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The US Direct-to-Consumer Marketplace for Autologous Stem Cell Interventions
Abstract
Hundreds of businesses and clinics in the United States are engaged in direct-to-consumer marketing of unproven and unlicensed stem cell-based interventions. This essay provides an overview of this marketplace, examines advertising techniques companies use to draw clients and legitimate marketing claims, and summarizes the roles the Food and Drug Administration (FDA) and other agencies are supposed to play in regulating the direct-to-consumer marketplace for stem cell interventions. The essay also reviews federal regulations, describes how many businesses selling purported "stem cell treatments" appear to violate these standards, and considers ethical issues and harms associated with widespread promotion of unapproved stem cell products.
... 9,10 Social science studies suggest that the general public considers stem cells as having the power to heal a variety of medical conditions, resulting in growing demand and subsequent emergence of a direct-to-consumer market where characteristically unspecialized and even predatory clinics offer unproven regenerative labeled therapies such as stem cells and more recently exosomes. [11][12][13][14] The term "unproven" is used to mean that there is varying levels of scientific evidence to demonstrate safety and efficacy of a SCRI but that many still lack sufficient scientific data to be marketed. ...
... 33,34 Despite these milestones and ongoing research efforts, there remains a direct-to-consumer market for unproven stem cell interventions, most notably in the United States. 12,15,35 ...
... It is estimated that there are over 2700 clinics in the United States offering SCRI. 12 While over 60% comprise musculoskeletal indications, all medical specialties are represented to some degree. 37,38 The uncertainty of the indications, nature of products being used, safety and qualification of providers performing some interventions creates a need for patients seeking regenerative solutions to search for help from trusted resources. ...
Introduction
Direct to consumer stem cell and regenerative interventions (SCRIs) for various medical conditions have increased in popularity due to unmet medical needs and the promise of SCRIs to meet those needs. These interventions may have varying levels of safety and efficacy data and many lack sufficient scientific data to be marketed. The direct to consumer SCRI industry has received significant attention due to potential physical, economic, and emotional harms to patients. Patients may seek the counsel of their primary care providers when considering stem cell therapy for their condition.
Methods
Here we describe strategies primary care providers can utilize when counseling patients.
Results
Although we recommend constructing these discussions around individual patients’ needs, one can utilize a general approach consisting of 4 parts. First, providers should recognize what information the patient is seeking and what is their understanding of stem cell and regenerative medicine. Next, providers should convey evidence-based information at the level of patients understanding so that they are aware of the risks, benefits, and descriptions of possible procedures. Throughout the conversations, attempts should be made to guide patients to a trusted resource that can provide additional information. Finally, providers should make an effort to address misinformation in a way that is nonjudgmental and patient-centered to make the patient feel safe and comfortable.
Conclusion
Effectively communicating risk information by primary care providers to patients is important given the harms reported from direct-to-consumer SCRIs. Correcting misinformation remains a priority when discussing SCRI’s. Providers should strive to offer patients with additional resources such as the opportunity for consultation with a specialist or a consultation service dedicated to informing patients about regenerative medicine.
... Providers of questionable SCT argue that freedom of choice and patient autonomy can be achieved through direct-to-customer marketing. However, they disregard the idea of informed-consent if they assume patients to make decisions based on unreliable and implausible claims or tokens (Turner, 2018). Online communication of SCTs mostly lacks medical information and truthful disclosure about a treatments details and efficacy (Connolly et al., 2014). ...
... They rarely publish actual data about their processes and the success rates (Gilbert, 2018). The studies they do point to, are generally poorly conducted with respect participant structure and study design (Turner, 2018). Since the questionable businesses involved in stem cell tourism use similar advertising techniques like legitimate medical authorities and facilities, it is hard for patients to distinguish malicious from lawful (Sipp et al., 2017). ...
... Many of those US companies advertise a plethora of unlicensed interventions for sundry conditions, some promote SCTs for more than 30 different diseases (Taylor-Weiner & Graff Zivin, 2015;Turner, 2018;Turner & Knoepfler, 2016). Unfortunately, local businesses involved with stem cell tourism are not yet subject to regulation concerning the therapies they promote the facilitating services they provide (Turner, 2015). ...
The targeted direct-to-customer marketing of unapproved stem cell treatments by a questionable online industry is directed at vulnerable users who search the Internet in the hope of a cure. This behavior especially poses a threat to individuals who find themselves in hopeless and desperate phases in their lives. They might show low reluctance to try therapies that solely promise a cure but are not scientifically proven to do so. In the worst case, they suffer serious side-effects. Therefore, this thesis examines the display of advertisements of unapproved stem cell treatments for Parkinson's Disease, Multiple Sclerosis, Diabetes on Google's results page. The company announced a policy change in September 2019 that was meant to prohibit and ban the practices in question. However, there was evidence that those ads were still being delivered. A browser extension for Firefox and Chrome was developed and distributed to conduct a crowdsourced Black Box analysis. It was delivered to volunteers and virtual machines in Australia, Canada, the USA and the UK. Data on search results, advertisements and top stories was collected and analyzed. The results showed that there still is questionable advertising even though Google announced to purge it from its platform.
... A regulatory framework we can only characterize as deficient allows unsubstantiated claims to persist in much of the world [39]. Nonetheless, keen interest from patients and the ability of providers to command cash remuneration (as many insurers do not pay for these treatments) has led to a rise in the number of stem cell clinics globally [79]. ...
... Although providers and researchers have questioned the appropriateness of wide use of these treatments based on the current evidence [32,39,66,79], in fact, several prospective trials with a comparison group (Table 1) and prospective and retrospective studies without a comparison group (Table 2) have shown favorable results for the clinical use of stem cell therapy. However, varying levels of evidence and the potential drawbacks of current studies make it difficult for clinicians to be certain whether stem cell-based therapies are appropriate for widespread use [32]; questions about cost-effectiveness [14] and safety concerns [5,49,54] also have been raised. ...
... Regulations for the clinical use of stem cell products around the world vary by country. Even in the United Volume 00, Number 00 Clinical Use of Stem Cells in Orthopaedics 11 States and European Union countries, which have strict regulations, businesses offering stem cells seem to be exploiting loopholes [22,23,79]. For instance, the United States FDA outlines a risk-based, three-tiered approach to the regulation of human cells, tissues, and cellular-and tissue-based products (Table 4) [27]. ...
... Over time, clinic websites became more "aesthetically appealing" and provided lists of questionable publications, accreditation, advisory and board members, and patents to signal their legitimacy (Connolly et al. 2014;Knoepfler 2019;Ogbogu et al. 2013;Sipp et al. 2017). Despite lacking FDA approval, several clinics also register their interventions as a trial on the US clinical trial database ClinicalTrials.gov to gain additional legitimacy (Turner 2018a(Turner , 2017Wagner et al. 2018). ClinicalTrials.gov ...
... In the United States, estimates range from 215 to 2754 clinics offering unproven SCIs in hotspots such as Los Angeles, New York City, and San Antonio as well as the US-Mexico border town of Tijuana, Mexico (Berger et al. 2016;Turner and Knoepfler 2016;Zarzeczny et al. 2018;Connolly et al. 2014;Chavez et al. 2021;Frow et al. 2019;. US clinics predominantly focus on orthopedic, pain, and sports conditions using autologous adipose or bone marrow-derived stem cells, since allogenic stem cells require FDA approval (Turner 2018a;. While most are run by physicians, only half are formally trained in the areas they are treating (Fu et al. 2019). ...
During the COVID-19 pandemic, investigational treatments have been made available to seriously ill patients through so-called expanded access programmes, such as compassionate use and named-patient programmes. Many countries have legal, ethical and professional frameworks in place to promote safe and responsible use of investigational treatments outside of clinical trial settings. However, these frameworks leave room for ambiguities regarding the roles and responsibilities of treating physicians, hospital-based pharmacists, pharmaceutical companies, and other stakeholders, and for practices to differ, not only between countries, but also within countries, between hospitals and individual healthcare providers. Current ambiguities with regard to physicians’ moral duties, for instance, allow physicians to withhold information from patients about options for expanded access, and to forego pursuing such options for their patients. This chapter describes the experiences with the use of Remdesivir and hydroxychloroquine in COVID-19-infected patients in the Netherlands during the first wave of the pandemic, and discusses an open question in relation to treating physicians’ duties, namely vis-à-vis information provision. This chapter proposes a prima facie obligation for healthcare professionals to inform eligible patients about relevant options for expanded access.
... Stem cell interventions have been marketed internationally for many years, 2 and more than 2,700 SCI clinics currently operate in the United States. 3,4 Unproven SCIs are promoted as therapy for a specific medical condition or as a panacea for a broad range of conditions. Direct advertising targets patients who have serious illnesses or painful injuries that are refractory to conventional treatments. ...
... Direct advertising targets patients who have serious illnesses or painful injuries that are refractory to conventional treatments. 3,5 Advertisements for treatments misinform patients by emphasizing the general promise of regenerative medicine and strongly imply that they are scientifically legitimate. Potential clients are targeted on websites, in seminars, and through social media, typically with testimonials from patients (actual or purported) and celebrities. ...
... Another interesting source of controversy for stem cell transplant therapy is the 716 for-profit businesses (as of 2018) offering some sort of stem cell therapy to treat a wide range of patient problems [29]. Interestingly, some of these clinics advertise stem cell therapy for cosmetic reasons, such as breast augmentation and face lifts, as well as clinics that advertise a broader range of therapies including the treatment of spinal cord injuries. ...
... Interestingly, some of these clinics advertise stem cell therapy for cosmetic reasons, such as breast augmentation and face lifts, as well as clinics that advertise a broader range of therapies including the treatment of spinal cord injuries. However, these clinics have seen many controversies and lawsuits that allege a range of things from fraudulent advertising and injury [29]. While these clinics shed light on a dangerous repercussion of mass marketization of stem cell therapies, it is nonetheless a positive step toward raising the awareness of stem cell therapies. ...
