Effect of a Skin Self-monitoring Smartphone Application on Time to Physician Consultation Among Patients With Possible Melanoma

Key Points Question Does a smartphone application that prompts monthly skin self-monitoring result in individuals with increased risk of melanoma having more timely or more frequent family practice consultations for skin changes? Findings In this phase 2 randomized clinical trial of 238 participants, there were no significant differences in skin consultation rates, measures of skin self-monitoring, or psychological harm. Meaning Because there was no evidence that a smartphone application increased skin self-examination or health care consulting rates among a family practice population at increased risk of melanoma, its implementation is not yet recommended.


Introduction
Melanoma is among the most lethal forms of skin cancer. 1 While it accounts for less than 5% of all cutaneous malignant neoplasms worldwide, melanoma is responsible for most skin cancer deaths. 2 Internationally, melanoma has among the fastest rising incidence rates of any cancer. 3 In the United States, during the 7 years from 2009 to 2016, raw incidence rates per 100 000 residents climbed from 22.2 to 23.6, with an estimated 76 380 new cases in 2016. 4 In England, in the decade from 2007 to 2016, age-standardized incidence increased by 37%, with 13 748 new cases and 1937 deaths in 2016. 5 Melanoma is largely preventable; more than 80% of newly diagnosed melanomas are associated with an increase in recreational sun exposure and tanning bed use. 6,7 Melanoma is also largely curable, with 5-year net-standardized survival of 100% for stage-1 tumors, and most tumors among patients with melanoma are stage-1 tumors. 8 However, among patients presenting with laterstage disease, overall survival rates fall significantly, and once the disease has spread beyond surgical intervention, metastatic melanoma remains largely incurable despite the recent introduction of systemic therapies extending survival. 9,10 There is growing evidence that time to patient presentation to health care and initial management in primary care are key determinants of patient outcomes for most cancers. 11,12 Compared with other cancers, melanoma has among the longest delays measured as median time to patient presentation. 13, 14 To understand possible reasons, recent studies have explored symptom appraisal and help-seeking among individuals recently diagnosed with melanoma. Factors contributing to later presentation to health care include having limited awareness of the seriousness of some skin changes, considering changes in skin as part of normal aging, and having concerns about wasting their own and their general practitioners' time. 15 Mass media campaigns have been the main population approach to reduce sun exposure and improve time to presentation. In Australia, public health campaigns such as Slip-Slap-Slop have been highly effective in primary prevention, and incidence rates for new melanoma are plateauing. 16 Mass media approaches in the United Kingdom, such as SunSmart and the Be Clear on Cancer Skin Cancer campaign, have been less effective in reducing sun exposure or promoting consultations to health care. Initiatives in the United States have focused on educational and clinician-led approaches to minimizing exposure among children and young adults with fair skin types to UV radiation. 17 Routine screening of the general population is not currently recommended internationally, although some countries (eg, the United Kingdom, Australia, New Zealand, Germany, the Netherlands) recommend regular skin checks and/or self-examination for certain subsets of patients with increased risk of melanoma. 18 More targeted interventions aimed at individuals with increased risk of melanoma could promote earlier presentation to health care. There is a great deal of interest in new technological approaches, such as smartphone applications. People have increasing access to smartphone applications; in 2017, more than 77% of the US and UK populations owned a smartphone. 19 Smartphone applications can be used to inform prevention and awareness messages, photograph skin lesions, and monitor possible skin changes. 20 We have demonstrated that it is possible to use a simple patient-completed risk assessment tool in the UK family practice setting to stratify the population into those with population risk and those with increased risk of melanoma. 21 Individuals with increased risk could receive targeted interventions to promote earlier presentation to health care.

JAMA Network Open | Dermatology
We chose the MySkinPal app as an exemplar for this study, following extensive phase 1 evaluation. Having reviewed the availability of potentially suitable smartphone skin self-monitoring (SSM) applications, also known as skin self-examination (SSE) applications, 20 we undertook qualitative research, using focus groups and interviews, with individuals with increased risk of melanoma to provide in-depth understanding of consumer views on the usefulness and usability of 2 short-listed applications. MySkinPal was selected for its superior ease of use, including photography, straightforward instructions, and built-in notifications to complete future skin self-monitoring 22 (eFigure in Supplement 1). We aimed to test the SSM application in a family practice population with increased risk of melanoma and measure its effect on time to consultation and consultation rates for skin changes.

Methods
The trial protocol has been published 22 and is available in Supplement 2; therefore, the methods are reported briefly here. This study was approved by the Cambridgeshire and Hertfordshire NHS research ethics committee. This report followed the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline.

Trial Design and Participants
This individually randomized phase 2 clinical trial was conducted in 12 family practices in Eastern England. Eligible participants were general practice attendees aged 18 to 75 years who owned a smartphone and were identified as having increased risk of melanoma after completing an electronic questionnaire (ie, MelaTools Q risk assessment tool 21 ) using tablet computers. Participants were able to read and write English and give informed consent. Exclusion criteria were having a severe psychiatric or cognitive disorder or a physical disorder severe enough to inhibit the use of a smartphone. Potentially eligible patients were given a trial appointment at their general practice.
Randomization was performed after written informed consent had been obtained.

