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Trial registered on ANZCTR


Registration number
ACTRN12617000691347
Ethics application status
Approved
Date submitted
24/03/2017
Date registered
15/05/2017
Date last updated
25/02/2020
Date data sharing statement initially provided
18/01/2019
Date results information initially provided
18/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The Melanoma Genomics Managing Your Risk Study: examining the impact of personal melanoma genomic risk information on prevention behaviours in the general population
Scientific title
The Melanoma Genomics Managing Your Risk Study: a randomised controlled trial of the efficacy of personal melanoma genomic risk of information, compared to standard prevention advice, in motivating reduced exposure to ultraviolet radiation in the general population
Secondary ID [1] 291106 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record
ACTRN12615000356561

Health condition
Health condition(s) or problem(s) studied:
melanoma 302622 0
Condition category
Condition code
Cancer 302143 302143 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants randomly allocated to the intervention arm will receive:
1. A mailed saliva collection kit for subsequent DNA extraction and genotyping.
2. Personal genetic risk of melanoma information. About 2-3 months after providing a saliva sample, participants will receive their genetic risk information in a hardcopy booklet sent via postal mail. The booklet, developed as part of our pilot trial (ACTRN12615000356561), presents and describes participants’ individual genetic risk of melanoma using evidence-based risk communication strategies, such as numerical and visual presentations of lifetime absolute risk. Participants reported high satisfaction with the genetic risk booklet in the pilot trial, and we have made minor modifications to enhance clarity for participants in the Managing Your Risk Study. The risk information includes:
*An absolute risk percentage showing their remaining lifetime risk of developing melanoma. For example, our pilot study observed remaining lifetime genomic risk estimates of up to 20% but the average risk was around 2-4%.
* A risk level: higher than average = top 25% of genomic risk, average = middle 50%, lower than average = bottom 25%; based on quartile cut-points within each age, sex and state strata.
The genetic risk booklet also contains simple explanatory information about how a person’s risk is calculated, and what they can do to reduce their risk.
3. A telephone call from the study genetic counsellor. The genetic counsellor will contact all participants in the intervention arm within two-weeks after their genetic risk information is sent via postal mail. The purpose of the phone call is to confirm receipt of the booklet and to answer any potential questions. We expect the phone call will last approximately 10 minutes, depending on the number of questions or discussion points raised by participants.
4. An educational booklet on melanoma preventive behaviours and skin examinations. The educational booklet, developed for our pilot trial (ACTRN12615000356561), is based on SunSmart campaign resources. It includes information on risk factors for melanoma and other skin cancers, recommendations for optimal sun exposure and sun protection behaviours, information about skin examinations including an online video showing step-by-step skin self-examination, and information about Vitamin D. Educational materials are widely used by the Australian general public and, as such, are considered ‘standard care’. In the pilot trial, this educational booklet was rated highly (more than 8 out of 10) in terms of satisfaction by participants.

Intervention code [1] 297600 0
Behaviour
Intervention code [2] 297601 0
Prevention
Intervention code [3] 297602 0
Early detection / Screening
Comparator / control treatment
Participants randomly allocated to the control arm will receive the same educational booklet provided to intervention arm participants on melanoma preventive behaviours including sun exposure, sun protection and skin examinations
Control group
Active

Outcomes
Primary outcome [1] 301572 0
The primary outcome is total daily Standard Erythemal Doses (SEDs), an objective measure of ultraviolet radiation (UVR) exposure, measured 12 months after the baseline assessment. SEDs will be measured using time-stamped electronic dosimeter badges, mounted in light-weight custom-made wristbands attached to the left wrist (similar to wearing a watch) during daylight hours. UV dosimeters will be worn by all participants for 10 days at baseline and again 12-months after baseline. A subgroup of ~240 participants will also wear a UV dosimeter 1-month after receipt of the booklet/s. The data collected on weekdays will be averaged over 5 days and the data collected on weekends will be averaged over 2 days to enable an average weekly and average daily dose to be calculated.
Timepoint [1] 301572 0
12 months follow-up
Secondary outcome [1] 333108 0
Daily Standard Erythemal Doses (SEDs) during: a) peak-time, b) morning, and c) afternoon periods of day. SEDs will be measured using time-stamped electronic dosimeter badges, mounted in light-weight custom-made wristbands attached to the left wrist (similar to wearing a watch) during daylight hours. UV dosimeters will be worn by all participants for 10 days at baseline and at 12-months after baseline. A subgroup of ~240 participants will also wear a UV dosimeter 1-month after receipt of the booklet/s. The data collected on weekdays will be averaged over 5 days and the data collected on weekends will be averaged over 2 days to enable an average weekly and average daily dose to be calculated.
Timepoint [1] 333108 0
Baseline, 1-month from receiving genomic risk information, and 12-months from baseline.
Secondary outcome [2] 333109 0
Sun protection behaviours, measured as the frequency of: sunscreen use, wearing a shirt with sleeves, wearing a hat, seeking shade, wearing sunglasses, limiting peak-time sun exposure. This will be measured Uuing questionnaire items, including the sun protection habits index, calculated as the mean of six 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 cover your shoulders? wear a hat? stay in the shade or under an umbrella? wear sunglasses? limit your time in the sun during midday hours?