Stem cell transplants, and neural stem cells (NSCs) in particular, hold tremendous potential in recreating axonal relays that bridge traumatic spinal cord injuries (SCIs). While currently there is no standardized transplant methodology, common themes emerge from reviewing recent studies. Current research focuses on injecting NSCs without damaging existing tissue, overcoming common hurdles such as glial scarring, immune reaction, and tumorigenesis and inducing proper differentiation into sensory and motor neurons. Notably, scaffolding holds promise in improving outcomes. Although animal trials have demonstrated NSC ability to improve motor function, human trials are mostly limited to verification of safety instead of efficacy. While controversy and debate surround the use of stem cells, NSCs for SCI merit further exploration.
... Achieving a balance that avoids overtly lax or strictly prohibitive regulatory measures over SCI has been a notoriously precarious aspect of legislation [40]. The marketing of uncharacterized and unproven SCI poses a controversy based on medical ethics [16,34]. While the "right to try" act may provide a legislative escape clause for the use of unproven "stem cell" therapies in certain fields, musculoskeletal disorders rarely satisfy the conditions of posing a threat to life and the exhaustion of alternative therapies [14••, 41]. ...
... An active, interdisciplinary, and wellcoordinated approach involving physicians, legislators, and professional communities as well as media and market stakeholders is required. Medical licensing boards could effectively curb the spread of the unindicated use of SCI through disciplinary actions ranging from issued warnings to revoking of licensure [16,34,43]. Civil litigation, including the aforementioned class-actions, could act as a deterrent against bland violations in the form of misrepresentation that invalidates informed consent [40]. ...
Purpose of review:
Cellular therapies, also known as "stem cell" interventions (SCI), have undergone a rapid popularization in the USA and worldwide. The current review aimed at outlining (1) the ethical challenges facing the implementation of SCI; (2) the applicability of the currently available SCI; and (3) recommendations to achieve ethical, well-regulated incorporation of SCI in the clinical setting.
Recent findings:
Concerns regarding the inadequate characterization, poor adverse effects disclosure, and unorthodox, often inappropriate, market practices have engendered a genuine concern regarding the SCI compliance with ethical standards. Six instances of litigation on the basis of misrepresentation or inappropriate informed consent were recorded between 2012 and 2018. Such concerns have been furthered by the loopholes in the regulatory aspect governing the use of SCI coupled with the unclear literature-reported efficacy and diverse spectrum of profess indications. Similarly, the application of SCI in the clinical field is yet to prove its value. The uncertain efficacy, coupled with obscure true-costs of utilization, impedes a value-based assessment. A multidisciplinary approach involving legislative and medical professional societies should continue to advance regulations that govern SCI. A well-regulated system that allows for the ethical integration of SCI with appositely evidenced-based described benefits and risks should be sought.
... [14] where clinics around the world advertise unproven regenerative and stem cell interventions that lack regulatory approval [15][16][17][18] and often are promoted with little or no supporting evidence. The US direct-to-consumer market for unlicensed cell-based products is perhaps the largest with estimates of approximately one thousand clinics offering unproven regenerative interventions [19][20][21]. Much has been written about the features and concerns surrounding the marketplace, summarized in Table 1. ...
... To qualitatively analyze EHR information written as free text, we developed a comprehensive codebook. We first developed a codebook deductively by analyzing empirical studies of clinic web-based marketing practices [7,[15][16][17]21,23,25,27,29,70,71] and interviews with patients traveling to clinics to receive unproven stem cell interventions [22,34,35,72,73]. This permitted us to consider information about patients including their general medical areas and specific conditions of concern. ...
Aim: To address the unmet needs of patients interested in regenerative medicine, Mayo Clinic created a Regenerative Medicine Consult Service (RMCS). We describe the service and patient satisfaction. Materials & methods: We analyzed RMCS databases through retrospective chart analysis and performed qualitative interviews with patients. Results: The average patient was older to elderly and seeking information about regenerative options for their condition. Patients reported various conditions with osteoarthritis being most common. Over a third of consults included discussions about unproven interventions. About a third of patients received a clinical or research referral. Patients reported the RMCS as useful and the consultant as knowledgeable. Conclusion: An institutional RMCS can meet patients’ informational needs and support the responsible translation of regenerative medicine.
... For example, a 2016 publication identified 351 businesses operating a total of 570 clinics in the United States (103). A follow-up publication describing the state of the U.S. DTC marketplace for SCBIs in 2017 documented 432 companies providing cell-based interventions at 716 distinct clinics (104). Eighty of these businesses marketed purported SCBI for respiratory diseases. ...
... In the United States, as well as in Australia, Canada, and many other countries, a majority of clinics market autologous SCBIs (102)(103)(104). Adipose tissue, bone marrow, and peripheral blood are common sources for these cellular products. ...
Respiratory diseases, such as chronic obstructive pulmonary disease and pulmonary fibrosis, result in severely impaired quality of life and impose significant burdens on healthcare systems worldwide. Current disease management involves pharmacologic interventions, oxygen administration, reduction of infections, and lung transplantation in advanced disease stages. An increasing understanding of mechanisms of respiratory epithelial and pulmonary vascular endothelial maintenance and repair and the underlying stem/progenitor cell populations, including but not limited to airway basal cells and type II alveolar epithelial cells, has opened the possibility of cell replacement-based regenerative approaches for treatment of lung diseases. Further potential for personalized therapies, including in vitro drug screening, has been underscored by the recent derivation of various lung epithelial, endothelial, and immune cell types from human induced pluripotent stem cells. In parallel, immunomodulatory treatments using allogeneic or autologous mesenchymal stromal cells have shown a good safety profile in clinical investigations for acute inflammatory conditions, such as acute respiratory distress syndrome and septic shock. However, as yet, no cell-based therapy has been shown to be both safe and effective for any lung disease. Despite the investigational status of cell-based interventions for lung diseases, businesses that market unproven, unlicensed and potentially harmful cell-based interventions for respiratory diseases have proliferated in the United States and worldwide. The current status of various cell-based regenerative approaches for lung disease as well as the effect of the regulatory environment on clinical translation of such approaches are presented and critically discussed in this review.
... But regulation of therapeutic goods exists in part because patients' capacities to assess complex medical information can be limited. This can leave them open to exploitation, and decision-making can be distorted by hope, desperation or the way information is presented [32]. Despite moves by the FDA to clarify regulations, the current regulation removes the requirement for collecting risk and benefit data from minimally manipulated, homologous use stem cell therapy, placing participants at unnecessary health risk. ...
Background
Regenerative medicine has the potential to treat genetic disorders and replace damaged or missing tissue. The use of donor or animal tissue raises many well-known issues, including limited tissue availability, the possibility of rejection and patient infection. Stem cell therapy raised hope of overcoming these issues, but created new risks including tumour formation and limited benefit if the desired target tissue does not form. The recent development of 3-dimensional tissues, including organoids, allows the creation of more complex tissues for personalised regenerative medicine.
Methods
This article details the potential health risks of 3-dimensional organoid and tissue therapy versus dissociated stem cell therapy. The current ethical and regulatory issues surrounding 3-dimensional organoid and tissue therapy are presented with a focus on the highly influential FDA and International Society of Stem Cell Research (ISSCR) guidelines.
Conclusions
The potential use of 3-dimensional organoid and tissue therapy may deliver greater patient benefits than other regenerative medicine approaches, but raises new health and ethical risks. Preclinical testing of these therapies will not mitigate some of their risks; they may only be understood after first-in-human trials. The potential irreversibility and high risk of these therapies affects how clinical trials should be structured, including post-trial care for participants.
... The reason for the association is perhaps due to misleading claims by some providers offering direct-to-consumer regenerative and stem cell interventions and building on the public awareness and hype surrounding stem cells. Orthopedics and sports medicine patients account for over 68% of such clinics' clients [2][3][4][5] . Many orthopedic and sports medicine professional societies have published statements advocating for the responsible use of autologous cell-based interventions [6][7][8][9] . ...
Stem cell therapies occupy a unique place in the American public’s consciousness which has led to excessive enthusiasm over their potential to cure orthopedic conditions. Much has been written about direct-to-consumer marketing of cell therapies for a myriad of medical conditions. Far less has been studied on the attitudes that drive many patients to seek stem cell and orthobiologic therapies for musculoskeletal conditions. Previously published research on patient motivations for seeking stem cell therapy to treat orthopedic maladies such as osteoarthritis and chronic tendinopathies has shown that some patients were motivated by factors not supported by current medical evidence. These differing responses strongly suggest the need for patient-centered counseling to address misinformation about stem cell therapies for musculoskeletal conditions and increase health literacy about outcomes of orthobiologics.
... This has contributed to inflated patient expectations and a skewed public understanding of such treatments 5 . Public demand for stem cell and regenerative interventions to some degree, have created a direct-to-consumer market with about 60% of these in the orthopedic space [6][7][8][9] . Furthermore, some orthobiologic options, like platelet rich plasma do not contain stem cells yet are captured within the "stem cell" treatment (SCT) market. ...
Despite patient demand for stem cell therapies (SCTs) for musculoskeletal conditions, there remains limited research on why patients seek SCTs or their sources of information. We employ three questions into a consult intake form: (1) Why are you interested in stem cell treatment for your condition? (2) How did you find out about stem cell treatment for your condition? (3) Have you contacted a stem cell clinic? Responses analyzed, using a qualitative content analysis approach to identify themes reveal many patients seek SCTs to treat pain or delay surgery which may align with some current clinical evidence while other patients express motivations as expected outcomes (e.g., SCTs are better than standard of care or can regenerate tissue) which are not supported by current medical evidence. These differences suggests that patient-centered counseling may help patients by addressing misconceptions and increasing health literacy about expected outcomes of SCTs for treating musculoskeletal conditions.
... There are more than 700 US clinics advertising unregulated (without oversight of a regulatory agency such as FDA) therapies. 19 Turner and Knoepfler identified 351 US businesses with over 570 clinics engaged in direct-to-consumer marketing of stem cell interventions. 17 Recent re-analysis of their original 2015-2016 cohort has shown that a majority of the firms have greatly expanded their presence and only a quarter had reduced their presence or closed. ...
