The coronavirus outbreak in 2019—officially the COVID-19 pandemic—still remains the most serious global public safety incident in recent years (1). COVID-19 has seriously affected public health, economic development, social stability, and even national security worldwide (2). Because of its extensive spread, this disease emerged as an urgent worldwide concern to citizens and governments alike (3). With the gradual decline in the severity and fatality rates of COVID-19 in combination with increased vaccination rates, some countries and regions have begun to relax their COVID-19 prevention and control measures (4, 5). On March 11, 2022, the Chinese government issued the Application of the COVID-19 Antigen Detection Program (6) to further implement its “dynamic zero-COVID-19” policy (7). The program allows anyone to obtain COVID-19 antigen detection reagents (ADRs) for self-testing in order to enhance early identification and treatment of COVID-19 (8). The China National Medical Products Administration (NMPA) had authorized 31 COVID-19 ADR products in accordance with government regulatory processes as early as April 29, 2022 (9). These ADRs are already available for purchase. Guangzhou, the capital of China's Guangdong Province, removed its city lockdown on December 1, 2022 in the face of a major COVID-19 infection, marking a turning point in the change of China's pandemic prevention policy (10). The government of Guangzhou supplies the public with free ADRs and encourages them to purchase ADRs for self-testing. ADRs will be mass-produced, sold, and utilized in China.

ADRs are classified as Class III medical devices under China's Regulation on the Supervision and Administration of Medical Devices (hereinafter Medical Devices Regulation). Class III medical devices pose a greater risk, necessitating stricter management controls to guarantee their safety and efficacy. No one is permitted to engage in the production or commercialization of Class III medical devices without authorization. The government should oversee medical device research, production, operation, and use. Third-party medical device inspection agencies (hereinafter “inspection agencies”) can provide quality certification services for the government and manufacturers of ADRs (11). They have become vital evaluators of quality certifications for medical devices being brought to the market (11). To develop high-quality products, medical device firms must pay substantial research and production expenses (12). Conversely, low-quality products normally have low production costs and large profit margins (12). Hence, ADR manufacturers frequently have a temptation to bribe inspection agencies (13, 14). This situation is difficult to control. In the presence of limited government supervision, ADR manufacturers tend to produce low-quality products and seek leniency from inspection agencies when obtaining marketing licenses. Lack of government monitoring and medical device inspection may lead to low-quality ADRs that have not undergone rigorous medical-standard manufacture (15). Low-quality ADRs sold to customers as a result of unethical business tactics can lead to an abundance of erroneous diagnostic results (i.e., false negative results and false positive results). As a result, those who self-test using substandard testing kits do not realize that their results may be misleading. Inaccurate self-testing results could cause SARS-CoV-2 to spread wider across the nation (16, 17).

China has experienced the above-mentioned problems. Falsified COVID-19 nucleic acid detection results hurt pandemic prevention efforts. In April 2022, some medical labs issued false testing results on numerous occasions, which has interfered with the overall pandemic prevention and control initiative (18). In May 2022, a testing center issued false positives to 13 residents in Shanghai within one day, but in the subsequent nucleic acid review, all tests were negative (19). These successive occurrences of false testing events are closely related to the profiteering aspect of nucleic acid detection work. Since the outbreak of the COVID-19 pandemic, statistics verify that several of these novel coronavirus detection reagent companies have achieved substantial revenue growth. The net profit of these institutions in the first quarter of 2022 reached 14.3 billion yuan, equivalent to a daily net profit of 158 million yuan (20). According to estimates by the Soochow Securities Research Institute, if all first- and second-tier cities in China (representing a total population of 505 million in 2021) were to implement normalized nucleic acid detection in the future, the monthly cost will be capped at 121.2 billion yuan; this total—equivalent to 1.45 trillion yuan per year—would equal 1.27% of China's nominal GDP in 2021 (21). Given the massive revenue-generating potential, some ADR manufacturers may purposely make low-quality ADRs that decrease the accuracy of nucleic acid detection kits.

