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Investigating Serious Games That Incorporate Medication Use for Patients: Systematic Literature Review

Investigating Serious Games That Incorporate Medication Use for Patients: Systematic Literature... Background: The United States spends more than US $100 billion annually on the impact of medication misuse. Serious games are effective and innovative digital tools for educating patients about positive health behaviors. There are limited systematic reviews that examine the prevalence of serious games that incorporate medication use. Objective: This systematic review aimed to identify (1) serious games intended to educate patients about medication adherence, education, and safety; (2) types of theoretical frameworks used to develop serious games for medication use; and (3) sampling frames for evaluating serious games on medication use. Methods: PubMed, Scopus, and Web of Science databases were searched for literature about medication-based serious games for patients. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for article selection. Results: Using PRISMA guidelines, 953 publications and 749 unique titles were identified from PubMed, Scopus, and Web of Science. A total of 16 studies featuring 12 unique serious games were included with components of medication adherence, education, and safety, published from 2003 to 2019. Of the 12 games included, eight serious games were tested in adolescents, three games were tested in young adults, and one game was tested in adults. Most studies (n=11) used small sample sizes to test the usability of serious games. Theoretical frameworks identified in the 12 serious games included information, motivation, and behavior theory; social cognitive theory; precede-proceed model; middle-range theory of chronic illness; adult learning theory; experiential learning theory; and the theory of reasoned action. Existing reviews explore serious games focused on the management of specific disease states, such as HIV, diabetes, and asthma, and on the positive impact of serious game education in each respective disease state. Although other reviews target broad topics such as health care gamification and serious games to educate health care workers, no reviews focus solely on medication use. Serious games were mainly focused on improving adherence, whereas medication safety was not widely explored. Little is known about the efficacy and usability of medication-focused serious games often because of small and nonrepresentative sample sizes, which limit the generalizability of existing studies. Conclusions: Limited studies exist on serious games for health that incorporate medication use. The findings from these studies focus on developing and testing serious games that teach patients about medication use and safety. Many of these studies do not apply a theoretical framework in the design and assessment of these games. In the future, serious game effectiveness could be improved by increasing study sample size and diversity of study participants, so that the results are generalizable to broader http://games.jmir.org/2020/2/e16096/ JMIR Serious Games 2020 | vol. 8 | iss. 2 | e16096 | p. 1 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Abraham et al populations. Serious games should describe the extent of theoretical framework incorporated into game design and evaluate success by testing the player’s retention of learning objectives. (JMIR Serious Games 2020;8(2):e16096) doi: 10.2196/16096 KEYWORDS games; medication adherence; patient safety; video games; systematic review internet subscription [14]. Serious games teach specific skills Introduction or learning objectives and are created for educational purposes rather than entertainment [15]. Background Serious games have proven to be successful at educating users An estimated 117 million Americans currently live with one or on various topics, including health, languages, computer science, more chronic conditions, many of which require medication mathematics, and geography [16]. Web game-based learning management [1]. Using many medications for chronic conditions has been shown to positively affect user attitudes toward is accompanied with a high risk of medication errors, insufficient learning as well as increase the retention time of acquired knowledge about appropriate use, and inadvertent adverse drug knowledge [7]. Current serious games focus on specific disease events. In the United States, a leading reason for injuries and states, making it difficult to generalize objectives to medication death is because of the estimated 1.5 million medication errors use [17]. Serious games have been reported to be desired for [2]. Common mistakes made by patients or caregivers outside learning by patients. In one study, children picking up of the hospital include taking a medication twice by accident, prescriptions in the pharmacy were reported to have asked for an incorrect dose, or the wrong medication [2]. interactive games to learn about their medications [18]. A common barrier to chronic disease management for many Some existing systematic reviews examining the use of serious patients is medication adherence. Approximately 50% of patients games include little information about medication use targeting do not take prescribed medication appropriately and consistently specific disease states, such as diabetes [19,20], HIV prevention [3]. Medication adherence or taking medications correctly is and care [21], asthma management [22,23], and epilepsy [24]. generally defined as the extent to which patients take medication Other systematic reviews include broad search criteria, such as as prescribed by their doctors [4]. Patients, health care providers, serious game use in health care [25], health care gamification and hospital systems would benefit immensely from helping [24], and serious games for young people living with long-term patients use medication correctly, consistently, and safely. The medical conditions [17]. health care system would benefit from gaining the estimated US $100 to US $300 billion every year because of nonadherence Objectives alone [5]. Patient knowledge on safe medication practices is The primary objective of this study was to assess the extent of critical in preventing unnecessary patient harm. For example, serious games intended to educate patients about medication recent reports from Poison Control state that approximately use and safety. In particular, this systematic review aimed to 60,000 children were sent to the emergency room every year explore (1) serious games intended to educate patients about because of taking medications without adult supervision [6]. medication adherence, education, and safety; (2) types of These findings show opportunities for patient education on safe theoretical frameworks used to develop serious games for medication use, storage, and disposal, particularly for young medication use; and (3) sampling frames for evaluating serious people and their family caregivers. games on medication use. Technology has a significant impact on education and health behavior reinforcement both in patients and providers [7]. Methods Devices such as mobile phones relay information, reinforce norms, and influence behaviors such as medication adherence Search Strategy [7]. The appeal of technology, particularly gaming, makes A literature search was conducted using PubMed, Scopus, and serious games an ideal approach to portray medication Web of Science databases. The key terms included in the search information [8]. Technology-based serious games are a novel were (serious game OR serious-games OR serious video-games method of delivering interactive health behavior education OR serious games OR serious digital games OR serious through skill-building exercises [9,10]. Serious games are digital electronic games OR serious gaming OR video game OR tools that offer engagement activities through a responsive video-game) (drug OR drugs OR medication OR medications narrative to educate participants through role-play and practicing OR prescription OR prescriptions) (treatment OR therapy). skills. Unlike traditional video games, serious games act to Search results from each database were exported to Microsoft convey meaningful information through interactive Excel, merged, and sorted for removal of duplicate citations. environments similar to real-life situations [11,12]. The use of Study Selection serious games on computer and mobile phone platforms to promote awareness of health issues has increased in popularity This review was conducted in accordance with the Preferred over the past decade [13]. Technology is readily accessible in Reporting Items for Systematic Reviews and Meta-Analyses the United States, with 89% of households owning a computer guidelines. Only original research articles were included in this or mobile phone device and 81% of households having an http://games.jmir.org/2020/2/e16096/ JMIR Serious Games 2020 | vol. 8 | iss. 2 | e16096 | p. 2 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Abraham et al systematic review. Initial screening of all abstracts and titles Data Extraction was conducted independently by SL and SB to determine A standard data extraction form was used to collect study whether to include or exclude an