Background:
Unproven cellular therapies are being offered to patients for a variety of conditions and diseases for which other treatments have failed. The use of untested cellular therapies is a worldwide problem. Practitioners (e.g., physicians, scientists, QA/QI facility managers, and policy advocates) are perhaps unaware of the risks involved with such therapies. Therefore, a critical need exists to bring attention to the potential limitations and adverse effects of these therapies to inform and limit misinformation.
Study design and methods:
We describe the extent of the unproven cellular therapy problem through a search of scientific literature and social media coverage. We also describe the regulatory framework that can be used by the practitioner to review and evaluate both proven and unproven cellular therapies.
Results:
We report on the current state of unproven cellular therapies across the globe. A workflow to facilitate an understanding of the regulatory processes involved in the approval of cellular therapies is provided as well as a list of warnings required by regulatory agencies on various products. It is hoped that this article will serve as a tool kit to educate the practitioner on navigating the field of unproven cellular therapy products.
Discussion:
Increasing awareness of the issues associated with unproven therapies through education is important to help in reducing misinformation and risks to patients.
... Before a clinical trial may begin, the IRB reviews and approves (or not) the study and patient materials [5]. The direct-to-consumer (DTC) SC businesses discussed in this article are all in the USA and may be attempting to circumvent these regulations by delivering non-FDA-approved SC treatments or circumventing 'minimally manipulated' guidelines [6]. The criteria in 21 CFR 1271.10(a)(1) and 21 CFR 1271.10(a)(2) for 'minimal manipulation' and 'homologous use' by the FDA may be circumvented by many SC clinics and is often used as a technique to avoid regulatory oversight [7][8][9]. ...
Aim: To attend stem-cell (SC) seminars hosted by US-based direct-to-consumer SC businesses either in person or via online ‘webinars’ to determine accuracy and regulatory oversight of the advertised SC therapies. Methods: The therapeutic claims, costs, risks, scientific evidence in support of a therapy and any regulatory oversight were collated using pre-established checklists. Participation consisted of one live attendance of a seminar, and following COVID-19 restrictions, review of seven recorded presentations available on the internet from SC businesses. Results & conclusion: None of the SC therapies advertised by direct-to-consumer clinics reviewed were supported by proper clinical evidence nor substantiated by peer reviewed literature.
... There have been broadened and exaggerated claims about their ability to rejuvenate the skin as a safer, more proven, and effective alternative with reduced time treatment [17]. In 2017, 432 companies in the United States online sold unproven stem cell-based products for the treatment of unspecified skin diseases, cosmetic-related concerns, or aging improvement [20]. Additionally, there are 87% out of 243 websites advertising stem cell therapies failed to mention either the possibility or the efficiency, and 75% of websites have not demonstrated about general risks of stem cell treatment or the disapproval of the Food and Drug Administration (FDA) for many diseases [21]. ...
Over the last decade, stem cell-associated therapies are widely used because of their potential in self-renewable and multipotent differentiation ability. Stem cells have become more attractive for aesthetic uses and plastic surgery, including scar reduction, breast augmentation, facial contouring, hand rejuvenation, and anti-aging. The current preclinical and clinical studies of stem cells on aesthetic uses also showed promising outcomes. Adipose-derived stem cells are commonly used for fat grafting that demonstrated scar improvement, anti-aging, skin rejuvenation properties, etc. While stem cell-based products have yet to receive approval from the FDA for aesthetic medicine and plastic surgery. Moving forward, the review on the efficacy and potential of stem cell-based therapy for aesthetic and plastic surgery is limited. In the present review, we discuss the current status and recent advances of using stem cells for aesthetic and plastic surgery. The potential of cell-free therapy and tissue engineering in this field is also highlighted. The clinical applications, advantages, and limitations are also discussed. This review also provides further works that need to be investigated to widely apply stem cells in the clinic, especially in aesthetic and plastic contexts.
... There currently exist a large number of US clinics offering stem-cell-based interventions (SCBIs) for many different medical conditions. Researchers have been tracking this marketplace, publishing studies that characterize these clinics and their care providers (Frow et al., 2019;Fu et al., 2019;Knoepfler and Turner, 2018;Turner, 2018;Turner and Knoepfler, 2016). Scientific and bioethical communities continue to call for stronger regulation and oversight of this sector, emphasizing the ''unproven'' nature of the SCBIs routinely on offer and highlighting the lack of evidence demonstrating their clinical efficacy (ISSCR, 2015;Sipp et al., 2017;Zarzeczny et al., 2018). ...
Hundreds of businesses across the United States offer direct-to-consumer stem-cell-based interventions that have not been approved by the Food and Drug Administration. Here, we characterize the types of evidence used on the websites of 59 stem cell businesses in the Southwest United States to market their services. We identify over a dozen forms of evidence, noting that businesses are less likely to rely on “gold-standard” scientific evidence, like randomized clinical trials, and instead draw substantially on forms of evidence that we identify as being “ambiguous.” Ambiguous evidence has some scientific or medical basis, but its interpretation is highly context-dependent. These findings highlight the interpretive responsibility placed on prospective patients. We identify actions for regulators and professional societies to assist with evaluating evidence, but caution that focusing on the (in)validity of particular evidence types is unlikely to eliminate demand for stem-cell-based treatments in this complex marketplace.
... The growth of the US unproven SCI market was noted to be about 570 clinics in 2015-2016 (Turner and Knoepfler, 2016), about 715 in 2017-2018 (Turner, 2018), and in 2019 is estimated to be about 1,000 (Knoepfler, 2019d). In 2017, the FDA revised their guidance on cellbased therapies, which reiterated that all human cells, tissues, and cellular-and tissue-based products (HCT/Ps) that are more than minimally manipulated and/or intended for non-homologous uses will be regulated as a drug, device, and/or biologic (U.S. Food and Drug Administration, 2017a, 2017b). ...
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.
... Similarly, unproven stem cell therapies are practiced in hundreds of clinics in India even though there are strict guidelines and regulations against fraudulent advertisements and clinical practice [49]. In the US, multiple business and clinics are engaged in 'direct-to-consumer' marketing of unproven stem cell therapies [50]. ...
Stem cells offer a promising therapeutic strategy to not only treat several incurable diseases but also regenerate damaged tissues. The current global boom in the field of stem cell and regenerative therapies had led to India becoming a global hotspot for stem cell-based therapies. In this review, we assess the current status of stem cell therapy trials in India and show that the bone marrow-derived stem cells, like mesenchymal stem/stromal cells (MSCs), are predominantly used. Phase 1 and 2 clinical trials have also used MSCs to alleviate symptoms of severe novel coronavirus infections. Recent breakthroughs in gene editing technologies, combined with stem cell therapy, can be effectively harnessed to devise large-scale and affordable treatments for haematological diseases that are highly prevalent in India, like beta-thalassemia and sickle cell diseases. Innovations in stem cell therapy in India can make treatments more affordable to address the needs of in-country patients.
... 1,2 Practitioners in these clinics use their patients' own cells to administer so-called autologous stem cell interventions (ASCI), and these clinics promote this service through direct-to-consumer (DTC) advertising. [3][4][5] This is a challenging space for consumers to navigate. Although the safety and efficacy of ASCIs for many conditions remain unestablished and unproven, these interventions are marketed to consumers in ways that readily create unrealistic and misconceived expectations. ...
Objective
This paper provides an update and overview of the law governing direct-to-consumer (DTC) advertising of autologous stem cell interventions (ASCIs) in Australia. It follows significant changes to the advertising regulations made in 2018.Methods
The paper reviews the three primary sources or 'centres' of law regulating ASCIs in Australia, together with the relevant guidance documents that supplement these sources. It provides analysis of how the post-2018 advertising regulations, contained in the Therapeutic Goods Act 1989 (Cwlth), apply to all 'biologicals', including ASCIs. It demonstrates how these three sources of law interact with one another and outlines the new tiered offence regime that applies to contraventions of these prohibitions.ResultsThe analysis demonstrates that DTC advertising of ASCIs in Australia is strictly controlled, with primary legislation prohibiting the advertising of biologicals altogether.Conclusions
The polycentric legal regime regulating biologicals in Australia clearly makes DTC advertising of ASCIs unlawful. Health practitioners who promote ASCIs, either online, in print or in other media forms, may be penalised in different ways and by different authorities.What is known about the topic?Although several analyses have examined the regulation of ASCIs in Australia, no analysis has studied the reforms made in 2018 relating to the advertising of biologicals. As such, this analysis contributes a fresh examination of these relatively recent reforms.What does this paper add?This analysis clarifies the effects of these new advertising regulations, providing clear guidance on the relevant legal provisions for the benefit of health practitioners and health professionals more generally.What are the implications for practitioners?Health practitioners, especially those who offer ASCIs, should be aware that civil and criminal penalties are likely to be imposed on individuals who promote biologicals in Australia by any means.
... While the safety profiles shown in clinical trials are generally promising, some outcomes of advanced clinical trials have fallen short of expectations (Heier et al., 2020). Overenthusiasm and optimism surrounding stem cell therapies have also caused a surge in for-profit "stem cell" clinics globally, forming a direct-to-consumer marketplace for autologous stem cell interventions (Turner, 2018;Nirwan et al., 2019;Hwang et al., 2020). These clinics are run without the oversight of regulatory agencies and offer scientifically unproven retinal cell therapy products, which are not prepared in a standard and rigorous manner (Shen, 2020). ...
Retinal degenerative diseases (RDDs) are a group of diseases contributing to irreversible vision loss with yet limited therapies. Stem cell-based therapy is a promising novel therapeutic approach in RDD treatment. Mesenchymal stromal/stem cells (MSCs) have emerged as a leading cell source due to their neurotrophic and immunomodulatory capabilities, limited ethical concerns, and low risk of tumor formation. Several pre-clinical studies have shown that MSCs have the potential to delay retinal degeneration, and recent clinical trials have demonstrated promising safety profiles for the application of MSCs in retinal disease. However, some of the clinical-stage MSC therapies have been unable to meet primary efficacy end points, and severe side effects were reported in some retinal “stem cell” clinics. In this review, we provide an update of the interaction between MSCs and the RDD microenvironment and discuss how to balance the therapeutic potential and safety concerns of MSCs' ocular application.
