Searching for information about stem cells online in an age of artificial intelligence: How should the stem cell community respond?

Patients and their families routinely use the Internet to learn about stem cell research. What they find, is increasingly influenced by ongoing changes in how information is filtered and presented online. This article reflects on recent developments in generative artificial intelligence and how the stem cell community should respond.

Using Google Analytics with Health Information-Seeking Model to Evaluate the Design of Health Information Websites.

Health information websites can be useful for information seekers, and their design is crucial for the success of accessing the needed information. While web analytical tools (e.g. Google Analytics) used by such websites can provide descriptive measures of users, there is a disconnection between this data and the current understanding of health information-seeking behaviour. In this work, we leverage a theoretical model to interpret the Google Analytics data. Drawn on the visualisation of user behaviours based on this model, our research shows that better website design can be informed, and the evaluation of health websites can be performed on the basis of different user profiles.

How Great a Risk Do You Take? A Qualitative Study Exploring Attitudes of Individuals with Friedreich Ataxia Toward Gene Therapy.

Scientists and pharmaceutical companies are working toward delivering gene therapy (GT) for Friedreich ataxia (FRDA). Understanding the views of people with lived experience of FRDA and their parents toward GT is essential to inform trial design and identify potential barriers to participation in clinical trials. The goals of this study were to identify the attitudes toward GT held by individuals with FRDA and parents of individuals with FRDA, and to explore how these may impact future trials for this condition. Audiorecorded, semistructured, qualitative interviews with 19 Australians explored experiences of FRDA, knowledge about clinical trials, views on GT, including risks and benefits, and potential barriers to participation in trials. Participants included thirteen individuals living with FRDA aged between 15-43 years, and six parents of children with FRDA aged 4-12 years of age. Thematic analysis of the interviews identified six main themes. Findings from this study indicate there is strong desire for information regarding GT in FRDA, however the current level of uncertainty around GT makes decision making challenging. The desire to maintain functional status and avoid additional risk of deterioration from an investigational treatment was apparent. Importantly, neurological targets were identified as preferred for GT trials. Further research is required to identify if attitudes and perceptions differ according to geographical location and disease stage.

International Society for Cell & Gene Therapy Position Paper: Key considerations to support evidence-based cell and gene therapies and oppose marketing of unproven products.

The field of regenerative medicine, including cellular immunotherapies, is on a remarkable growth trajectory. Dozens of cell-, tissue- and gene-based products have received marketing authorization worldwide while hundreds-to-thousands are either in preclinical development or under clinical investigation in phased clinical trials. However, the promise of regenerative therapies has also given rise to a global industry of direct-to-consumer offerings of prematurely commercialized cell and cell-based products with unknown safety and efficacy profiles. Since its inception, the International Society for Cell & Gene Therapy Committee on the Ethics of Cell and Gene Therapy has opposed the premature commercialization of unproven cell- and gene-based interventions and supported the development of evidence-based advanced therapy products. In the present Guide, targeted at International Society for Cell & Gene Therapy members, we analyze this industry, focusing in particular on distinctive features of unproven cell and cell-based products and the use of tokens of scientific legitimacy as persuasive marketing devices. We also provide an overview of reporting mechanisms for patients who believe they have been harmed by administration of unapproved and unproven products and suggest practical strategies to address the direct-to-consumer marketing of such products. Development of this Guide epitomizes our continued support for the ethical and rigorous development of cell and cell-based products with patient safety and therapeutic benefit as guiding principles.

Participatory Design and Evaluation of the "Stem Cells Australia" Website for Delivering Complex Health Knowledge: Mixed Methods Study.

