Unproven stem cell interventions: A global public health problem requiring global deliberation.

The unproven stem cell intervention (SCI) industry is a global health problem. Despite efforts of some nations, the industry continues to flourish. In this paper, we call for a global approach and the establishment of a World Health Organization (WHO) Expert Advisory Committee on Regenerative Medicine to tackle this issue and provide guidance. The WHO committee can harmonize national regulations; promote regulatory approaches responsive to unmet patient needs; and formulate an education campaign against misinformation. Fostering an international dialog and developing recommendations that can be adopted by member states would effectively address the global market of unproven SCIs.

Reflection on the enactment and impact of safety laws for regenerative medicine in Japan.

Japan's Act on the Safety of Regenerative Medicine (ASRM) created an innovative regulatory framework intended to safely promote the clinical development of stem cell-based interventions (SCBIs) while subjecting commercialized unproven SCBIs to greater scrutiny and accountability. This article reviews ASRM's origins, explains its unprecedented scope, and assesses how it envisions the regulation of SCBIs. This analysis is used to highlight three key insights that are pertinent to the current revision of the ASRM: clarifying how the concept of safety should be defined and assessed in research and clinical care settings; revisiting risk criteria for review of SCBIs; and taking stronger measures to support the transition from unproven interventions to evidence-based therapies. Finally, the article reflects on lessons drawn from Japanese experiences in dealing with unproven SCBIs for international endeavors to regulate SCBIs.

From the margins to mainstream: How providers of autologous 'stem cell treatments' legitimise their practice in Australia.

This article examines how Australian providers of unproven autologous 'stem cell treatments' legitimise these products and their practices. We focus on the strategies employed by providers in their efforts to create and sustain a market for procedures that have yet to be proven safe and clinically efficacious. Drawing on the work of Thomas Gieryn and Pierre Bourdieu and the findings of research involving an analysis of direct-to-consumer online advertising of clinics that sell purported 'stem cell treatments' and interviews with clinicians who provide them, we examine the mechanisms by which medical legitimacy for these products is established and defended. We argue that Australian providers employ a number of strategies in order to create medical legitimacy for the use and sale of scientifically unproven therapies. A key strategy employed by providers of stem cell treatments is to use markers of social distinction, drawing strongly on the symbols of science, to confirm their legitimacy and differentiate their own practices from those of other providers, who are posited as operating outside the boundary of accepted practice and hence illegitimate. We argue there is a paradox at the heart of the autologous stem cell treatment market. Providers aim to create legitimacy for their work by emphasising the potential benefits of their 'treatments', their expertise and the professionalisation of their practices in an environment where regulators are yet to take a firm stance; they are also required to undertake the challenging task of managing patients' hopes and expectations that both enable and potentially jeopardise their operations and revenue. We conclude by suggesting that providers' creation of symbolic capital to establish medical legitimacy is a crucial means by which they seek to bring unproven 'stem cell treatments' from the margins of medicine into the mainstream and to portray themselves as medical pioneers rather than medical cowboys who exploit vulnerable patients.

Australian regulation of autologous human cell and tissue products: implications for commercial stem cell clinics.

In 2018, Australia's Therapeutic Goods Administration introduced regulatory reforms that set stricter criteria around the regulation of products derived from a patient's own cells and tissues, posing significant implications for clinics offering stem cell treatments. We review the regulatory framework and discuss its potential commercial implications, including the ambiguities that may arise from it in practice, as well as the likely impact it will have on product development and advertising practices in the future.

Rogue stem cell clinics.

Cell therapies hold significant promise for the treatment of injured or diseased musculoskeletal tissues. However, despite advances in research, there is growing concern about the increasing number of clinical centres around the world that are making unwarranted claims or are performing risky biological procedures. Such providers have been known to recommend, prescribe, or deliver so called 'stem cell' preparations without sufficient data to support their true content and efficacy. In this annotation, we outline the current environment of stem cell-based treatments and the strategies of marketing directly to consumers. We also outline the difficulties in the regulation of these clinics and make recommendations for best practice and the identification and reporting of illegitimate providers. Cite this article: Bone Joint J 2020;102-B(2):148-154.

The direct-to-consumer market for stem cell-based interventions in Australia: exploring the experiences of patients.

The prevalence of businesses selling autologous stem cell-based interventions to patients in Australia has raised serious concerns about how weaknesses in regulation have enabled the emergence of an industry that engages in aggressive marketing of unproven treatments to patients. Little is known about how patients experience this marketing and their subsequent interactions with practitioners. This paper reports results from 15 semistructured interviews with patients and carers, and also draws upon discussion conducted with patients, carers and family members (22 participants) in a workshop setting. We explore how Australian patients and carers understand and experience these interventions, and how their presumptions about the ethics of medical practice, and the regulatory environment in Australia have conditioned their preparedness to undergo unproven treatments.

Regulatory and policy tools to address unproven stem cell interventions in Canada: the need for action.