... Clinics around the world offer unproven SCRIs for a host of conditions to patients with few to no clinical options [1]. As of early 2017, there were estimates of 716 clinics offering SCRIs in the USA alone [2,3] -a number that has likely grown since then [4]. Using aggressive marketing primarily through patient testimonials and online information that is often exaggerated and incorrect, many clinics offer scientifically under-or untested interventions that have been shown to result in physical, emotional and financial harm [5][6][7][8]. ...
... The patient may not be made aware of this outcome. Furthermore, the costs can render patients less able to pay for or have their insurance cover standard-of-care treatments of proven benefit for their heart failure [18]. This not only is detrimental to patients themselves, but in a broader sense, to both the field of cell therapy and society at large. ...
Background:
Although a large body of information exists relating to cellular therapies, much of this information is either anecdotal or has been obtained from relatively small clinical trials, so that the level of evidence available to direct adoption of therapeutic approaches is quite limited. Despite this, a large number of clinics offer various cellular treatments without having gone through the processes of FDA approval. Florida is considered a "hotspot" of such sites, with a large number of clinics relative to the population.
Methods:
To better understand the magnitude and scope of this issue with a specific focus on cardiovascular disease, we surveyed clinics in Florida advertising "cell therapy for heart failure". We identified only 8 clinics that "treat cardiac conditions, including heart failure." Data on administration route, cell type used, dose, success rate, cost, and training of persons performing procedures were collected when available, via email, telephone, or website information.
Results:
A total of 20,135 patients were identified as treated: 2157 for cardiac conditions. All clinics reported administering cells intravenously, using either adipose- or umbilical-derived sources. Doses ranged from 30 to 150 million cells per treatment. The "success rate" ranged from 65 to 85%, with costs from $6000 to $20,700. Procedures were performed by PAs, MDs, and DOs.
Conclusion:
Large numbers of patients (> 10% of all 20,135 patients) have been and presumably are still are being treated for "cardiac conditions." We conclude that implementation of uniform data collection with an outcome registry, as well as creation of a public database listing FDA-approved cell-based clinical trials, would be useful to patients and the cardiovascular field at large.
... As numerous stem cell clinics continue to operate in the USA, Canada, as well as overseas [42,43], it is imperative to assess public representations of the clinical evidence, or lack therefore of, supporting the therapies being marketed. Further, as public cord-blood initiatives continue to expand -alongside a growing presence of private cord blood banking companies -it is necessary to help patients determine whether the services offered align with the current clinical evidence. ...
Aim: This study examined how umbilical cord blood (UCB) use was portrayed in the English language North American popular press. Methods: Directed content analysis was conducted on 400 articles from 2007 to 2017 containing ‘cord blood,’ published by the most read Canadian and American news sources. Results: A total of 86.3% of the articles detailed UCB treatments and therapies, the majority of which align with clinical evidence. Some articles portrayed speculative/experimental therapies as efficacious. Public and private banking initiatives received substantial attention, and were portrayed diversely. Promotional narrative messaging was evident around private banking. Conclusion: Findings demonstrate the need for continual monitoring of the media portrayals of UCB as stem cell and transplantation research develops and as clinics continue to operate.
... 19,20 As of May 2017, 432 distinct US businesses were selling 'stem cell' based treatments provided at 716 clinics, and this number appears to be rising rapidly. 21 Such companies are particularly widespread in certain states in the USA, with 67% of clinics located in California, Florida, Texas, Arizona, and Colorado. 13 Most clinics market cell preparations, derived from autologous fat and bone marrow with the majority targeting orthopaedic conditions including osteoarthritis (OA) and chondral lesions. ...
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
... 24 A review paper by Leigh Turner, Associate Professor at the University of Minnesota, has documented the dynamics and size of the stem cell market and observes that there is no evidence that they work. 25 Many stem cell clinics state that they do not need FDA approval, because the cells are harvested and returned within the "same surgical procedure," thus negating the need for a biological license. Although the FDA states that it disagrees with this position, at the time of writing, only a handful of clinics have received warnings. ...
... For example a 2018 study of 432 US businesses engaged in direct-to-consumer marketing of stem cell interventions found that 387 businesses offered services for musculoskeletal conditions (orthopedic conditions, pain relief, sports injuries). 21 These high-cost interventions have not been shown to be effective but have been associated with significant harms. ...
... Strikingly, the Berger study found that the USA is the top global destination for stem cell clinic firms in terms of locations. The clinic problem has continued to worsen as the number of unproven stem cell clinics in the USA reportedly had increased by 2017 to approximately 715 [7]. Yet less than a decade earlier in 2008, there were no such American clinics identified that were advertising on the internet [8], indicating this is a relatively new phenomenon. ...
Aim: The industry of unproven stem cell clinics has rapidly mushroomed throughout the USA, posing risks to patients and the research field. In this study, the aim was to better define how this industry changes. Methods: I analyzed a large cohort of US stem cell clinic firms and their distinct clinic locations as defined in 2015–2016 for their status now in 2019. Results: About a quarter of the firms no longer marketed stem cells. Some lacked active websites, while others dropped stem cell services. Even so, the total number of clinics in this group increased because some firms greatly expanded their clinic numbers. Conclusion: Overall, the unproven clinic industry is a moving target requiring ongoing study and regulatory oversight.
... The spread of clinics marketing these interventions can also lead to the financial exploitation of patientsincluding the problematic use of crowdfunding [12] and may, over the long term, damage public trust in legitimate regenerative technologies, thus adversely impacting their future development and translation [13]. This is particularly so given that both the clinics offering these interventions and the associated media coverage often misleadingly portray these interventions as effective, routine and safe [6,[14][15][16] thus creating false expectations regarding the state of the science and readiness for clinical use. ...
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.
... This said, the low overall percentage of businesses in the Southwest affiliating with a franchise (20%) suggests that the barriers to entry for a stem cell business are relatively low. It seems realistic to suggest that the Southwest is representative of the situation across the United States as a whole; together, these three franchises list just over 200 clinics across the country (as of (Turner, 2018) and is likely to be even higher now. That 70%-80% of stem cell businesses are operating outside of franchises may limit the effectiveness of pursuing regulatory action by targeting franchises. ...
There are currently hundreds of businesses across the United States offering direct-to-consumer stem cell treatments that have not been through regulatory approval by the Food and Drug Administration (FDA). Here, we provide a detailed characterization of nearly 170 stem cell businesses operating in the Southwest United States. We draw specific attention to two as-yet understudied facets of these businesses. First, we identify differences in the degree to which a given business focuses their practice on stem cell treatments. Second, we compare the stated expertise of the care providers in stem cell businesses with the range of conditions they purport to treat. These findings deepen our knowledge of the growing industry around unapproved stem cell treatments, and are used here to offer suggestions for how the FDA might target its resources with respect to regulatory oversight. : Frow and colleagues provide a detailed characterization of 169 direct-to-consumer stem cell businesses operating in the Southwest US. They identify differences in the degree to which individual clinics focus on providing stem cell treatments, and compare physician expertise with the types of conditions treated. These findings are used to offer suggestions for regulatory oversight of direct-to-consumer stem cell businesses. Keywords: stem cell clinics, direct-to-consumer treatments, FDA, policy, regulation
... To date, results of these studies have generally been disappointing 3 , and the widespread use of these treatments is not currently supported by rigorous evidence. Nonetheless, as of May 2017, 716 clinics in the United States alone were engaged in direct-to-consumer marketing of "stem cell"-based interventions, the vast majority of which are promoted for musculoskeletal injuries 4 . ...
BACKGROUND:
The lack of a standardized system for describing cell therapies acts as a barrier to advancement in clinical and basic research and practice. The aim of this study was to establish an international expert consensus on strategies to improve standardization and transparency when describing cell therapies. The secondary aim was to develop a consensus among experts on the contents of a standardized tool for describing cell therapies.
METHODS:
The need for expert consensus on strategies to improve cell therapy communication was confirmed at the American Academy of Orthopaedic Surgeons/National Institutes of Health Optimizing Clinical Use of Biologics Symposium in 2018. A working group of 6 experts convened an international consensus process involving clinicians and basic scientists using validated Delphi methodology. This iterative process was used to define statements on communication of cell therapies and develop a standardized tool for describing cell therapies.
RESULTS:
Thirty-four experts completed 3 rounds survey with use of the Delphi process. After 3 rounds, 27 statements relating to existing nomenclature, solutions to improve communication, ideal characteristics of a framework, mandatory elements of a new framework, and future work to facilitate application reached consensus with >80% agreement and <5% disagreement. Consensus was reached on the contents of a tool for improving standardization and transparency when describing cell therapies. This tool, dubbed "DOSES," is based on the reporting of 5 core items: donor (i.e., autologous, allogeneic, xenogeneic), origin of tissue, separation from other cell types/preparation method, exhibited cell characteristics associated with behavior, and the site of delivery.
CONCLUSIONS:
This study has established expert consensus on the communication of cell therapies. The DOSES tool has been developed to improve standardization and transparency in describing cell therapies.
CLINICAL RELEVANCE:
The DOSES tool for describing cell therapies can be utilized by researchers, clinicians, regulators, and industry professionals to improve standardization and transparency when describing cell therapies. The use of this tool may allow clinicians and patients to better understand the characteristics of current and future cell preparations.
... Despite such successes and attempts to validate regenerative medicine interventions, there lies an industry fueled by hype and misinformation, attempting to sell invalid and unapproved stem cell and regenerative therapies, with growing markets worldwide, perhaps most notably in the USA [26][27][28]. ...
... In recent years there has been a global expansion of unregulated, dubious stem cell clinics. Although developed nations are beginning to face this problem more frequently (Turner, 2018), stereotypically it is thought that this phenomenon is more rampant in developing countries due to a lack of policy and regulation (Berger et al., 2016). However, this is not the case in India. ...