BACKGROUND: The internet has become a commonly used information source for people seeking to understand their health care options. However, inconsistent representation about what stem cell treatments are available and from whom, coupled with the lack of transparency about what has been shown to work or is even safe, can distract and mislead users. Given these challenges, there is a need to develop effective evidence-based tools for delivering information about health care options involving stem cells. OBJECTIVE: A need to redesign an existing website in Australia was identified to provide trustworthy information about stem cell research and to counter misinformation. Using a participatory design approach to generate an understanding of what information users need for stem cell treatments, the Stem Cells Australia website serves as a case study for the development and evaluation of websites delivering complex messages about science and health. METHODS: This study comprised 3 steps. First, a focus group and several one-on-one interviews with a purposive sample of users (n=12) were conducted to identify their needs and requirements. Second, we designed a new version of the website based on findings from the focus group and interviews. Finally, for evaluating the participatory design process, we collected 180 days of Google Analytics data for both the original and redesigned versions (90 days for each) and compared their differences using 2-sample z tests. RESULTS: The feedback from participants was grouped into 3 themes-needed and unwanted information, how and where to obtain information, and their information preferences. These were translated into requirements for rebuilding the website. The redesigned version reached users in other continents, despite the daily numbers of users (-61.2%; P<.001) and sessions (-61.7%; P<.001) decreasing. The redesigned version also showed substantial decrease in daily bounce rate (-97.2%; P<.001), significant increase in the daily average of page reads per session (+110.8%; P<.001), and long daily average for session duration (+22.9%; P=.045). Navigation flow analysis showed more traffic toward web pages related to health conditions in the redesigned version. CONCLUSIONS: Websites about stem cell research need to provide content for vulnerable global audiences. Participatory design that addresses knowledge gaps and information needs can produce better performance and engagement, which can be evaluated using Google Analytics, a common web analytics tool used by many websites. Learnings for improving the metrics regarding website identity, research updates, and clinical trials are concluded, which can inform the future design of websites seeking to engage users and provide reliable and accessible science and health information including but not limited to stem cell research and therapies.

Ethical analysis of the first porcine cardiac xenotransplantation.

In this article, we provide an ethical analysis of the first porcine cardiac xenotransplant, performed in Maryland, USA in early 2022. David Bennett was offered the experimental procedure after he was deemed ineligible for human heart transplantation and mechanical circulatory support, based on a history of non-compliance. It was reported that Mr Bennett's previous instances of non-compliance were for medically non-life-threatening conditions years earlier, where the risks of non-compliance were not as high. We argue that, in Mr Bennett's case, a history of non-compliance in a different context, should not necessarily rule him ineligible for a potentially life-saving treatment now. Furthermore, using previous non-compliance to exclude individuals from donor organs may have the unintended effect of placing the burden of testing xenotransplantation on those who are already disadvantaged. We then argue that it is not enough to rely on patient consent to ethically justify xenotransplantation research. Taking a broad ethical perspective is crucial when mapping a clinical pathway for xenotransplantation.

Critical considerations for public engagement in stem cell-related research.

Public engagement is increasingly recognized as being integral to basic and translational research. Public engagement involves effective communication about research along with the mutual exchange of views and opinions among a wide variety of members in society. As such, public engagement can help to identify issues that must be addressed in order for research to be ethically sound and trustworthy. It is especially critical in research that potentially raises ethical concerns, for example research involving embryos, germline genome editing, stigmatized conditions, and marginalized communities. Therefore, it is not surprising that there have been prominent recent calls for public engagement in the emerging sciences. However, given that there is arguably little agreement about how this should be done and the best ways of doing so, those involved with planning and implementing public engagement can benefit from understanding a broad range of prior experiences on related issues.

Knowledge, views and experiences of Australian optometrists in relation to ocular stem cell therapies.

