Santander Global Summit in Transplantation: Supporting Global Convergence in the Shared Goals of Sufficiency, Transparency, and Oversight

Abstract

The transplantation of human organs, tissues and cells is a life-saving and live-enhancing procedure for the treatment of conditions that mostly result from noncommunicable diseases (NCDs).1 Organ transplant activities have been steadily increasing during the last decades, an evolution only interrupted by the COVID-19 pandemic.2,3 However, the volume of organ transplants barely covers 5%–10% of the global needs.4,5 For tissues and cells, the current understanding of the world landscape is fragmented and incomplete. This applies not only to those tissues and cells obtained and distributed within individual countries but also to those exchanged internationally. Public health interventions are fundamental to diminish the burden of diseases treatable with transplantation and to reduce progression to end-stage organ failure. However, the demand for the transplantation of human organs, tissues, and cells must also be addressed, and the expansion of transplantation is critical to decreasing premature mortality caused by NCDs. Figure 1 displays 2022 national organ transplant rates in relation to the human development index, which suggest that a transplant program is difficult to implement in countries below a minimum level of development. The figure also reveals marked variations in transplant activities across countries, either when comparing high-income countries or low- and middle-income countries. According to the Global Kidney Health Atlas, an international survey representing 98% of the global population conducted by the International Society of Nephrology, the availability of publicly funded dialysis increased from 2015 to 2019 in most countries, whereas kidney transplantation remained stagnant or even decreased in low- and middle-income countries during the same period.6 Advocacy is needed to ensure that donation and transplantation are included in national and international healthcare agendas, as they may be overlooked because of competing healthcare priorities. Transplantation may also be neglected in healthcare budgets as a result of economic interests that may influence investment in, for example, dialysis.FIGURE 1.: Organ transplant rates pmp in countries reporting data to the Global Observatory in Donation and Transplantation, in relation to the human development index. Year 2022. Countries are classified by regions of the WHO. AFR, African Region; AMR, Region of the Americas; EMR, Eastern Mediterranean Region; EUR, European Region; HDI, Human Development Index; pmp, per million population; SEAR, South-East Region; WHO, World Health Organization; WPR, Western Pacific Region.Several countries have nevertheless made remarkable progress in expanding the donor pool and increasing the availability of organs for clinical use, for example, through the recovery of organs via donation after the circulatory determination of death (DCDD) (Figure 2). DCDD now accounts for 23% of deceased organ donors worldwide.4 However, this type of donation has been implemented in a relatively small number of countries. The development of DCDD programs in other jurisdictions is hindered mainly by legal and ethical concerns, including the lack of a universal standard for the definition of death.7 In addition, advancements in the preservation of DCDD organs to improve posttransplant outcomes and increase organ utilization have led to ethical debates, particularly around the in situ preservation of organs with oxygenated blood by the use of extracorporeal membrane oxygenation with normothermic regional perfusion.8FIGURE 2.: Deceased organ donors pmp in countries reporting data to the Global Observatory in Donation and Transplantation, by donor type. Year 2022. Deceased donation activities reported in 71 of 91 countries reporting data to the Global Observatory in Donation and Transplantation. Globally, 41 792 deceased organ donors were reported (32 248 DBD and 9544 DCD donors). DBD, donors after brain death; DCD, donors after the circulatory determination of death; pmp, per million population.There are also important variations across jurisdictions in terms of living donor organ transplant activities. Some countries rely solely on living donors to address the transplant needs of their population.4 Living donation programs should be run after universally accepted ethical principles and be subject to rigorous oversight to protect donors and prevent the trafficking of persons for organ removal and the illegal trade in human organs. Oversight of transplant practices by health authorities is insufficient in many countries, as indicated by the limited sharing of data with the Global Observatory on Donation and Transplantation.9 Governments must oversee the practice of transplantation, among others, by mandating the collection of data regarding every transplant performed in their jurisdictions. The field of transplantation is impacted by armed conflicts, natural disasters, and humanitarian crises that drive migration, particularly among disadvantaged and vulnerable populations. These realities increase the risk of trafficking in persons for the purpose of organ removal and trafficking in human organs and deepen disparities in access to therapies involving human cells, tissues, and organs.10 The Global Observatory on Donation and Transplantation also keeps documenting the movement of persons across jurisdictions for the purpose of organ transplantation.4 Though some progress has been made in providing guidance for authorities and professionals to deter and combat unethical travel for transplantation and transplant-related crimes,11,12 determined and structured responses are still urgently needed. Innovation is a hallmark of transplant medicine. Over the last years, we have witnessed the increased use of substances of human origin (SoHO) to manufacture novel products, leading to advancements in medical treatments and patient outcomes.13 When SoHO are substantially manipulated in the manufacturing process or are used for specific clinical indications, they have been labeled as (advanced therapy) medicinal products or medical devices in several regions, such as the European Union (EU). However, the unique origin of substances from which these products are manufactured—the human being—underscores the necessity to uphold fundamental ethical principles that protect donors, ensure equity in access to these therapies, and safeguard the sustainability of healthcare systems financing these treatments.14,15 In this context, a Global Summit entitled “Towards Global Convergence in Transplantation: Sufficiency, Transparency and Oversight” was convened by the Organización Nacional de Trasplantes under the 2023 Spanish Presidency of the Council of the EU. The event was co-organized by the European Directorate for the Quality of Medicines and Healthcare of the Council of Europe, the European Society for Organ Transplantation, and The Transplantation