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The Achieving Self-directed Integrated Cancer Aftercare Intervention for Detection of Recurrent and Second Primary Melanoma in Survivors of Melanoma: Pilot Randomized Controlled Trial

Background Melanoma is common with increasing incidence. Guidelines recommend monthly total skin self-examinations (TSSEs) by survivors to detect recurrent and new primary melanomas. TSSE is underperformed despite evidence of benefit. Objective This study compares the effect on psychological well-being and TSSE practice of a self-directed digital intervention with treatment as usual in patients treated for a first stage 0 to IIC primary cutaneous melanoma within the preceding 60 months. Methods This randomized clinical trial was conducted at 2 UK National Health Service hospitals (Aberdeen Royal Infirmary, Grampian, and Addenbrooke’s, Cambridge). Adults (≥18 years) diagnosed with a first 0 to IIC primary cutaneous melanoma were randomized to receive Achieving Self-directed Integrated Cancer Aftercare (ASICA), a tablet-based intervention prompting and supporting TSSE in survivors of melanoma, or to usual care. The hypothesis was that ASICA would increase TSSE practice in users affected by melanoma and compared with controls without affecting psychological well-being. The main primary outcomes were melanoma worry (Melanoma Worry Scale), anxiety and depression (Hospital Anxiety and Depression Scale), and quality of life (EQ-5D-5L) as well as secondary outcomes collected using postal questionnaires 3, 6, and 12 months following randomization. Results A total of 240 recruits were randomized (1:1) into the ASICA (n=121, 50.4%) or control (n=119, 49.6%) groups. There were no significant differences between groups for melanoma worry at 12 months (mean difference: 0.12, 95% CI −0.6 to 0.84; P=.74), 3 months (0.23, 95% CI −0.31 to 0.78; P=.40), or 6 months (−0.1, 95% CI −0.7 to 0.51; P=.76). The ASICA group had lower anxiety scores at 12 months (−0.54, 95% CI −1.31 to 0.230; P=.17), 3 months (−0.13, 95% CI −0.79 to 0.54; P=.71), and significantly at 6 months (−1.00, 95% CI −1.74 to −0.26; P=.009). Depression scores were similar, being lower at 12 months (−0.44, 95% CI −1.11 to 0.23; P=.20) and 3 months (−0.24, 95% CI −0.84 to 0.35; P=.42) but only significantly lower at 6 months (−0.77, 95% CI −1.41 to −0.12; P=.02). The ASICA group had significantly higher quality of life scores at 12 months (0.044, 95% CI 0.003-0.085; P=.04) and 6 months (0.070, 95% CI 0.032-0.107; P<.001) and nonsignificantly at 3 months (0.024, 95% CI −0.006 to 0.054; P=.11). ASICA users reported significantly more regular (>5) TSSEs during the study year and significantly higher levels of self-efficacy in conducting TSSE. They also reported significantly higher levels of planning and intention to perform TSSE in the future. Conclusions Using ASICA for 12 months does not increase melanoma worry, can reduce anxiety and depression, and may improve quality of life. ASICA has the potential to improve the well-being and vigilance of survivors of melanoma and enable the benefits of regular TSSE. Trial Registration ClinicalTrials.gov NCT03328247; https://clinicaltrials.gov/ct2/show/NCT03328247 International Registered Report Identifier (IRRID) RR2-10.1186/s13063-019-3453-x


INTRODUCTION 2a-i) Problem and the type of system/solution
The aim of this pilot study was to evaluate the ASICA self-directed digital intervention in a patient-focused randomized controlled trial among those treated for a first stage 0-2C primary cutaneous melanoma within the preceding 60 months. The primary objective of the pilot study was to determine the impact of using ASICA on patient's melanoma worry, anxiety and depression and quality of life. The secondary objective was to provide information on the feasibility of processes for a full-scale national trial of the ASICA intervention 2a-ii) Scientific background, rationale: What is known about the (type of) system The aim of this pilot study was to evaluate the ASICA self-directed digital intervention in a patient-focused randomized controlled trial among those treated for a first stage 0-2C primary cutaneous melanoma within the preceding 60 months. The primary objective of the pilot study was to determine the impact of using ASICA on patient's melanoma worry, anxiety and depression and quality of life. The secondary objective was to provide information on the feasibility of processes for a full-scale national trial of the ASICA intervention Does your paper address CONSORT subitem 2b?
