The following electronic databases that host peer-reviewed multidisciplinary research articles were chosen as the sources: •

Google Scholar (http://scholar.google.com/).

NFTs are a new technology with the potential to revolutionize healthcare. However, research on NFTs in healthcare is still in its early stages. Figure 2 shows the distribution of papers by year of publication. As indicated in the figure, there has been a significant increase in research in 2022 and 2023. In 2021, two papers focused on patient-centric data management were published (21, 24). There are still few publications on applications of NFTs in healthcare compared to publications focusing on implementing blockchain in healthcare—a core technology underlying NFTs (39). The countries of the host institutions of the researchers were used to show the geographic distribution of the research. Most of the research on NFTs has been conducted in Asia, with 15 of the 19 articles published in this area coming from Asian institutions.

All the NFT-backed blockchain solutions portrayed in the selected papers can be applied to suit any context, thus allowing for solutions developed in high-income contexts to be adopted in low-income ones. However, there is a lack of research on NFTs in healthcare in developing countries due to the emergent nature of this technology. These countries often prioritize addressing more pressing social and economic issues (17). Like blockchain, NFTs offer vast opportunities to solve complex social and economic problems, such as empowering and providing patient-centred healthcare (8, 19). NFTs can also be used to provide traceability in the drug supply chain to counter counterfeit drugs (40). Despite the early adoption of NFTs in other subdomains, such as art, collectables, and gaming, the healthcare sector still lags behind. More research on applying NFTs in healthcare needs to be conducted in developing countries to identify use cases.

The specific channels of publication are shown in Table 3. This information may help researchers identify journals and conferences to publish in or search for new research on NFTs in healthcare (19).

This section reports on the types of papers selected and their methodological approach. In terms of the latter, and as shown in Figure 3, most (15) articles used a design science approach to designing and testing artefacts. The remaining four articles used a quantitative method with an experimental and descriptive focus. With NFTs being a new technology, designing qualitative research studies well-grounded in theory to generate meaningful insights is a challenge; hence, qualitative research was not used in the selected papers.

Figure 4 illustrates the distribution of papers by publication type. Ten papers developed concepts (models and frameworks), while nine concerned the development of fully-fledged prototypes. It is evident that the developed prototypes have yet to be implemented in real-world systems. The lack of implemented prototypes could be due to the development of NFTs in healthcare being in its infancy. The same challenges and obstacles faced in implementing blockchain technology (17) may also affect the implementation of NFTs. There is, therefore, a gap in the literature on identifying the challenges and obstacles preventing the implementation of NFTs in real-world healthcare systems.

In terms of the scope of application of NFTs in healthcare, Figure 5 illustrates that 14 papers addressed the use of NFTs from a patient-centric data management perspective (19–23, 26, 28–30, 32, 33, 35–37). Four papers discussed using NFTs to track the provenance of healthcare products and services in a supply chain (26, 28, 32, 35). The aim of doing so was to ensure the authenticity and quality of the products through the supply chain. Three of the four papers represented the object being traced as a virtual product (digital twin) (25, 26, 32). The emergence of NFTs presents a unique opportunity to enhance transparency, traceability, security and streamlining of operations. However, further research and development are needed to develop clear and comprehensive regulations to facilitate the broader adoption of NFTs in healthcare. Furthermore, standardized data-sharing protocols and interoperability must be developed across different platforms.

One of the most popular use cases of NFTs in healthcare is the management of medical records, such as electronic medical records (EMRs), which often contain sensitive information about patients undergoing treatment or post-treatment management. EMRs are frequently shared among stakeholders, from primary stakeholders such as health practitioners, pharmacists, and patients to secondary stakeholders, such as researchers and medical aid companies (41). The purpose of an EMR [also called an electronic health record (EHR)] system is to create, maintain, manage, and store client data while allowing access to only authorized users. Most of the papers (74%) in this systematic review focused on using NFTs to encapsulate EMRs to make patient-centric data management more effortless. This is consistent with other research (19) which focused on blockchain technology in healthcare. In this study, 48% of the 65 papers selected for review identified EMR use cases as the primary research topic in the literature. This consistency is not surprising since NFTs are built on blockchain technology. Due to their uniqueness, verifiability, and transferability, NFTs provide proof of data ownership.