Control
A research nurse invited participants in the control group to complete the baseline questionnaire; the nurse and participants then had a brief discussion about skin health, using the Cancer Research UK leaflets "Be sunsmart-cut your cancer risk" and "Skin cancer-how to spot the signs and symptoms." Participants then received usual care at their general practice.

Intervention
In addition to consultation with a nurse, participants randomized to the intervention group had the SSM application loaded on their smartphones and were given verbal and written instructions on its use. A monthly prompt to self-monitor for skin changes was set on the applications, and participants were reimbursed with a voucher for £10 (US $13) to cover the cost of the application.

Outcomes and Measures
We collected information on sociodemographic and clinical variables as follows: age, sex, marital status, postcode, highest educational level, occupation, history of skin cancer, skin and hair type, and number of raised moles on both arms at baseline. 21,23 The coprimary clinical outcomes of this trial were as follows: (1) family practice consultation rates and (2) patient interval (ie, time between first noticing a change and consultation 24 ) for any skin changes or pigmented skin lesions. Data on consultations in the year before the trial and for 12 months after the trial consultation were collected through audits of general practitioner medical records. Data on the patient interval were measured using the Skin Questionnaire. This self-completed questionnaire, based on the Symptom instrument, [25][26][27] obtains data on presenting symptoms and their duration before consultation.

JAMA Network Open | Dermatology
Monthly electronic searches of general practitioner medical records identified recent skin consultations. Participants were sent (electronically or by mail) a Skin Questionnaire to complete regarding skin changes associated with that consultation.
This was a phase 2 randomized clinical trial of a complex intervention, 28  Participant-completed measures were collected at baseline, 1 month, and 12 months. Health service utilization data were collected at 12 months by general practice medical record audit.

Sample Size
This feasibility trial was designed to have a sample size of 200, with 100 participants in each group.
This would provide sufficient data on ease of recruitment and attrition and to estimate effect size to inform a future phase 3 randomized clinical trial. 22

Randomization
Eligible patients who consented to participate were randomized 1:1 to either the control or intervention group. Randomization was performed using an online system, and a block randomization method was applied using computer-generated, randomly permuted blocks of sizes 2, 4, and 6, established by a professional independent randomization service (King's College London Clinical Trials, United Kingdom).

Masking
Outcomes assessed by self-report obviated the need for researcher masking. For the extraction and analysis of health service data, research staff were masked to group assignment. All statistical analyses were performed masked to group assignment.

Statistical Analysis
We wrote a statistical analysis plan (agreed on by F.M.W., M.E.B., and C.L.S.), including outlines of all results tables and all analysis code, before exploring any data, and unmasking only occurred after all the analyses had been completed. These methods followed our previously reported approach to this analysis, published in the study protocol. This plan appears in Supplement 2. 22 Poisson regression was used to analyze the consultation rate primary outcome, and linear regression was used to analyze the patient interval primary outcome, with practice-level random effects to account for possible clustering of outcomes within general practices. Secondary outcomes were analyzed using linear (continuous outcomes) or logistic (binary outcomes) regression, with participant-level random effects to account for the similarity of answers when participants responded at both 6 and 12 months follow-up. Formal statistical comparisons were only made when rates of missing data were similar (prespecified as a difference of 10 percentage points or less). We made no correction for multiple testing, using a 2-sided P < .05 as the threshold for statistical significance. All analyses were performed using Stata version 15 (StataCorp).

Results
We recruited patients from 12 general practices in 7 clinical commissioning groups (CCGs) across

Coprimary Outcomes
There was no evidence of difference in consultation numbers and rates between the control group and the intervention group (adjusted risk ratio, 0.96; 95% CI, 0.56-1.66; P = .89). However, the mean (SD) consultation rate per person in the intervention group was higher in the 12 months before the trial than in the 12 months during the trial (0.29 [0.61] vs 0.21 [0.66]) (eTable in Supplement 1).
Adjusting for age, sex, and clustering within general practices did not change the results. We did not perform formal statistical testing for the patient interval coprimary outcome because of differences in the rates of missing data between the control and intervention groups ( Table 2). Table 2, Table 3, and Table 4 present the results of the participant-reported secondary outcomes, ie, skin self-examination benefits and barriers, self-efficacy for consulting without delay, perceived melanoma risk, sun protection habits, melanoma worry, anxiety and depression, and quality of life.

Secondary Outcomes
There were no statistically significant differences between trial groups on any of the secondary outcome measures (eg, measures of SSM: adjusted mean difference, 0.08; 95% CI, −0.83 to 1.00; P = .86; Melanoma Worry Scale: adjusted mean difference, −0.12; 95% CI, −0.56 to 0.31; P = .58). A sensitivity analysis additionally adjusting for age and sex showed similar results.