The aim of this pilot study was to evaluate the ASICA self-directed digital intervention in a patient-focused randomized controlled trial among those treated for a first stage 0-2C primary cutaneous melanoma within the preceding 60 months. The primary objective of the pilot study was to determine the impact of using ASICA on patient's melanoma worry, anxiety and depression and quality of life. The secondary objective was to provide information on the feasibility of processes for a full-scale national trial of the ASICA intervention METHODS 3a) CONSORT: Description of trial design (such as parallel, factorial) including allocation ratio ASICA was a two-arm, open, two-centre randomised controlled pilot trial (RCT) comparing the ASICA digital intervention with a control group receiving usual follow-up only ( Figure 1). The study sites were Aberdeen Royal Infirmary and Addenbrooke's Hospital, Cambridge. Adults (≥18 years) treated within the preceding 60 months for a previous stage 0-IIC primary cutaneous melanoma were sent information about the study, a consent form and baseline questionnaire by post. Individuals diagnosed with stage 3 and 4 melanoma, recurrent melanoma within the last 60 months or unable to consent and/or complete questionnaires were excluded. Those interested in participating in the study were contacted by the recruiting site to discuss further. Participants were randomised after informed written consent had been obtained. 3b) CONSORT: Important changes to methods after trial commencement (such as eligibility criteria), with reasons This is not applicable as there were no changes 3b-i) Bug fixes, Downtimes, Content Changes This is not applicable as there were no bug fixes, downtime or content changes 4a) CONSORT: Eligibility criteria for participants Eligibility criteria are included in the manuscript 4a-i) Computer / Internet literacy This was not an appropriate eligbility criteria for this study 4a-ii) Open vs. closed, web-based vs. face-to-face assessments: The study sites were Aberdeen Royal Infirmary and Addenbrooke's Hospital, Cambridge. Adults (≥18 years) treated within the preceding 60 months for a previous stage 0-IIC primary cutaneous melanoma were sent information about the study, a consent form and baseline questionnaire by post.

4a-iii) Information giving during recruitment
The study sites were Aberdeen Royal Infirmary and Addenbrooke's Hospital, Cambridge. Adults (≥18 years) treated within the preceding 60 months for a previous stage 0-IIC primary cutaneous melanoma were sent information about the study, a consent form and baseline questionnaire by post. 4b) CONSORT: Settings and locations where the data were collected Baseline data were collected from secondary care records by a research nurse at each site before randomisation. The co-primary outcomes were Melanoma Worry Scale (MWS), anxiety and depression (HADS) and quality of life (EQ-5D-5L) [19]. Secondary outcomes were adherence to TSSE recommendations, self-efficacy and future intention and planning to perform TSSE [22]. Primary and secondary outcomes were collected by postal questionnaires at baseline, 3, 6-and 12-months after randomisation. Tertiary outcomes were new primary and recurrent melanomas and patterns of skinrelated NHS resource use. These were collected 12 months after randomisation from secondary care records by research nurses blind to allocation. 4b-i) Report if outcomes were (self-)assessed through online questionnaires Baseline data were collected from secondary care records by a research nurse at each site before randomisation. The co-primary outcomes were Melanoma Worry Scale (MWS), anxiety and depression (HADS) and quality of life (EQ-5D-5L) [19]. Secondary outcomes were adherence to TSSE recommendations, self-efficacy and future intention and planning to perform TSSE [22]. Primary and secondary outcomes were collected by postal questionnaires at baseline, 3, 6-and 12-months after randomisation. Tertiary outcomes were new primary and recurrent melanomas and patterns of skinrelated NHS resource use. These were collected 12 months after randomisation from secondary care records by research nurses blind to allocation. 4b-ii) Report how institutional affiliations are displayed This project received full approval from the North of Scotland Research Ethics Committee on 28th April 2017 ((17/NS/0040). Written informed consent was obtained from all study participants. The trial was conducted according to the principles of good clinical practice provided by Research Governance Guidelines. Consent for publication did not apply 5) CONSORT: Describe the interventions for each group with sufficient details to allow replication, including how and when they were actually administered 5-i) Mention names, credential, affiliations of the developers, sponsors, and owners The necessary information is provided in the manuscript 5-ii) Describe the history/development process This has been described in an earlier publication 5-iii) Revisions and updating These items are beyond the scope if the trial report 5-iv) Quality assurance methods Not applicable to the current study 5-v) Ensure replicability by publishing the source code, and/or providing screenshots/screen-capture video, and/or providing flowcharts of the algorithms used These items are not relevant to the current trial report and available elsewhere

5-vi) Digital preservation