article based on selection authors, article title, year published, journal title, study design, criteria. Inclusion criteria were original research studies brief description of methods, primary outcome measures, and published in English for patients as end users involving a serious conclusions by all the authors for the articles included for game, which focus on medication use and safety, addressing at full-text inclusions in the last step. References of the papers least one of the following topics: (1) medication safety, (2) initially found were not included for evaluation. medication adherence, and (3) medication education. During the abstract and title screening phase, a level of agreement on Results inclusion and exclusion was achieved among the authors. A third author, HS, reconciled disagreements to achieve mutual Literature Overview consensus before moving to full-text review. Full-text articles A total of 953 records were obtained after searching PubMed, were assessed for inclusion, and reasons were documented for Web of Science, and Scopus. After removing duplicates, 749 all excluded papers. articles with unique titles were identified for title reviews. After Definitions of key terms are as follows: title review, 558 studies were removed, and another 152 studies were removed after abstract review for not meeting the inclusion • Serious games: A digital or computerized game designed criteria. Studies were removed if they did not include a serious for patients to increase their knowledge and awareness game focusing on patients as end users and based on medication about medications or help them with medication use and use, adherence, and safety. A comprehensive review of 49 safety. full-text articles was conducted, 33 of which were excluded. • Games for medication adherence: Games that promote Systematic reviews, serious games for end users other than players to take medication at least as prescribed. patients, nonmedication-related games, and nonvideo games • Games for medication education: Games that teach players were excluded (see Figure 1). As a result, 16 articles were how medications work in the body or why the medication included in this systematic review. The results are presented is an important component of patients’ treatment plan. below based on the following three specific aims of the paper: • Games for medication safety: Games about taking and (1) serious games intended to educate patients about medication handling medications in the proper way or safely to prevent adherence, education, and safety; (2) types of theoretical medication errors. frameworks used to develop serious games for medication use; and (3) sampling frames for evaluating serious games on medication use. Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram of the included studies. http://games.jmir.org/2020/2/e16096/ JMIR Serious Games 2020 | vol. 8 | iss. 2 | e16096 | p. 3 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Abraham et al A total of 16 articles on serious games published between 2003 Wheezie had a single medication learning objective of proper and 2019 were found to incorporate medication use targeted inhaler use and used the precede-proceed model, which involves toward patients. The 16 articles found focused on 12 unique incorporating components such as predisposing, enabling, and serious games. Moreover, eight games were tested in adolescent reinforcing factors into game development [34]. One published populations, three games were tested in young adults, and one study with an unnamed computer game used the pain and game was tested in adults only. In some cases, there were medication model to teach players of any age how to manage multiple articles focused on a single serious game. As shown activities of daily living through balancing activity level with in Multimedia Appendices 1 and 2, the included games could the quantity of medication taken postoperatively [40]. The be grouped based on the disease state or education on a specific theoretical framework used in development was a blend of the topic. All 12 games are described in Multimedia Appendices 1 middle-range theory of chronic illness, adult learning theory, and 2. and the experiential learning theory. The middle-range theory of chronic illness involves reflection and decision making, such Intention of the Serious Game as choosing when to take pain medication [40]. The adult Most of these articles studied the change in patients’ knowledge learning theory incorporates self-directed learning methods, about medications as an assessment of medication adherence. which is a preferred learning method for adults [40]. The The following are examples of 8 games that assessed patients' experiential learning theory involves learning through understanding of medications for managing chronic and acute observation, abstract conceptualization, and experimentation health conditions. [40]. CSI Web Adventures used the theory of reasoned action to display the negative consequences of abusing prescription • Games for antiretroviral therapy (ART) and pre-exposure drugs, such as opioids in two separate case studies [38]. prophylaxis (PrEP) adherence: Viral Combat, Adherence Warrior, Epic Allies, and Battle Viro were developed to Sampling Frames Primary Results promote adherence to ART and PrEP [26-30] Viral Combat, Adherence Warrior, Epic Allies, and Battle Viro • Game for cancer treatment medication adherence: were developed to promote adherence to ART and PrEP [26-30]. Re-Mission [31] The target audience was aged between 13 and 35 years in all • Game for diabetes medication education and adherence: HIV-focused games [8,27-30]. Each game used three to four L’Affaire Birmann [32,33] modalities to achieve learning objectives, summarized in • Game for asthma medication education: Wee Willie Multimedia Appendices 1 and 2. Wheezie [34] • Games for microbiology and antibiotic education: Microbe Viral Combat, an iPhone gaming app published only through Quest and e-Bug Junior and Senior [35-37] the game development phase, incorporated a Smart Pill Bottle • Game for prescription drug abuse education: CSI Web Cap and text messages to patients aged 18 to 35 years to Adventures [38] promote adherence to PrEP [26]. A Smart Pill Bottle Cap reports • Game for over-the-counter (OTC) medication safety: to the app when the medication bottle is opened [26]. A small Alchemy Knights [39] trial of nine participants showed an 88% satisfaction toward the game, and 100% of the participants would recommend it to a Types of Theoretical Frameworks Used to Develop friend [30]. Serious Games for Medication Use Adherence Warrior, a mobile gaming app for patients aged 13 Of the 16 studies, seven used a theoretical model or framework to 24 years, promoted adherence while maintaining player in the game design process. The theories used in each game are privacy. Text messages were sent to patients to promote ART mentioned in Multimedia Appendix 1. In Viral Combat, the adherence [27]. A mixed method study had 12 participants information, motivation, and behavior (IMB) theory was used having rank level of agreement on a scale of 1 to 5, with 5 being to promote medication behavior change [26]. Adherence strong agreement to game characteristics. The study reported a Warrior, another game for HIV adherence, was guided by the median score of 5 of having fun while playing (P=.03), and social cognitive theory. Social cognitive theory goals included players preferred to play games about topics other than the increased player self-efficacy, knowledge of HIV treatment immune system (P=.01) [27]. No statistical significance was goals, and social support [27]. Battle Viro was the only found to support whether participants would play the game if HIV-related game incorporating educational modules and did it were available or if they would use the game to take HIV not report a specific theoretical framework or model that guided medications [27]. game development. In Epic Allies, the IMB model framework was used to develop objectives of increased ART adherence Battle Viro, an iPhone gaming app targeted to patients aged 14 and social support. In Re-Mission, a game for cancer medication to 26 years, incorporated a Smart Pill Bottle Cap, text messages, adherence, the behavioral objectives were developed based on and educational modules. Learning outcomes were to improve the social cognitive theory and social learning theory [31]. The ART adherence, increase social support, increase HIV- and social cognitive theory was used to measure patient’s confidence ART-related knowledge, and visualize progress. In a randomized in their ability to carry out adherence behaviors to reach a goal controlled trial of 61 participants starting with a detectable viral [31]. The social learning theory connects medication adherence load, the experimental condition had 23% greater adherence to a social component such as a multiplayer serious game [31]. (P=.05) compared with the control group and a 0.96 log greater L’Affaire Birman was a serious game for type 1 diabetes decrease in viral load (P=.04) [8,30]. education and did not use a theoretical framework. Wee Willie http://games.jmir.org/2020/2/e16096/ JMIR Serious Games 2020 | vol. 8 | iss. 2 | e16096 | p. 4 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Abraham et