Sunscreen use is assessed using an item: Have you used sunscreen in the past month? (Yes/No). If participants respond ‘Yes’ they are asked the following items:
- Was this usually a high protection sunscreen (SPF 30 or more)? (Yes/No).
- How often on average have you used sunscreen in the past month? (Less than one a week, 1-2 days a week, 3-5 days a week, 6-7 days a week)
- On days that you have used sunscreen in the past month, how often did you apply it? (free-text response, restricted to numbers)
- Did you usually apply sunscreen (select one of the following): to all parts of your body exposed to the sun OR only to parts of your body that are prone to sunburn.
Hat wear is assessed an additional item: Please select the option which is most similar to your usual headwear when in the sun in the past month. Response options are: no headwear, beanie, cap, legionnaires, bucket hat, wide brimmed, veil/burkha.
Timepoint [2] 333109 0
Baseline, 1-month from receiving genomic risk information, and 12-months from baseline
Secondary outcome [3] 333110 0
Skin examinations (self-, partner- or doctor-conducted). This will be measured using questionnaire items: frequency of skin examinations conducted by participants, their partners and doctors.
Timepoint [3] 333110 0
Baseline, 1-month from receiving genomic risk information, and 12-months from baseline
Secondary outcome [4] 333111 0
Intentional tanning frequency, measured using a questionnaire item ‘How often do you spend time in the sun in order to get a tan?’ measured on a 5-point Likert scale (1=never, 5=always).
Timepoint [4] 333111 0
Baseline, 1-month from receiving genomic risk information, and 12-months from baseline
Secondary outcome [5] 333112 0
Sunburn frequency, measured using a questionnaire item: sunburn frequency recalled over the previous month.
Timepoint [5] 333112 0
Baseline, 1-month from receiving genomic risk information, and 12-months from baseline
Secondary outcome [6] 333113 0
Skin cancer-related worry, measured using 3 questionnaire items shown to be associated with the frequency of skin self-examination in people without melanoma. These items have been adapted from other research on skin examination behaviour (Kasparian et al, Skin Examination Behavior, Arch Dermatol. 2012;148(10):1142-1151)
Timepoint [6] 333113 0
Baseline, 1-month from receiving genomic risk information, and 12-months from baseline
Secondary outcome [7] 333114 0
Psychological distress and well-being, measured using the 5-item version of the Mental Health Inventory (MHI-5) designed for primary care settings.
Timepoint [7] 333114 0
Baseline, 1-month from receiving genomic risk information, and 12-months from baseline
Secondary outcome [8] 333115 0
The cost-effectiveness of the genomic risk intervention compared to standard prevention advice alone, from the Australian health system perspective. This will be a two-stage analysis:
(i) A within-trial economic evaluation at 12 months, reporting the cost for a defined reduction in daily SEDs, stratified by phenotypic risk group (i.e. primary outcome).
(ii) A modelled evaluation will extrapolate the intermediate trial outcomes over the longer term to report definitive health outcomes including the cost per melanoma or other skin cancer avoided, and the cost per life year saved.
Resource use will be identified and cost estimates for these resources will be taken from the trial questionnaire data and Medicare Benefits Schedule claims data. In the questionnaire, we will ask about sun protection item(s) purchased during follow-up (e.g. hat, sunscreen, beach tents, UV protective swimwear, etc.) and their cost, clinical visits for skin checks, procedures to test or remove suspicious skin spots and diagnoses of melanoma or keratinocyte cancers (during the study).
Data linkage to the Medicare Benefits Schedule database, Australian cancer registries and the National Death Index will enable collection of future resource use and costs of skin excisions, and incidence of melanoma and keratinocyte cancers and mortality information. Data will be collected from the Medicare Benefits Schedule and Cancer Registries from 2017-2021 to inform within-trial analysis. A second wave of data from cancer registries will enable long-term incidence of melanoma to be recorded. A comprehensive approach to costing the intervention will be undertaken using actual trial costs including costs of DNA extraction and genotyping by AGRF, personalized risk calculation reports, booklet preparation, freight costs for saliva samples and booklets, and genetic counsellor phone calls. Any costs incurred in hospital will be derived from relevant routine figures such as the relevant national efficient price (NEP) and the national weighted activity unit (NWAU).
Timepoint [8] 333115 0
1-month from receiving genomic risk information, and 12-months from baseline
Secondary outcome [9] 333751 0
Demographic characteristics and covariates will include age, country of birth, education, marital status, employment status, socioeconomic index; family history of melanoma, personal history of keratinocyte skin cancers, skin colour, skin reaction to repeated sun exposure, self-reported time spent outdoors on weekdays and weekends, and phenotypic risk factors e.g. hair colour, moles using valid, reliable questions.
Timepoint [9] 333751 0
Demographic factors will be collected at baseline only.
Secondary outcome [10] 334732 0
We will measure possible mediators of behaviour change using questions previously developed, tested and widely implemented for skin cancer research and based on well-established health behaviour theories: the Health Belief Model (related to risk perception, barriers and benefits) and Social Cognitive Theory (related to self-efficacy, social norms and environmental influences). These factors have been shown to be important influences on sun-related behaviours.
Timepoint [10] 334732 0
Baseline, 1-month from receiving genomic risk information, and 12-months from baseline
Secondary outcome [11] 334733 0
Feelings of genetic fatalism will be measured using questionnaire items adapted from other research studies examining the psychological and ethical aspects of delivering genomic risk information.
Timepoint [11] 334733 0
Baseline, 1-month from receiving genomic risk information, and 12-months from baseline
Secondary outcome [12] 334734 0
Participant satisfaction with the study and the general educational booklet will be measured using questionnaire items developed for this study
Timepoint [12] 334734 0
1-month from receiving genomic risk information, and 12-months from baseline
Secondary outcome [13] 334735 0
For participants in the intervention arm, we will measure participant satisfaction with the genetic risk booklet and genetic counsellor follow-up call using questionnaire items developed for this study
Timepoint [13] 334735 0
1-month from receiving genomic risk information, and 12-months from baseline
Secondary outcome [14] 334736 0
We will measure the specific impact of result disclosure after genetic testing using the validated Multidimensional Impact of Cancer Risk Assessment (MICRA) scale
Timepoint [14] 334736 0
1-month from receiving genomic risk information, and 12-months from baseline
Secondary outcome [15] 334737 0
Health literacy will be measured using a questionnaire item "how confident are you filling out medical forms by yourself?"
Timepoint [15] 334737 0
Baseline only
Secondary outcome [16] 334738 0
Risk taking behaviours will be measured using "A Domain-Specific Risk-Taking (DOSPERT) scale for adult populations"
Timepoint [16] 334738 0
Baseline only

