear sunglasses?"
Timepoint [2] 294811 0
3-months after delivery of the genetic risk information
Primary outcome [3] 294812 0
Skin examination (self- or doctor-conducted). Measured as a general skin check of the whole body by oneself, partner or a health professional. "In the past 12 months, have you had your skin checked for skin cancer from head to toe by a health professional? In the past 12 months, have you or a partner examined your entire body, including your back, for skin cancer?"
Timepoint [3] 294812 0
3-months after delivery of the genetic risk information
Secondary outcome [1] 313866 0
Uptake and acceptability of telephone genetic counselling.

Timepoint [1] 313866 0
Measured by self-report questionnaire 3-months after delivery of the genetic risk information, and as the number of calls received throughout the study.
Secondary outcome [2] 314114 0
Acceptability of the information on personal genetic risk of melanoma, including satisfaction with the written materials including the presentation of the risk information.
Timepoint [2] 314114 0
Measured by self-report questionnaire 3-months after delivery of the genetic risk information
Secondary outcome [3] 314115 0
Participation rates
Timepoint [3] 314115 0
Measured during the study based on number invited/consented/completed the study.
Secondary outcome [4] 314116 0
Hypothesized mediators of behaviour change, including:
* Perceived risk of developing melanoma
* Perceived severity of melanoma
* Perceived barriers and benefits of genetic testing
* Self-efficacy, including perceived control over developing melanoma, confidence in checking one’s own skin
* Social norms, such as attitudes to tanning and sun protection.
* Health literacy
* Risk taking
Timepoint [4] 314116 0
Measured by self-report questionnaire 3-months after delivery of the genetic risk information
Secondary outcome [5] 314117 0
Psychological issues arising from the study, including:
Skin cancer-related worry using 3 items shown to be associated with the frequency of skin self-examination in people without melanoma.
Psychological distress and well-being using the 5-item version of the Mental Health Inventory (MHI-5) designed for primary care settings.
Timepoint [5] 314117 0
Measured by self-report questionnaire 3-months after delivery of the genetic risk information
Secondary outcome [6] 314118 0
Ethical issues arising from the study, including:
* Feelings of genetic ‘destiny’ or fatalism
* How to best communicate genomic risk information to recipients and within families
* If they have any regrets about receiving the information
Timepoint [6] 314118 0
Measured by self-report questionnaire 3-months after delivery of the genetic risk information
Secondary outcome [7] 314119 0
Social issues arising from the study, including:
* sharing of genetic risk information between family and friends
* Satisfaction with the communication process including preferences for the method of disclosure of their lifetime risk information
We will use questions previously developed, tested and widely implemented for skin cancer research
Timepoint [7] 314119 0
Measured by self-report questionnaire 3-months after delivery of the genetic risk information
Secondary outcome [8] 314120 0
Economic aspects arising from the study, including:
* Number visits to the GP and specialist doctors
* Number and type of procedures undertaken for the removal of skin lesions (eg. excisions, biopsies, cryotherapy).
* Patient out-of-pocket costs for the purchase of sun protection materials such as hats, sunscreen or shade cover over the previous month.
* Number of telephone calls with a genetic counsellor for both intervention and control groups, and the length of the calls, so that we can value this item of resource use.
Timepoint [8] 314120 0
Measured by self-report questionnaire 3-months after delivery of the genetic risk information. Number of telephone calls and length to be collected during the study.
Secondary outcome [9] 314121 0
Frequency of sunburn recalled over the previous month
Timepoint [9] 314121 0
Measured by self-report questionnaire 3-months after delivery of the genetic risk information

Eligibility
Key inclusion criteria
People aged 18-69 years from the general population, who have never had melanoma (since this study is aimed at prevention), have sufficient English to complete the study questionnaires, and have registered with the Cancer Council NSW 'Join a Research Study' database.
Minimum age
18 Years
Maximum age
69 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Outside the eligible age range, insufficient English to complete the study questionnaires, previous melanoma diagnosis.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Potential participants will be identified and selected through the Cancer Council NSW ‘Join a Research Study’ initiative. The 'Join a Research Study' is a register of people who have agreed to be included on a database for potential research projects. The 'Join a Research Study' database maintains information about people, currently mostly from NSW, who have consented to be contacted by researchers conducting ethically approved studies for the purposes of cancer research. These individuals have completed a basic demographic questionnaire and have supplied some health information including medication, individual and family cancer diagnosis. The database is managed by the Cancer Research Division at Cancer Council NSW, and has ethics approval from Cancer Council NSW Human Research Ethics Committee. Randomisation will be provided by the Australia and New Zealand Melanoma Trials Group (ANZMTG) or the NHMRC Clinical Trials Centre, ensuring allocation concealment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
We will use 1:1 weighting, and Minimisation (dynamic/adaptive random allocation) to ensure the groups are balanced by risk score (low or average; high), skin colour (fair; olive or brown) and sex (male; female) as the behavioural effects of the intervention may differ according to these factors.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Primary analyses will be an intention-to-treat comparison of intervention and control arms for differences in sun exposure, sun protection and skin examination outcomes at 3 months. We will also compare the psychological and socio-ethical outcomes. Where possible, we will conduct subgroup analyses stratified by genetic risk level (high, average, low) and skin colour (fair, olive/brown). Two-sided tests will be used for all analyses. For binomial outcome variables (e.g. proportion having a whole-body skin examination), we will use log-binomial models to estimate relative risks and 95% confidence intervals; for continuous outcome measures (e.g. mean time spent outdoors) we will use ANCOVA. Both will be adjusted for baseline values. We will use mixed models to account for repeated measures when comparing behavioural outcomes over time. Mediator analyses will be conducted using autoregressive mediation path models for individual mediators using Mplus. We will use established methods to adjust for the effects of measurement error in the relative risk estimate for self-reported sun exposure by: 1) calculating a validity coefficient between the self-reported and objective UV dosimeter measures of sun exposure; and 2) using this validity coefficient to adjust the relative risk for the self-reported sun exposure association. Importantly, we will be able to assess for differential misclassification by assessing whether the validity coefficients differ between the three genetic risk strata.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 291022 0
Government body
Name [1] 291022 0
Sydney Catalyst Translational Cancer Centre pilot and seed funding grant
Address [1] 291022 0
Sydney Catalyst Central Office
Chris O'Brien Lifehouse Building
Level 6, 119-143 Missenden Rd, Camperdown, NSW, 2050
Mail: Locked Bag 77, Camperdown NSW 1450
Country [1] 291022 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
Camperdown NSW 2006
Country
Australia
Secondary sponsor category [1] 289698 0
None
Name [1] 289698 0
Address [1] 289698 0
Country [1] 289698 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292604 0
The University of Sydney Human Research Ethics Committee (HREC)
Ethics committee address [1] 292604 0
Research Integrity
Research Portfolio
Level 6, Jane Foss Russell
The University of Sydney
NSW 2006
Ethics committee country [1] 292604 0
Australia
Date submitted for ethics approval [1] 292604 0
Approval date [1] 292604 0
10/02/2015
Ethics approval number [1] 292604 0
2014/868