The intervention has been archieved 5-vii) Access Briefly, intervention group participants attended a 30-minute training session at which they were issued with a seven-inch Samsung Galaxy tablet and given instruction on the intervention and how the tablet computer-base application (app) should be used to support them to conduct a thorough full-body TSSE in response to a monthly SMS text reminder sent from the trial team. The nurse demonstrated the function of the app and answered any questions about TSSE or the intervention. The app included information about the importance of monthly TSSE, instructional videos demonstrating how to perform a TSSE and take good photographs of skin lesions, a digital map of the patient's own skin, a structured checkbox list of body parts to check, prompts for the patient to plan their next TSSE and the capability to take photographs of suspicious skin lesions and send them to a dermatology nurse practitioner for review along with a text-based report of the TSSE outcomes including a description of any concerns. All participants who submitted text-based reports of any skin concerns were followed-up by the dermatology nurse practitioner.The monthly prompt was sent on a single occasion and no reminders were sent to individuals who did not complete the TSSE that month, but they would continue to be reminded on each subsequent month. The control group also completed the baseline questionnaire. All participants (intervention and control) continued to attend their usual structured melanoma follow-up as determined by local guidelines 5-viii) Mode of delivery, features/functionalities/components of the intervention and comparator, and the theoretical framework Briefly, intervention group participants attended a 30-minute training session at which they were issued with a seven-inch Samsung Galaxy tablet and given instruction on the intervention and how the tablet computer-base application (app) should be used to support them to conduct a thorough full-body TSSE in response to a monthly SMS text reminder sent from the trial team. The nurse demonstrated the function of the app and answered any questions about TSSE or the intervention. The app included information about the importance of monthly TSSE, instructional videos demonstrating how to perform a TSSE and take good photographs of skin lesions, a digital map of the patient's own skin, a structured checkbox list of body parts to check, prompts for the patient to plan their next TSSE and the capability to take photographs of suspicious skin lesions and send them to a dermatology nurse practitioner for review along with a text-based report of the TSSE outcomes including a description of any concerns. All participants who submitted text-based reports of any skin concerns were followed-up by the dermatology nurse practitioner.The monthly prompt was sent on a single occasion and no reminders were sent to individuals who did not complete the TSSE that month, but they would continue to be reminded on each subsequent month. The control group also completed the baseline questionnaire. All participants (intervention and control) continued to attend their usual structured melanoma follow-up as determined by local guidelines 5-ix) Describe use parameters Briefly, intervention group participants attended a 30-minute training session at which they were issued with a seven-inch Samsung Galaxy tablet and given instruction on the intervention and how the tablet computer-base application (app) should be used to support them to conduct a thorough full-body TSSE in response to a monthly SMS text reminder sent from the trial team. The nurse demonstrated the function of the app and answered any questions about TSSE or the intervention. The app included information about the importance of monthly TSSE, instructional videos demonstrating how to perform a TSSE and take good photographs of skin lesions, a digital map of the patient's own skin, a structured checkbox list of body parts to check, prompts for the patient to plan their next TSSE and the capability to take photographs of suspicious skin lesions and send them to a dermatology nurse practitioner for review along with a text-based report of the TSSE outcomes including a description of any concerns. All participants who submitted text-based reports of any skin concerns were followed-up by the dermatology nurse practitioner.The monthly prompt was sent on a single occasion and no reminders were sent to individuals who did not complete the TSSE that month, but they would continue to be reminded on each subsequent month. The control group also completed the baseline questionnaire. All participants (intervention and control) continued to attend their usual structured melanoma follow-up as determined by local guidelines 5-x) Clarify the level of human involvement Briefly, intervention group participants attended a 30-minute training session at which they were issued with a seven-inch Samsung Galaxy tablet and given instruction on the intervention and how the tablet computer-base application (app) should be used to support them to conduct a thorough full-body TSSE in response to a monthly SMS text reminder sent from the trial team. The nurse demonstrated the function of the app and answered any questions about TSSE or the intervention. The app included information about the importance of monthly TSSE, instructional videos demonstrating how to perform a TSSE and take good photographs of skin lesions, a digital map of the patient's own skin, a structured checkbox list of body parts to check, prompts for the patient to plan