al Epic Allies was the only HIV medication adherence mobile CSI Web Adventures simulated a prescription drug abuse crime gaming app that did not incorporate an electronic pill bottle or scene and took players through the science of forensic analysis text messages. The target age for this game was 16 to 29 years [38]. This computer game was targeted toward people aged 14 [28,29]. The distinguishing modality of Epic Allies was a to 18 years. A sample of 179 players conveyed negative attitudes dashboard displaying various lifestyle behaviors, such as toward illegal crimes in the baseline and game testing phases smoking, medication adherence, and mood [28]. A sample size [38]. CSI Web Adventures is reported to need more testing of 20 study participants through focus groups supported game before significant results can contribute to specific opioid acceptability [28,29]. safety-related learning objectives [38]. Re-Mission focused on increasing oral chemotherapy adherence Alchemy Knights, a serious game available on the Web, was and strategizing the use of medications to treat the side effects geared toward ages 9 to 12 years. The game taught players about of oral chemotherapy for people aged 12 to 29 years [31]. responsible OTC medication safety, drug-drug interactions, and Players control a robot, Roxxi, with the goal of adhering to oral the consequences of misusing medications [39]. A pilot study chemotherapy and combating negative effects through taking of nine participants showed 78% increased knowledge in medications such as stool softeners and antibiotics [31]. A medication safety from a pretest to posttest analysis [39]. Results randomized control trial of 375 participants yielded no will be used to improve the game for future use [39]. significant results for adherence but a 9.8% increase in Trimethoprim and Sulfamethoxazole adherence (P=.01) [31] Discussion and a significant increase in player’s self-efficacy for medication Overview adherence (P=.01) [31]. This systematic review offers valuable additions to the current Two studies on one game specifically included a diabetic evidence-based literature by examining serious games for medication-centered learning objective [28,29]. Target ages in patients that incorporate medication adherence, education, and published studies ranged from 10 to 19 years [32,33]. L’Affaire safety. Existing systematic reviews explore serious games for Birman was a serious game targeted toward children living with health focused on the management of specific disease states, type 1 diabetes [32]. Players used a strategic approach to adjust such as HIV, diabetes, and asthma, and on the positive impact the game character’s insulin based on lifestyle factors such as of serious game education in each respective disease state food intake, physical activity, and glucose levels. With no results [19-24]. Although other reviews target broad topics such as or sample characteristics reported, the authors suggested that health care gamification and serious games to educate health further testing is needed to assess the effectiveness in the clinical care workers [7,17,25], no reviews focus solely on examined setting [32]. medication use [7,15-17,19,20]. The identified serious games Wee Willie Wheezie, a 3-level computer-assisted instruction that incorporate the use of medications are mainly focused on program targeted toward children aged 7 to 12 years, had a improving adherence, whereas medication safety is not widely single medication learning objective of proper inhaler use [34]. explored. In addition, there is a lack of research on the efficacy The players chose the correct medication to avoid asthma and usability of medication-focused serious games often because symptoms, exacerbations, and hospital trips [34]. A randomized of small and nonrepresentative sample sizes, which limit the controlled trial of 148 participants found no significant generalizability of existing studies. Very few serious games improvement in player’s asthma symptoms or quality of life described how theoretical frameworks were incorporated during parameters [34]. development, showing an area for improvement in literature [26,28,34]. This systematic review signifies the need for the In an unnamed game, patients learned safe medication regimens creation of serious games focused on medication adherence, by using the icons in the game to learn about the side effects of education, safety, testing of existing serious games for efficacy each medication. [40]. An evaluation study of 20 participants and effectiveness, an evidence-based theory-driven approach aged 24 to 67 years found an increase in knowledge on strategies for serious game design, and large-scale testing with randomized to manage pain (P<.001) [40]. samples to improve generalizability. e-Bug Junior and Senior were multiple-module educational Medication Incorporation adventure computer games targeted toward students ranging in age from 9 to 12 years and 13 to 15 years, respectively [35,36]. Each serious game included in this review was analyzed for the Each game had one module teaching the purpose of antibiotics extent and quality of medication-related topics. The included and the importance of taking the full course. An evaluation games had a medication-related learning objective incorporated study of 129 students yielded 98% positive comments about into a gameplay feature. Of the 12 unique serious games the senior game and no efficacy results [35,36]. included in this study, most did not have medication as a principal component. The sole content in Re-Mission, Alchemy Microbe Quest was a mobile gaming app targeted to patients Knights, and the unnamed pain management game were aged 9 to 12 years [37]. A single level of gameplay introduced medication adherence, education, and safety, respectively the concept of antibiotic resistance as a consequence of not [31,39,40]. ART and PrEP adherence was incorporated in Viral finishing a full course of antibiotics [37]. No statistically Combat, Adherence Warrior, Epic Allies, and Battle Viro significant results in learning objective retention were found in through social support, text reminders, computerized pill bottles, the initial pilot study of 19 participants [37]. and various point incentives [8,26-30]. Microbe Quest, e-Bug, Wee Willie Wheezie, and CSI Web Adventures included a single http://games.jmir.org/2020/2/e16096/ JMIR Serious Games 2020 | vol. 8 | iss. 2 | e16096 | p. 5 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Abraham et al medication-related module [34-38]. Although medication is not Sampling Frames extensively incorporated into serious games, this demonstrates This study recognizes that the majority of serious games a modality of patient education to be explored in the future. included in this study were tested for usability and functionality with very small sample sizes. Only five of the included studies Theoretical Frameworks had more than 100 participants [29,31,34,38]. These small Validated social, behavioral, and game theories such as IMB sample sizes limit the external validity of these studies, thus theory, social cognitive theory, precede-proceed model, reducing the generalizability of the results to larger populations. middle-range theory of chronic illness, adult learning theory, In the future, the effectiveness of these serious games must be experiential learning theory, and the theory of reasoned action assessed using larger sample sizes to investigate their impact as included in this review are developed and defined iteratively on patient’s knowledge and understanding about medication over time. Using these theories for game development and adherence, education, and safety. testing can improve the effectiveness of these serious games [26,30]. On the evaluation of the 12 serious games identified Regarding geographical distribution of samples used in the in this study, six incorporated varying degrees of theoretical studies, only one study included patients from outside of a single frameworks to support game development and testing. A total state [31], whereas other articles used convenient samples from of three articles about two serious games extensively focused a single clinic, city, or state [8,26,27,29,30,32,34-38]. By on IMB theory for game development [26,28,29]. The goal of limiting the participants to a single site, geographical location the IMB model in Epic Allies and Battle Vivo was to change or a specific age group, the external validity of the results from specific health-related behaviors such as medication adherence these games is again compromised. Of the 12 serious games, through a combination of health education, self-motivation, and eight were tested in adolescents, three were tested in young gaining required skills [26,28,29]. Game mechanics in Epic adults, and one was tested in adults. Although adolescents Allies were designed to motivate ART adherence in young men benefit from serious games, adults could also benefit from who have sex with men and long-term game use [28,29]. serious games and should be a future area of exploration in Another article extensively described the use of the serious game usability studies. In the future, more studies with precede-proceed model in game design of Wee Willie Wheezie randomized and diverse populations