Hundreds of clinics in India offer unproven stem cell therapies despite having remarkably stringent guidelines and regulations for fraudulent advertisements and clinical practice. We discuss the challenges with current regulations, how a recently proposed amendment may further legitimize unproven stem cell therapies, and discuss paths forward in a global context. Hundreds of clinics in India offer unproven stem cell therapies despite having remarkably stringent guidelines and regulations for fraudulent advertisements and clinical practice. We discuss the challenges with current regulations, how a recently proposed amendment may further legitimize unproven stem cell therapies, and discuss paths forward in a global context.
... Stem cell clinics are mostly found through the internet. Direct-to-consumer (DTC) advertising targets the patients rather than the health care providers (Lau et al., 2008;Ryan et al., 2010;Ogbogu et al., 2013;Turner & Knoepfler, 2016;Sipp et al., 2017;Datta, 2018;Julian et al., 2018;Turner, 2018). This is done through clinic websites and social media accounts that advertise compelling patient testimonials or make claims or suggestions that dupe patients into opting for unproven SCI that often lack safety and/or efficacy data (Ryan et al., 2010). ...
p> Background: Current researches on Stem Cell Interventions (SCI) are mostly at various stages of clinical translation, and not ripe for immediate marketing. However, there is a global rise in patients opting for unproven SCI from dubious stem cell clinics.
Objectives: To describes the usual stages of SCI’s clinical translation, factors fuelling the increase in unproven SCI and possible strategies for tackling the situation that have been mentioned in research articles and patient information sources.
Conclusion: Stem cell tourism is on the rise. Direct to customer marketing of SCI through websites and social media using emotional narratives, patient testimonials and false claims of benefits, and unrealistically positive portrayal on social media are contributing factors. The situation may be addressed by treating stem cells as medical innovation and speeding up their clinical translation using modifications like expedited, conditional marketing approval. Medical societies can generate meta-analyses and updates for keeping clinicians informed about the latest therapies so they can guide patients. These along with organisations like ALSuntangled, can generate patient information booklets to help patients make informed decisions. Also, Patient Information Campaigns on social media and media’s coverage of increasing SCI related lawsuits can possibly help raise public awareness about unproven SCI. </em
Stem cells and regenerative medicine have been hyped over the past two decades as a cure for hundreds of diseases and disabilities. However, the clinical therapies have yet to live up to the hype.
Regenerative medicine consists of Cell, Gene and Tissue (CGT) therapies, novel therapeutic technologies that can treat and sometimes cure various illnesses and ailments. Many stem cell facilities and regenerative clinics operating in the United States are immeasurable globally, primarily throughout Latin America, Europe, Asia, China, Israel and the Middle East. In recent times, cell and gene therapies have shown tremendous clinical effectiveness and have been authorized for commercial use by regulators. They are mainly being used to treat blood malignancies, metabolic disorders and immune system disorders. Cell, gene and tissue therapies are globally regulated by authorities that govern patients’ safety, potency, and efficacy in each region. Regulators of medicines, devices and therapies across the globe require producers of the therapy products to meet several criteria and comply with regulations before commercializing a cell-based treatment. Occasionally, a few unscrupulous clinics and bad players advertise untested treatments as “cures”—for a fee—and have preyed on individuals eager to find a remedy for their specific ailment after traditional medicine fails to offer one. Unchecked, few bad players lead the patients towards a dangerous trend of stem cell tourism, where the cost to patients is high, and so the danger involved with these experimental therapies and the profit margin for the clinic are substantial. This chapter summarizes the regulatory environment and industry compliance for regenerative therapies globally for all the stakeholders involved in this process. Authorities globally are establishing guidelines and restrictions on regenerative therapies on a risk-based basis. These include regulatory oversight of the investigational product’s preclinical and clinical evaluation, compliance with applicable premarket or post-market approval requirements, and demonstration that the product is manufactured per current good manufacturing practices (cGMP) to ensure the product’s safety, purity, and potency before reaching a patient. These scientifically rigorous regulatory products and procedures must substantiate any claims made regarding the safety, potency and efficacy of stem cell therapy. Apart from ICH and country-specific pharmacopoeial standard-setting organizations, many more international organizations are currently establishing standards in their respective fields of competence and then implementing them to worldwide standards or guidelines. This chapter will serve as a quick reference guide to international regulatory and quality requirements related to cell, gene and tissue therapies and regenerative medicine.KeywordsStem cellsRegulatory frameworkComplianceCell therapiesGene therapiesRegenerative medicine
Objective:
To explore the experiences, approaches, and challenges of physicians consulting patients about experimental stem cell and regenerative medicine interventions (SCRIs).
Participants and methods:
From August 21, 2018, through July 30, 2019, semistructured interviews of 25 specialists in cardiology, ophthalmology, orthopedics, pulmonology, and neurology were conducted and qualitatively analyzed using modified grounded theory.
Results:
All specialists used informational approaches to counsel patients, especially orthopedists. Informational approaches included explaining stem cell science, sharing risks, and providing principles. Several specialists also used relational counseling approaches including emphasizing that physicians want what is best for patients, acknowledging suffering, reassuring continued care, empathizing with patients and families, and underscoring that patients have the final decision. Many specialists reported being comfortable with the conversation, although some were less comfortable and several noted challenges in the consultation including wanting to support a patient's decision but worrying about harms from unproven SCRIs, navigating family pressure, and addressing stem cell hype and unrealistic expectations. Specialists also desired that additional resources be available for them and patients.
Conclusion:
Physicians relied more heavily on providing patients with information about SCRIs than using relational counseling approaches. Efforts should be directed at helping physicians address the informational and relational needs of patients, including providing tools and resources that inform physicians about the unproven SCRI industry, building skills in empathic communication, and the creation and dissemination of evidence-based resources to offer patients.
The stem cells have abundant potential for innovative therapeutic programs to replace or regenerate cells or tissues having functional impairment. Since the introduction of stem cell therapy using embryonic stem cells in 1998, the clinical use of the stem cells has increased. On the scientific ground, it is necessary to pass the clinical trials, otherwise, it may be recognised as an unproven therapy. The market of unproven stem cell therapy got attention when stem cell clinics started to advertise and claim to cure untreatable diseases. Indian Government has thus considered stem cell as a drug, and stem cells gone under clinical trials for market approval. In this study, we studied research trends related to clinical trials using stem cells as a therapeutic agent based on data obtained from the Clinical Trial Registry of India (CTRI). Our study showed that many clinical trials on the stem cells have been registered in the CTRI database, but only few of the clinical trials has been focusing on the actual stem cell drug development process. The greatest part of these trials were interventional and focused on bone marrow stem cells. On the other hand, only 2% of clinical trials actually focused on iPSCs. There is need to promote randomized clinical trials than single arm trials then our reliability on outcome from clinical trials may increases.
Background and Aims
Premature commercialization of unproven stem cell interventions (SCIs) has received significant attention within the regenerative medicine community. Patients considering SCIs may encounter misinformation and seek out guidance from their physicians who are trusted brokers of health information. However, little is known about the perspectives of academic physician specialists toward the SCI industry. The purpose of this study was to capture the attitudes of physician specialists with experience addressing patient questions about unproven SCIs.
Methods
The authors undertook 25 semi-structured interviews with academic physicians in cardiology, ophthalmology, orthopedics, pulmonology and neurology primarily from one academic center.
Results
The authors identified two major themes: concerns and mediators of appropriateness of offering SCIs as therapies to patients. Specialists were generally aware of the industry and reported scientific and commercial concerns, including the scientific uncertainty of SCIs, medical harms to patients, misleading marketing and its impact on patient informed consent and economic harms due to large out-of-pocket costs for patients. All specialists outside of orthopedics voiced that it was inappropriate to be offering SCIs to patients today. These views were informed by previously expressed concerns surrounding safety and properly informing patients, levels of evidence needed prior to offering SCIs therapeutically and desired qualifications for clinicians. Among the specialties, orthopedists reported that under certain conditions, SCIs may be appropriate for patients with limited clinical options but only when safety is adequate, expectations are managed and patients are well informed about the risks and chances of benefit. Most participants expressed a desire for phase 3 studies and Food and Drug Administration approval prior to marketing SCIs, but some also shared the challenges associated with upholding these thresholds of evidence, especially when caring for out-of-option patients.
Conclusions
The authors’ results suggest that medical specialists are aware of the industry and express several concerns surrounding SCIs but differ in their views on the appropriateness and clinical evidence necessary for offering SCIs currently to patients. Additional educational tools may help physicians with patient engagement and expectation management surrounding SCIs.
Stem cells play critical roles in biological processes, such as tissue development and homeostasis; they also present great promise toward promoting breakthroughs in regenerative medicine. Stem cells may be used to explore disease modeling, for screening of new drugs, and for the treatment of intractable diseases. The transition of stem cell biology from basic research to clinical applications has involved both hope and hype. Indeed, premature application of stem cell therapy as a clinical “cure-all” without sufficient experimental, preclinical, or clinical research has led to shady practices and false promises. While this is, understandably, fueled by patients in need of cures for unmanageable chronic and degenerative diseases, hype-based practices have promoted the spread of clinically unproven therapies. These therapies may have no impact on the disease process or may result in devastating outcomes. Stem cells may ultimately have the capacity to treat intractable diseases, including diabetes, cardiovascular disorders, metabolic disorders, hematopoietic disorders, and immunodeficiency disorders. However, and despite significant promise, there remains a need to elucidate numerous misunderstandings associated with stem cell therapy and to define the current barriers and obstacles faced by those involved in stem cell research and its therapeutic applications. As such, the main goal of this chapter was to provide the reader with an overview of basic concepts in stem cell research and review the facts and the unfortunate hype with respect to current clinical applications and disease treatments.
Purpose of review:
Progressive supranuclear palsy (PSP) is a progressive adult-onset neurodegenerative disease. Abnormally, phosphorylated forms of the microtubule-associated protein tau containing four repeat domains (4R-tau) aggregate in neurons. Additionally, increasing evidence suggests that secretion and uptake of fragments of abnormal 4R-tau may play a role in disease progression. This extracellular tau is a natural target for immunotherapy.