Summary
Brief summary
This pilot study aims to determine whether knowledge of personal genetic risk of melanoma, compared to standard prevention advice, can motivate behaviour change among the general population.

Who is it for?
People aged 18-69 years from the general population, who have never had melanoma and have registered with 'Join a Research Study' database.

Study details
All participants in this study will be required to provide a saliva sample and have their DNA tested to determine their risk of melanoma. Participants are then randomly allocated (by chance) to one of two groups. Participants in one group will receive personal information about their melanoma genetic risk, with access to telephone-based genetic counselling as well as written educational materials on melanoma preventive behaviours including sun exposure, sun protection and skin examinations. Participants in the other group will receive only written educational materials on melanoma preventive behaviours during the intervention period. This group will then be offered genetic risk information at the end of the study (about 8 months after the saliva sample).

The aim of this study is to pilot methods for an intervention that provides information on personal genetic risk of melanoma to participants from the general population, and to gather pilot and feasibility data regarding its short-term effectiveness on sun protection, sun exposure and skin examination behaviours, as well as the broader impact on ethical, social, psychological and economic outcomes.
Trial website
Trial related presentations / publications
Amelia K Smit, David Espinoza, Ainsley J Newson, Rachael L Morton, Georgina Fenton, Lucinda Freeman, Kate Dunlop, Phyllis N Butow, Matthew H Law, Michael G Kimlin, Louise A Keogh, Suzanne Dobbinson, Judy Kirk, Peter A Kanetsky, Graham J Mann, Anne E Cust. A pilot randomised controlled trial of the feasibility, acceptability and impact of giving information on personalised genomic risk of melanoma to the public. Cancer Epidemiology, Biomarkers & Prevention. 2016 Oct 4. pii: cebp.0395.2016

Amelia K Smit, Ainsley J Newson, Phyllis N Butow, Kate Dunlop, Rachael L Morton, Judy Kirk, David Espinoza, Anne E Cust. Does personalised melanoma genomic risk information trigger conversations about skin cancer prevention and skin examination with, friends and health professionals? British Journal of Dermatology. Reviewed 20 February 2017, under revision by the authors and will be resubmitted to the British Journal of Dermatology.

The results have also been presented at several national and international scientific conferences including the International Agency for Research on Cancer (IARC) 50th Anniversary Conference, Lyon, France; American Society for Clinical Oncology (ASCO) annual meeting, Chicago; Australasian Epidemiological Association Conference, Canberra; and the Sydney Cancer Conference, Sydney.
Public notes

Contacts
Principal investigator
Name 56082 0
Dr Anne Cust
Address 56082 0
Cancer Epidemiology and Services Research (CESR)
Level 6 - North, The Lifehouse
119-143 Missenden Rd,
Camperdown, NSW 2050


Country 56082 0
Australia
Phone 56082 0
+61 2 8627 1565
Fax 56082 0
Email 56082 0
anne.cust@sydney.edu.au
Contact person for public queries
Name 56083 0
Dr Anne Cust
Address 56083 0
Cancer Epidemiology and Services Research (CESR)
Level 6 - North, The Lifehouse
119-143 Missenden Rd,
Camperdown, NSW 2050
Country 56083 0
Australia
Phone 56083 0
+61 2 8627 1565
Fax 56083 0
Email 56083 0
anne.cust@sydney.edu.au
Contact person for scientific queries
Name 56084 0
Dr Anne Cust
Address 56084 0
Cancer Epidemiology and Services Research (CESR)
Level 6 - North, The Lifehouse
119-143 Missenden Rd,
Camperdown, NSW 2050
Country 56084 0
Australia
Phone 56084 0
+61 2 8627 1565
Fax 56084 0
Email 56084 0
anne.cust@sydney.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary