A Mobile Game for Patients With Breast Cancer for Chemotherapy Self-Management and Quality-of-Life Improvement: Randomized Controlled Trial.

BACKGROUND
The application of game-based learning in clinical practice has shown potential advantages in previous studies. However, there have been little efforts to use smartphone-based mobile games in the management of adult patients with cancer.


OBJECTIVE
The objective of our study was to evaluate if patient education using a mobile game may increase drug compliance, decrease physical side effects of chemotherapy, and improve psychological status in breast cancer patients.


METHODS
A total of 76 patients with metastatic breast cancer who were planned to receive cytotoxic chemotherapy were enrolled in this trial. Study participants were randomly assigned to a mobile game play group (game group, n=36) or a conventional education group (control group, n=40) in a ratio of 1:1. The patients were unblinded and followed prospectively for 3 weeks. Outcome measures included time spent for education, compliance to medication, physical side effects, and psychological side effects including quality of life (QoL).


RESULTS
Overall, 72 out of 76 patients completed the study after 3 weeks (95%). The subjects in the game group showed high levels of satisfaction with the app. The time spent playing the mobile game in the game group was longer than that spent for self-education in the control group (mean 22.2, SD 6.1 vs mean 5.5, SD 4.0 minutes a day; P<.001). The mobile game group showed better drug adherence (Korean version of the Medication Adherence Rating Scale; mean 7.6, SD 0.7 vs mean 6.5, SD 0.5; P<.001). The use of the mobile game was associated with lower rates of chemotherapy-related side effects, such as nausea, fatigue, numbness of hand or foot, and hair loss, than the control group. The game group exhibited better QoL during chemotherapy (mean 74.9, SD 3.5 vs mean 72.2, SD 5.3; P=.01). However, there were no significant differences in terms of depression and anxiety scales.


CONCLUSIONS
This study suggests the feasibility and potentiality of the use of smartphone mobile games for patients with breast cancer receiving chemotherapy. Education using a mobile game led to better patient education, improved drug compliance, decreased side effects, and better QoL compared with conventional education. Mobile games can be used as easy, fun, and effective measures for patient education and have the potential to improve treatment outcomes.


TRIAL REGISTRATION
ClinicalTrials.gov NCT03205969; http://clinicaltrials.gov/ct2/show/NCT03205969 (Archived by WebCite at http://www.webcitation.org/71jfSBOq9).


INTRODUCTION 2a-i) Problem and the type of system/solution
These side effects may cause poor drug compliance, prohibiting successful anticancer treatment. Poor education is one of the main determinants of poor adherence to chemotherapy. Therefore, proper education contribute to improved clinical outcomes 2a-ii) Scientific background, rationale: What is known about the (type of) system Recent studies with health-related internet games have shown positive effects, such as improving coping strategies for health problems Does your paper address CONSORT subitem 2b?
We hypothesized that mobile gaming would lead to increased drug compliance, decreased physical side effects of chemotherapy, and improved psychological status among patients.

3a) CONSORT: Description of trial design (such as parallel, factorial) including allocation ratio
A flow diagram of the study is shown in Figure 2. 3b) CONSORT: Important changes to methods after trial commencement (such as eligibility criteria), with reasons We inserted sentences 3b-i) Bug fixes, Downtimes, Content Changes Our study was very short term study and this address was not in the ms.

4a) CONSORT: Eligibility criteria for participants
We address the CONSORT 4a-i) Computer / Internet literacy The exclusion criteria were as follows 4a-ii) Open vs. closed, web-based vs. face-to-face assessments: We The patients were unblinded 4a-iii) Information giving during recruitment Informed consent was obtained from all patients during hospitalization for chemotherapy after explaining the design, protocol 4b) CONSORT: Settings and locations where the data were collected We explained description as follow up of cell-phone 4b-i) Report if outcomes were (self-)assessed through online questionnaires The questions were assessed using a self-reported scale of 10 levels with 10 indicating 4b-ii) Report how institutional affiliations are displayed 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 A mobile game, ILOVEBREAST (CLGAMES, Seoul, Korea) was developed 5-ii) Describe the history/development process 5-iii) Revisions and updating 5-iv) Quality assurance methods 5-v) Ensure replicability by publishing the source code, and/or providing screenshots/screen-capture video, and/or providing flowcharts of the algorithms used Representative screenshots of the ILOVEBREAST game.