Eligibility
Key inclusion criteria
People from the general population aged 18-69 years with European ancestry, who have never had a melanoma (since this study is primarily aimed at prevention), and have sufficient English to complete the study questionnaires.
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, personal history of melanoma, no European ancestry, insufficient English to complete the study questionnaires

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)
The biostatistician performing the randomisation will assign participants to their study group (intervention or control) based on a list of study numbers and stratification factors. The biostatistician will not have access to participants’ identifying details such as participant names or contact details. Randomisation will be performed in batches where possible. Staff involved in the day-to-day running of the project will not be involved in the randomisation process apart from providing the list of variables to the biostatistician.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation to the intervention or control arm (allocation ratio 1:1) will be conducted by a biostatistician not involved in the day-to-day running of the project using a computer-based system after collection of baseline data. A minimisation procedure will be used, to ensure that the groups are balanced by phenotypic risk (low, high), sex, state of residence and age-group (18–44, 45–69).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
N/A
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample size:
Sample size calculations are based on detecting a 20% difference in the primary outcome of average daily SEDs between intervention and control arms, in each of the low- and the high-risk phenotype groups. SEDs will be analysed as a continuous measure due to the skewed nature of the SED exposure data. The sample size was calculated using a t-test with a geometric mean ratio (geometric mean SEDs in intervention group /geometric
mean SEDs in control group) of 0.8, coefficient of variation 0.9, 80% power and a of 0.05.

