The ethics and economics of organoid commercialization: potential donors’ perspectives | BMC Medical Ethics

The goal of this study was to identify and assess underlying reasons for potential donors’ reservations regarding commercial involvement in organoid research. To our knowledge, this was the first qualitative focus group study that specifically focused on the perspectives of potential donors regarding the commercialization of organoids. Commercial involvement included collaboration between academic and commercial parties or independent research by commercial parties. In the focus groups, we discussed only commercial involvement, therefore all findings refer exclusively to that context.

We hypothesized that differences in organoids would lead to variations in respondents’ answers due to differences in ethical sensitivity. However, our data did not show any substantial differences other than the strong urgency expressed by people with neurodegenerative diseases to speed up drug development and a lenience to accept commercialization as long as its related to gaining access to effective drugs. These findings must be viewed within the context of our study design, which included a specific set of participants and specific organoid models. Differences in perspectives may emerge when including different participant groups, with diverse cultural, medical, and/or socio-economic backgrounds, and when presenting them with different organoid models.

We identified four themes: While respondents recognized the benefits of commercial involvement, they also expressed concerns (theme 1). Many highlighted a lack of trust in the parties involved (theme 2) and emphasized the need for control over the use of organoids derived from donated biospecimens by commercial parties (theme 3). Additionally, respondents frequently voiced the desire for more appreciation as donors (theme 4). The themes identified in our study are applicable to broader contexts of commercialization involving human biospecimens, indicating that our findings are valuable beyond the specific context of organoids.

In what follows, we reflect on our results from which we derive recommendations for practice. We connect findings to broader literature and highlight underexplored topics. We particularly focus on what researchers and commercial parties can do as this is within the scope of our study.

Reflection and recommendations for practice

To address the themes that were identified, we reflect on implications of our findings after which we propose several recommendations to help mitigate these issues.

Transparent and effective communication

In this study, we observed a lack of participants’ understanding of commercialization and who is involved in the process [23]. Some participants in our study were unaware that they had previously consented to commercialization purposes in biospecimen donation for organoid research. This confusion may stem from the vague or insufficient definitions of commercialization and commercial access in informed consent documents, which is also seen in the broader literature on biobanking documents [23]. In addition, many respondents expressed a certain fear about the commercialization of organoids, which may partly arise from lack of communication resulting in misconceptions on what is technically and/or legally possible with organoids, for example organ trade and selling personal data to insurance companies.

Recommendations

Based on this study’s findings, we can conclude that transparent and effective communication by researchers and commercial parties is crucial to help donors understand what commercialization is and to increase their willingness to donate. Therefore, we recommend that donors should receive clear information about where the organoids derived from their biospecimens are used for, where they are stored, who has access to them and what the roles and responsibilities of parties involved in the commercialization process are.

Additionally, transparent and effective communication can help to address potential donors’ concerns about commercialization. Therefore, it is important that researchers and commercial parties explain what is technically and legally possible, both now and in the future. Although it is impossible to predict future developments, researchers and commercial parties should provide follow-up communication after donation if new applications arise. Furthermore, to understand the origin of donors’ concerns with commercialization, social scientists should investigate how these concerns emerge from historical, contextual and social circumstances (including negative experiences with the healthcare system) [24].

To meet the need for transparent and effective communication of participants, researchers and commercial parties should invest in consent models that move toward dynamic consent. Dynamic consent refers to personalized, digital platforms that support both the consent process and ongoing communication between researchers and participants [25]. These platforms can accommodate various types of consent depending on the research context and objectives, and they can facilitate continuous engagement between researchers and potential donors [25].