Tokens are non-fungible and distinguishable, thus representing a tamper-proof and non-repudiable proof of data ownership (22)⁠. Patients can grant temporary ownership of their medical records to third parties and assign specific rights and access time to their NFTs (20). The unique nature of NFTs allows data traceability, whereby patients can view and track their records (23, 30, 34). The medicine supply chain stakeholders should provide a means to track and trace pharmaceutical supplies that pass along the supply chain (42). NFTs represent a perfect digital twin of any physical item that passes along a supply chain and provides for traceability processes (25, 26). An entity in the supply chain, the token owner, can invoke a smart contract through their private key to pass the token to the following entity in the supply chain. The next actor (entity) will be able to check the status of the NFT and verify the ownership of the previous entity. Counterfeit actors are identified if a deviation between the “real world” and what is on the digital ledger occurs (35)⁠. Lastly, regarding consent management, NFTs can represent patient consent. This can be done by recording and transmitting patient consent as NFTs (33). Using NFTs allows consent to access data to be verified for legitimacy without needing a third party. In this approach, patients can record their consent, allowing data consumers who may be researchers, insurance companies or other parties interested in health data to request data from data providers. Data providers are custodians of patient data, meaning they are responsible for storing and protecting it. Patients or data providers can revoke consent at any time.

Distributed ledger technology provides a data-sharing platform between providers and consumers (43). Data democratization refers to making data available to third parties that might require it. In this approach, NFTs enable patients or data providers to claim ownership of their records, which they can then share with other interested parties. Thus, NFTs empower patients to control their data and choose with whom they want to share the data. Access to patients' stored records can be through mobile applications (29). Data providers can view their medical information and track who can access it through NFTs. NFTs allow the dual ownership of patient data between the patient and the hospital, thus creating an avenue for the patient to derive value through monetizing their data. Several approaches have been proposed for using NFTs to incentivize healthcare data sharing. In one approach, data owners (patients and other stakeholders) can sell NFTs representing their healthcare data to third parties (37, 38). The price of the NFT can be determined based on the sensitivity of the data and the costs incurred in creating the NFT (44). In another approach, the patient is incentivized to maintain and share their records using several factors, such as data quality and relevance or willingness to share the data (24). The incentive can be tokens such as the ERC20 (37, 38). ERC20 tokens provide a platform for patients to be incentivized to share their data for research and development in a transparent, accountable, and secure way because the underlying blockchain technology offers transparency and accountability and fosters trust among stakeholders. However, it should be noted that blockchain, the underlying technology, suffers from scalability limitations, which may challenge large-scale data management in healthcare data.

NFT-based health information systems can be implemented as an alternative to ensure data security, privacy, and immutability (36). Because NFT schemes are based on blockchain technology, they adopt the intrinsic properties of blockchain, such as immutability, which improves the security of health data since it cannot be easily corrupted, altered or accessed by a third party (32). All the health data on the blockchain is encrypted, time-stamped and appended in chronological order, and because the data is saved on a blockchain using cryptographic keys, it protects the patient's identity or privacy (27). Additionally, the blockchain platform's distributed nature improves NFT systems' availability. In the event of an attack, data can be gathered from other nodes where the data would have been replicated (19).

Data can be stored on-chain if it is stored directly on the blockchain or off-chain if not. On-chain storage, however, leads to higher storage costs and scalability issues (28). Most NFT-based implementations store large volumes of data such as lab reports, x-rays, and other medical records off-chain on a decentralized platform such as the Interplanetary File System (IPFS), and referenced in the blockchain using a hash value to improve security and efficiency (21). In addition to enabling compact NFTs to be developed, storing data off-chain also enables quick access to data (20).