BACKGROUND: The marketing of unproven direct-to-consumer stem cell interventions is becoming widespread in Canada. There is little evidence supporting their use and they have been associated with a range of harms. Canada has been slower to act against clinics offering these interventions than other jurisdictions, including the United States. Here, we outline the regulatory and policy tools available in Canada to address this growing problem. MAIN BODY: Health Canada's regulations governing cell therapies are complex, but recent statements make it clear that Health Canada believes it has jurisdiction over many of the currently marketed stem cell interventions. Still, further regulatory clarity is needed from Health Canada, as are increased directed enforcement efforts on interventions that fall within their scope. The Competition Bureau, via the Competition Act, prohibits advertisers from making materially false or misleading promotional representations. The Competition Bureau could collaborate with the scientific community to analyze the claims of existing clinics in Canada, and impose sanctions upon those who breach the established standard. Professional regulators, including provincial colleges of physicians and surgeons, have considerable power over what products and services their members can offer. Every college of physicians in Canada requires, via policy and codes of ethics, that doctors maintain evidence-based practices. This requirement is incompatible with offering many unproven stem cell interventions. Litigation may be another tool, including the use of fraud, misrepresentation and/or negligence claims for failing to meet the required standard of care. Finally, political pressure on federal and provincial lawmakers could encourage changes to marketing, cell therapy and professional regulations that would allow a more comprehensive response. CONCLUSIONS: In sum, there are many existing tools that can be used to protect the public from unproven stem cell interventions. Increased bureaucratic will and grassroots efforts are needed in order to effect a positive policy response.

Ethical development of stem-cell-based interventions.

The process of developing new and complex stem-cell-based therapeutics is incremental and requires decades of sustained collaboration among different stakeholders. In this Perspective, we address key ethical and policy challenges confronting the clinical translation of stem-cell-based interventions (SCBIs), including premature diffusion of SCBIs to clinical practice, assessment of risk in trials, obtaining valid informed consent for research participants, balanced and complete scientific reporting and public communications, regulation, and equitable access to treatment. We propose a way forward for translating these therapies with the above challenges in mind.

Unproven stem cell therapies: is it my right to try?

BACKGROUND: Nowadays one of the most critical aspects of innovative cell-based therapies is the unregulated industry, as it is becoming a competitor of the regulated system. Many private clinics, worldwide, advertise and offer cell-based interventions treatments directly to the consumer and this poses a risk to both vulnerable patients and health systems. Several countries have implemented Compassionate Use Programmes (CUP) that provide patients with medicines that have not yet completed the approval pathway, in the event that no reasonable alternative exists. Recently, in the public discourse, compassionate use has been increasingly associated with a patient's right to try. Thus, the aim of this study was to assess public knowledge of the clinical trials process with specific reference to innovative stem cell treatments, and trust in the institutions responsible for regulatory activities. We also asked people about their "right" to use unregulated therapies. METHODS: We developed an ad hoc questionnaire on three main areas of concern and administered it to 300 people in the patient waiting room at an Italian university hospital. RESULTS: Our findings suggest that people have a good knowledge of the clinical trials process and trust in healthcare institutions. Nonetheless, one person in two believes it is a right to use unregulated therapies. CONCLUSIONS: We stress the need, in the age of cellular therapies, for a commitment to support vulnerable patients and to strengthen awareness among the public about the substantial boundary that differentiates experimental therapies from unproven therapies. There should not be a "right to try" something that is unsafe but rather approved treatments and in line with good clinical practice. The trend, which emerged on this issue from our study, is quite different, confirming the urgent need to improve health information so that it is as complete as possible.

Stem Cells and Tissue Engineering in Medical Practice: Ethical and Regulatory Policies.

Stem Cell Research and Tissue Engineering, in present time, have emerged as a legalized and regulated stem cell treatment option globally, but scientifically, their success is unestablished. Novel stem cell-based therapies have evolved as innovative and routine clinical solutions by commercial companies and hospitals across the world. Such rampant spread of stem cell clinics throughout UK, US, Europe and Asia reflect the public encouragement of benefits to incurable diseases. However, ever growing stem cell therapy developments need constant dogwatch and careful policy making by government regulatory bodies for prompt action in case of any untoward public concern. Therefore, researchers and physicians must keep themselves abreast of current knowledge on stem cells, tissue engineering devices in treatment and its safe legal limits. With this aim, stem cell scienctific developments, treatment options and legal scenario are introduced here to beginner or actively inolved scientists and physicians. Introduction to stem cell therapy will provide basic information to beginner researchers and practice physicians on engineered stem cell research concepts and present stem cell therapy federal regulations in different North American, European and Asian countries. FDA, CDC, EU, ICMR government policies in different countries include information on the current legal position, ethical policies, regulatory oversight and relevant laws.

Mapping and driving the stem cell ecosystem.

The stem cell and regenerative medicine arena has become increasingly complicated in recent years with thousands of people involved. There are as many as a dozen or more main groups of stakeholders, who together may be viewed as one ecosystem that is now rapidly evolving. The nature of the ecosystem and its evolution have major implications for not just those within it, but also for medicine and society at large. Here, I describe this ecosystem and its evolution, as well as the negative impacts within the ecosystem of a constellation of hundreds of unproven for-profit clinics and related businesses. Finally, I propose approaches for how to positively influence and drive the future of the global stem cell ecosystem.

Selling stem cell 'treatments' as research: prospective customer perspectives from crowdfunding campaigns.

AIM: To better understand how prospective customers interpret claims of businesses marketing unproven stem cell products that they are engaging in research activities. MATERIALS & METHODS: The authors examined 408 crowdfunding campaigns for unproven stem cell interventions for references to research activities. RESULTS: The authors identified three overarching themes: research as a signifier of scientific credibility; the experimental nature of stem cells as a rationale for noncoverage by insurers; and contributing to the advancement of science by engaging in research. CONCLUSION: The NIH, US FDA and others should be concerned about being co-opted to misrepresent the nature of these businesses' activities. Efforts are also needed to better inform those considering purchasing unproven stem cell interventions about their relationship to legitimate research.