Donor engagement and appreciation

Our study highlights the importance of ensuring that donors feel appreciated for their (voluntary) contributions. Our study shows that financial rewards are not seen as a primary motivation to donate biospecimens for organoid development by potential donors. Instead, efforts made by researchers to involve donors via patient participation and research updates were seen as ways to appreciate the voluntary donation of donors. However, when researchers and/or commercial parties are expected to generate profit from organoids derived from donated biospecimens, benefit-sharing becomes more important. In these instances, donors feel that the exchange is to be more transactional. This is particularly true when the organoid is not acquired by a research party directly, but instead by an intermediate party, such as a commercial biobank, where the organoid itself is sold for profit. In line with existing literature, patients increasingly appreciate compensation when their biospecimens are used for for-profit research [26]. However, a lack of clarity on the level of financial compensation remains, as respondents had difficulty specifying what they considered fair or appropriate.

Recommendations

To sustain willingness to donate in future organoid research, researchers and commercial parties should recognize donors as integral partners in the research process and demonstrate respect for their contributions. Meaningful donor engagement, such as regular research updates, personalized thank-you notes and tangible examples of scientific advancements enabled by their contributions, serves as a way to appreciate their role. This aligns with broader literature, which describes that research dissemination and participant recognition fulfill the social contract between researchers and participants, ultimately validating their participation and encouraging continued participation in future research [27, 28]. Additionally, active patient participation, in which donors are invited to provide input, helps transform the role of the donor from a passive study subject to an active (patient) partner, which gives donors a shared sense of purpose and makes them feel valued. This shift fits within a larger movement in medical research, where the role of patient participation is increasingly seen as collaborative rather than simply contributory [29, 30].

Oversight and legislation

Control was deemed important by potential donors when discussing the commercialization of organoids. Concerns about misuse by commercial parties were present at a national level and even more profound in the context of international collaboration. Our study indicates that potential donors value clear oversight of organoid use by commercial parties. In addition, they seek assurance that ethical standards and values of their country apply to the use of their donated biospecimens for organoid development. Many participants thought responsibility for this oversight could be appointed to ethical committees within universities. However, some participants in our study suggested that an independent party is necessary because ethical committees are still linked to the university and therefore might be biased.

Recommendations

To address concerns of potential donors, we advise researchers and commercial parties to work towards establishing regulations and mechanisms that enforce robust and transparent oversight. This requires two considerations.

First, independent parties must be appointed to ensure that oversight mechanisms are implemented by neutral organizations, minimizing the risk of conflicts of interest with both commercial and academic stakeholders. Similar to ethical committees, these independent parties should evaluate and approve the ethical integrity of research proposals involving organoids while maintaining oversight and influence over the use of donated biospecimens intended for organoid development, both now and in the future. Establishing these mechanisms at a national level helps building trust that donations are used ethically and responsibly. However, as organoid research often requires international collaboration, stressing the need for international standards. Such standards ensure consistency and transparency on how organoids are used across countries and provide assurance that the same standards apply. In addition, when international oversight differs from national standards, these limitations and challenges should be clearly communicated to the donor.

Second, researchers and commercial parties should align their practices with emerging legislation, such as the European Regulation on Substances of Human Origin (expected to come into force in 2027), which may provide additional ethical guidance on the commercialization of organoids. Meanwhile, organoid research and development continues to advance rapidly, raising questions about whether new legislation can keep pace with this progress. At the same time, legislation leaves room for interpretation. While the principle of non-commercialization of Substances of Human Origin (SoHo) is a core legal foundation of the Council of Europe, certain loopholes exist [31]. The sale of organs, tissues and blood is prohibited, yet technical services performed on these materials, such as within organoid research, may result in reasonable and proportional profit [31]. This creates a gray area, as making organoids involves processing SoHO, which can later be commercialized for profit [31]. Furthermore, the concept of ‘reasonable donor compensation’ remains undefined in both medical and research contexts, leaving it open to interpretation [31]. As a result, this loophole can be exploited to turn donations into disproportionate profits [31]. Therefore, researchers and commercial parties should seek a transparent pricing model that allows proportionate profit for commercial parties [31]. As such, further research is needed to explore what reasonable donor compensation entails and how these legislations can be effectively implemented in organoid research and treatment development with commercial parties, reducing uncertainties and increasing transparency for potential donors.

