Applications of blockchain in the medical field: A narrative review

Background: As a distributed technology, blockchain has attracted increasing attention from stakeholders in the medical industry. Although previous studies have analyzed blockchain applications from the perspective of technology, business or patient care, few studies have focused on actual use-case scenarios of blockchain in healthcare. In particular, the outbreak of pandemics such as COVID-19 also brings about new ideas for the application of blockchain in medical practice. More importantly, with the development of a new generation of information technology, the emerging integration of blockchain with other high-tech technologies also provides the potential for the large-scale application of blockchain technology. Objective: This paper aims to provide a systematic review of the current and projected uses of blockchain technology in a healthcare system and to identify the corresponding utilization challenges and limitations to provide a direction for future research. In addition to the framework structure of blockchain and application scenarios, its integration with other emerging technologies in healthcare is also discussed. Methods: We searched databases such as PubMed, EMBASE, Scopus, IEEE, and Springer using a combination of terms related to blockchain and healthcare. Potentially relevant papers were then compared to determine their relevance and reviewed independently for either inclusion or exclusion. Through a literature review, we summarized some medical scenarios using blockchain technology. Results: We found 1,535 relevant studies, 60 unique studies of which were included in this review. These studies report a variety of uses for blockchain. We divide the medical application scenarios of blockchain into four major categories: personalized health data storage and authorization, management and education, medical research, and health monitoring and tracking. Moreover, four challenges, confidentiality issues, efficiency issues, security issues, and regulatory policy issues, are summarized. Conclusions


Table of Contents
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Background
With the development of medical informatization, the amount of available healthcare data is increasing extremely fast. The sharing and use of medical information have played an important role in the optimization of medical resource allocation, clinical decision-making assistance, medical quality monitoring, precision medicine, and disease risk assessment and prediction [1][2][3]. However, data security and privacy concerns, data dictatorship, insufficient autonomy of the subject, increased social unfairness and other risks have occurred. Moreover, the sudden development of the COVID-19 pandemic event has also posed new challenges for personal health data sharing and mining. As another world-changing technology based on cloud computing, the Internet of Things (IoT) and artificial intelligence (AI), blockchain may provide a solution to the abovementioned problems due to its unique characteristics, such as decentralization, autonomy, credibility and transparency [4,5].
Therefore, it is necessary to explore the impact of blockchain on the medical industry to further clarify the potential value of the medical application of blockchain technology in the context of medical informatization.

Objectives
Although previous studies have analysed blockchain applications from the perspective of technology, business or patient care, few studies have focused on its actual use-case scenarios in healthcare. In particular, the outbreak of COVID-19 brought about some ideas for the application of blockchain in medical practice. Therefore, this paper aims to provide a systematic review of the use of blockchain technology in healthcare. In addition to summarizing the basic principles and framework, this study highlights the different characteristics based on blockchain and concludes the application of blockchain in clinical practice. Furthermore, integration with other technologies is also discussed, which provides a reference for future research. To do this, we first describe the framework and perform specific technical analysis from a theoretical standpoint. Then, we conclude the application in medical scenarios and sort them into three parts according to the characteristics of blockchain from a practical point of view. Furthermore, we summarize use cases of blockchain in fighting against the COVID-19 pandemic, including the prevention of infectious diseases, location sharing and contact tracing, and the supply chain of injectable medicines. Finally, we explore the integration of blockchain with new technology and point out some of their challenges. By depicting a blueprint of interconnected ecosystems in healthcare, we aim to provide some reflections for engineers and decision-makers in the medical industry.

Design
A systematic review design with narrative methods was used to analyse the existing evidence.
More precisely, a review methodology was conducted to form a conception of the application of blockchain technology in healthcare.

Search strategy
We conducted a comprehensive literature search on May 10, 2021. The following electronic databases were searched with the assistance of an information specialist at a medical library: PubMed, EMBASE, Scopus, IEEE and Springer. The review was limited to texts published in English between 2016 and 2021, for which abstracts were available. These publication years were chosen due to a dramatic improvement in information technology during this period. The review was also limited to studies of blockchain technology in the healthcare domain. The initial search terms we used were as follows: (blockchain) OR (distributed ledger technology) OR (smart contract) AND (healthcare). After reviewing the literature identified through these search terms, we added the search terms "health data", "clinical", "biomedical research", "supply chain", "drug safety" and "health monitoring" to capture the relevant studies found in the references of the articles retrieved during the initial search.

2.3.Inclusion/Exclusion Criteria
A total of 1,647 search results were screened using their title or abstracts for relevance, and 60 articles were fully reviewed and discussed in this study. Our inclusion criteria were as follows: 1) application studies that demonstrated the effectiveness of blockchain technology, including data preservation and sharing, medical insurance and supply chain, clinical and biomedical research, drug safety, medical education, electronic prescription anti-counterfeiting, wearable devices, and epidemic prevention; 2) English language studies published in scientific journals; 3) studies of which full text was available; and 4) completed studies. This study did not restrict the study location, and any international study written in English was eligible. Our exclusion criteria were papers describing the process of blockchain design, books or book chapters, letters, statistical reviews, dissertations, editorials, and study protocols.

2.4.Study selection
The research selection included four steps. First, three authors (XY, JY Z, and HL W) independently screened all titles and abstracts related to the systematic review (n=1,647). Second, the abstracts of all related articles were qualified by five authors: PR L, SX L, TT H, YY D, and Z D.
Third, the full texts of eligible publications were obtained and screened (XY and LL) according to the inclusion and exclusion criteria. If there were any different opinions between the decisions made, these documents were discussed until a consensus was reached, with the support of ZW Y. Fourth, the reference list of all included papers and the system overview identified in the original search were checked to identify other publications that met our inclusion criteria.

Search findings
The search identified 1,647 potentially relevant documents after a review of titles and abstracts, of which 60 satisfied the inclusion criteria after a full-text review ( Figure 2).

Distributed ledger and the characteristics of blockchain
Although traditional databases can have built-in redundancy, they do not have the advantage of replication on every node [8,9,11]. In the nodes of blockchain, only cryptography and programs are used to realize point-to-point transactions and complete cooperation and established tasks. In this mode, the problems of low efficiency, high cost and data security caused by centralized systems can be solved [9][10][11]. There are some characteristics of blockchain in Table 1 and closely related applications. By maintaining an immutable, tamper-proof, consecutive list of transactional data in a distributed network, blockchain has created several disruptions in incumbent business processes and provides a promising new distributed framework for amplifying the integration of healthcare information across a range of stakeholders [1,2,3,6,7].

Framework structure of blockchain
The framework and structure of blockchain can be divided into six layers: The application layer carries out the accounting, transferring and verifying functions on the client side. Then, the contract layer behind the application layer includes the script code, algorithm mechanism and smart contract, which performs transaction identification. The incentive layer involves the distribution mechanisms.
The consensus layer ensures the consistency of the distributed systems, and that consensus can be reached even if there are malicious nodes in the network. This layer also avoids the problem of a "double-spend attack'' and ensures the generation time of blocks. In addition, the network layer is the mechanism for which we use the P2P network to complete communication and confirmation, and the data layer includes a series of encryption and storage technologies [8][9][10]12,13].

3.2.1.3.Classification of blockchain
Generally speaking, blockchain can be divided into public chains, consortium chains and private chains, as is shown in Table 2 [14]. Hasselgren et al. [15] counted the current medical use of various types of blockchains and frameworks and found that the consortium chain is the most widely used.
Currently, Ethernet and hyper ledger fabric are the most popular frameworks. Hasavari et al. [16] showed that hyper ledger fabric is the most effective frame structure combined with medical treatment at present. One solution to the problem regarding the combination of blockchain and medical treatment is to replace patient care reports with electronic health records so that they can interoperate with other EHRs. Another solution suggests the integration of the hyper ledger platform with an interplanetary file system (IPFS), which is a point-to-point method for storing and sharing media in distributed file systems that use BitTorrent technology. The data themselves are stored on the IPFS, and its hash pointer is stored on the blockchain. MedRec [17] is a decentralized record management system utilizing blockchain for authentication, confidentiality, responsibility and data sharing. At present, most medical data-sharing and distribution solutions use the allowed blockchain technology and rely on business process integration; that is, customers run code on each node and go through a specific process until they store the data in the ledger [18].

Application scenarios in healthcare
Blockchain technology can use cryptography to program and operate smart contracts composed of data encryption and automated script codes and also provide distributed infrastructure and economic incentives [4,5,6,7,13,14,17,18,19]. Based on previous studies, we summarized three main blockchain-based medical scenarios ( Table 4) and discussed the integration of blockchain and emerging technologies in the future.

Overview
With the accumulation of a large amount of individual health information, a reliable storing and sharing approach is needed to ensure the safety of patients' private information. The existing medical data management systems are generally based on a set of centralized servers, which build a large site system or centralized relational database system. Blockchain is an open distributed ledger based on peer-to-peer networks and consensus algorithms and has natural advantages in solving these problems.