could increase the statistical [34]. Two games mentioned the social cognitive theory, and power of these results. one game mentioned the theory of reasoned action, but neither The published literature on medication-based serious games of them described any specific details about using and has a strong focus on game design, mechanics, and integrating the theory in game design and mechanics methodologies rather than the effectiveness of the game. Of the [8,27,30,38]. Future goals in Alchemy Knights indicate included articles, seven focused on game design and the plans examining theoretical contributions for further game for future game development without elaboration on outcomes development [39]. Although most of the serious games involving and game efficacy [8,27,29,30,33-36]. A total of four studies theory in their design used small sample sizes for testing their focused on the intended outcomes of the games and whether efficacy and effectiveness, positive outcomes were still they were met [26,31,37]. The common method of evaluation demonstrated by a few [26,28,38]. A common theme identified was surveys on gameplayers’ satisfaction while playing but not was a lack of statistical power to test the efficacy of theory the information that they sustained and retained from the games. outcomes because of the small sample size or result usability Quantifying whether learning objectives were met is necessary [8,26-30,34,39,40]. Future literature describing serious game to determine the success of serious games for future studies. development should incorporate more thorough descriptions of Thus, future serious game design development should include the theoretical frameworks used and larger sample sizes. plans for rigorous testing of efficacy. Medication Adherence, Education, and Safety Limitations Of the 12 serious games included in this study, six focused on The authors recognize key limitations of this study. First, only improving medication adherence [7,8,26-31,38,40], three 3 databases were used for the literature search. Although the targeted medication education [29,32], and three were aimed at extent of duplicates supported a thorough search, there is a providing medication safety [35-39]. Medication nonadherence chance that there are relevant papers that were not included. is a prominent issue in health care, which leads to increased Second, only papers written in English were included. This may costs and comorbidities. By using innovative approaches to have excluded papers from non-English–speaking countries. teach patients the value of adhering to medication, serious games Finally, small sample sizes were used to test most games can assist in improving medication therapy outcomes. Serious included in this study. None of the literature discussed the games educating users on medication misuse or promoting safe sustainability of the games post study, and most of the included usage of medication were lacking in the literature. Although games did not have long-standing follow-up data on their the authors recognize that there is a thin line between medication participants. safety and education, there were many more games with education and adherence components when compared with Conclusions medication safety components such as preventing inappropriate There have been limited studies on serious games for health use [36-40]. Future serious games with medication use as a that incorporate medication use. The findings from these studies component should incorporate learning objectives targeting focus on developing and testing serious games that teach patients medication safety principles to prevent adverse drug events. about medication use and safety. Most of these studies do not http://games.jmir.org/2020/2/e16096/ JMIR Serious Games 2020 | vol. 8 | iss. 2 | e16096 | p. 6 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Abraham et al apply a theoretical framework in the design and assessment of the potential to reduce patients’ knowledge gaps and address these games. The development of serious games for patient misconceptions, which may lead to improved medication medication use, education, and adherence should incorporate adherence and reduced errors. This review shows that there has evidence-based and theory-driven methods to ensure maximum been an increased interest in the application of serious games retention of the learning objectives by study participants and to improve medication use outcomes, and it is expected that game players. More diverse, randomized studies with long-term this review will help advance the effectiveness of game data collection need to be conducted to demonstrate the development in the future. effectiveness of serious games in this area. Serious games have Acknowledgments The authors would like to thank Lisa Szela at the University of Wisconsin–Madison (UW) School of Pharmacy for assisting with editing the manuscript. The authors thank Maeleigh Tidd at UW School of Pharmacy for reviewing the manuscript and providing constructive feedback. This study was supported by KL2 grant KL2 TR002374-03 and grant UL1TR002373 to UW Institute for Clinical and Translational Research by the Clinical and Translational Science Award program, through the National Institutes of Health (NIH) National Center for Advancing Translational Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Conflicts of Interest None declared. 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J Am Pharm Assoc (2003) 2017;57(1):38-46.e2 [FREE Full text] [doi: 10.1016/j.japh.2016.08.019] [Medline: 27843107] 19. Theng YL, Lee JW, Patinadan PV, Foo SS. The use of videogames, gamification, and virtual environments in the self-management of diabetes: a systematic review of evidence. Games Health J 2015 Oct;4(5):352-361. [doi: 10.1089/g4h.2014.0114] [Medline: 26287926] 20. DeShazo J, Harris L, Pratt W. Effective intervention or child's play? A review of video games for diabetes education. Diabetes Technol Ther 2010 Oct;12(10):815-822. [doi: 10.1089/dia.2010.0030] [Medline: 20807119] 21. Hightow-Weidman LB, Muessig KE, Bauermeister JA, LeGrand S, Fiellin LE. The future of digital games for HIV prevention and care. Curr Opin HIV AIDS 2017 Sep;12(5):501-507 [FREE Full text] [doi: 10.1097/COH.0000000000000399] [Medline: 28692490] 22. Drummond D, Monnier D, Tesnière A, Hadchouel A. A systematic review of serious games in asthma education. Pediatr Allergy Immunol 2017 May;28(3):257-265. [doi: 10.1111/pai.12690] [Medline: 27992659] 23. Baptist AP, Islam N, Joseph CL. Technology-based interventions for asthma-can they help decrease health disparities? J Allergy Clin Immunol Pract 2016;4(6):1135-1142. [doi: 10.1016/j.jaip.2016.04.024] [Medline: 27286777] 24. Rahim MI, Thomas RH. Gamification of medication adherence in epilepsy. Seizure 2017 Nov;52:11-14 [FREE Full text] [doi: 10.1016/j.seizure.2017.09.008] [Medline: 28934624] 25. Kearns C. Prescription play: A primer on innovative use of video games technology in healthcare. J Vis Commun Med 2015;38(3-4):152-163. [doi: 10.3109/17453054.2015.1100981] [Medline: 26828542] 26. Whiteley L, Mena L, Craker LK, Healy MG, Brown LK. Creating a theoretically grounded gaming app to increase adherence to pre-exposure prophylaxis: lessons from the development of the viral combat mobile phone game. JMIR Serious Games 2019 Mar 27;7(1):e11861 [FREE Full text] [doi: 10.2196/11861] [Medline: 30916652] 27. Castel AD, Qasmieh S, Greenberg D, Ellenberger N, Howell TH, Griffith C, et al. Digital gaming to improve adherence among adolescents and young adults living with HIV: Mixed-Methods study to test feasibility and acceptability. JMIR Serious Games 2018 Oct 15;6(4):e10213 [FREE Full text] [doi: 10.2196/10213] [Medline: 30322838] 28. LeGrand S, Muessig KE, McNulty T, Soni K, Knudtson K, Lemann A, et al. Epic Allies: development of a gaming app to improve antiretroviral therapy adherence among young HIV-positive men who have sex with men. JMIR Serious Games 2016 May 13;4(1):e6 [FREE Full text] [doi: 10.2196/games.5687] [Medline: 27178752] 29. LeGrand S, Muessig KE, Platt A, Soni K, Egger JR, Nwoko N, et al. Epic Allies, a gamified mobile phone app to improve engagement in care, antiretroviral uptake, and adherence among young men who have sex with men and young transgender women who have sex with men: protocol for a randomized controlled trial. JMIR Res Protoc 2018 Apr 5;7(4):e94 [FREE Full text] [doi: 10.2196/resprot.8811] [Medline: 29622527] 30. Whiteley L, Brown LK, Mena L, Craker L, Arnold T. Enhancing health among youth living with HIV using an iPhone game. AIDS Care 2018;30(sup4):21-33 [FREE Full text] [doi: 10.1080/09540121.2018.1503224] [Medline: 30626196] 31. Kato PM, Cole SW, Bradlyn AS, Pollock BH. A video game improves behavioral outcomes in adolescents and young adults with cancer: a randomized trial. Pediatrics 2008 Aug;122(2):e305-e317. [doi: 10.1542/peds.2007-3134] [Medline: 18676516] 32. Joubert M, Armand C, Morera J, Tokayeva L, Guillaume A, Reznik Y. Impact of a serious videogame designed for flexible insulin therapy on the knowledge and behaviors of children with type 1 diabetes: The Ludidiab Pilot Study. Diabetes Technol Ther 2016 Feb;18(2):52-58. [doi: 10.1089/dia.2015.0227] [Medline: 26440963] 33. Friess R, Kolas N, Knoch J. Game Design of a Health Game for Supporting the Compliance of Adolescents With Diabetes. : Springer; 2014 Oct Presented at: Proceedings of the 4th conference on gaming and playful interaction in healthcare; 2014-10; Furtwangen, Germany p. 37 URL: https://link.springer.com/content/pdf/10.1007/978-3-658-07141-7.pdf#page=46 [doi: 10.1007/978-3-658-07141-7] http://games.jmir.org/2020/2/e16096/ JMIR Serious Games 2020 | vol. 8 | iss. 2 | e16096 | p. 8 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Abraham et al 34. Huss K, Winkelstein M, Nanda J, Naumann PL, Sloand ED, Huss RW. Computer game for inner-city children does not improve asthma outcomes. 