Kato 2008.

Methods	Randomized controlled trial
Participants	The study location was 34 academic medical centers and community practices in the United States, Canada and Australia 197 participants were randomized to the intervention group and 178 participants were randomized to the control group The inclusion criteria were ages 13 to 29 years, had a malignancy diagnosis (newly diagnosed or relapsed), and were undergoing treatment (chemotherapy, radiation, or stem cell transplantation) that was expected to last at least 4 months after enrollment The exclusion criteria were a history of seizures as a result of photosensitivity (e.g. flashing lights); inability to communicate with study personnel in English, French, or Spanish; or inability to follow the study schedule or directions
Interventions	Intervention: CANCER TARGETED VIDEO GAME The intervention participants were given a mini‐computer containing commercial game plus the intervention game, which was a video PC game called Re‐Mission47. In this game, players control a nanobot, "Roxxi", in 3‐dimensional environments within the bodies of young patients with cancers that commonly are diagnosed in AYA. Game content was engineered to address behavioral issues that were identified in literature reviews and preproduction targeting studies as critical for optimal AYA patient participation in cancer treatment. Video‐game play includes destroying cancer cells and managing common treatment‐related adverse effects such as bacterial infections, nausea, and constipation by using chemotherapy, antibiotics, antiemetics, and a stool softener as ammunition. To win, players control the nanobot, Roxxi, to ensure strategically that virtual patients engage in positive self care behaviors, such as taking oral chemotherapy to fight cancer cells, taking antibiotics to fight infection, taking stool softeners to prevent bowel perforations, practicing good mouth care to combat mucositis, using relaxation techniques to reduce stress, and eating food to gain energy. Neither the nanobot nor any of the virtual patients "die" in the game. If players "fail" at any point in the game, then the nanobot powers down and players are given the opportunity to try the mission again. Players had to complete missions successfully before moving on to the next level. Participants were instructed to play for at least 1 hour per week during the 3‐month period Control: COMMERCIAL VIDEO GAME The control patients were provided a commercial video game ‐ a PC version of Indiana Jones and the Emperor's Tomb served as the control game because the play structure and controller interface closely resembled that of Re‐Mission
Outcomes	The adherence measures were CDCL (Chronic Disease Compliance Instrument), MAS (medication adherence scale), plasma assessment of 6MP by HPLC and MEMS. The measurements were made at 1 and 3 months. Patient outcomes were self efficacy to manage cancer, knowledge about cancer, health locus of control, stress, and quality of life. All the outcomes were measured by self report at 1 and 3 months
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computerized randomization. (pg e306) "Computer allocation was randomized within sites (as blocks) on the basis of a computerized random‐number generator."
Allocation concealment (selection bias)	Low risk	After baseline assessments, a site associate contacted a study co‐ordinator at a central office, who gave the associate a number indicating a specific computer to be distributed to the participant (i.e. a computer implementing the control or experimental condition). Computer allocation was randomized within sites (as blocks) on the basis of a computerized random‐number generator. Condition assignment of each participant was concealed from study personnel, but participants became aware of their treatment assignment once they logged onto their assigned computers
Selective reporting (reporting bias)	Low risk	The study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre‐specified
Other bias	Unclear risk	Authors note the following limitations: (pg e314) "Limitations include the heterogeneity of cancer diagnoses and treatment regimens and the nonuniform trial entry at varying treatment stages. Although this heterogeneity may reduce statistical power, it may improve generalizability of the findings for application in a broad array of AYA patients with cancer. Direct measures of adherence to TMP/SMX and oral 6‐MP were obtained from the subset of the sample who were prescribed these medications, thus making it impossible to determine whether patients who are prescribed other medications would show similar patterns of adherence to their medications if exposed to the intervention game. Male patients were overrepresented among study participants, perhaps because of greater appeal of video games to that audience; however, intervention effects were similar for both genders but with a somewhat greater impact on oral TMP/SMX adherence for female patients. A final limitation involves suboptimal adherence to the video game intervention, which was used less than the requested amount by most participants in this study."
Blinding of outcome assessment (detection bias) Adherence measure	Low risk	(PRIMARY) MEMS ‐ MEMS not likely to be affected by outcome assessors
Blinding of outcome assessment (detection bias) Patient outcome	Low risk	(PRIMARY) FACT‐G ‐ Condition assignment of each participant was concealed from study personnel (pg e306)
Blinding of participants (performance bias) Adherence measure	High risk	(PRIMARY) MEMS ‐ Participants aware of the measure due to the nature of intervention and obtrusive nature of MEMS
Blinding of participants (performance bias) Patient outcome	High risk	(PRIMARY) FACT‐G ‐ Patients aware of group allocation and intervention; subjective outcome
Blinding of personnel (performance bias) Adherence measure	Low risk	(PRIMARY) MEMS ‐ MEMS not likely to be affected by key study personnel
Blinding of personnel (performance bias) Patient outcome	Low risk	(PRIMARY) FACT‐G ‐ Condition assignment of each participant was concealed from study personnel (pg e306)
Incomplete outcome data (attrition bias) Adherence measure	Low risk	(PRIMARY) MEMS ‐ Missing data balanced across groups
Incomplete outcome data (attrition bias) Patient outcome	Low risk	(PRIMARY) FACT‐G ‐ Missing data balanced across the groups