their next TSSE and the capability to take photographs of suspicious skin lesions and send them to a dermatology nurse practitioner for review along with a text-based report of the TSSE outcomes including a description of any concerns. All participants who submitted text-based reports of any skin concerns were followed-up by the dermatology nurse practitioner.The monthly prompt was sent on a single occasion and no reminders were sent to individuals who did not complete the TSSE that month, but they would continue to be reminded on each subsequent month. The control group also completed the baseline questionnaire. All participants (intervention and control) continued to attend their usual structured melanoma follow-up as determined by local guidelines 5-xi) Report any prompts/reminders used Briefly, intervention group participants attended a 30-minute training session at which they were issued with a seven-inch Samsung Galaxy tablet and given instruction on the intervention and how the tablet computer-base application (app) should be used to support them to conduct a thorough full-body TSSE in response to a monthly SMS text reminder sent from the trial team. The nurse demonstrated the function of the app and answered any questions about TSSE or the intervention. The app included information about the importance of monthly TSSE, instructional videos demonstrating how to perform a TSSE and take good photographs of skin lesions, a digital map of the patient's own skin, a structured checkbox list of body parts to check, prompts for the patient to plan their next TSSE and the capability to take photographs of suspicious skin lesions and send them to a dermatology nurse practitioner for review along with a text-based report of the TSSE outcomes including a description of any concerns. All participants who submitted text-based reports of any skin concerns were followed-up by the dermatology nurse practitioner.The monthly prompt was sent on a single occasion and no reminders were sent to individuals who did not complete the TSSE that month, but they would continue to be reminded on each subsequent month. The control group also completed the baseline questionnaire. All participants (intervention and control) continued to attend their usual structured melanoma follow-up as determined by local guidelines 5-xii) Describe any co-interventions (incl. training/support) Briefly, intervention group participants attended a 30-minute training session at which they were issued with a seven-inch Samsung Galaxy tablet and given instruction on the intervention and how the tablet computer-base application (app) should be used to support them to conduct a thorough full-body TSSE in response to a monthly SMS text reminder sent from the trial team. The nurse demonstrated the function of the app and answered any questions about TSSE or the intervention. The app included information about the importance of monthly TSSE, instructional videos demonstrating how to perform a TSSE and take good photographs of skin lesions, a digital map of the patient's own skin, a structured checkbox list of body parts to check, prompts for the patient to plan their next TSSE and the capability to take photographs of suspicious skin lesions and send them to a dermatology nurse practitioner for review along with a text-based report of the TSSE outcomes including a description of any concerns. All participants who submitted text-based reports of any skin concerns were followed-up by the dermatology nurse practitioner.The monthly prompt was sent on a single occasion and no reminders were sent to individuals who did not complete the TSSE that month, but they would continue to be reminded on each subsequent month. The control group also completed the baseline questionnaire. All participants (intervention and control) continued to attend their usual structured melanoma follow-up as determined by local guidelines 6a) CONSORT: Completely defined pre-specified primary and secondary outcome measures, including how and when they were assessed Baseline data were collected from secondary care records by a research nurse at each site before randomisation. The co-primary outcomes were Melanoma Worry Scale (MWS), anxiety and depression (HADS) and quality of life (EQ-5D-5L) [19]. Secondary outcomes were adherence to TSSE recommendations, self-efficacy and future intention and planning to perform TSSE [22]. Primary and secondary outcomes were collected by postal questionnaires at baseline, 3, 6-and 12-months after randomisation. Tertiary outcomes were new primary and recurrent melanomas and patterns of skinrelated NHS resource use. These were collected 12 months after randomisation from secondary care records by research nurses blind to allocation. 6a-i) Online questionnaires: describe if they were validated for online use and apply CHERRIES items to describe how the questionnaires were designed/deployed Baseline data were collected from secondary care records by a research nurse at each site before randomisation. The co-primary outcomes were Melanoma Worry Scale (MWS), anxiety and depression (HADS) and quality of life (EQ-5D-5L) [19]. Secondary outcomes were adherence to TSSE recommendations, self-efficacy and future intention and planning to perform TSSE [22]. Primary and secondary outcomes were collected by postal questionnaires at baseline, 3, 6-and 12-months after randomisation. Tertiary outcomes were new primary and recurrent melanomas and patterns of skinrelated NHS resource use. These were collected 12 months after randomisation from secondary care records by research nurses blind to allocation. 