5-vii) Access
For patients in the game group, the study mobile game (ILOVEBREAST) was installed on the participants' smartphones 5-viii) Mode of delivery, features/functionalities/components of the intervention and comparator, and the theoretical framework They were interviewed every week via cell phone until the end of the study 5-ix) Describe use parameters They were recommended to play the game for >30 minutes a day, 3 times per week 5-x) Clarify the level of human involvement 5-xi) Report any prompts/reminders used They were interviewed every week via cell phone until the end of the study 5-xii) Describe any co-interventions (incl. training/support) They were interviewed every week via cell phone until the end of the study 6a) CONSORT: Completely defined pre-specified primary and secondary outcome measures, including how and when they were assessed The game group also showed improved compliance to medications compared with the control group (K-MARS score) 6a-i) Online questionnaires: describe if they were validated for online use and apply CHERRIES items to describe how the questionnaires were designed/deployed 6a-ii) Describe whether and how "use" (including intensity of use/dosage) was defined/measured/monitored The time spent on game playing in the mobile game group was higher than that spent for self-education in the control group 6a-iii) Describe whether, how, and when qualitative feedback from participants was obtained The patients in the game group were requested to assess their level of satisfaction with ILOVEBREAST 6b) CONSORT: Any changes to trial outcomes after the trial commenced, with reasons We explained description as follow up of cell-phone 7a) CONSORT: How sample size was determined 7a-i) Describe whether and how expected attrition was taken into account when calculating the sample size Because this study was a proof-of-concept trial, the sample size calculation was done on a practical basis 7b) CONSORT: When applicable, explanation of any interim analyses and stopping guidelines The game group also showed improved compliance to medications compared with the control group (K-MARS score) 8a) CONSORT: Method used to generate the random allocation sequence Our participants were allocated with random number generation 8b) CONSORT: Type of randomisation; details of any restriction (such as blocking and block size) We use simple randomization 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 utilizing an interactive Web randomization system. 10) CONSORT: Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions The statistician who was independent department performed randomization 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 Our study was devided into two groups, not blinded 11a-ii) Discuss e.g., whether participants knew which intervention was the "intervention of interest" and which one was the "comparator" Patients were randomly assigned to education using mobile game play (game group) or conventional education (control group) 11b) CONSORT: If relevant, description of the similarity of interventions These are also education about toxicities of chemotherapy 12a) CONSORT: Statistical methods used to compare groups for primary and secondary outcomes Medication Adherence Rating Scale (K-MARS), which has a Cronbach reliability alpha of .71 12a-i) Imputation techniques to deal with attrition / missing values Among them, 2 were excluded because of severe depressive and anxiety symptoms, 4 for having difficulties in using the mobile game, and 1 for withdrawal of consent for an unspecified reason.ntrol group) 12b) CONSORT: Methods for additional analyses, such as subgroup analyses and adjusted analyses Continuous variables were compared with independent t tests or Mann-Whitney U-tests as appropriate. The Chi-square test or Fisher's exact test was used for dichotomous variables RESULTS 13a) CONSORT: For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analysed for the primary outcome Among the 76 female patients who were finally enrolled, 36 and 40 were randomly assigned to the mobile game and control groups, respectively 13b) CONSORT: For each group, losses and exclusions after randomisation, together with reasons Among them, 2 were excluded because of severe depressive and anxiety symptoms, 4 for having difficulties in using the mobile game, and 1 for withdrawal of consent 13b-i) Attrition diagram

14a) CONSORT: Dates defining the periods of recruitment and follow-up
Patients with pathologically proven, clinical stage IV breast cancer were enrolled in this study at Chung-Ang University Hospital, Korea, from September 2013 to September 2014 14a-i) Indicate if critical "secular events" fell into the study period 14b) CONSORT: Why the trial ended or was stopped (early) Our study was finished after the 3-weeks follow-up of 76 female patients.

15) CONSORT: A table showing baseline demographic and clinical characteristics for each group
The baseline characteristics of the study subjects are summarized in Table 1.

15-i) Report demographics associated with digital divide issues
Because of easy-to-use Web-based game, beginners were not different from experienced participants 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 Our analysis was performed with number of participants (denominator) included in each analysis 16-ii) Primary analysis should be intent-to-treat 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) the significance level alpha was set at.05, 17a-i) Presentation of process outcomes such as metrics of use and intensity of use 17b) CONSORT: For binary outcomes, presentation of both absolute and relative effect sizes is recommended We didn't use the binary outcomes 18) CONSORT: Results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing pre-specified from exploratory We didn't use subgroup analyses and adjusted analyses 18-i) Subgroup analysis of comparing only users

19) CONSORT: All important harms or unintended effects in each group
Our study didn't occurred SAE. Also, unintended effects were not observed 19-i) Include privacy breaches, technical problems

20) CONSORT: Trial limitations, addressing sources of potential bias, imprecision, multiplicity of analyses 20-i) Typical limitations in ehealth trials
The major limitation of this study is the small sample size and the short study period. 21) CONSORT: Generalisability (external validity, applicability) of the trial findings 21-i) Generalizability to other populations 21-ii) Discuss if there were elements in the RCT that would be different in a routine application setting 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) The mobile game ILOVEBREAST was developed to help patients with advanced breast cancer learn more about the disease course, properties of medications, and expected adverse drug reactions.

22-ii) Highlight unanswered new questions, suggest future research
We believe this fact provides an important lesson for future developers. Other information 23) CONSORT: Registration number and name of trial registry NCT03205969 24) CONSORT: Where the full trial protocol can be accessed, if available We summarized the trial protocol at "Study Procedure" section 25) CONSORT: Sources of funding and other support (such as supply of drugs), role of funders This research study was supported by a grant of Nexon 2014 and a grant from the Korea Creative Content Agency, Ministry of Culture, Sports and Tourism (2013040436).

X26-i) Comment on ethics committee approval
The Chung-Ang University Hospital Institutional Review Board approved the research protocol for this study (Number C20141447) x26-ii) Outline informed consent procedures Informed consent was obtained from all patients during hospitalization for chemotherapy after explaining the protocol, and consequences of the study.