Based on these calculations, a sample of 756 people (378 in the high traditional-risk group and 378 in the low traditional-risk group, split evenly between the intervention and control arms, will provide 80% power to detect a 20% reduction in the primary outcome in favor of the intervention with either low or high traditional risk. Allowing up to 15% with incomplete follow-up at 12 months, we will need to recruit 892 people (446 in each of intervention and control arms). A secondary analysis unstratified by phenotypic risk will give >97% power to detect a 20% difference in SEDs between the intervention and control groups.

Analysis plan:
The primary analysis will be an intention-to-treat comparison of intervention and control arms for mean differences in UVR exposure measured as log-transformed daily SEDs at 12 months, stratifying by phenotypic risk (high, low). UV dosimeter values will be log-transformed as we anticipate that their distribution will be right-skewed, and log-transformed values will be interpreted as a percentage change in the geometric mean of SEDs/day. Generalized linear mixed models (GLMMs) with random intercepts will be fitted to outcome measures collected over the study to assess the overall intervention effect and the effect at fixed follow-up time points (1 month and 12 months) adjusted for baseline scores. For continuous outcomes, we will estimate the mean difference and 95% confidence intervals between intervention and control groups overall and at pre-specified follow-up time points. For binomial outcome variables, we will estimate relative risks and 95% CI overall and at pre-specified follow-up time points. The GLMM approach allows us to account for correlation due to repeated measures on each individual and different types of outcome variables (continuous, binary). All tests will be two sided with a nominal value of 0.05. The effects of potential mediators in facilitating behavior change will be evaluated, using methods such as autoregressive mediation path models and the change-in-estimate.

The following subgroup analyses will also be performed because the effect of the intervention on behaviour change or psycho-social outcomes may be influenced by these factors:
* Sex: male vs. female
* Age: 18–44 vs. 45–69 years
* State of residence: Qld, NT, WA, NSW vs. SA, Vic, Tas
* Health literacy: good vs. poor
* Family history of melanoma or a personal history of non-melanoma skin cancer: yes vs. no
* Education: school-only vs higher education
* Socio-Economic Indexes for Areas (SEIFA) Index: high vs. low using median cut-point
* Has children: yes vs. no
* Genomic risk level among the intervention group only: higher than average vs. average vs. lower than average
* Discordant genotype/phenotype groups:
(i) low-risk phenotype but high-risk genotype, vs.
(ii) high-risk phenotype but low-risk genotype, vs.
(iii) all other combinations
* Risk taking propensity: risk-averse vs risk-seeking

Some analyses will also be conducted on the intervention arm participants, to investigate the broader impact of receiving genetic testing results. These analyses will be stratified by genetic risk level (lower than average, average, higher than average).

We will use a chi-square test to see if the attrition rate differs by arm. If more than 15% of participants drop out we will use logistic regression to compare baseline characteristics of participants who completed the intervention versus those who did not. Each variable will be examined for the presence of missing data and if >10% is observed on key variables, sensitivity analysis will be performed using complete case analysis or multiple imputation methods. For participants who do not have UV dosimeter (SED) data for both weekday and weekend exposures, we will estimate their missing exposure using imputation methods based on the participant’s available weekday or weekend SEDs and SEDs data from the same age-group, gender, traditional-risk group and state. We will collect 12-month follow-up dosimeter data for all participants, but will restrict collection of 1-month follow-up dosimeter data on a sample of ~240 study participants due to resource constraints. In a sensitivity analysis, we will use the 1-month dosimeter data to adjust for the effects of measurement error in the relative risk estimate for self-reported sun exposure, using established methods.

Recruitment
Recruitment status
Active, not recruiting
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)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 295546 0
Government body
Name [1] 295546 0
National Health and Medical Research Council
Address [1] 295546 0
16 Marcus Clarke St Canberra ACT 2601
Country [1] 295546 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
The University of Sydney Camperdown NSW 2006
Country
Australia
Secondary sponsor category [1] 294365 0
None
Name [1] 294365 0
Address [1] 294365 0
Country [1] 294365 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296867 0
Human Research Ethics Committee, The University of Sydney
Ethics committee address [1] 296867 0
Ethics and Research Integrity, Margaret Telfer Building (K07) University of Sydney NSW 2006
Ethics committee country [1] 296867 0
Australia
Date submitted for ethics approval [1] 296867 0
06/03/2017
Approval date [1] 296867 0
10/04/2017
Ethics approval number [1] 296867 0
Project no. 2017/163

Summary
Brief summary
The primary purpose of the Managing Your Risk Study is to evaluate the efficacy of personal genetic risk of melanoma information, compared to standard prevention advice, in motivating preventative behaviours in the general population.