Academic research into the regulation of ADR product quality has significant implications for public health (22). To date, however, the academic community has failed to fully addressed the problem of low-quality ADRs and erroneous diagnostic results. In an effort to resolve this problem, the authors of this paper employ evolutionary game theory. First, our examination and analysis of the current literature reveals that researchers have focused solely on the accuracy, potential applications and product advances of antigen detection, while ignoring the product quality of ADRs. Second, we design a tripartite evolutionary game model with ADR manufacturers, inspection agencies, and regulatory authorities as the primary entities and assess the strategic stability of each player and the impact of each variable on their best strategic decisions. Third, a simulation analysis is performed using MATLAB 2021a to validate the model's validity and sensitivity under various scenarios. Lastly, based on the findings, we provide countermeasures and recommendations to enhance the quality of ADR in China from a legislative and enforcement standpoint. This paper's discussion may serve as a resource for other developing nations pursuing similar answers.

Recent research on ADRs has focused on three major areas: the accuracy of antigen detection, the potential applications of ADRs, and product advancements for SARS-CoV-2 antigen detection kits.

Numerous academics have demonstrated the accuracy of antigen detection. In periods of high viral load, Zhan et al. found that reverse transcriptase polymerase chain reaction (RT-PCR) testing and rapid antigen test (RAT) provided equivalent results, with RAT showing a high level of sensitivity when utilized for continuous screening (23). Aoki et al. investigated the Espline(R) SARS-CoV-2 antigen test. They discovered that the antigen test could identify high-risk groups with high virus loads, potentially preventing a pandemic (24). Favresse et al. proposed that sensitive detection of Nucleocapsid-antigen (N-antigen) in serum might assist in identifying individuals at risk of developing severe COVID-19 and, therefore, better optimize intensive care consumption (25). Gupta et al. stated that antigen-based rapid diagnostic tests (RDTs) with high specificity and moderate sensitivity might aid in the quick identification, isolation, and treatment of COVID-19 patients (26). Hober et al. discovered that serologic assays based on several SARS-CoV-2 antigen combinations provide particular and sensitive multiplex serologic testing for COVID-19 (27). Beck et al. found that antibody microarray assays have clinical sensitivity and specificity equivalent to FDA-approved antigen testing (28). According to Grant et al., antigen-based SARS-CoV-2 tests may offer higher clinical sensitivity than serological assays (29).

Several researchers concentrated on the potential applications of ADRs. Lv et al. reviewed the methodologies and requirements for assessing the clinical performance of quick diagnostic tests for SARS-CoV-2 antigen detection and intended application scenarios of ADRs (30). Hauser et al. found that the LIAISON SARS-CoV-2 antigen test had excellent specificity but low sensitivity and should only be used for preliminary screening (31). Candel et al. observed that major health organizations, such as WHO and the Ministry of Health of Spain, support employing antigenic testing in various pandemic response methods (32). Williams et al. discovered that using plant platforms producing recombinant proteins as COVID-19 diagnostic reagents might reduce the cost of diagnostic kits (33). According to Varotto-Boccazzi et al., L. tarentolae is an efficient method for viral antigen synthesis in low-tech cell factories, with sensitivity and repeatability equivalent to reference antigens generated in human cells (34). Kritikos et al. suggested that RATs might assist in the reduction of the sporadically observed reagent scarcity in RT-PCR tests (35). Shao concluded that while SARS-CoV-2 antigen test findings cannot be utilized to diagnose COVID-19 directly, they may be used for early triage and immediate care of questionable groups. SARS-CoV-2 antigen testing is susceptible to false-positive and false-negative findings due to technical limitations (36). According to Fournier et al., antigen testing is unsatisfactory due to its lack of sensitivity. However, there is a global scarcity of reagents and kits. ADRs have evolved into a necessary alternative (37). Ellipilli et al. claimed that antigen tests could produce findings in <2 h and that diagnostic reagents could be purchased for <$5.00. There are currently commercially accessible lateral flow diagnostic kits with immobilized antibodies that enable patients to be diagnosed at home (38). Singh et al. described an inducer-based SARS-CoV-2 salivary antigen test using low-cost reagents ($3.20/visit) and a commercially available glucometer. This technology offers a low-cost, quick, and accurate diagnostic tool for large-scale distributed screening for SARS-CoV-2 infection (39).