Preservation of electronic medical records
With the increased specialization of healthcare services and high levels of patient mobility, accessing healthcare services across multiple hospitals or clinics has become very common for diagnosis and treatment, particularly for patients with chronic diseases. Based on blockchain, Dubovitskaya et al. [22] developed ACTION-EHR, an EHR data management system for radiation treatment of cancer. The synchronous nodes in the blockchain network can immediately find data changes and prevent malicious tampering with the data. Similarly, HealthChain [25], a novel patientcentred blockchain framework designed by Hylock, offers patients and providers access to consistent and comprehensive medical records. To integrate patient referral data from the NHIA's (National Health Insurance Administration) national medical referral system, a blockchain-enabled framework for acquiring EMR and EHR data of patients in hospitals and community-based clinics was developed by Lo [26]. The framework assists in the establishment of an alliance-based medical referral service to promote trusting relationships and transaction security among patients, family doctors, and specialists. In addition, Yue [28] proposed the Health Care Data Gateway, a medical data network that not only enables a patient to control their own data easily but also untrusted third parties to process health data securely. By expounding the working principle and process of Healthchain in detail, Xiao et al. [27] verified the feasibility of using blockchain in electronic medical records. As a major direction of telemedicine, the blockchain-based storing system of health data will play a vital role in protecting the privacy of patients and ensuring credibility.

Exchange of patients' medical data
Traditional medical records are stored in the central database of various hospitals, which leads to the phenomenon of an "isolated island of information" in the medical field

Simplifying the process of medical insurance
In the field of medical insurance, the insurance process involves patients, medical institutions, and insurance service providers, but the speed of information exchange among them is slow. Based on Blockchain, the process can be simplified. A blockchain-based medical insurance storage system named MIStore was proposed by Zhou et al. [40], they deployed it on the Ethereum blockchain and provided a platform between insurance companies and hospitals. The system improved the efficiency of the information storage process, so the insurance companies can quickly settle claims and preauthorize payments to patients. Based on blockchain, the real-time circulation and sharing of bills can be realized, and can ensure the payment of claims and reduce user advances. The technical framework of medical insurance based on blockchain was depicted in Figure 3 as follows: wearable devices, smartphones, clouds, and wireless systems, the integration of these devices can be applied to tracking the health status of patients with chronic diseases. By using blockchain-based transmission and storage mechanisms, they can upload health information to the cloud more accurately and in a more timely manner [41][42][43]. Brogan et al. [44] demonstrated that it was feasible to use a distributed ledger to receive authenticated activity data from a wearable device. Griggs et al. [45] proposed the utilization of blockchain-based smart contracts to evaluate information collected by healthcare devices and log transactions in a wireless body area network (WBAN). A quickresponse system based on the blockchain can detect emergencies such as asthma attacks and alert the closest emergency services in real-time to provide immediate relief. Continuous monitoring can not only detect adverse health events early and reduce the risk of such events, but also improve the monitoring of medication compliance and reduce unnecessary treatments [46,47]. Based on blockchain, wearable devices can potentially reduce patients' needs for more complex interventions, which in turn reduce the number of emergency department visits and hospitalizations, caregiver burden, and healthcare costs.

Promoting the management of social and public health Overview
The management of social and public health is involved in many aspects, including disease prevention and control, management of drugs, authentication of health records, and medical insurance. Due to the lack of information exchange, the process often becomes inefficient. Based on the characteristics of blockchain, such as traceability and immutability, we can apply it to simplify the process of insurance, administration of medicine, anticounterfeiting electronic prescriptions and controlling pandemic issuance.

Administration of medicine
The bringing about the benefits of vast objects' connectivity and features to process and record a large amount of medical information with more efficiency, privacy, and security [49].
Due to the particularity of drug production, the legitimacy and authenticity of drugs can be effectively guaranteed by using blockchain anti-counterfeiting technology [54][55]. [57] proposed a framework for improving the claims process by using blockchain, which makes the adjudication process more patient-centric and prevents drug fraud and abuse.
The primary function of blockchain in the circulation of drugs can be summarized as follows: (1) track and trace pharmaceutical raw materials and finished products in an immutable digital ledger, (2) provide greater transparency of fake drugs by allowing participants to verify their authenticity, (3) integrate anti-counterfeit devices into the "Internet of Things" and provide better authentication, and (4) serve as an underlying technology to enhance information exchange across different actors in the drug supply chain [56,57].