6a-ii) Describe whether and how "use" (including intensity of use/dosage) was defined/measured/monitored These are beyond the scope of the current paper and reported in a separate publication 6a-iii) Describe whether, how, and when qualitative feedback from participants was obtained A separate qualitative manuscript has been submitted 6b) CONSORT: Any changes to trial outcomes after the trial commenced, with reasons Baseline data were collected from secondary care records by a research nurse at each site before randomisation. The co-primary outcomes were Melanoma Worry Scale (MWS), anxiety and depression (HADS) and quality of life (EQ-5D-5L) [19]. Secondary outcomes were adherence to TSSE recommendations, self-efficacy and future intention and planning to perform TSSE [22]. Primary and secondary outcomes were collected by postal questionnaires at baseline, 3, 6-and 12-months after randomisation. Tertiary outcomes were new primary and recurrent melanomas and patterns of skinrelated NHS resource use. These were collected 12 months after randomisation from secondary care records by research nurses blind to allocation. 7a) CONSORT: How sample size was determined 7a-i) Describe whether and how expected attrition was taken into account when calculating the sample size 7b) CONSORT: When applicable, explanation of any interim analyses and stopping guidelines Baseline data were collected from secondary care records by a research nurse at each site before randomisation. The co-primary outcomes were Melanoma Worry Scale (MWS), anxiety and depression (HADS) and quality of life (EQ-5D-5L) [19]. Secondary outcomes were adherence to TSSE recommendations, self-efficacy and future intention and planning to perform TSSE [22]. Primary and secondary outcomes were collected by postal questionnaires at baseline, 3, 6-and 12-months after randomisation. Tertiary outcomes were new primary and recurrent melanomas and patterns of skinrelated NHS resource use. These were collected 12 months after randomisation from secondary care records by research nurses blind to allocation. 8a) CONSORT: Method used to generate the random allocation sequence Participants were randomised 1:1 to intervention or control using a remote automated computer-allocated application hosted at the Centre for Healthcare Randomised Trials (CHaRT) in Aberdeen, UK. An algorithm minimised imbalance in sex and centre between groups [21]. Due to the nature of the intervention, both participants and researchers were not masked to randomised allocation. 8b) CONSORT: Type of randomisation; details of any restriction (such as blocking and block size) Participants were randomised 1:1 to intervention or control using a remote automated computer-allocated application hosted at the Centre for Healthcare Randomised Trials (CHaRT) in Aberdeen, UK. An algorithm minimised imbalance in sex and centre between groups [21]. Due to the nature of the intervention, both participants and researchers were not masked to randomised allocation. 9) CONSORT: Mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned Participants were randomised 1:1 to intervention or control using a remote automated computer-allocated application hosted at the Centre for Healthcare Randomised Trials (CHaRT) in Aberdeen, UK. An algorithm minimised imbalance in sex and centre between groups [21]. Due to the nature of the intervention, both participants and researchers were not masked to randomised allocation. 10) CONSORT: Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions Participants were randomised 1:1 to intervention or control using a remote automated computer-allocated application hosted at the Centre for Healthcare Randomised Trials (CHaRT) in Aberdeen, UK. An algorithm minimised imbalance in sex and centre between groups [21]. Due to the nature of the intervention, both participants and researchers were not masked to randomised allocation. 11a) CONSORT: Blinding -If done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how 11a-i) Specify who was blinded, and who wasn't Blinding was not possible in this study 11a-ii) Discuss e.g., whether participants knew which intervention was the "intervention of interest" and which one was the "comparator" participant knew if they were in the intervention or control group 11b) CONSORT: If relevant, description of the similarity of interventions There was only one intervention trialled 12a) CONSORT: Statistical methods used to compare groups for primary and secondary outcomes A statistical analysis section is provided in the manuscript 12a-i) Imputation techniques to deal with attrition / missing values These were not employed in the current study 12b) CONSORT: Methods for additional analyses, such as subgroup analyses and adjusted analyses There were no subgroup analyses conducted RESULTS 13a) CONSORT: For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analysed for the primary outcome This information is within the results section and tables 13b) CONSORT: For each group, losses and exclusions after randomisation, together with reasons A study flow diagram is included in the manuscript 13b-i) Attrition diagram A study flow diagram is included in the manuscript 14a) CONSORT: Dates defining the periods of recruitment and follow-up Between 24 January 2018 and 8 March 2019, 240 participants were randomised (121 to the ASICA intervention,119 to usual care).