Researchers have also looked at product advancements for SARS-CoV-2 antigen detection kits. According to Zhang et al., SARS-CoV-2 fluorescent immunochromatographic test strips can detect the virus quickly, sensitively, and accurately and meet clinical demands for on-site viral testing (40). Ramanujam et al. produced an ultra-fast SARS-CoV-2 detection sensor capable of detecting coronavirus proteins in saliva in <100 milliseconds (41). Nafian et al. examined several approaches based on clustered regularly interspaced short palindromic repeats (CRISPR) and discussed their advantages and disadvantages for point-of-care detection (POCT) of suspected SARS-CoV-2 infection at home or in small clinics (42).

Academic viewpoints and remarks on the sensitivity, application possibilities, and product innovation of ADRs may be found in the extant scientific literature. Most of these researchers feel that ADRs can compensate for deficiencies in nucleic acid detection. Based on antigen detection experimental data, the majority of the literature focuses on the practicability, validity, and dependability of ADRs. However, the current research does not explore the microscopic product quality concerns that emerge throughout the production and marketing of ADRs. Numerous false-positive and false-negative results might come from product quality issues, which are detrimental to the successful execution of public health efforts (e.g., personal distancing). Researchers have observed that the marketing of ADRs involves stakeholders such as government agencies, patients, and manufacturers (32, 43–46).

Nonetheless, it is obvious that researchers have not exhaustively analyzed the behavior patterns of different participants. Evolutionary game theory has not applied to the stakeholders in this situation. Evolutionary games offer significant application potential for simulating the behavioral tactics of various participants (47, 48). From a microscopic vantage point, it is possible to examine the strategic decisions and evolutionary logic of many players in the control of ADR product quality. Evolutionary game theory has been utilized extensively in the disciplines of COVID-19 public health governance (49), free riders in healthcare policy (50), and COVID-19 information disclosure (17).

There is little doubt that the government may strengthen public health governance by providing subsidies and imposing administrative fines to assure the product quality of ADRs and the prompt diagnosis of COVID-19 patients. However, inadequate financial resources may not guarantee sufficient subsidies for ADR manufacturers, and weak enforcement capacities may prevent early administrative sanctions for manufacturers of low-quality ADRs. The wider the product profit margin of ADRs, the greater the probability that ADR manufacturers would bribe inspection agencies to submit fraudulent test results, and the more difficult it would be to halt the manufacturing of low-quality ADRs. This requires further research.

Few researchers have examined the actions and decisions of regulatory authorities, inspection agencies, and ADR manufacturers from the standpoint of ADR product quality. In addition, no researcher has included these three parties in an analytical framework to investigate the effects of their interactions and the resulting societal impacts. Consequently, the following contribution is made by this study to the current body of knowledge: we employ a model based on evolutionary game theory that integrates regulatory authorities, inspection agencies, and ADR manufacturers into the analytical framework. We study the equilibrium results of their mutual activities and the accompanying social repercussions. Using the economic premise that people are rational, the evolutionary game model analyzes the learning and adjustment process underlying the behavioral decisions of regulatory authorities, inspection agencies, and ADR manufacturers.

Three evolutionary stabilization strategies are obtained by calculating and analyzing the model. In order to more intuitively observe the evolution trajectory of each stakeholder and their parameter sensitivity, this paper uses MATLAB 2021a to simulate the evolutionary stabilization strategies and the related parameters.

The significance of investigating ADR production and circulation became increasingly evident as we dealt with the practical challenges brought on by the COVID-19 pandemic. This paper examines the process of ADR production, certification, and marketing and further attempts to construct an evolutionary game model to consider each stakeholder's optimal strategy. The point (0, 0, 0) represents the optimal evolutionary stabilization strategy, which is the most likely to promote social welfare. Under this tripartite evolutionary game model scenario, manufacturers produce high-quality ADRs, inspection agencies refuse illegal incentives, and regulatory agencies exercise proper, non-invasive supervision.

First, legislators should integrate ADRs into the drug price monitoring system (DPMS) and restrict the number of illicit incentives (K). Illegal bribes are financed by product earnings. The greater the product's profit margin, the greater the number of bribes given to inspection agencies by ADR manufacturers, and the greater the possibility of successful bribery (55). As demonstrated in Figure 5B, in the face of considerable financial temptation, inspection agencies will eventually accept illegal incentives, resulting in the proliferation of low-quality ADRs on the market.