Anti-counterfeiting of electronic prescriptions
With the continuous development of medical treatment on the internet, the establishment of online consultation platforms has facilitated consultation needs. Currently, individuals can conduct medical consultations through online platforms, purchase drugs from certified online pharmacies and provide services such as drug delivery in the same city [58]. However, fake symptoms and irregular electronic prescriptions continued to emerge, which leads to the behaviour of relying on fake prescriptions to buy drugs. Based on the decentralized and traceable blockchain system, a blockchain online consultation platform can be established to ensure the storage of large sample data and the sharing of health information [2,3,5,7]. The framework is shown in Figure 4. Such a project mainly realizes the functions of hospital management, physician management, user management, online consultation and prescriptions through a doctor-patient online consultation platform and achieves information credibility with the help of blockchain digital authentication, integral management and other technologies. In this framework, users can be divided into doctors, ordinary users (patients) and administrators. Doctors need to pass the qualification examination to achieve the functions of prescribing medicine and diagnosing diseases, while patients need to register their personal information and submit a description of their illness to obtain a prescription. The consultation information was uploaded and recorded in personal medical records to prevent patients from fabricating false health information [59]. According to the results of physical examination records, medical diagnosis and prescription opinions uploaded; the above-mentioned process can ultimately be realized in this blockchain-based tamper-proof system.

Prevention and control of pandemic (Case of COVID-19)
The COVID-19 spread rapidly around the world during 2020, and ways to prevent and control epidemics have attracted much attention. Scientists are struggling to find a model to fight COVID- 19. Blockchain technology has several potential use cases that can help tackle the current pandemic crisis. It can be used to simplify the clinical trial processes for vaccines and drugs, raise public awareness, transparently track donations and fundraising activities, and act as a reliable data tracker.
Compared with traditional supply information management, blockchain smart contracts can guarantee the rights and obligations between nodes and the judgement of contract execution [60,61,62,65,67,68]. A joint Walmart-IBM project demonstrated how tracking the sources of contamination in green vegetables, a task that previously took months, could be achieved within seconds using blockchain [62]. In the control of epidemics and pandemics, many experts have made meaningful attempts. Mashamba et al. [63] proposed a blockchain-based and artificial intelligencecoupled self-testing and tracking system for infectious diseases. Based on blockchain, ICD codes (current and previous versions) can be used to map the causes of death and observe disease trends and pattern changes across geographical locations over time. Bansal et al. [64] suggested the use of a blockchain-based system to mitigate the falsification of test reports and encourage people to contact individuals with immunity-based licences. Blockchain also enables information to be collected from individuals without identifying them by using a system of public and private keys. The DeepTrace system based on the blockchain can provide anonymized personal identification while allowing regulators and healthcare providers to contact people who are at risk of being potentially infected [65]. In addition, Abdel-Basset et al. [66] proposed a framework integrating different disruptive technologies and blockchain to provide governance with an integrated vision towards managing the COVID-19 pandemic. Although epidemics and pandemics have seriously affected our lives, they also promoted the advancement of scientific technologies in the process of combating viruses and enhanced our capabilities in facing such emergencies [67][68][69].

Empowering the credibility of medical education and research
Overview Medical education and research are promising areas where the introduction of blockchain may bring about benefits. Based on a blockchain system, reports and procedures at different stages of study, as well as test results, congress and course attendance in medical education could be easily archived and serve as digital proof of acquired competencies performed. Since real clinical and experimental data are inseparable from high-quality medical research, the source and reliability of data are essential for researchers. Based on the immutability and transparency of blockchain, the uploading of experimental data records can accelerate clinical data sharing and prevent academic misconduct.

Medical education
Medical education is constantly changing and must adapt to address advances in biomedical sciences, improvements in learning theory, new regulatory policy, technological innovation, and efforts to have healthcare professionals perform at the highest level of competency. Blockchain technology in medical education has the potential to help solve many of the challenges currently faced by academic administrators, faculty, learners and institutions. Since medical education is a lifelong learning process, a blockchain framework and measurable public exchanges between learners and teachers allow for the transmission of content, feedback about instructional designs, evaluation of learners, competency assessment and certification.
A blockchain-based structure for the recording, crediting, and appraisal of educational deliverables could be a robust way for educators to track the value that their academic and system achievements create. In medical schools, blockchain can be used to store and track students' scores and abilities acquired through a range of different clinical environments. Doctors can then decide whether they are willing to share such information so that verified certificates and diplomas can be issued more easily and the process can be more cost-effective and tamper-proof [70,71]. Verde F et al. [70] proposed that the introduction of blockchain in academic radiology settings can be valuable for monitoring resident progress over the years. MIT launched a pilot program in 2017, which included the issuance of digital diplomas to students' smartphones via an app called Blockcerts Wallet, which is based on blockchain [72]. Blockchain could optimize the use of administrative resources by reducing bureaucratic workload, with the added benefit of increased transparency, as records stored via blockchain can be automatically verified. Objectively speaking, blockchain implementation in the educational system could be in the assessment of faculty member competencies and academic performance in a secure and unalterable fashion.