Society. The Summit was co-sponsored by the World Health Organization (WHO) and supported by the International Society of Nephrology. AIM OF THE GLOBAL SUMMIT The goals of the Global Summit were to critically review the situation of organ donation and transplantation, as well as that of other SoHO, delve into the aforementioned key issues, and devise the future of transplantation in the global arena. All the organizations involved in the Global Summit have been actively working in the transplantation field over the last decades and were determined to join efforts for a coordinated response to the challenges that transplantation is facing. CONDUCT OF THE GLOBAL SUMMIT Eighty international experts were identified and assigned to one of the thematic working groups selected by the Summit organizers. The themes of each working group were: transplantation as a healthcare priority, challenges in donation and transplantation, innovation in donation and clinical application of SoHO, and ethical challenges. Each group was led by 2 co-chairs. Each working group described and documented preidentified challenges in their respective areas of work, analyzed national and international models or initiatives of success in addressing those challenges, and proposed key priority actions on the part of countries, international organizations and nongovernmental actors. Work was performed online from May 1, 2023, to October 15, 2023, and a draft concept article was delivered by each working group. The Summit took place in Santander (Spain) on November 9–10, 2023. Face-to-face and online participation were provided. The Summit was attended by 183 experts in donation and transplantation from 57 countries, including specialists in the field, representatives from national health authorities, and representatives from the EU, the Council of Europe, the WHO, and nongovernmental state actors. During the Summit, panelists selected by each working group presented the results of their analyses and deliberations during dedicated round tables, where the draft recommendations resulting from their work were refined according to the feedback received from participants. After the Summit, each working group finalized their manuscripts taking into account the perspectives from different regions. High-priority recommendations from each working group also served as a basis for the elaboration of the Santander Statement, which was drafted by two designated rapporteurs, refined by the organizers and working group chairs, and presented at the end of the Summit. The Statement was finalized during the Summit based on the deliberations among participants, who endorsed the final version of the document. RESULTS OF THE GLOBAL SUMMIT The Santander Summit was an opportunity to critically review the current situation of donation and use of SoHO and SoHO-based therapies worldwide, elaborate and describe a set of key challenges that the field is confronting, and shape the future of transplantation by proposing solutions and implementation resources. In this issue of Transplantation, the Santander Statement is presented.16 The Statement provides high-level recommendations aimed at improving patient care, making progress toward sufficiency in transplantation, ensuring transparency and oversight of practices, strengthening the prevention of human trafficking for the removal of SoHO and trafficking in SoHO, and fostering responsible innovation in the clinical use of SoHO. Importantly, on May 29, 2024, the World Health Assembly approved a Resolution on increasing availability, ethical access, and oversight of transplantation of human cells, tissues, and organs.17 The Resolution was drafted on the background provided by the Global Summit and the Santander Statement and was later subject to consultation with Member States and formal adoption during the 77th World Health Assembly. The document urges Member States to take actions that align with the recommendations of the Santander Statement and requests the WHO Secretariat to support Member States, among others, through the development of a Global Strategy in transplantation, expected to be presented in the 2026 World Health Assembly. The present issue of Transplantation also includes the articles elaborated by the 4 working groups involved in the Santander Summit. Muller et al18 discuss how, if transplantation is prioritized in the healthcare agenda, it will contribute to the achievement of several of the United Nations Sustainable Development Goals, especially Goal 3 (good health and well-being), Goal 8 (sustained, inclusive and sustainable economic growth, and employment for all), and Goal 13 (combat climate change and its impact). The authors also describe how the quality and resilience of healthcare systems will improve as a consequence of the development of the infrastructure required for transplantation. Gardiner et al19 acknowledge the need for a universal definition of human death and envision the unified concept of death, based on the permanent cessation of brain functions, as the standard of reference that will help to expand deceased donation in general terms and DCDD in particular. The unified concept of death also reconciles the use of normothermic regional perfusion in DCDD procedures with the previous diagnosis of death.19 Lentine et al20 advocate for the promotion of ethical living donation by improving education and outreach, and by implementing measures to enhance decision-making and donor protection. Spiro et al21 discuss the need to develop registries reporting activity and outcome data for both living donors and recipients, including donor source, as an essential means to ensure ethical, legal, and clinically robust transplant practices with appropriate oversight and adequate resources. Martin et al22–24 author 3 articles in which they delve into the ethical complexities involved in fostering financial neutrality in donation of organs, tissues, and cells, the prevention of trafficking and, finally, the promotion of equity in global access to SoHO-based therapies. Finally, innovation in transplantation is acknowledged as key in ensuring that patients receive the best and most effective healthcare. In this issue, Cuende et al25 propose how to drive the incorporation of scientific advancements into SoHO-based therapies such that these remain equitably and widely accessible, under a framework consistent with the altruistic nature of donation and the human origin of these therapies. In conclusion, the Santander Summit was a crucial turning point in organ donation and transplantation, laying the groundwork and guiding global efforts for the next decade and, thus, contributing to achieving the United Nations Sustainable Development Goals. A number of articles resulted from the work performed before, during and after the Summit, and this special issue of Transplantation encapsulates the wisdom and consensus reached by the participants, which will shape global action and has already started inspiring international policies and practices.

Topics & Concepts