Article 62 of the Law of the People's Republic of China on Basic Medical and Health Care and the Promotion of Health (hereinafter Basic Health Law) stipulates that the state establishes and improves a drug price monitoring system, conducts investigations into prices, strengthens drug price supervision, and provides inspections. The DPMS envisaged by Article 62, however, does not apply to medical devices. The government does not regulate the prices of medical products, resulting in price manipulation, price fraud, and unfair competition. Clinical trials, medical research, patent applications, and marketing authorization for medical devices are governed by the Civil Code, the Biosafety Law, the Patent Law, and the Physicians Law, respectively. These laws continue to exclude the DPMS for medical devices. The government does not have the legal jurisdiction to monitor ADR prices. Therefore, China's legislators should amend the law to include medical devices, such as ADR, in the existing DPMS to combat price manipulation, price fraud, and unfair competition and promote industry-wide competition.

Second, the government should improve law enforcement and reduce regulatory costs (C_r). In practice, it is extremely challenging for the government to regulate the research, production, operation, and use of medical devices, as well as the companies and individuals involved. Information asymmetries in the medical device industry are quite severe, creating regulatory gaps. Article 75 of the Medical Devices Regulation stipulates that the regulatory authorities in the law enforcement assigned to inspect medical devices must delegate qualified medical device inspection agencies and bear the costs of inspection. The inspection cost has certainly raised regulatory expenses (C_r), impeding the authorities' ability to enforce the law effectively.

If regulatory authorities deregulate ADR manufacturers due to exorbitant regulatory costs, low-quality ADR will become a threat to public health. If ADR manufacturers and inspection agencies are found to be in breach of the law, they should ultimately be responsible for the inspection costs associated with law enforcement by regulatory authorities. In addition, regulatory authorities can utilize blockchain technology to construct a traceable network for monitoring clinical trials, medical research, patent applications, and marketing authorization of ADRs, thereby minimizing the expense of constant monitoring.

Third, the government should safeguard the people's right to freedom of expression and prevent a loss of government credibility (P_g). People's right to freedom of expression is not properly guaranteed in China (56). A preference for a lax regulatory strategy that allows low-quality ADRs to circulate on the market has resulted from the absence of effective public oversight and the low level of government credibility incurred by regulatory authorities.

Article 62 of the Medical Devices Regulation gives individuals the right to report adverse incidents associated with medical devices to regulatory authorities or inspection agencies. However, the Medical Devices Regulation does not establish the regulatory authority's responsibilities upon receipt of a citizen's report. In other words, regulatory authorities may disregard adverse incidents discovered by citizens involving medical devices. Internal government oversight finds it challenging to alter the strategy of regulatory authorities. Public criticism from citizens is a significant factor in convincing regulators to implement stringent policies. The Chinese government should build an online information platform for reporting adverse events associated with medical devices and permit citizens to submit queries. Faced with a further loss of government credibility, the regulatory authorities will need to implement a stringent regulatory policy to halt the production and registration of low-quality ADRs.

Considering the possible rent-seeking behaviors of ADR manufacturers and inspection agencies, this paper constructs a tripartite evolutionary game model that includes ADR manufacturers, inspection agencies, and regulatory authorities. We analyze the stability of the optimal strategy choice of each party, the stability of the equilibrium strategy combination of the game system, and the influence relationship of each element, and verify the validity of the results through simulation analysis. However, there are still certain shortcomings in this research. Different methodologies can be tested. For example, taking the perspective of a legal case study to explore how to improve the punishment for violations of the law in the ADR industry. The effectiveness of different strategies can be analyzed through either qualitative or quantitative methods. Besides, accepting bribes is common in developing countries. However, it is less common in developed countries. It means that the model in this paper may not be valid in developed countries. Nevertheless, this paper's findings could still provide helpful insights for many developing countries regulating the product quality of ADR.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.

ZH and BC conducted the modeling and data analysis and drafted of the manuscript. ZH, ZF, and XW conceptualized the study, designed the experiment, and contributed to the manuscript. ZH, ZF, and BC contributed to the acquisition and computation of data. All authors critically revised the manuscript for important intellectual content and approved the final version.