Stem cell ‘therapy’ advertisements in China: Infodemic, regulations and recommendations

Abstract During the COVID‐19 pandemic, in addition to the pandemic itself, a phenomenon called an ‘infodemic’—defined by the World Health Organization as the spread of misleading information on the pandemic—has also gained attention. In the field of stem cell research, researchers and regulators have been fighting against false and misleading information, particularly advertisements for unproven and unauthorized stem cell–based interventions for decades. However, how existing legal and regulatory measures, which vary by country, can be employed to combat such false information is unclear. In this article, we examine the situation in China, where the spread of unauthorized stem cell ‘therapies’ has drawn patients from not only within China but also from abroad. First, we assess how and to what extent online advertisements promote unproven and unauthorized stem cell–based interventions directly to patients and prospective health consumers in China. Next, we survey the landscape for existing regulatory and administrative measures that may be used to combat false and misleading advertisements in this area. Finally, based on our analysis, we provide three main recommendations that may improve the effectiveness and efficiency of the regulatory measures in curtailing illegitimate advertising of unproven and unauthorized stem cell–based interventions in China. In conclusion, we also call for international collaboration among researchers and regulators in studying and strengthening regulations in this critical area that has so far been neglected in scholarly and policy discussions.


because scientists and regulators have been fighting against
Internet-based, direct-to-consumer advertisements (DTCA) for unproven and unauthorized stem cell-based interventions for approximately two decades. 5 Internet-based, direct-to-consumer advertisement is a key component of the business models of clinics and biotech companies selling unproven and unauthorized stem cell-based interventions, with the aim to attract patients residing domestically and abroad. 6 These treatments pose serious safety and financial risks to patients and their families. 7 By raising their expectations and spreading misinformation, the companies also undercut efforts to develop safe and effective stem cell-based treatments for patients whose diseases or conditions currently have no effective treatment. 8 Although the detrimental effects of false and misleading advertising of unproven and unauthorized stem cell-based interventions have been widely acknowledged, few studies have addressed the regulatory issues related to such advertising activities in China.
In this article, we take China as an example and assess how challenging it may be to combat false and misleading advertisements of stem cell-based interventions. Our findings reveal that China has relevant regulations and policy documents that can be useful in combating false and misleading advertisements in this area.
Nevertheless, to successfully curtail this phenomenon, the legal status of stem cell-based interventions needs to be clarified, and relevant regulatory agencies need to work together to enforce these measures. Overseeing the development, market authorization and post-market regulation of stem cell-based interventions is a shared challenge for regulators around the world; therefore, we consider our study the first step in systematically reviewing and comparing nation-level regulatory measures in this area. Such joint efforts will, we hope, contribute to promoting the sustainable development and healthy flourishing of stem cell-based treatments and relevant industries in China and other countries.

| ADVERTIS ING AND PROMOTION OF S TEM CELL-BA S ED INTERVENTI ON S IN CHINA
No stem cell-based intervention has received market authorization in China, and advertisements for such products remain illegal.
Nevertheless, we used 'stem cell therapy' as the search term in China's largest search engine Baidu (https://www.baidu.com) and retrieved 38.9 million results (search conducted on 10 September 2020). Upon analysing the content of the first 10 pages of those search results, we identified more than half of the results as DTCA.
We then analysed the content of those advertising materials. We deployed the same methods to search and analyse the advertising content on the biggest e-commerce platform in China, Alibaba (https://www.1688.com). We identified 2596 online stores selling stem cell-related products directly to consumers and analysed their advertisements (search conducted on 14 September 2020).
The aforementioned advertising materials were generated by a range of actors, including companies, research sponsors, manufacturers, importers, pharmacists, health professionals and health services marketers. Based on the primary resources that the advertisers utilized to create their advertisements, we categorized the advertisements into three groups: those relying on case reports and patient testimonies, those highlighting the credentials of the actors and those utilizing educational materials concerning stem cell research.
First, some providers claim that unproven stem cell-based interventions can cure several serious diseases. For example, a company that mainly provides services such as cellular immunotherapy and stem cell therapy for treating diabetes and other diseases advertised on its website that it had successfully treated more than 1200 patients through a stem cell-based intervention. The company's homepage even displays a 'guarantee of effectiveness' and other attractive slogans. 9 Another company claimed on its website that stem cell 'therapy' can effectively treat diseases and offered anti-ageing, male and female reproductive and sexual function treatments and treatments for diabetes, osteoarthritis, gout, stroke, cardiovascular disease and cancer. 10 Notably, the company offers two stem cellbased products for treating azoospermia and premature ovarian failure. The company also publishes patient treatment testimonies and successful cases of testicular stem cell transplantation for mumps and azoospermia on its website.
Second, some providers portray themselves on their websites as trustworthy providers of stem cell-based interventions by publicizing their 'achievements and honours' using various materials such as scientific publications, patents, registered clinical trials, conferences organized and certificates of various types. For instance, one company promotes that its independent research and development of 'GLP-1 and FGF21-modified autologous adipose stem cells for treating type 2 diabetes' technology has achieved a major breakthrough.
It also alleged to have applied for China's National Key Research and Development Project on 'stem cell and translation research' and conducted clinical research. 11 Such information is misleading. Few outside the scientific and medical fields would know that, for instance, merely registering a study on clinicaltrials.gov does not mean this study has been approved by the regulatory body in China, and thus, such registration does not constitute a legitimate clinical trial.
Nevertheless, advertisers often indicate otherwise. 12 Third, some providers use educational materials to publicize the efficacy of their stem cell-based intervention(s). Because the rigour of such educational materials varies and so-called 'scientific popularization' articles often describe stem cells as a panacea, these materials are easily repurposed by providers of unauthorized stem cell therapies as evidence of the effectiveness of their products, thus misleading the public. For instance, a company that sells stem cell facials claims that its facials 'activate the renewal of stem cells in tissues and improve skin circulation'. 13 In all three groups, those advertising unproven and unauthorized stem cell-based interventions online take advantage of the information asymmetry between the generator and the targeted receptor of the content-in this context, the receptors are often vulnerable patients and their families. Although the considerable profit that selling such unauthorized products brings to the advertiser explains their motivation, the current regulatory situation may contribute to the scope and scale of this problem. That is the question we investigate next.