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The impact of science education games on prescription drug abuse attitudes among teens: a case study. J Drug Educ 2013;43(3):255-275. [doi: 10.2190/DE.43.3.d] [Medline: 25445507] 39. Abraham O, Feathers A, Grieve L, Babichenko D. Developing and piloting a serious game to educate children about over‐the‐counter medication safety. J Pharm Health Serv Res 2019;10(2):235-241. [doi: 10.1111/jphs.12292] 40. Ingadottir B, Blondal K, Thue D, Zoega S, Thylen I, Jaarsma T. Development, usability, and efficacy of a serious game to help patients learn about pain management after surgery: an evaluation study. JMIR Serious Games 2017 May 10;5(2):e10 [FREE Full text] [doi: 10.2196/games.6894] [Medline: 28490419] Abbreviations ART: antiretroviral therapy IMB: information, motivation, and behavior NIH: National Institutes of Health OTC: over-the-counter PrEP: pre-exposure prophylaxis PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses UW: University of Wisconsin Edited by G Eysenbach; submitted 17.10.19; peer-reviewed by E Unni, T Baranowski, L Santos; comments to author 03.12.19; revised version received 23.01.20; accepted 04.02.20; published 29.04.20 Please cite as: Abraham O, LeMay S, Bittner S, Thakur T, Stafford H, Brown R JMIR Serious Games 2020;8(2):e16096 URL: http://games.jmir.org/2020/2/e16096/ doi: 10.2196/16096 PMID: 32347811 ©Olufunmilola Abraham, Sarah LeMay, Sarah Bittner, Tanvee Thakur, Haley Stafford, Randall Brown. Originally published in JMIR Serious Games (http://games.jmir.org), 29.04.2020. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Serious Games, is properly cited. The complete bibliographic information, a link to the original publication on http://games.jmir.org, as well as this copyright and license information must be included. http://games.jmir.org/2020/2/e16096/ JMIR Serious Games 2020 | vol. 8 | iss. 2 | e16096 | p. 9 (page number not for citation purposes) XSL FO RenderX http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JMIR Serious Games JMIR Publications

Investigating Serious Games That Incorporate Medication Use for Patients: Systematic Literature Review

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2291-9279
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10.2196/16096
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Abstract

Background: The United States spends more than US $100 billion annually on the impact of medication misuse. Serious games are effective and innovative digital tools for educating patients about positive health behaviors. There are limited systematic reviews that examine the prevalence of serious games that incorporate medication use. Objective: This systematic review aimed to identify (1) serious games intended to educate patients about medication adherence, education, and safety; (2) types of theoretical frameworks used to develop serious games for medication use; and (3) sampling frames for evaluating serious games on medication use. Methods: PubMed, Scopus, and Web of Science databases were searched for literature about medication-based serious games for patients. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for article selection. Results: Using PRISMA guidelines, 953 publications and 749 unique titles were identified from PubMed, Scopus, and Web of Science. A total of 16 studies featuring 12 unique serious games were included with components of medication adherence, education, and safety, published from 2003 to 2019. Of the 12 games included, eight serious games were tested in adolescents, three games were tested in young adults, and one game was tested in adults. Most studies (n=11) used small sample sizes to test the usability of serious games. Theoretical frameworks identified in the 12 serious games included information, motivation, and behavior theory; social cognitive theory; precede-proceed model; middle-range theory of chronic illness; adult learning theory; experiential learning theory; and the theory of reasoned action. Existing reviews explore serious games focused on the management of specific disease states, such as HIV, diabetes, and asthma, and on the positive impact of serious game education in each respective disease state. Although other reviews target broad topics such as health care gamification and serious games to educate health care workers, no reviews focus solely on medication use. Serious games were mainly focused on improving adherence, whereas medication safety was not widely explored. Little is known about the efficacy and usability of medication-focused serious games often because of small and nonrepresentative sample sizes, which limit the generalizability of existing studies. Conclusions: Limited studies exist on serious games for health that incorporate medication use. The findings from these studies focus on developing and testing serious games that teach patients about medication use and safety. Many of these studies do not apply a theoretical framework in the design and assessment of these games. In the future, serious game effectiveness could be improved by increasing study sample size and diversity of study participants, so that the results are generalizable to broader http://games.jmir.org/2020/2/e16096/ JMIR Serious Games 2020 | vol. 8 | iss. 2 | e16096 | p. 1 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Abraham et al populations. Serious games should describe the extent of theoretical framework incorporated into game design and evaluate success by testing the player’s retention of learning objectives. (JMIR Serious Games 2020;8(2):e16096) doi: 10.2196/16096 KEYWORDS games; medication adherence; patient safety; video games; systematic review internet subscription [14]. Serious games teach specific skills Introduction or learning objectives and are created for educational purposes rather than entertainment [15]. Background Serious games have proven to be successful at educating users An estimated 117 million Americans currently live with one or on various topics, including health, languages, computer science, more chronic conditions, many of which require medication mathematics, and geography [16]. Web game-based learning management [1]. Using many medications for chronic conditions has been shown to positively affect user attitudes toward is accompanied with a high risk of medication errors, insufficient learning as well as increase the retention time of acquired knowledge about appropriate use, and inadvertent adverse drug knowledge [7]. Current serious games focus on specific disease events. In the United States, a leading reason for injuries and states, making it difficult to generalize objectives to medication death is because of the estimated 1.5 million medication errors use [17]. Serious games have been reported to be desired for [2]. Common mistakes made by patients or caregivers outside learning by patients. In one study, children picking up of the hospital include taking a medication twice by accident, prescriptions in the pharmacy were reported to have asked for an incorrect dose, or the wrong medication [2]. interactive games to learn about their medications [18]. A common barrier to chronic disease management for many Some existing systematic reviews examining the use of serious patients is medication adherence. Approximately 50% of patients games include little information about medication use targeting do not take prescribed medication appropriately and consistently specific disease states, such as diabetes [19,20], HIV prevention [3]. Medication adherence or taking medications correctly is and care [21], asthma management [22,23], and epilepsy [24]. generally defined as the extent to which patients take medication Other systematic reviews include broad search criteria, such as as prescribed by their doctors [4]. Patients, health care providers, serious game use in health care [25], health care gamification and hospital systems would benefit immensely from helping [24], and serious games for young people living with long-term patients use medication correctly, consistently, and safely. The medical conditions [17]. health care system would benefit from gaining the estimated US $100 to US $300 billion every year because of nonadherence Objectives alone [5]. Patient knowledge on safe medication practices is The primary objective of this study was to assess the extent of critical in preventing unnecessary patient harm. For example, serious games intended to educate patients about medication recent reports from Poison Control state that approximately use and safety. In particular, this systematic review aimed to 60,000 children were sent to the emergency room every year explore (1) serious games