14a-i) Indicate if critical "secular events" fell into the study period
This is not relevant to the current study 14b) CONSORT: Why the trial ended or was stopped (early) This is not relevant to the current study 15) CONSORT: A table showing baseline demographic and clinical characteristics for each group This is included in the manuscript 15-i) Report demographics associated with digital divide issues Demographics are reported in the paper 16a) CONSORT: For each group, number of participants (denominator) included in each analysis and whether the analysis was by original assigned groups 16-i) Report multiple "denominators" and provide definitions This information is reported in the paper

16-ii) Primary analysis should be intent-to-treat
The analysis was by the intention-to-treat principle 17a) CONSORT: For each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% confidence interval) This information is reported in the results section and the tables 17a-i) Presentation of process outcomes such as metrics of use and intensity of use This information has been presented in another publication 17b) CONSORT: For binary outcomes, presentation of both absolute and relative effect sizes is recommended This information is reported in the paper 18) CONSORT: Results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing pre-specified from exploratory All relevant analyses are reported in the paper

18-i) Subgroup analysis of comparing only users
This is not relevant to the current study

19) CONSORT: All important harms or unintended effects in each group
This information is reported in the manuscript 19-i) Include privacy breaches, technical problems This is not relevant to the current manuscript 19-ii) Include qualitative feedback from participants or observations from staff/researchers Qualitative feedback is being reported in another related publication DISCUSSION 20) CONSORT: Trial limitations, addressing sources of potential bias, imprecision, multiplicity of analyses 20-i) Typical limitations in ehealth trials We provide a structured discussion in the paper 21) CONSORT: Generalisability (external validity, applicability) of the trial findings 21-i) Generalizability to other populations We provide a structured discussion in the paper 21-ii) Discuss if there were elements in the RCT that would be different in a routine application setting We provide a structured discussion in the paper 22) CONSORT: Interpretation consistent with results, balancing benefits and harms, and considering other relevant evidence 22-i) Restate study questions and summarize the answers suggested by the data, starting with primary outcomes and process outcomes (use) We provide a structured discussion in the paper

22-ii) Highlight unanswered new questions, suggest future research
We provide a structured discussion in the paper Other information 23) CONSORT: Registration number and name of trial registry This information is provided 24) CONSORT: Where the full trial protocol can be accessed, if available The full protocol is reference in the paper 25) CONSORT: Sources of funding and other support (such as supply of drugs), role of funders This information is provided in the manuscript X26-i) Comment on ethics committee approval This project received full approval from the North of Scotland Research Ethics Committee on 28th April 2017 ((17/NS/0040). Written informed consent was obtained from all study participants. The trial was conducted according to the principles of good clinical practice provided by Research Governance Guidelines. Consent for publication did not apply x26-ii) Outline informed consent procedures Those interested in participating in the study were contacted by the recruiting site to discuss further. Participants were randomised after informed written consent had been obtained.

X26-iii) Safety and security procedures
These are not specifically discussed in the current trial report X27-i) State the relation of the study team towards the system being evaluated This information is provided in the manuscript