Reasonable trust and trustworthiness

Our study showed that (re)establishing trust is an important prerequisite for the responsible commercialization of organoid research. Within the CF focus group, issues were raised with Vertex’s Elexacaftor/Tezacaftor/Ivacaftor drug™, which has drastically improved life expectancy and lung function for people with CF but is also one of the most expensive drugs on the market [32, 33]. Therefore, global access remains limited, particularly for low-and middle-income countries [32, 34]. These high prices, which are considered unjustifiable by some experts, have resulted in significant damage to trust in pharmaceutical companies within the CF community [32, 33]. Lack of trust among potential participants towards commercial parties in research has been outlined in the international literature about biobanks and is not unique to organoids. For example, a review examining public perspectives on biobanking found that respondents from different countries, including those in North America, Africa, and Asia, consistently expressed greater trust in academic researchers compared to those funded by private-sector organizations, pharmaceutical companies or insurance providers [35].

Recommendations

(re)Establishing trust necessitates extra efforts by researchers and specifically by commercial parties. First, researchers and commercial parties should require a good understanding of what it means to be worthy of trust within a particular cultural context [36]. This includes remaining attentive to the social, political and cultural climate within which organoid research operates, and engagement with these communities could be a way to realize this [36]. Second, researchers and commercial parties should maintain trust by acting in a trustworthy manner [36]. This means for instance to transparently and comprehensively describe challenging aspects of commercialization of organoids instead of deliberately using vague language to describe commercialization in informed consent letters. Third, researchers and commercial parties must recognize that some groups have reasonable distrust due to historical exploitation in research (e.g. the case of Henrietta Lacks) or past experiences with pharmaceutical companies that set high drug prices (e.g. Vertex), making treatments unaffordable and accessible only to a select group. Re-establishing trust with groups that have been priorly harmed will demand extra efforts and safeguards, including sensitivity to past harm and community engagement [32, 33].

Limitations

The results of this study should be interpreted within the context of several limitations. First, the majority of respondents, particularly those within the CF groups, demonstrated a strong connection to and interest in research. Many had previously donated to organoid research or were already familiar with it. This prior engagement may have introduced selection bias. It could have shaped their perspectives, potentially making them more positive or negative about organoid commercialization compared to less-informed groups. Second, the focus groups included participants who were predominantly born, raised and living in The Netherlands, reflecting mainly a Dutch perspective on the commercialization of organoids. Conducting similar studies in different global regions may yield different views and opinions on the commercialization of organoids. Third, we used vignettes to guide the focus groups. While this provided structure and clarity on the topic, it may have influenced the spontaneity of respondent’s answers and potentially steered their responses in a particular direction. To minimize this potential bias, the vignettes were reviewed by a master’s student in a pilot interview. Fourth, group dynamics in focus groups may have influenced individuals’ responses, as participants might conform to dominant opinions or participants with strong viewpoints. To minimize this effect, moderators aimed to actively engage less outspoken participants to encourage diverse perspectives. Fifth, the study is influenced by the positionality of the researchers. Different researchers might have focused on different aspects of the respondent’s answers and categorized the codes and themes differently. To mitigate this, the role of the moderator in the focus group was alternated and transcripts were coded individually by two authors with diverse backgrounds (a bioethicist and a health economist). Sixth, the sample size per focus group was rather small (n = 4–6), with a total sample size of n = 19. Qualitative studies aim for analytical generalizability and information saturation rather than statistical generalizability. In this study, key themes were consistently raised across multiple focus groups, and no new themes emerged in the last group. As such, the analysis of this study showed abstract insights concerning the ethical and economic dimensions of organoid commercialization, making the findings potentially applicable to similar contexts when examining the procedures, methodologies and analysis strategies [37]. Additionally, the analytic generalizability was strengthened by analyzing the focus groups with multiple team members and by triangulating the results with existing literature.