The most common use case for NFTs in healthcare is patient-centric data management, with 73% of the published papers focusing on this topic. Other use cases include digital twins and supply chain management. However, the number of identified use cases is still relatively small compared to those for blockchain in healthcare. In a previous systematic review of blockchain in healthcare, five use cases were identified: data sharing, health records, access control, audit, and supply chain (9). Similarly, six different use cases, namely, EMR, pharmaceutical supply chain, biomedical research and education, remote patient monitoring, health insurance claims, and health data analytics, were identified in another systematic review (19). The fact that relatively few use cases for NFTs in healthcare have been identified indicates that this is still an emerging area of research and development. However, the potential benefits of NFTs in healthcare are significant, especially in biomedical research, where NFTs can be used to manage genomic data and provide integrity and transparency in clinical trials.

The challenges NFTs face are due to them being coupled with blockchain platforms, leading to scalability issues (23, 37). As the number of transactions increases, latency becomes an issue, with few transactions processed per second due to network congestion (20, 25, 28). An increase in the number of transactions leads to a growth in Ethereum gas prices (28). NFT interoperability also poses a limitation to implementing data exchange between disparate systems. Most healthcare systems have different platforms that might need to interoperate (21).

Furthermore, the healthcare industry has heavily invested in infrastructure, and integrating blockchain and NFT-based systems with legacy systems poses challenges (28). A further limitation is the high cost of minting, trading, and pricing NFTs, which may impact their wide acceptance (25, 34). Poorly designed and implemented smart contracts pose a security risk in NFT-based systems. Malicious users can use bugs in smart contracts to execute unauthorized operations (32). Additionally, there is currently no standard way for coding a smart contract save for the ERC-721 standard for writing NFTs (28). Smart contract vulnerabilities and security risks thus remain the main challenges for NFT-based systems.

Using NFTs in healthcare also invokes many challenges in distributing and managing encryption keys (32). Key management places an overhead on the systems' operations and costs (21). The healthcare sector is highly regulated with centralized control to protect various stakeholders, especially patients. The issues of ethics and legality of granting and revoking patient consent outside a central authority are challenging ones (51). An additional challenge is engaging patients to share and manage their data. NFTs and blockchain are relatively new technologies; thus, they may lack experts (28), impacting their scalability.

NFTs allow patients to take ownership and have more control over their data and how it can be utilized (38). Minting health data into NFTs will enable owners to track and decide with whom to share and sell their data. Organizations will also benefit from utilizing NFTs to incentivize patients to share their data for research. Other parties can also benefit from using health digital markets to access patient data directly (23). With all these identified benefits, further inquiry is needed to determine if patients would be willing to share their data with third parties, what data they would be willing to share, and the price and cost of minting.

On the other hand, organizations might not be willing to “share” the profits of ownership of health information. Therefore, there is a need to develop dual ownership models. Moreover, price determination of the data might also be a challenge. Hence, further research will be needed to develop pricing strategies for data owners and consumers. Another open issue that must be addressed is the cost of minting, trading, and pricing NFTs. With the development of the ERC-1,155 token standard (52), there is scope for decongesting the network and lowering the gas cost. For NFTs to be widely accepted in healthcare, there is a need for further development of platforms that offer lower costs for minting NFTs.

Data is typically stored on-chain or off-chain. Storing large volumes of data on-chain is costly but more secure than off-chain storage (22). ⁠There is a need to research how to store data more efficiently either on-chain or off-chain with improved security. The challenges of scalability, security, and privacy of NFT-based applications are open issues which warrant further research.