CLINICAL RELEVANCE: Findings from this study examining Australian optometrists' insights into ocular stem cell (SC) therapies have capacity to inform continuing professional development (CPD) about these interventions. BACKGROUND: This study investigated Australian optometrists' knowledge, views, experiences, and preferred education sources regarding ocular SC therapies. METHODS: An online survey was distributed to optometrists via Optometry Australia, Mivision magazine, professional groups, and social media from August 2020 to March 2021. Data were collected on demographics, and SC knowledge, awareness and experience. RESULTS: Of 81 optometrists who completed the survey, many were metropolitan-based (85%), worked in independent practice (47%), female (56%) and >46 years of age (45%). Approximately one-fifth indicated awareness of ocular SC therapies used in standard practice; one-third had knowledge of SC clinical trials. The most noted SC therapies were for corneal disease in the United States [US] (72%) and Australia (44%). Respondents identified the availability of SC therapies for dry eye disease in Australia and the US (39% and 44% respectively), despite no regulatory-approved treatments for this indication. Clinical trials investigating inherited retinal and corneal diseases in Australia were the most commonly identified (44% and 36%, respectively). Half the respondents felt 'unsure' about the quality of evidence for treating eye conditions using SCs. One-fifth indicated concerns with these therapies; of these, most mentioned efficacy (82%), safety (76%) and/or cost (71%). About one-fifth reported being asked for advice about SCs by patients. Two-thirds felt neutral, uncomfortable, or very uncomfortable providing this advice, due to lack of knowledge or the topic being beyond their expertise. Over half (57%) were unsure if clinical management should change if patients received SC therapies. Respondents were receptive to face-to-face education. CONCLUSION: Some optometrists responding to this survey were aware of ocular SC therapies and/or clinical trials. CPD programs may assist with maintaining currency in this evolving field.

Developing a Reflexive, Anticipatory, and Deliberative Approach to Unanticipated Discoveries: Ethical Lessons from iBlastoids.

In this paper, we explore the recent creation of "iBlastoids," which are 3-D structures that resemble early human embryos prior to implantation which formed via self-organization of reprogrammed adult skin cells. We explore some of the ethical, philosophical, social, and regulatory issues related to this research, with focus particularly on what it means to "anticipate" research outcomes when using novel methods or when serendipitous discoveries are made. We defend the need for reflexive, anticipatory, and deliberative ethical and conceptual work by researchers working in emerging and contentious research domains, in collaboration with interdisciplinary scholars, as well as regulators, funders, and publics.

Ethical issues and public communication in the development of cell-based treatments for COVID-19: Lessons from the pandemic.

The significant morbidity and mortality of coronavirus disease 19 (COVID-19) prompted a global race to develop new therapies. These include interventions using cell- or cell-derived products, several of which are being tested in well-designed, properly controlled clinical trials. Yet, the search for cell-based COVID-19 treatments has also been fraught with hyperbolic claims; flouting of crucial regulatory, scientific, and ethical norms; and distorted communication of research findings. In this paper, we critically examine ethical issues and public communication challenges related to the development of cell-based therapeutics for COVID-19. Drawing on the lessons learned from this ongoing process, we argue against the rushed development of cell-based interventions. We conclude by outlining ways to improve the ethical conduct of cell-based clinical investigations and public communication of therapeutic claims.

Academic Physician Specialists' Approaches to Counseling Patients Interested in Unproven Stem Cell and Regenerative Therapies-A Qualitative Analysis.

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.

Regulating autologous stem cell interventions in Australia: updated review of the direct-to-consumer advertising restrictions.

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. Results The 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.

ISSCR Guidelines for Stem Cell Research and Clinical Translation: The 2021 update.

The International Society for Stem Cell Research has updated its Guidelines for Stem Cell Research and Clinical Translation in order to address advances in stem cell science and other relevant fields, together with the associated ethical, social, and policy issues that have arisen since the last update in 2016. While growing to encompass the evolving science, clinical applications of stem cells, and the increasingly complex implications of stem cell research for society, the basic principles underlying the Guidelines remain unchanged, and they will continue to serve as the standard for the field and as a resource for scientists, regulators, funders, physicians, and members of the public, including patients. A summary of the key updates and issues is presented here.

Academic physician specialists' views toward the unproven stem cell intervention industry: areas of common ground and divergence.

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.

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

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