| REG UL ATORY FR AME WORK IN CHINA
To a certain extent, the proliferation of deceptive advertising and the promotion of unproven stem cell-based interventions have a close relationship with the current regulatory framework and enforcement in China. Thus, it is necessary to understand the relevant regulatory system before analysing its implementation or providing suggestions.

| Regulatory scheme governing stem cell-based interventions
In China, policies and regulations governing stem cell-based interventions have reflected indecision as to whether the law considers them to be a drug or a medical technology. 14 Under two principle regula- However, no legal opinion or court decision in China clearly defines it as a drug. Therefore, deciding whether stem cell-based interventions are a drug or medical technology critically affects the regulation of advertising and promotion in this field because they may advertise and promote stem cell-based interventions as drugs or medical services.

| General laws on consumer protection
In general, administrative, civil and criminal penalties may apply if providers of stem cells do not comply with legal requirements concerning the advertisement and promotion of products or services in China (Table 1). General laws such as the Protection of Consumer Rights and Interests Law (PCRIL) 17 and Chinese Advertising Law (CAL) 18 apply to the advertising of any goods or services and protect the interests of consumers. The PCRIL explicitly stipulates that if business operators present commodities or services through false advertising or any other means of misleading promotion, consumers may request the competent administrative departments to punish the advertising agents or publishers who engaged in false advertising. 19 The CAL stipulates that advertising content shall be expressed in a true and lawful manner 20 and that advertisements shall not have any false or misleading content to defraud or mislead consumers. 21 Regarding false or misleading advertisements, the CAL defines a false advertisement as any advertisement that defrauds or misleads consumers through any false or misleading content. 22  In addition, to promote fair market competition and protect legitimate business operators, the Anti-Unfair Competition Law (AUCL) prohibits false advertising by business operators. 24 According to the AUCL, a business shall not conduct any false or misleading commercial publicity with respect to the performance, functionality, quality, sales, product reviews and honours received of its commodities to defraud or mislead consumers. Neither shall a business help another business conduct any false or misleading commercial publicity by organizing false transaction or through any other means. 25 Furthermore, the Chinese Criminal Law (CCL) 26 has a provision for the crime of false advertising. The CCL stipulates that where, in violation of the State regulations, an advertiser, advertising agent or advertisement publisher, who uses advertisements to publicize goods or services falsely, and when the circumstances are serious, he/she shall be sentenced to not more than 2 years of fixed-term imprisonment or criminal detention, and may in addition or exclusively be fined. 27 In what follows, we introduce and analyze more specific legal and regulatory measures that exist in China regulating, respectively, the advertising of pharmaceutical products and medical services.

| Regulations for the advertisement and promotion of pharmaceutical products
In addition to aforementioned general instructions to all advertisers, the CAL contains relatively specific provisions regarding the particularity of pharmaceutical advertisements. Article

| Specifying the legal definition of false advertising and its criteria
In surveying relevant legal and regulatory documents, we found that for hosting false medical advertisements on its advertising system AdWords and was fined US$500 million. 41 We propose increasing the penalties for false medical or pharmaceutical advertisements to the equivalent amount in China.
However, above all, what will make a substantial difference in regulating advertising and promotion activities in this area is for regulators to change the mode of regulation by shifting from a postevent investigatory scheme to a system in which they take a more

| CON CLUS ION
While the world continues fighting the COVID-19 pandemic and its associated infodemic, here, we took a deep dive into the phenomenon of false and misleading DTCA for novel therapies that have been a troublingly persistent blight on the field of stem cell research. Our analysis of the regulatory situation in China revealed that to effectively curtail medical misinformation that targets particular patient groups or the public in general, having relevant laws and regulations in place may be a good start but is not enough. The specificity of novel therapies and their complexities need to be considered when designing more effective regulations and intervention measures. Coordination among multiple regulatory agencies is often required, and a proactive regulatory mode, as opposed to a mode in which only post-event investigations are conducted, is recommended to prevent misleading information from harming patients or the public interest. Given that Internet-based, direct-to-consumer advertising of unproven, unauthorized stem cell-based interventions has a global reach and contributes to the phenomenon of 'stem cell tourism', we recommend further investigations into regulatory situations in other jurisdictions whose joint results will provide an evidentiary basis for a coordinated global regulatory effort to fight this particular infodemic.

CO N FLI C T O F I NTE R E S T
The authors declare no competing interests.

DATA AVA I L A B I L I T Y S TAT E M E N T
Data sharing is not applicable to this article as no new data were created or analysed in this study.