Recent findings:
Three monoclonal antibodies targeting extracellular tau are in clinical stages of development. ABBV-8E12 and BIIB092 were safe in Phase 1, but both Phase two studies recently failed futility analyses. UCB0107 recently reported (in abstract form) Phase 1 safety results, and a Phase 2 study is under consideration. Stem cell therapy and the infusion of plasma are also being explored clinically.
Summary:
The likely role of extracellular tau in the progression of PSP makes tau a natural target for targeted immunotherapy. Clinical trials are still in early stages, and although tau immunotherapy has largely been shown to be safe, efficacy has yet to be demonstrated.
Multiple disease-modifying medications with regulatory approval to treat multiple sclerosis (MS) are unable to prevent inflammatory tissue damage in the central nervous system (CNS), and none directly promote repair. Thus, there is an unmet clinical need for therapies that can arrest and reverse the persistent accumulation of disabilities associated with progressive forms of MS (P-MS). Preclinical research has revealed an unexpected ability of neural stem cell (NSC) therapies to provide neurotrophic support and inhibit detrimental host immune responses in vivo following transplantation into the chronically inflamed CNS. We discuss NSC transplantation as a promising therapy for P-MS, elaborate on the necessities of clinical trial validation and formalized usage guidelines, and caution about unscrupulous ‘clinics’ marketing unproven therapies to patients.
The United States Food and Drug Administration (FDA) is responsible for protecting and promoting public health through rules and regulations. Over the past few years, the field of regenerative medicine and cell therapy have garnered significant interest, and this evolving new biology is changing fast and challenging regulatory bodies. The FDA has published a series of guidance documents outlining steps to protect consumers against potentially dangerous and unproven treatments. The agency has offered a grace period for “stem cell clinics” until November 2020 to come into compliance by obtaining Investigational New Drug applications and working to secure premarket approval of their products. With the documentation of hundreds of “stem cell clinics,” the FDA needs to enforce the adherence to their outlined standards to protect patients. The aim of this review was to provide an overview of these FDA regulations and some current issues within the industry. The purpose is to educate and inform the musculoskeletal community about the current government regulations of this new expanding biology.
Level of Evidence
Level V, expert opinion.
Aim: This study examines online enquiries received by two prominent stem cell science initiatives operating in different geographical jurisdictions. Materials & methods: Combined quantitative and qualitative analysis undertaken of internet-based queries (n = 1047) received by Stem Cells Australia and EuroStemCell from members of the public over a two-year period (May 2014–2016). Results: Findings reveal striking similarities between the two datasets and highlight the range of uncertainties, priorities and needs of those seeking information about stem cells online. Conclusion: Sustained and in-depth tailored guidance is needed to effectively meet the diverse stem cell-related information-based needs of communities internationally. Such efforts should be prioritized by regenerative medicine research initiatives and organizations, given the trust and hope diverse publics appear to place in these groups.
Recently, stem cells in aesthetics have attracted increased attention, especially as they have become a popular trend that is being mass-marketed to consumers on the Internet and social media. Unfortunately, studies have shown this marketing to be misleading as it portrays many purported benefits of stem cells that have yet to be proven in the limited studies that are available. It is important for clinicians to understand the evidence and marketing behind any new trends, especially in the fast-paced world of aesthetics, where treatments often outpace current medical understanding. As clinicians, we have bioethical and professional obligations to educate ourselves on current trends, ensure adequate patient safety, and advocate for continued consumer education.
More than 700 US clinics advertise unproven stem cell treatments.¹ Hematopoietic stem cell transplants to treat various hematologic disorders are evidence-based whereas most other stem cell interventions are investigational. This study examined the characteristics and scope of training of clinicians performing unproven stem cell procedures.
Over the past decade, there has been an increased interest in the use of biologic therapies in sports medicine. Although these technologies are in relatively early stages of development, there have been substantial increases in marketing, patient demand, and clinical utilization of biologics, including platelet-rich plasma, bone marrow aspirate concentrate, and other cell-derived therapies. Direct-to-consumer marketing of biologics has also proliferated but is largely unregulated, and clinicians must accurately convey the safety and efficacy profiles of these therapies to patients. Because most insurance companies consider biologic treatments to be experimental or investigational for orthopaedic applications given the lack of high-quality evidence to support their efficacy, patients receiving these treatments often make substantial out-of-pocket payments. With a range of treatment costs among centers offering biologics, there is a need for appropriate and sustainable pricing and reimbursement models. Clinicians utilizing biologics must also have a thorough understanding of the recently clarified Food and Drug Administration guidelines that regulate the clinical use of cell and tissue products. There is a lack of consensus on the optimal preparation, source, delivery method, and dosing of biologic therapies, which has been exacerbated by a lack of sufficient experimental detail in most published studies. Future research must better identify the biologic target of treatment, adhere to better standards of reporting, and better integrate researchers, industry, and regulatory bodies to optimize applications.
Aim:
This study examines marketing claims of Canadian businesses engaged in direct-to-consumer advertising of putative stem cell treatments.
Methods:
Internet searches were used to locate Canadian businesses selling stem cell interventions. Company websites were subjected to detailed analysis.
Results:
In total, 30 Canadian businesses sell stem cell interventions provided at 43 clinics. Autologous stem cells are the most common types of products promoted by such businesses. Company websites minimize risks while making strong claims about benefits of stem cell interventions.
Discussion:
Businesses' representations could result in patients making health-related decisions informed by marketing claims rather than best available scientific evidence.
Conclusion:
Although there is absent development of new regulations and guidance, the Canadian direct-to-consumer marketplace for stem cell interventions appears poised for expansion.
We report on a roundtable event hosted in Singapore that sought to identify some of the ethical and regulatory challenges in translating autologous cell-based interventions, particularly those claiming to involve stem cells, into safe and effective therapies and to propose some solutions to encourage responsible innovation with these products. Challenges are identified in the three areas of cell manufacturing and processing, innovative uses of autologous cells in clinical practice and standards of evidence. Proposed solutions are discussed within a co-operative model of statutory laws and regulations that can enable product development with autologous cells and professional codes and standards that can encourage ethical conduct in clinical practice. Future research should be directed toward establishing regional networks for the development of internationally consistent standards in manufacturing and ethical codes of conduct for innovating with stem cells, and other autologous cells, and fostering ongoing exchange between jurisdictions.
We assessed the extent to which the publication of clinical trial results of innovative cell-based interventions reflects International Society for Stem Cell Research best practice guidelines. We assessed: (1) characteristics and time to publication of completed trials; (2) quality of reported trials; and (3) results of published trials. We identified and analyzed publications from 1,052 novel stem cell clinical trials: 179 (45.4%) of 393 completed trials had published results; 48 trials were registered by known stem cell tourism clinics, none of which reported results. Completed non-industry-sponsored trials initially published more rapidly, but differences with industry-sponsored trials decreased over time. Most publications reported safety, and 67.3% (mainly early-stage trials) reported positive outcomes. A higher proportion of industry trials reported positive efficacy. Heightened patient expectations for stem cell therapies give rise to ethical obligations for the transparent conduct of clinical trials. Reporting guidelines need to be developed that are specific to early-phase clinical trials.
We report results in a 77-year-old male patient with visual loss from long-standing serpiginous choroidopathy treated with bone marrow derived stem cells (BMSC) within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an Institutional Review Board approved clinical trial and the largest ophthalmology stem cell study registered at the National Institutes of Health to date (ClinicalTrials.gov Identifier: NCT01920867). Eight months after treatment by a combination of retrobulbar, subtenon, intravitreal and intravenous injection of BMSC, the patient's best corrected Snellen acuity improved from 20/80 - to 20/60 +1 in the right eye and from 20/50 - to 20/20 -3 in the left eye. The Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity continued to improve over the succeeding 8 months and the optical coherence tomography macular volume increased. The increases in visual acuity and macular volume are encouraging and suggest that the use of BMSC as provided in SCOTS may be a viable approach to treating serpiginous choroidopathy.
Significance:
This article focuses on the strategies used to recruit patients via for-profit stem cell clinic seminars and the marketing claims made as well as the impact on the public and the stem cell translational medicine field. Although the field is very aware of the existence of such seminars, this piece is significant and novel for reporting first-hand on the specific factual details of one such seminar. Stem cell clinics conducting such self-described stem cell educational seminars use a number of marketing strategies to recruit customers and make specific testable medical claims, which may, in some instances, misinform the public and potentially pose a threat to the stem cell field. Potential ways to address this growing challenge are discussed.
Background:
This pilot study was used to evaluate safety and subjective outcomes in a small series of Peyronie's disease patients using a combination of autologous stromal vascular fraction (SVF) and penile shock wave treatments. SVF can be procured and deployed into Peyronie's plaques, enabling the surgeons to procure and mobilize significant numbers of both adult mesenchymal stem cells and antiinflammatory cytokines released from the adipose collagen matrix after collagen digestion. Penile shock wave therapy stimulates targeted tissues and may activate stem cells found in the SVF and promote healing and fibrosis mitigation.
Methods:
SVF isolated from lipoaspirate was deployed by injection into 11 patients with Peyronie's plaques in combination with a series of shock wave treatments. Subjective outcomes tests performed at baseline and at 6 months included the Erectile Hardness Grading Score and the Peyronie's Disease Questionnaire (Questions 1-6).
Results:
All patients noted subjective improvement in curvature and subjective reduction in plaque size. Seven patients reported improvement in erectile function. Mean Erectile Hardness Grading Score increased from 2.7 to 3.5, and mean Peyronie's Disease Questionnaire scores decreased from 15.0 to 8.7.
Conclusions:
SVF is known to have scar mitigation, antiinflammatory, immunomodulatory, and regenerative effects, and it has been used for a variety of conditions on an investigational basis. SVF containing mesenchymal stem cells can be procured in a closed surgical system from lipoaspirate in a same-day setting and deployed directly into Peyronie's plaques in combination with penile shock wave therapy resulting in plaque mitigation.
Permitting patients to pay for participation in clinical research threatens the principles of social value and fair subject selection as well as robust clinical trial design.