Summary
To our knowledge, this is among the first trials worldwide to investigate the potential effect of a behavioral intervention using an SSM application to promote help-seeking in patients with increased risk of melanoma. We combined evidence-based approaches to identify people at increased risk in the family practice setting with new approaches using smartphone applications for SSM. We were  unable to demonstrate any effect on consultation rates or patient interval, but importantly, there was no evidence of psychological harm from the intervention during the following 12 months. At the same time, there was also no evidence of any beneficial effect on sun protection habits, skin selfexamination behavior, or perceived risk of developing melanoma among those receiving the intervention. Trial recruitment, retention, and initial delivery of the intervention were all feasible.

JAMA Network Open | Dermatology
However, we have no data on the actual use of the SSM app; this process measure is an important further dimension to assess before making a feasibility decision regarding a larger trial powered to demonstrate effects on either consultation rates or the primary care interval.
The intervention, including uploading the app, demonstrating use of the app, and providing regular reminders, was not found to alter consultation rates or help-seeking for skin symptoms. This may have been because of the short follow-up time and possibly influenced by seasonal variation in detecting skin changes. 36 We also found no differences in our quantitative measurements of sun  These barriers could be addressed by several of the features of smartphone applications that enable self-monitoring among individuals with increased risk of melanoma. Our findings relate to the concept of using an SSM application rather than the properties of the specific application selected following extensive evaluation of more than 40 available applications in 2016. 20 The Achieving Selfdirected Integrated Cancer Aftercare intervention is a rigorously developed, theoretically based, digitally supported application that uses specified behavior-change techniques to prompt users to perform regular, high-quality SSE and gives appropriate clinical responses when they raise a concern 45 ; it is currently under evaluation in a UK randomized clinical trial among individuals recently treated for primary melanoma. 22 Both the Achieving Self-directed Integrated Cancer Aftercare trial and our trial depend on patients using the applications optimally. We have no knowledge of how much the application was used in this trial, although no participants in either trial group reported that they had contaminated the trial by downloading other SSM smartphone applications.

Limitations
This study has limitations. The study was designed as a phase 2 trial of a complex intervention. 28 We based the coprimary outcomes of family practice skin consultation rates and the patient interval on the intervention logic model. Encouraging people with increased risk of melanoma to self-monitor their own skin and consult their general practitioner if they have any concerns could reduce potential diagnostic delay for melanoma and could result in the detection of earlier-stage disease. Therefore, the coprimary outcomes were the most suitable intermediate measures along this causal pathway.
Nevertheless, no participants were diagnosed with melanoma, and few consulted with their general practitioners during the 12-month follow-up period despite the participant population having increased risk of melanoma. This trial was not designed to have sufficient statistical power to detect a meaningful difference; a much larger trial would be needed for sufficient power to detect differences in the patient interval or skin consultation rates and an even larger trial to detect differences in time to diagnosis, stage at diagnosis, or mortality from melanoma.
Although the feasibility outcomes around recruitment were satisfactory, older individuals were less likely to consent to participate. More than half of those found to be eligible for the trial consented to participate. The randomized groups were well-balanced, and few participants were lost to follow-up over 12 months (16 [6.7%]). However, there were fewer than expected events across both groups (ie, 51 skin consultations) and a low response (ie, 37%) to the Skin Questionnaire, meaning that we were unable to report on the effect of the intervention on the time to consultation (ie, patient interval). The control group received a brief discussion about skin health and Cancer Research UK leaflets. While intended as an attention control, this could potentially have increased consultations about skin changes and reduced the effect size of the intervention. We were unable to accurately assess the use of the application by participants (either by direct or electronic questioning) and cannot say whether it was used regularly for skin self-monitoring or whether that contributed to the absence of effect on consultation rates in the intervention arm. We consider the findings generalizable beyond the East of England because of the recruitment of patients from 12 general practices located in urban and rural areas with a range of size of patient lists and socioeconomic deprivation.

Conclusions
In this phase 2 randomized trial, the use of a SSM smartphone application did not have an effect on the rate at which participants with higher risk of melanoma consulted with family practice physicians regarding skin changes. Therefore, significant uncertainty remains regarding the best strategies to promote early detection of melanoma. For those with moderate risk of melanoma, behavioral approaches, such as using an SSM smartphone application to prompt timely consultation, remain an option, promoted particularly among policy makers, but our trial does not offer even preliminary randomized clinical trial evidence to support this. While such applications have not been shown to have value in diagnosing melanoma, 46 they may have more promise as monitoring tools to identify skin changes. Further evidence on how to ensure people with increased risk of melanoma engage with and use these applications and whether this leads to earlier detection is needed. Until then, the role of smartphone applications as a strategy to detect melanoma earlier remains unclear.

ARTICLE INFORMATION
Accepted for Publication: December 15, 2019.