Ownership of personal health data is a sensitive issue that needs further scrutiny. In the European Union (EU), legislation specifically regulates the ownership right of data. Thus, in the EU, secure access to data can be guaranteed but data cannot be owned (24). Like cryptocurrencies, NFTs also face the same barriers of strict management and the need for regulation from authorities (4). Further research is, therefore, needed on how to properly regulate the use of technology in healthcare while providing some form of autonomy when it comes to digital health data exchanges. The selected papers did provide various solutions, such as models, architectures, and prototypes, but these lacked implementation in practical settings. There is, thus, scope for further research to identify the challenges and obstacles limiting the implementation of prototypes in an actual medical setting.

Further, adoption frameworks for implementing the systems can also be explored. There is a need for an open standard to guarantee and speed up the interoperability of different NFT ecosystems. NFTs in healthcare are in their infancy, and the focus is on their feasibility. However, for NFTs to be fully adopted and deployed in practical healthcare environments, open standards for interoperability need to be defined. Ethical issues such as the right to be forgotten are all open research issues that need to be addressed to further the adoption of NFTs in healthcare.

Systematic reviews on the use of NFTs in healthcare are limited. Existing reviews (9, 19) have primarily focused on the blockchain, the underlying technology of the NFTs. Other research papers have explored the technical aspects and potential applications of NFTs in healthcare, but NFTs are still in the early stages of adoption in this field. In contrast, NFTs are widely used in other areas, such as art, collectables, and gaming (2). Therefore, a comprehensive systematic literature review on NFTs in healthcare was needed to identify use cases, design models, and challenges, and to set an agenda for future research.

This study identified new areas of inquiry on the application of NFTs in healthcare and further explores new research questions. The study revealed that the primary use cases of NFTs in healthcare are patient-centric data management, supply chain management, and digital twin development. However, all the NFT-backed blockchain solutions identified in the review were developed in high-income countries, even though these solutions could be adapted to any context. There is a lack of research on NFTs in healthcare in developing countries, such as sub-Saharan Africa, which is missing out on opportunities to empower patients through NFT ownership of their medical records, improve supply chain provenance and integrity, and experiment with digital twins to improve healthcare systems.

Design science research methodology was used to design and test artefacts in most of the studies reviewed. However, many developed solutions were prototypes or conceptual frameworks without real-world implementation or evaluation. Therefore, to ensure more comprehensive acceptance of NFTs in healthcare, there is a need for real-world implementation and evaluation of such systems.

The Ethereum blockchain platform, along with some of its derivatives like Quorum, is the most widely used platform for minting NFTs, as Ethereum pioneered smart contracts. However, new platforms that offer lower transaction costs and higher performance, such as Solana, Flow, and Tezos, are now being explored.

Research on NFTs in healthcare is centred on four areas: data governance, monetization, protection, and storage. The focus is on developing solutions that empower patients to control their medical records while keeping them private and secure. Data monetization is also being explored to allow patient data to be minted as NFTs and made commercially available. Additionally, storage options are being explored to enable the development of compact NFTs that allow quick data access.

This study's findings could help to understand NFT adoption in healthcare. While three use cases of NFTs in healthcare were identified, more research is needed in other areas, such as genomic data management and clinical trial management. It is also worth noting that 79% of the papers studied used Ethereum to mint NFTs. Other platforms offering lower transaction costs and improved performance should be explored. As mentioned in Section 8 of this paper, other areas of investigation include stakeholder perceptions on the commercialization of healthcare data and governance considerations for NFTs in healthcare. Different data storage models appropriate for NFT implementation in healthcare could also be explored.

The findings of this study could be used to educate healthcare practitioners, decision-makers, patients, and all stakeholders on the potential benefits and challenges of using NFTs in healthcare. Additionally, the findings could be used to develop new products and services that use NFTs to improve health outcomes, such as secure, auditable, and patient-controlled access to healthcare information and improved drug supply chains.

There is a lack of research on adopting NFTs, data storage models and infrastructure, and governance issues in healthcare. Given the considerable advantages of NFTs in healthcare, it can be argued that all stakeholders, particularly policymakers, need to develop strategies to promote the adoption of NFTs in healthcare.