intended to educate patients about because of taking medications without adult supervision [6]. medication adherence, education, and safety; (2) types of These findings show opportunities for patient education on safe theoretical frameworks used to develop serious games for medication use, storage, and disposal, particularly for young medication use; and (3) sampling frames for evaluating serious people and their family caregivers. games on medication use. Technology has a significant impact on education and health behavior reinforcement both in patients and providers [7]. Methods Devices such as mobile phones relay information, reinforce norms, and influence behaviors such as medication adherence Search Strategy [7]. The appeal of technology, particularly gaming, makes A literature search was conducted using PubMed, Scopus, and serious games an ideal approach to portray medication Web of Science databases. The key terms included in the search information [8]. Technology-based serious games are a novel were (serious game OR serious-games OR serious video-games method of delivering interactive health behavior education OR serious games OR serious digital games OR serious through skill-building exercises [9,10]. Serious games are digital electronic games OR serious gaming OR video game OR tools that offer engagement activities through a responsive video-game) (drug OR drugs OR medication OR medications narrative to educate participants through role-play and practicing OR prescription OR prescriptions) (treatment OR therapy). skills. Unlike traditional video games, serious games act to Search results from each database were exported to Microsoft convey meaningful information through interactive Excel, merged, and sorted for removal of duplicate citations. environments similar to real-life situations [11,12]. The use of Study Selection serious games on computer and mobile phone platforms to promote awareness of health issues has increased in popularity This review was conducted in accordance with the Preferred over the past decade [13]. Technology is readily accessible in Reporting Items for Systematic Reviews and Meta-Analyses the United States, with 89% of households owning a computer guidelines. Only original research articles were included in this or mobile phone device and 81% of households having an http://games.jmir.org/2020/2/e16096/ JMIR Serious Games 2020 | vol. 8 | iss. 2 | e16096 | p. 2 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Abraham et al systematic review. Initial screening of all abstracts and titles Data Extraction was conducted independently by SL and SB to determine A standard data extraction form was used to collect study whether to include or exclude an article based on selection authors, article title, year published, journal title, study design, criteria. Inclusion criteria were original research studies brief description of methods, primary outcome measures, and published in English for patients as end users involving a serious conclusions by all the authors for the articles included for game, which focus on medication use and safety, addressing at full-text inclusions in the last step. References of the papers least one of the following topics: (1) medication safety, (2) initially found were not included for evaluation. medication adherence, and (3) medication education. During the abstract and title screening phase, a level of agreement on Results inclusion and exclusion was achieved among the authors. A third author, HS, reconciled disagreements to achieve mutual Literature Overview consensus before moving to full-text review. Full-text articles A total of 953 records were obtained after searching PubMed, were assessed for inclusion, and reasons were documented for Web of Science, and Scopus. After removing duplicates, 749 all excluded papers. articles with unique titles were identified for title reviews. After Definitions of key terms are as follows: title review, 558 studies were removed, and another 152 studies were removed after abstract review for not meeting the inclusion • Serious games: A digital or computerized game designed criteria. Studies were removed if they did not include a serious for patients to increase their knowledge and awareness game focusing on patients as end users and based on medication about medications or help them with medication use and use, adherence, and safety. A comprehensive review of 49 safety. full-text articles was conducted, 33 of which were excluded. • Games for medication adherence: Games that promote Systematic reviews, serious games for end users other than players to take medication at least as prescribed. patients, nonmedication-related games, and nonvideo games • Games for medication education: Games that teach players were excluded (see Figure 1). As a result, 16 articles were how medications work in the body or why the medication included in this systematic review. The results are presented is an important component of patients’ treatment plan. below based on the following three specific aims of the paper: • Games for medication safety: Games about taking and (1) serious games intended to educate patients about medication handling medications in the proper way or safely to prevent adherence, education, and safety; (2) types of theoretical medication errors. frameworks used to develop serious games for medication use; and (3) sampling frames for evaluating serious games on medication use. Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram of the included studies. http://games.jmir.org/2020/2/e16096/ JMIR Serious Games 2020 | vol. 8 | iss. 2 | e16096 | p. 3 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Abraham et al A total of 16 articles on serious games published between 2003 Wheezie had a single medication learning objective of proper and 2019 were found to incorporate medication use targeted inhaler use and used the precede-proceed model, which involves toward patients. The 16 articles found focused on 12 unique incorporating components such as predisposing, enabling, and serious games. Moreover, eight games were tested in adolescent reinforcing factors into game development [34]. One published populations, three games were tested in young adults, and one study with an unnamed computer game used the pain and game was tested in adults only. In some cases, there were medication model to teach players of any age how to manage multiple articles focused on a single serious game. As shown activities of daily living through balancing activity level with in Multimedia Appendices 1 and 2, the included games could the quantity of medication taken postoperatively [40]. The be grouped based on the disease state or education on a specific theoretical framework used in development was a blend of the topic. All 12 games are described in Multimedia Appendices 1 middle-range theory of chronic illness, adult learning theory, and 2. and the experiential learning theory. The middle-range theory of chronic illness involves reflection and decision making, such Intention of the Serious Game as choosing when to take pain medication [40]. The adult Most of these articles studied the change in patients’ knowledge learning theory incorporates self-directed learning methods, about medications as an assessment of medication adherence. which is a preferred learning method for adults [40]. The The following are examples of 8 games that assessed patients' experiential learning theory involves learning through understanding of medications for managing chronic and acute observation, abstract conceptualization, and experimentation health conditions. [40]. CSI Web Adventures used the theory of reasoned action to display the negative consequences of abusing prescription • Games for antiretroviral therapy (ART) and pre-exposure drugs, such as opioids in two separate case studies [38]. prophylaxis (PrEP) adherence: Viral Combat, Adherence Warrior, Epic Allies, and Battle Viro were developed to Sampling Frames Primary Results promote adherence to ART and PrEP [26-30] Viral Combat, Adherence Warrior, Epic Allies, and Battle Viro • Game for cancer treatment medication adherence: were developed to promote adherence to ART and PrEP [26-30]. Re-Mission [31] The target audience was aged between 13 and 35 years in all • Game for diabetes medication education and adherence: HIV-focused games [8,27-30]. Each game used three to four L’Affaire Birmann [32,33] modalities to achieve learning objectives, summarized in • Game for asthma medication education: Wee Willie Multimedia Appendices 1 and 2. Wheezie [34] • Games for microbiology and antibiotic education: Microbe Viral Combat, an iPhone gaming app published only through Quest and e-Bug Junior and Senior [35-37] the game development phase, incorporated a Smart Pill Bottle • Game for prescription drug abuse education: CSI Web Cap and text messages to patients aged 18 to 35 years to Adventures [38] promote adherence to PrEP [26]. A Smart Pill Bottle Cap reports • Game for over-the-counter (OTC) medication safety: to the app when the medication bottle is opened [26]. A small Alchemy Knights [39] trial of nine participants showed an 88% satisfaction toward the game, and 100% of the participants would recommend it to a Types of Theoretical Frameworks Used to Develop friend [30]. Serious Games for