Copyright © 2015, American Association for the Advancement of Science.
In this report, we present the results of a single patient with optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an Institutional Review Board approved clinical trial and is the largest ophthalmology stem cell study registered at the National Institutes of Health to date- www.clinicaltrials.gov Identifier NCT 01920867. SCOTS utilizes autologous bone marrow-derived stem cells in the treatment of optic nerve and retinal diseases. Pre- and post-treatment comprehensive eye exams were independently performed at the Wilmer Eye Institute at the Johns Hopkins Hospital, USA. A 27 year old female patient had lost vision approximately 5 years prior to enrollment in SCOTS. Pre-treatment best-corrected visual acuity at the Wilmer Eye Institute was 20/800 Right Eye (OD) and 20/4,000 Left Eye (OS). Four months following treatment in SCOTS, the central visual acuity had improved to 20/100 OD and 20/40 OS.
Background
The pursuit of unproven stem cell-based interventions (“stem cell tourism”) is an emerging issue that raises various concerns. Physicians play different roles in this market, many of which engage their legal, ethical and professional obligations. In Canada, physicians are members of a self-regulated profession and their professional regulatory bodies are responsible for regulating the practice of medicine and protecting the public interest. They also provide policy guidance to their members and discipline members for unprofessional conduct.
Methods
We conducted semi-structured telephone interviews with representatives from six different provincial Colleges of Physicians and Surgeons in Canada to discuss their experiences and perspectives regarding stem cell tourism. Our focus was on exploring how different types of physician involvement in this market would be viewed by physicians’ professional regulatory bodies in Canada.
Results
When considering physicians’ professional obligations, participants drew analogies between stem cell tourism and other areas of medical tourism as well as with some aspects of complementary alternative medicine where existing policies, codes of ethics and regulations provide some guidance. Canadian physicians are required to act in the best interests of their patients, respect patient autonomy, avoid conflicts of interest and pursue evidence-based practice in accordance with accepted standards of care. Physicians who provide unproven treatments falling outside the standard of care, not in the context of an approved research protocol, could be subject to professional discipline. Other types of problematic conduct include referrals involving financial conflict of interest and failure to provide urgent medically necessary care. Areas of ambiguity include physicians’ obligations when asked for information and advice about seeking unproven medical treatments, in terms of providing non-urgent follow-up care, and when asked to support efforts to go abroad by providing tests or procedures in advance that would not otherwise be medically indicated.
Conclusions
Specific policy guidance regarding the identified areas of tension or ambiguity may prove helpful for physicians struggling with these issues. Further consideration of the complex interplay of factors at issue in how physicians may (should) respond to patient demands related to unproven medical interventions while meeting their professional, legal and ethical obligations, is warranted.
This Article examines the convergence of three corporations that have attempted to capitalize on translating emerging research into clinical procedures by manufacturing and facilitating the process for patients to obtain mesenchymal stem cell (MSC) injections. Although the Food and Drug Administration (FDA) has asserted its authority to regulate somatic cell therapy products like MSCs under the Public Health Service Act and the Food, Drug, and Cosmetic Act, some manufacturers have attempted to circumvent FDA regulation through various mechanisms and argue that their products do not fall within the definition of a biological product or drug. However, scientific knowledge of using MSCs for clinical therapy remains in its infancy, and MSCs pose a number of serious risks to patients. This Article focuses on the development of Celltex, a company based in Sugar Land, Texas that manufactures and facilitates the injection of autologous MSCs; RNL Bio, a company that licenses its operations technology to Celltex; and Regenerative Sciences, a company based in Broomfield, Colorado that was recently involved in litigation with the FDA. Corporate circumvention of intended regulatory oversight exposes patients to potentially inefficacious products that could contribute to serious medical injuries such as viruses, myocardial infarction, cancer, or death.
Autologous adult stem cells (ASCs) are being administered by physicians for indications that have not been demonstrated as safe and effective in formal clinical trials. Examination of regulatory frameworks across five countries suggests that balancing the demands of research with clinical freedom has created structural weaknesses that are being exploited.
The Food and Drug Administration (FDA) has sought an injunction to prevent a US-based company from offering an autologous adult stem cell treatment for musculoskeletal and spinal injuries. Given the alarming number of clinics promoting stem-cell-based interventions, the outcome of this case could have wide-ranging implications.
Persons with serious and disabling medical conditions have traveled abroad in search of stem cell treatments in recent years. However, weak or nonexistent oversight systems in some countries provide insufficient patient protections against unproven stem cell treatments, raising concerns about exposure to harm and exploitation. The present article, the first of two, describes and analyzes stem cell tourism in Russia and India and addresses several scientific/medical, ethical, and policy issues raised by the provision of unproven stem cell-based treatments within them. The distinction between treatment based on proven clinical research and "innovative treatment" is addressed and the authors conclude that the innovations at issue constitute neither. Regulatory measures need to be developed or strengthened in accord with internationally accepted standards in such countries to protect those seeking stem cell treatments.
Few areas of recent research have received as much focus or generated as much excitement and debate as stem cell research. Hope for the therapeutic promise of this field has been matched by social concern associated largely with the sources of stem cells and their uses. This interplay between promise and controversy has contributed to the enormous variation that exists among the environments in which stem cell research is conducted throughout the world. This variation is layered upon intra-jurisdictional policies that are also often complex and in flux, resulting in what we term a 'patchwork of patchworks'. This patchwork of patchworks and its implications will become increasingly important as we enter this new era of stem cell research. The current progression towards translational and clinical research among international collaborators serves as a catalyst for identifying potential policy conflict and makes it imperative to address jurisdictional variability in stem cell research environments. The existing patchworks seen in contemporary stem cell research environments provide a valuable opportunity to consider how variations in regulations and policies across and within jurisdictions influence research efficiencies and directions. In one sense, the stem cell research context can be viewed as a living experiment occurring across the globe. The lessons to be gleaned from examining this field have great potential for broad-ranging general science policy application.
By clarifying its position on the handling and therapeutic use of human cell–based products, the FDA has signaled its intention to regulate a broad swath of highly manipulated cellular materials as biologic drugs. This move is welcome, but more remains to be done.
A 77-year-old woman with exudative macular degeneration underwent bilateral intravitreal injections of “stem cells” at a clinic in Georgia. One month and 3 months after injection, she developed retinal detachments in the left and right eyes, respectively. Increased awareness within the medical community of such poor outcomes is critical so that clinics offering untested practices that have been shown to be potentially harmful to patients can be identified and brought under U.S. Food and Drug Administration oversight.
[ Ophthalmic Surg Lasers Imaging Retina . 2017;48:772–775.]
Commercial promotion of unsupported therapeutic uses of stem cells is a global problem that has proven resistant to regulatory efforts. Here, we suggest a coordinated approach at the national and international levels focused on engagement, harmonization, and enforcement to reduce the risks associated with direct-to-consumer marketing of unproven stem cell treatments. © Copyright 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.
Numerous US businesses that engage in direct-to-consumer advertising of stem cell interventions that are not US FDA-approved also recruit clients by listing 'pay-to-participate' studies listed on ClinicalTrials.gov . Individuals considering enrolling in such studies and NIH officials responsible for overseeing the database need to be aware that some businesses are using the registry to promote unapproved stem cell interventions that study subjects are charged to receive. Inclusion of such studies in ClinicalTrials.gov reveals that the database needs better screening tools. In particular, screening should evaluate whether studies submitted to the registry have been reviewed and permitted to proceed by the FDA in the case of clinical studies requiring FDA clearance in addition to institutional review board approval.
Using two legal research platforms, we identified 193 stem-cell-related legal cases that were decided in US courts. Classifying the cases by category, we examined historical trends in the types of legal cases related to stem cells. Major types of cases involved plaintiffs seeking to overturn denial of health insurance coverage decisions, disputes related to intellectual property, false advertising, breaches of contract, exposure to hazardous agents, regulatory decisions, stem cell procedures and professional standard of care, use of stems cells in research, and public funding of embryonic stem cell research. Analysis of court decisions provides insight into contemporary and historical legal issues related to stem cells and reveals the breadth of stem-cell-related cases now being decided by US courts.
Adipose tissue-derived "stem cells"have been increasingly used by "stem-cell clinics" in the United States and elsewhere to treat a variety of disorders. We evaluated three patients in whom severe bilateral visual loss developed after they received intravitreal injections of autologous adipose tissue-derived "stem cells"at one such clinic in the United States. In these three patients, the last documented visual acuity on the Snellen eye chart before the injection ranged from 20/30 to 20/200. The patients' severe visual loss after the injection was associated with ocular hypertension, hemorrhagic retinopathy, vitreous hemorrhage, combined traction and rhegmatogenous retinal detachment, or lens dislocation. After 1 year, the patients' visual acuity ranged from 20/200 to no light perception.
To ensure that the emerging field of stem-cell therapy fulfills its promise to patients, we must first understand its risks and benefits and develop therapeutic approaches based on sound science. That requires a commitment to the principles of evidence generation.
A structured search reveals that online marketing of stem-cell-based interventions is skewed toward developed economies including the United States, Ireland, Australia, and Germany. Websites made broad, imprecise therapeutic claims and frequently failed to detail procedures. Widespread marketing poses challenges to regulators, bioethicists, and those seeking realistic hope from therapies.
Direct-to-consumer marketing of unapproved stem cell interventions is a well-known phenomenon in countries with lax medical regulations. However, an examination of Internet-based marketing claims revealed widespread promotion of such interventions by businesses based in the United States. Such commercial activity suggests that regulatory agencies must better oversee this marketplace. Direct-to-consumer marketing of unapproved stem cell interventions is a well-known phenomenon in countries with lax medical regulations. However, an examination of Internet-based marketing claims revealed widespread promotion of such interventions by businesses based in the United States. Such commercial activity suggests that regulatory agencies must better oversee this marketplace.