Who is it for?
You may be eligible to enroll in this trial if you are aged between 18 and 69 years, have European ancestry, and have never had a melanoma.

Study details
All participants enrolled in this trial will be randomly allocated (by chance) to receive personalised genetic risk of melanoma information and an educational booklet on melanoma preventive behaviours, or to receive the educational booklet only. Participants allocated to the group receiving their genetic risk information will provide a saliva sample using the kit sent via postal mail. This will be used for genetic testing and 2-3 months later, these participants will receive a booklet in the mail containing information on their personal genetic risk of melanoma. With their genetic risk information, participants will be given an educational booklet on melanoma preventive behaviours including sun exposure, sun protection and skin examinations. Within 2 weeks of receiving the mailed booklets, participants will receive a phone call from a genetic counsellor to answer any questions about the information. The other group of participants will receive the educational booklet only, and no genetic risk information information or phone call. All participants will have be able to contact a study-dedicated genetic counsellor at the time of consent to ask any questions they may have.

All participants will be asked to complete questionnaires and to wear a specialised wrist-worn device (similar in appearance to a watch or a fitbit) which measures sun exposure for 10 days. All participants will be asked to complete a questionnaire and wear a UV dosimeter at baseline, complete a questionnaire at 1-month after they are sent their booklet(s) and complete a questionnaire and wear a UV dosimeter at 12 months after baseline. A subgroup of ~240 participants will also be asked to wear a UV dosimeter at 1-month after they are sent their booklet(s).

It is hoped that the findings from this trial will provide information on whether providing information on personalised genetic risk of melanoma motivates people to undertake preventative and early detection behaviours.
Trial website
http://sydney.edu.au/medicine/public-health/research/cancer-epidemiology-prevention/managing-risk.php
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 72278 0
Prof Anne Cust
Address 72278 0
The Lifehouse, Level 6 - North
119-143 Missenden Rd
Camperdown NSW 2050
Country 72278 0
Australia
Phone 72278 0
+61 2 8627 1565
Fax 72278 0
Email 72278 0
anne.cust@sydney.edu.au
Contact person for public queries
Name 72279 0
Ms Amelia Smit
Address 72279 0
The Lifehouse, Level 6 - North
119-143 Missenden Rd
Camperdown NSW 2050
Country 72279 0
Australia
Phone 72279 0
+61 2 8627 1530
Fax 72279 0
Email 72279 0
amelia.smit@sydney.edu.au
Contact person for scientific queries
Name 72280 0
Prof Anne Cust
Address 72280 0
The Lifehouse, Level 6 - North
119-143 Missenden Rd
Camperdown NSW 2050
Country 72280 0
Australia
Phone 72280 0
+61 2 8627 1565
Fax 72280 0
Email 72280 0
anne.cust@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD will not be available for this trial as ethics approval has not been obtained for this.
What supporting documents are/will be available?
Study protocol
Statistical analysis plan
How or where can supporting documents be obtained?
Type [1] 6516 0
Study protocol
Citation [1] 6516 0
Smit AK, Newson AJ, Morton RL, Kimlin M, Keogh L, Law MH, Kirk J, Dobbinson S, Kanetsky PA, Fenton G, Allen M, Butow P, Dunlop K, Trevena L, Lo S, Savard J, Dawkins H, Wordsworth S, Jenkins M, Mann GJ, Cust AE. The melanoma genomics managing your risk study: A protocol for a randomized controlled trial evaluating the impact of personal genomic risk information on skin cancer prevention behaviors. Contemp Clin Trials. 2018;70:106-16.
Link [1] 6516 0
Email [1] 6516 0
Other [1] 6516 0
Attachment [1] 6516 0
Type [2] 6517 0
Statistical analysis plan
Citation [2] 6517 0
Link [2] 6517 0
Email [2] 6517 0
Other [2] 6517 0
The statistical analysis plan will be published in a peer-reviewed scientific journal.
Attachment [2] 6517 0
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary