Artificial intelligence (AI) and serious games are both relevant topics in the health sector, and the body of studies and literature is continuously growing. Interestingly, in terms of the research landscape, the 2 topics are not connected; rather, existing research views them independently.

The use of games for educational and serious purposes is nearly as old as the history of humankind and is an integral part of our culture [1]. In 1970, Abt [2] used the term “serious games” for the first time in his book with the same name. Sawyer and Smith [3] take a broad definition and consider serious games as “any computerized game whose chief mission is not entertainment and all entertainment games which can be reapplied to a different mission other than entertainment.” What serious games have in common is that they pursue a concrete (pedagogical) intention and aim to provide information on a specific topic (eg, health) that is accessible in an entertaining and interactive way to deepen competencies or to achieve a change in behavior [4].

Serious games for health can be used in the fields of medical diagnostics, therapy, and prevention, as well as health promotion and medical or patient education [5]. From a didactic and learning psychology perspective, the effect of serious games is based on the integration of the motivating and multimedia aspects of computer and video games. Serious games can increase engagement, motivation, enthusiasm, and interest [6,7]. There are several existing use cases in health contexts [8-11]. One example is the game EndeavorRx. In 2020, the US Food and Drug Administration permitted its marketing as the first game-based digital therapeutic device to improve attention function in children with attention-deficit/hyperactivity disorder (ADHD) [12]. The game Re-Mission was developed for children with cancer and showed good results regarding compliance and the understanding of disease-related issues in the target group [13]. EMERGE is a simulation game that recreates an emergency department in real time to improve the clinical reasoning skills of physicians [14].

Next to serious games, gamification has emerged as a major trend in the health sector, which is reflected in a growing number of publications, including several meta-analyses [15-17]. The most used definition of this concept is “the use of game design elements in non-game contexts” [18]. The motivational effect of the game elements can be explained in different ways. Sailer et al [19] established the link between various gamification elements (eg, points, leaderboards, and badges) and the self-determination theory proposed by Ryan and Deci [20]. As a theory of motivation, this defines three universal psychological basic needs that determine human action: (1) competence, (2) autonomy, and (3) social inclusion. If ≥1 of these needs are addressed (eg, through gamification elements), this has positive effects on behavior and its determinants [19]. In the health sector, there are numerous studies that have demonstrated the effects of using gamification on motivation, performance, engagement, health, and well-being status [5,21,22].

According to Westera et al [23], computer games have been linked with AI since the first computer was programmed to play chess [24]. New AI methods have been used in computer games, for instance, to generate levels, scenarios, and storylines; to balance complexity; or to add intelligent behaviors to nonplayer characters (NPCs) [25]. However, over the years, various authors have pointed at the marginal penetration of academic game AI methods in industrial game production [26]. AI techniques will become indispensable to coordinate the ever-growing complexity and dynamics of games [23]. AI-driven adaptation and assessment systems are used to offer learner-centered environments [27]. As an example, NPCs controlled by AI can adapt to the behavior of the gamer and can enrich immersive and challenging experiences within the game play.

When transferring these principles to health care, the interaction between AI and games could provide a benefit, especially in the management of chronic diseases, which most game designs already target. The possibility to quickly adapt to new game-generated data or performance and provide live feedback could lead to more individual and thus more patient-centered game design in both illness detection and treatment. This could increase motivation and engagement for patients, leading to higher therapy adherence through more personal involvement. The vast body of evidence in the field of serious games and gamification, along with the growing body of evidence in the use of AI, may thus form a new field of research.

Therefore, this scoping review sought to generate an overview of the currently existing literature on the interaction of AI and game-based approaches in health care. At this point, to the best of our knowledge, this is the only review that targets this interaction.

The primary objective was to analyze the current body of evidence based on (1) the disease or health issue being evaluated, (2) the process of care in which these projects are located, and (3) the kind of AI and type of game-based approach used and the interaction of both techniques.

A secondary objective was to obtain an overview of publications on the interaction of AI and game-based approaches such as serious games, gamification, commercial games, and game periphery. Another secondary objective was to analyze the quality of the existing studies in this field regarding their grade of evidence and the conducted study types.

For this scoping review, we applied the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols; Figure 1) guidelines [28]. Furthermore, we used the recommendations of the Cochrane Consortium for conducting systematic reviews and the RefHunter website as guidance [29].

Before starting the review process, we defined the inclusion and exclusion criteria (Textbox 1).

For this review, we conducted the following steps:

We applied the search terms primarily in the database PubMed on February 2, 2022. We tested and honed different search terms and Boolean operators (Multimedia Appendix 1) until sufficiently fitting results seemed to have been obtained (n=305). The final search term was defined as follows:

[“game” OR “gamification”] AND “artificial intelligence”

The search was extended to more open databases to assess studies that target AI and serious games in medicine-related research areas or interprofessional approaches that may include medical professions and in more technically oriented databases such as IEEE Xplore [30] to include papers from informatics and engineering with a focus on technical issues.

The same search term ([“game” OR “gamification”] AND “artificial intelligence”) AND “artificial intelligence”) was used for IEEE Xplore (n=98), Cochrane Library [31] (n=25), and PubPsych [32] (n=89). In Scopus, the search term used in the other databases showed fewer results and were modified to extend the range of hits (“serious” AND “game” AND “artificial intelligence”; n=41).

In addition, we conducted a search in Google Scholar [33]. However, the results from Google Scholar were not precise enough for inclusion in a review, which is consistent with the results of several studies [34-36].

After deduplication using Rayyan software (Rayyan Systems Inc), the combined search in these databases identified 545 (97.7%) publications out of the initial 558 identified. We then performed a manual deduplication, which resulted in 60 (11%) of the 545 publications being excluded; thus 485 (89%) publications remained (Multimedia Appendices 1 and 2; Multimedia Appendix 3 [37-51]).

For the second step of the scoping review (title and abstract screening), we used Rayyan software. The results from the literature search were transferred to the citation software Zotero (version 5.0.85; Rayyan) and to Rayyan software [52]. This software automatically identified duplicates. After iterative deduplication, the publications were subjected to manual screening. The first screening step was conducted using Rayyan and permitted publication inclusion based on their titles and abstracts. Given the volume of the publications to be screened, the title and abstract screening was distributed among 2 authors of this paper (JS and DT). To ensure the uniformity of the screening, the authors conducted several training sessions in Rayyan with the coreviewers. In addition, the authors randomly double-checked some of the excluded publications (25/485, 5.2%) to warrant the consistency of the screening by the other reviewer. This step was conducted independently by both researchers and was followed by a discussion of the results between the 2. As all analysis steps were conducted independently by the 2 researchers, a discussion of differently categorized literature (marked as “Conflict” in Rayyan) and subsequent adaptation were necessary in this step. Overall, only a few adjustments were necessary, and a good agreement between the 2 researchers could be reached. Possible conflicts and all included articles were discussed with a third team member (SK). The data generated by Rayyan can be found in Multimedia Appendix 2.

After the primary screening, full-text publications were screened by the 2 lead authors. Toward this end, a table was prepared to compile relevant information (Textbox 2).

Some of the studies (4/16, 25%) showed an overlap among different categories (eg, in level of care). In these cases, double classifications were performed. All eligible studies were categorized and coded in detail (Multimedia Appendix 3 [37-51]).

After conducting the scoping review, we additionally used the “snowballing” approach described by Greenhalgh and Peacock [57], who have stated that in reviews of complex and heterogeneous evidence, formal protocol-driven search strategies may fail to identify important evidence. Informal approaches such as browsing and asking colleagues can substantially increase the efficiency of search efforts. Snowballing methods such as pursuing references of references and electronic citation tracking are very useful for identifying high-quality sources in obscure locations. Therefore, to validate the results of the review, the 2 reviewers searched the literature references used in meta-analyses, reviews, and papers that were closely related to the topic of the search. In addition to using the snowballing method, the method of asking colleagues, as recommended by Greenhalgh and Peacock [57], was applied as a last step.

When applying the aforementioned search terms, we initially identified 335 studies on the topic of games and the use of AI in health care in the last 20 years. The subsequently performed step of title and abstract screening reduced the number of the initially identified studies from 335 to 47 (14%). In the next step, assessing the actual full-text literature, of the 47 papers, 3 (6%) were excluded because their full text was not in English, and the aforementioned inclusion and exclusion criteria were applied to the remaining 44 (94%). After the full-text screening, 10 (23%) of the 44 papers met all inclusion criteria. Using the snowballing method, 1 additional paper could be identified. Asking colleagues revealed 5 additional papers, which led to an overall total of 16 eligible papers (Figure 1). Not all criteria showed hits (eg, function type showed hits only in 2 categories, whereas level of care showed no hits in nursing).

Currently, there are only a limited number of studies involving a combination of game-based methods and AI in health. Almost one-third of the included studies (5/16, 31%) were centered on addressing motion impairment. The primary emphasis of the research was on rehabilitation. In addition, most of the studies (9/16, 56%) focused on prevention and diagnostics. In terms of AI technology, machine learning was the most commonly used approach (12/16, 75%). Furthermore, serious games were used in most of the studies (11/16, 69%).

When analyzing the studies by disease category, most of the studies (5/16, 31%) used a rehabilitation approach for different aspects of motion impairment (eg, in poststroke conditions, phantom limb pain or limb absence, and rheumatoid arthritis). In this field, studies have a focus on providing individual, at-home, and complex training opportunities for improving motoric limb function, in which therapeutic concepts rely on long-term and self-guided exercising. Games take the role of a training tool, enhancing at-home training motivation and providing multidimensional and exercises compared with the current standard of care. In addition, in some of the studies (5/16, 31%), the integration of virtual reality and augmented reality provided an immersive experience. The role of AI in this context is diverse, sometimes to analyze and classify collected data to improve game setup and level, sometimes to analyze data resulting from game play itself.

In a second cluster, studies for neurological diseases, including those handling cognitive impairment in older adults as well as 1 study for ADHD in younger patients, there was a clear focus on diagnostic evaluations. Here, different sets of games were used to assess various cognitive subdomains, with AI processing these different data inputs and calculating scores and predictions. The advantages in this field are the wide range of possible game designs and the feasibility to play these games individually at home. This could reduce health professionals’ time in assessing cognitive function during face-to-face visits or supplement them by enabling longitudinally acquired data sets and trajectories. The first results show promising results in comparison with standard clinical scores obtained using, for instance, the MMSE.

The direct interaction between the games approach and AI technology was only described in 3 (19%) of the 16 studies. Most of the time, the 2 entities follow each other, with the AI technology not analyzing live in-game playing data. However, direct interaction holds a promise of benefit through an AI-enabled assessment of the patient’s ability during game play and individualized live adjustments of game design and difficulty. Examples using this approach showed good technical functioning and positive user feedback [42]. Even so, the limited number of published studies suggest that the potential of this integrated approach has so far not been fully used yet. This is rather surprising, given the fact that the direct link between AI and games is widely prevalent in the commercial games sector. The reasons for this are purely speculative. The transition of findings from 1 field to another is still pending, perhaps because studies in the commercial games field have a different scope than those in medicine and health. Another reason could be the resource-intensive nature of research. However, the future potential of this interaction seems promising, with the stimulation of user motivation by game design and gamification elements and with AI being used to process large and multimodal data sources and to perform individualized adaptations.

When analyzing further categories, our review shows that the studies so far have produced very limited quality evidence (all studies have an evidence level of 4 or 5, except for 1 study that has an evidence level of 3b), with most of the studies presenting either a rather technical proof of concept (15/16, 94%) or performing usability testing with a small sample size of healthy individuals and patients (14/16, 88%). Higher-quality studies with control groups and end points focusing on specific clinical outcomes are missing.

Of note, the research field is still young. All studies were conducted in the last 8 years, with 13 (81%) of the 16 studies being published in the last 3 years. All research settings however bear the potential of conducting higher-quality studies with bigger sample sizes and specific medical outcomes in the near future.

However, the studies in this review already show promising results, with overall well-functioning technical implementation of the game elements and high accuracy and usefulness of the AI integration. From the patients’ and healthy individuals’ perspective, generally high usability, motivation, and satisfaction were found, mostly assessed by established usability questionnaires and qualitative interviews. This is an encouraging perspective for the future because individualized patient-driven at-home diagnostic and therapeutic approaches are increasingly relevant in all fields of medicine.

All 16 studies identified in this review have a relatively low level of evidence (3b: n=1, 6%; 4: n=10, 63%; and 5: n=5, 31%). The risks of bias in these studies are multifaceted. Pilot studies, often conducted to assess the feasibility of a full-scale study, typically featured small sample sizes and often lacked rigorous methodology, randomization, and blinding procedures. As a result, they are susceptible to a range of biases, including selection bias, performance bias, and detection bias. Studies were characterized by weaker methodologies, which can lead to biases in data collection, analysis, and reporting. Nonrandomized studies were prone to selection bias, confounding, and other methodological flaws. The high heterogeneity of the identified studies encompassed a wide range of disease or health issues, populations, and interventions. This heterogeneity makes it challenging or impossible to integrate data and limits overall conclusions.

First, as described earlier, the field of research is still very interdisciplinary, and the studies carried out are very diverse based on the vast variety of game-based approaches and therapeutic interventions.

This review only covered original studies in English, which were found in the PubMed, Scopus, IEEE Xplore, Cochrane Library, and PubPsych databases and published in the last 20 years. Although these are widely recognized and commonly used databases in the field of health care research, restricting the review to these 5 databases may have resulted in the exclusion of relevant studies published in other databases owing to this high interdisciplinarity. However, efforts have been made to minimize this limitation using comprehensive search strings, snowballing, and asking colleagues to identify additional relevant literature. In addition, this review also includes interdisciplinary databases such as the more technical-oriented IEEE Xplore and the more pedagogical-oriented PubPsych.

It especially remains unclear whether all projects conducted especially with a more technical focus have been published in scientific journals at all. For future reviews, a more holistic approach should be taken to assess more results from projects that may not have been included in a publication.

In addition, there might be a lack of awareness that research in the engineering, gaming, and fitness spectrum has a direct connection with health-related issues. Thus, it seems possible that certain publications were not fully covered by our already broad search strategy or that promising interventions have not been related to health care yet. This should be mitigated in future studies, considering the growing attention to this young research field.

Another limitation is that this review focused on therapeutic medical interventions rather than on health interventions. AI and game-based approaches in the field of prevention and health promotion have not been included, although this is an important aspect of population health. Game-based approaches especially are used a lot in this field to reach the target groups [8,9,21,22,59-61].

In the near future, the potential of games, which is already established in the commercial games sector, should be applied to the field of serious games and AI. Adaptive game design can be suitable in health care to improve the intervention outcome via AI-driven health care games that assess the skills level of the patient and adapt the difficulty in feedback loops, which could lead to a better harmonization with traditional therapy sessions. NPCs could be used as virtual patients or other health care personnel or relatives to simulate the interprofessional working environment and to improve the interaction and communication with virtual patients [26,27,34].

Finally, the integration of AI and games should carefully consider the ongoing discussions regarding ethical, moral, and data protection issues. In particular, studies describing ethical issues using game-based approaches are scarce [62,63].

Analyzing the currently limited evidence with promising future possibilities in study design and quality, as well as a dynamic research field, it seems, at this stage, that another review should be conducted in the next few years to assess this rapidly growing research field.