Medication Use Adherence Warrior, a mobile gaming app for patients aged 13 Of the 16 studies, seven used a theoretical model or framework to 24 years, promoted adherence while maintaining player in the game design process. The theories used in each game are privacy. Text messages were sent to patients to promote ART mentioned in Multimedia Appendix 1. In Viral Combat, the adherence [27]. A mixed method study had 12 participants information, motivation, and behavior (IMB) theory was used having rank level of agreement on a scale of 1 to 5, with 5 being to promote medication behavior change [26]. Adherence strong agreement to game characteristics. The study reported a Warrior, another game for HIV adherence, was guided by the median score of 5 of having fun while playing (P=.03), and social cognitive theory. Social cognitive theory goals included players preferred to play games about topics other than the increased player self-efficacy, knowledge of HIV treatment immune system (P=.01) [27]. No statistical significance was goals, and social support [27]. Battle Viro was the only found to support whether participants would play the game if HIV-related game incorporating educational modules and did it were available or if they would use the game to take HIV not report a specific theoretical framework or model that guided medications [27]. game development. In Epic Allies, the IMB model framework was used to develop objectives of increased ART adherence Battle Viro, an iPhone gaming app targeted to patients aged 14 and social support. In Re-Mission, a game for cancer medication to 26 years, incorporated a Smart Pill Bottle Cap, text messages, adherence, the behavioral objectives were developed based on and educational modules. Learning outcomes were to improve the social cognitive theory and social learning theory [31]. The ART adherence, increase social support, increase HIV- and social cognitive theory was used to measure patient’s confidence ART-related knowledge, and visualize progress. In a randomized in their ability to carry out adherence behaviors to reach a goal controlled trial of 61 participants starting with a detectable viral [31]. The social learning theory connects medication adherence load, the experimental condition had 23% greater adherence to a social component such as a multiplayer serious game [31]. (P=.05) compared with the control group and a 0.96 log greater L’Affaire Birman was a serious game for type 1 diabetes decrease in viral load (P=.04) [8,30]. education and did not use a theoretical framework. Wee Willie http://games.jmir.org/2020/2/e16096/ JMIR Serious Games 2020 | vol. 8 | iss. 2 | e16096 | p. 4 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Abraham et al Epic Allies was the only HIV medication adherence mobile CSI Web Adventures simulated a prescription drug abuse crime gaming app that did not incorporate an electronic pill bottle or scene and took players through the science of forensic analysis text messages. The target age for this game was 16 to 29 years [38]. This computer game was targeted toward people aged 14 [28,29]. The distinguishing modality of Epic Allies was a to 18 years. A sample of 179 players conveyed negative attitudes dashboard displaying various lifestyle behaviors, such as toward illegal crimes in the baseline and game testing phases smoking, medication adherence, and mood [28]. A sample size [38]. CSI Web Adventures is reported to need more testing of 20 study participants through focus groups supported game before significant results can contribute to specific opioid acceptability [28,29]. safety-related learning objectives [38]. Re-Mission focused on increasing oral chemotherapy adherence Alchemy Knights, a serious game available on the Web, was and strategizing the use of medications to treat the side effects geared toward ages 9 to 12 years. The game taught players about of oral chemotherapy for people aged 12 to 29 years [31]. responsible OTC medication safety, drug-drug interactions, and Players control a robot, Roxxi, with the goal of adhering to oral the consequences of misusing medications [39]. A pilot study chemotherapy and combating negative effects through taking of nine participants showed 78% increased knowledge in medications such as stool softeners and antibiotics [31]. A medication safety from a pretest to posttest analysis [39]. Results randomized control trial of 375 participants yielded no will be used to improve the game for future use [39]. significant results for adherence but a 9.8% increase in Trimethoprim and Sulfamethoxazole adherence (P=.01) [31] Discussion and a significant increase in player’s self-efficacy for medication Overview adherence (P=.01) [31]. This systematic review offers valuable additions to the current Two studies on one game specifically included a diabetic evidence-based literature by examining serious games for medication-centered learning objective [28,29]. Target ages in patients that incorporate medication adherence, education, and published studies ranged from 10 to 19 years [32,33]. L’Affaire safety. Existing systematic reviews explore serious games for Birman was a serious game targeted toward children living with health focused on the management of specific disease states, type 1 diabetes [32]. Players used a strategic approach to adjust such as HIV, diabetes, and asthma, and on the positive impact the game character’s insulin based on lifestyle factors such as of serious game education in each respective disease state food intake, physical activity, and glucose levels. With no results [19-24]. Although other reviews target broad topics such as or sample characteristics reported, the authors suggested that health care gamification and serious games to educate health further testing is needed to assess the effectiveness in the clinical care workers [7,17,25], no reviews focus solely on examined setting [32]. medication use [7,15-17,19,20]. The identified serious games Wee Willie Wheezie, a 3-level computer-assisted instruction that incorporate the use of medications are mainly focused on program targeted toward children aged 7 to 12 years, had a improving adherence, whereas medication safety is not widely single medication learning objective of proper inhaler use [34]. explored. In addition, there is a lack of research on the efficacy The players chose the correct medication to avoid asthma and usability of medication-focused serious games often because symptoms, exacerbations, and hospital trips [34]. A randomized of small and nonrepresentative sample sizes, which limit the controlled trial of 148 participants found no significant generalizability of existing studies. Very few serious games improvement in player’s asthma symptoms or quality of life described how theoretical frameworks were incorporated during parameters [34]. development, showing an area for improvement in literature [26,28,34]. This systematic review signifies the need for the In an unnamed game, patients learned safe medication regimens creation of serious games focused on medication adherence, by using the icons in the game to learn about the side effects of education, safety, testing of existing serious games for efficacy each medication. [40]. An evaluation study of 20 participants and effectiveness, an evidence-based theory-driven approach aged 24 to 67 years found an increase in knowledge on strategies for serious game design, and large-scale testing with randomized to manage pain (P<.001) [40]. samples to improve generalizability. e-Bug Junior and Senior were multiple-module educational Medication Incorporation adventure computer games targeted toward students ranging in age from 9 to 12 years and 13 to 15 years, respectively [35,36]. Each serious game included in this review was analyzed for the Each game had one module teaching the purpose of antibiotics extent and quality of medication-related topics. The included and the importance of taking the full course. An evaluation games had a medication-related learning objective incorporated study of 129 students yielded 98% positive comments about into a gameplay feature. Of the 12 unique serious games the senior game and no efficacy results [35,36]. included in this study, most did not have medication as a principal component. The sole content in Re-Mission, Alchemy Microbe Quest was a mobile gaming app targeted to patients Knights, and the unnamed pain management game were aged 9 to 12 years [37]. A single level of gameplay introduced medication adherence, education, and safety, respectively the concept of antibiotic resistance as a consequence of not [31,39,40]. ART and PrEP adherence was incorporated in Viral finishing a full course of antibiotics [37]. No statistically Combat, Adherence Warrior, Epic Allies, and Battle Viro significant results in learning objective retention were found in through social support, text reminders, computerized pill bottles, the initial pilot study of 19 participants [37]. and various point incentives [8,26-30]. Microbe Quest, e-Bug, Wee Willie Wheezie, and CSI Web Adventures included a single http://games.jmir.org/2020/2/e16096/ JMIR Serious Games 2020 | vol. 8 | iss. 2 | e16096 | p. 5 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Abraham et al medication-related module [34-38]. Although medication is not Sampling Frames extensively incorporated into serious games, this demonstrates This study recognizes that the majority of serious games a modality of patient education to be explored in the future. included in this study were tested for usability and functionality with very small sample sizes. Only five of the included studies Theoretical Frameworks had more than 100 participants [29,31,34,38]. These small Validated social, behavioral, and game theories such as IMB sample sizes limit the external validity of these studies, thus theory, social cognitive theory, precede-proceed model, reducing the generalizability of the results to larger populations. middle-range theory of chronic illness, adult learning theory, In the future, the effectiveness of these serious games must be experiential learning theory, and the theory of reasoned action assessed using larger sample sizes to investigate their impact as included in this review are developed and defined iteratively on patient’s knowledge and understanding about medication over time. Using these theories for game development and adherence, education, and safety. testing can improve the effectiveness of these serious games [26,30]. On the evaluation of the 12 serious games identified Regarding geographical distribution of samples used in the in this study, six incorporated varying degrees of theoretical studies, only one study included patients from outside of a single frameworks to support game development and testing. A total state [31], whereas other articles used convenient samples from of three articles about two serious games extensively focused a single clinic, city, or state [8,26,27,29,30,32,34-38]. By on IMB theory for game development [26,28,29]. The goal of limiting the participants to a single site, geographical location the IMB model in Epic Allies and Battle Vivo was to change or a specific age group, the external validity of the results from specific health-related behaviors such as medication adherence these games is again compromised. Of the 12 serious games, through a combination of health education, self-motivation, and eight were tested in adolescents, three were tested in young gaining required skills [26,28,29]. Game mechanics in Epic adults, and one was tested in adults. Although adolescents Allies were designed to motivate ART adherence in young men benefit from serious games, adults could also benefit from who have sex with men and long-term game use [28,29]. serious games and should be a future area of exploration in Another article extensively described the use of the serious game usability studies. In the future, more studies with precede-proceed model in game design of Wee Willie Wheezie randomized and diverse populations could increase the statistical [34]. Two games mentioned the social cognitive theory, and power of these results. one game mentioned the theory of reasoned action, but neither The published literature on medication-based serious games of them described any specific details about using and has a strong focus on game design, mechanics, and integrating the theory in game design and mechanics methodologies rather than the effectiveness of the game. Of the [8,27,30,38]. Future goals in Alchemy Knights indicate included articles, seven focused on game design and the plans examining theoretical contributions for further game for future game development without elaboration on outcomes development [39]. Although most of the serious games involving and game efficacy [8,27,29,30,33-36]. A total of four studies theory in their design used small sample sizes for testing their focused on the intended outcomes of the games and whether efficacy and effectiveness, positive outcomes were still they were met [26,31,37]. The common method of evaluation demonstrated by a few [26,28,38]. A common theme identified was surveys on gameplayers’ satisfaction while playing but not was a lack of statistical power to test the efficacy of theory the information that they sustained and retained from the games. outcomes because of the small sample size or result usability Quantifying whether learning objectives were met is necessary [8,26-30,34,39,40]. Future literature describing serious game to determine the success of serious games for future studies. development should incorporate more thorough descriptions of Thus, future serious game design development should include the theoretical frameworks used and larger sample sizes. plans for rigorous testing of efficacy. Medication Adherence, Education, and Safety Limitations Of the 12 serious games included in this study, six focused on The authors recognize key limitations of this study. First, only improving medication adherence [7,8,26-31,38,40], three 3 databases were used for the literature search. Although the targeted medication education [29,32], and three were aimed at extent of duplicates supported a thorough search, there is a providing medication safety [35-39]. Medication nonadherence chance that there are relevant papers that were not included. is a prominent issue in health care, which leads to increased Second, only papers written in English were included. This may costs and comorbidities. By using innovative approaches to have excluded papers from non-English–speaking countries. teach patients the value of adhering to medication, serious games Finally, small sample sizes were used to test most games can assist in improving medication therapy outcomes. Serious included in this study. None of the literature discussed the games educating users on medication misuse or promoting safe sustainability of the games post study, and most of the included usage of medication were lacking in the literature. Although games did not have long-standing follow-up data on their the authors recognize that there is a thin line between medication participants. safety and education, there were many more games with education and adherence components when compared with Conclusions medication safety components such as preventing inappropriate There have been limited studies on serious games for health use [36-40]. Future serious games with medication use as a that incorporate medication use. The findings from these studies component should incorporate learning objectives targeting focus on developing and testing serious games that teach patients medication safety principles to prevent adverse drug events. about medication use and safety. Most of these studies do not http://games.jmir.org/2020/2/e16096/ JMIR Serious Games 2020 | vol. 8 | iss. 2 | e16096 | p. 6 (page number not for citation purposes) XSL FO RenderX JMIR SERIOUS GAMES Abraham et al apply a theoretical framework in the design and assessment of the potential to reduce patients’ knowledge gaps and address these games. The development of serious games for patient misconceptions, which may lead to improved medication medication use, education, and adherence should incorporate adherence and reduced errors. This review shows that there has evidence-based and theory-driven methods to ensure maximum been an increased interest in the application of serious games retention of the learning objectives by study participants and to improve medication use outcomes, and it is expected that game players. More diverse, randomized studies with long-term this review will help advance the effectiveness of game data collection need to be conducted to demonstrate the development in the future. effectiveness of serious games in this area. Serious games have Acknowledgments The authors would like to thank Lisa Szela at the University of Wisconsin–Madison (UW) School of Pharmacy for assisting with editing the manuscript. The authors thank Maeleigh Tidd at UW School of Pharmacy for reviewing the manuscript and providing constructive feedback. This study was supported by KL2 grant KL2 TR002374-03 and grant UL1TR002373 to UW Institute for Clinical and Translational Research by the Clinical and Translational Science Award program, through the National Institutes of Health (NIH) National Center for Advancing Translational Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Conflicts of Interest None declared. 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JMIR Serious Games 2017 May 10;5(2):e10 [FREE Full text] [doi: 10.2196/games.6894] [Medline: 28490419] Abbreviations ART: antiretroviral therapy IMB: information, motivation, and behavior NIH: National Institutes of Health OTC: over-the-counter PrEP: pre-exposure prophylaxis PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses UW: University of Wisconsin Edited by G Eysenbach; submitted 17.10.19; peer-reviewed by E Unni, T Baranowski, L Santos; comments to author 03.12.19; revised version received 23.01.20; accepted 04.02.20; published 29.04.20 Please cite as: Abraham O, LeMay S, Bittner S, Thakur T, Stafford H, Brown R JMIR Serious Games 2020;8(2):e16096 URL: http://games.jmir.org/2020/2/e16096/ doi: 10.2196/16096 PMID: 32347811 ©Olufunmilola Abraham, Sarah LeMay, Sarah Bittner, Tanvee Thakur, Haley Stafford, Randall Brown. Originally published in JMIR Serious Games (http://games.jmir.org), 29.04.2020. 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Published: Apr 29, 2020

Keywords: games; medication adherence; patient safety; video games; systematic review

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