The way science is represented to the public can influence understanding and expectations, frame policy debates, and affect the implementation and use of emerging technologies. Inaccurate representations of research may, for example, lead to public confusion about the readiness of a technology for clinical application. As a result, the issue of science “hype”—in which the state of scientific progress, the degree of certainty in models or bench results, or the potential applications of research are exaggerated—is receiving increased attention from the popular press, the research community, and scientific societies ( 1 ). In newly issued guidelines on the ethical conduct of human pluripotent stem cell research and clinical translation ( 2 ), the International Society for Stem Cell Research (ISSCR) explicitly recognizes and confronts the issue of science hype. By placing a clear obligation on researchers, the ISSCR hopes to make balance in public representations of research a norm associated with scientific integrity. The focus on public communication, which is new to this version of the guidelines, is the result of both specific concerns regarding how stem cell research has been portrayed in the public sphere and the growing recognition that researchers play an important role in the science communication process.
"Stem cell tourism" is a rising Internet-based industry that aims to offer unproven procedures to patients with incurable diseases. This unregulated activity is reaching the neurologist's office as well as across the world, as patients request information or clearance for such procedures. Herein, we posit the need for medical societies and licensing boards to bring this issue to the forefront of neurology because it has the potential to affect patient care with risk of morbidity and mortality, as well as to undermine public confidence in legitimate stem cell research for incurable neurological diseases such as multiple sclerosis and amyotrophic lateral sclerosis.
Patient-funded trials (PFTs) are gaining traction as a means of accelerating clinical translation. However, such trials sidestep mechanisms that promote rigor, relevance, efficiency, and fairness. We recommend that funding bodies or research institutions establish mechanisms for merit review of patient-funded trials, and we offer some basic criteria for evaluating PFT protocols.
Copyright © 2015 Elsevier Inc. All rights reserved.
Scholarship on patients accessing unproven stem cell interventions is dominated by research addressing 'stem cell tourism' to such countries as China, India, Mexico, and the Ukraine. However, clinics marketing 'adipose-derived mesenchymal stem cell treatments' are proliferating across the USA. These businesses typically claim to operate in compliance with federal regulations, but careful review of their commercial practices suggests that such clinics are marketing unapproved and noncompliant biological drugs.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Funding support for clinical research is traditionally obtained from any of several sources, including government agencies, industry, not-for-profit foundations, philanthropies and charitable and advocacy organizations. In recent history, there have also been a limited number of cases in which clinical research programs were established in which funding was provided directly by patients in turn for the ability to participate as nonrandomized subjects. This approach to clinical research funding, which I refer to here as the 'pay-to-participate' model, has been both criticized and rationalized on ethical grounds, with reference to its implications for issues, including equipoise, therapeutic misconception, justice, autonomy and risk-benefit balance. Discussion of the scientific implications of this funding scheme, however, has been more limited. I will briefly review the history of the pay-to-participate model in the context of experimental cell and tissue treatments to date and highlight the many ethical and, particularly, scientific challenges that unavoidably confound this approach to the funding and conduct of clinical research.
To stimulate a broad discussion between academics, practicing physicians, corporate managers, and members of the regulatory community, we describe a proposal for a new regulatory pathway for human cell- and tissue-based products. The new components of the pathway are intended to accelerate patient access to a wide array of novel therapeutics, strengthen R&D infrastructure, and expand patient numbers and timelines for efficacy testing through a transparent and publicly accessible website for real-time reporting of outcome data and 5- to 10-year, long-term follow-up.
There is a large, poorly regulated international market of putative stem cell products, including transplants of processed autologous stem cells from various tissues, cell processing devices, cosmetics, and nutritional supplements. Despite the absence of rigorous scientific research in the form of randomized clinical trials to support the routine use of such products, the market appears to be growing and diversifying. Very few stem cell biologics have passed regulatory scrutiny, and authorities in many countries, including the United States, have begun to step up their enforcement activities to protect patients and the integrity of health care markets.
The Cayman Islands have long offered safe harbor to financial institutions and tourists alike. (A British Overseas Territory, the Cayman Islands have no income tax, nonresident tax, capital gains tax, or corporate tax.1) Due to recent actions by the US Food and Drug Administration (FDA), the islands may, as well, enhance their reputation as safe harbor to companies developing stem cell treatments. More important, however, is the issue of whether actions by the FDA in relation to stem cell treatments mean that the agency has officially stepped over the line and, at least in this instance, is now regulating the practice of medicine.
The FDA's primary charge is to ensure the safety, efficacy, and security of drugs, biological products, medical devices, the nation's food supply, cosmetics, and products that emit radiation.2 A drug includes “articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease.”3 The FDA states that this broad definition also includes therapeutic biological products such as cells and tissues.4
For almost 20 years, stem cells have been harvested, preserved, and reinfused to help patients recover from cancer treatments.5–8 Although devices for separating stem cells are within FDA jurisdiction,9 the FDA acknowledges it is not authorized to regulate the practice of medicine.10 It is, however, authorized to regulate drugs.4 So how do stem cells become drugs subject to FDA oversight? That question has been answered by a case involving Regenerative Sciences, Inc, a Colorado-based clinic that offers bone marrow–derived stem cell procedures to treat injuries and degenerative joint conditions.11
On July 25, 2008, the FDA notified Regenerative Sciences that, “based on information posted on your website, mesenchymal stem cells utilized in your Regenexx™ procedure are drawn from a patient's bone marrow, sent to a …
Premarketing approval by the federal government should ensure not only safety, but efficacy as well.
Research into the biological properties and clinical potential of stem cells has spurred strong public investment, industry development, media coverage, and patient interest in recent years. To date, however, few clinical applications of demonstrated safety and efficacy have been developed with the exception of uses of hematopoietic stem cells in the treatment of diseases of the blood and immune systems. This lack of an evidence basis notwithstanding, hundreds of companies and private clinics around the world now sell putative stem cell treatments for an enormously broad range of medical and quality-of-life conditions. This represents a major challenge for legitimate scientists working in the field, for authorities seeking to protect their constituencies, and for patients and consumers targeted by such companies' marketing strategies. In this review, I provide an overview of the global industry in pseudomedical stem cell treatments, with an investigation of claims in a single disease area (amyotrophic lateral sclerosis), and make recommendations for the introduction and enforcement of appropriate regulatory responses to this problem.
Stem cell research has attracted an extraordinary amount of attention and expectation due to its potential for applications in the treatment of numerous medical conditions. These exciting clinical prospects have generated widespread support from both the public and private sectors, and numerous preclinical studies and rigorous clinical trials have already been initiated. Recent years, however, have also seen alarming growth in the number and variety of claims of clinical uses of notional 'stem cells' that have not been adequately tested for safety and/or efficacy. In this article, I will survey the contours of the stem cell industry as practiced by alternative medicine providers, and highlight points of commonality in their strategies for marketing.
Part I of this article, published in the March 2010 issue of the Kennedy Institute of Ethics Journal, traces and addresses the provision of unproven stem cell treatments in Russia and India, examines the concept of innovative treatment, and concludes that stronger regulations are needed to protect the health and informed choices of patients. The current paper, Part II, proposes that the regulatory frameworks for the development of safe and efficacious treatments in effect in the United States and the United Kingdom provide examples of strong oversight measures from which countries seeking to obtain international credibility for their biotechnological competence could draw when developing regulations for stem cell treatments. Major sources of information available to persons who consider receiving such unproven treatments are explored in order to understand and address their concerns. The paper concludes with proposed measures to inform those considering the pursuit of unproven stem cell treatments abroad more accurately about their efficacy and safety and provide them with improved medical and social support in their home countries.
While the clinical promise of much stem cell research remains largely theoretical, patients are nonetheless pursuing unproven stem cell therapies in jurisdictions around the world--a phenomenon referred to as "stem cell tourism." These treatments are generally advertised on a direct-to-consumer basis via the Internet. Research shows portrayals of stem cell medicine on such websites are overly optimistic and the claims made are unsubstantiated by published evidence. However, anecdotal evidence suggests that parents are pursuing these "treatments" for their children, despite potential physical and financial risk. Physicians are in a unique position as they can be expected to be involved in, or privy to, such decisions. In this paper, we consider what duties physicians may have toward minor patients whose parents/guardians wish to engage in stem cell tourism on their behalf. We use the Canadian perspective to address the broadly relevant issues raised by this trend.
Driven by hype surrounding stem cell research, a number of clinics around the world currently offer 'stem cell therapies' to patients. These unproven interventions have attracted policy interest owing to the risks they may pose to patients and to the progress of legitimate translational stem cell research, yet remarkably little data exists about the patients who undergo these unproven therapies or their experiences. We sought to characterize this patient population.
We developed a comprehensive data set of blogs written by patients (or their caretakers) about their experiences with unproven stem cell therapies.
Analyzing these data suggests that unproven stem cell therapies are increasing rapidly in popularity and are attracting a wide range of patients--both young and old and with a diverse collection of medical conditions. These results should help clinicians advise individual patients and help policymakers devise strategies to mitigate the risks these treatments pose.
Unverified medical treatments based on stem cells are proliferating and need oversight.
Despite the immature state of stem cell medicine, patients are seeking and accessing putative stem cell therapies in an "early market" in which direct-to-consumer advertising via the internet likely plays an important role. We analyzed stem cell clinic websites and appraised the relevant published clinical evidence of stem cell therapies to address three questions about the direct-to-consumer portrayal of stem cell medicine in this early market: What sorts of therapies are being offered? How are they portrayed? Is there clinical evidence to support the use of these therapies? We found that the portrayal of stem cell medicine on provider websites is optimistic and unsubstantiated by peer-reviewed literature.
An Experiment That Blinded Three Women Unearths the Murky World of Stem Cell Clinics
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Want to Enroll in a Clinical Trial? NIH Database Is Huge but Lacks a Few Key Details
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Trend Sees Patients Paying for Their Own Clinical Trials, but Critics Raise Ethical Concerns
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Feds Bust Alleged Scam to Sell Stem Cells to the Dying
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Associate of Egg Harbor City Doctor Sentenced to 33 Months for Scheme to Defraud ALS Patients
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Egg Harbor City Doctor Sentenced to 57 Months for Scheme to Defraud ALS Patients
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