Clinical trials
The integrity of data in a clinical trial is essential, but the current data management process is too complex and highly labour intensive. By applying blockchain technology to medical research, the data can be time-stamped and transparent [73,74]. Wong et al. [74] illustrated that a blockchainbased file and data structure could be used to reliably safeguard data in a clinical trial network. Omar et al. [75] proposed a blockchain-based framework for CT data management in clinical trials. Hirano T et al. [76] conducted a project to demonstrate data management under a regulatory sandbox and tested the system through a clinical trial for breast cancer. Cichosz et al. [77] explored the operational concept of the use of blockchain to improve data management and analyse diabetes in clinical observations. Nugent [80] showed that smart contracts can act as trusted administrators, able to improve the transparency of data reporting in clinical trials. In addition, Engel et al. [81] proposed that blockchain can play an essential role in improving surgical outcome research and trial design.
Even before clinical trials begin, all plans, agreements, scenarios, and possible results can be stored on blockchain [82]. This approach can transform our thinking about trial design and produce truly verifiable and immutable data, which in turn can lead to better data reproducibility.

Biomedical research
Biomedical data sharing has always been a cornerstone of scientific development. In the open world of science, it is inevitable to share, access, analyse, and learn from different sources of data for a meaningful result [85,86,89,90]. Blockchain can not only help in clinical trials but also accelerate biomedical research and reduce reporting selectivity and fabrication, which are widespread problems in today's science fields. This can be achieved by integrating the consensus model of blockchain into current solutions to decentralized data storage and analysis. Jin et al. [83] introduced LifeCODE.ai, a blockchain-based genomics big data platform, which aims to provide relatively safe and trustworthy data storage for genomic stakeholders. It is a decentralized approach in which each owner has complete control over their data-where it is stored, who can access it and when it is updated. This approach may be the best way of sharing scientific data.
The majority of the recent approaches to personalized medicine in oncology and other diseases have relied on various data types, including multiple types of genomic, transcriptomic, microRNA, proteomic, antigen, imaging, physiological and other data. Research institutions can use DNA data stored in blockchain to conduct advanced searches to find topics of interest for potential genomic research. However, biomedically, the data are often personal, private and sensitive, and should thus be treated carefully. There are currently a few similar proposals to help protect the data for academia.
The first is the Cancer Gene Trust (CGT) being developed by the Global Alliance for Genomics and Health (GA4GH) Consortium, and the second is the CrypDist project. Both projects have similar properties, where summary data such as somatic cancer variation data are kept and distributed in a blockchain system [87]. In addition, Johnson et al. [88] also described a decentralized app (DApp) to build a secure biomedical data-sharing system in biomedical and healthcare communities. This unprecedented progress has brought us into an era of genomic data-driven medicine and drug development, and blockchain technology will bring us into an era of genomics in an all-around way [89][90][91].

Integration with emerging technology in healthcare
Currently, the combination of the unsustainable cost of care, an ageing population, the need for improved access to care and the growth of precision medicine has ignited the ideal platform for disruptive innovation through blockchain and digital health [1,2,3,90,91,92,93,99,100]. Based on the distributed ledger, blockchain can be integrated with artificial intelligence, cloud computing, big data and the Internet of Things; gaining more application scenarios and aiding the development of the health industry [91,92]. We summarize the practical usage in Table 5. Additionally, cloud computing is a new technique that provides different services by minimizing cost and infrastructure and can be used with the blockchain system to support communication and sharing data among stakeholders in healthcare [96]. X. Liang et al. [97] presented ProvChain, a blockchain-based data provenance architecture, to provide assurance of data operations in a cloud computing and storage application while simultaneously enhancing privacy and availability.
Furthermore, big data can be generated from different sources, such as wearable devices, electronic health records (EHRs), magnetic resonance imaging (MRI) and computed tomography (CT) imaging. By integrating information about multiple features of diseases, big data offers an enormous amount of data in real time to reduce health risks and optimize health outcomes [90,96,97,99]. As we discussed in a previous study, wearable devices can be used to perceive, record, analyse, regulate and intervene to maintain health and can even be used to treat diseases with the support of various technologies for identification, sensing, connection, cloud services and storage [42,98,99]. Then, the IoT can play an essential role in the supply chain and tracing of drugs, apparatuses, and data from wearable devices. Based on blockchain and IoT, Tiago et al. [98] details the design and implementation of a system that enhances continuous glucose monitoring (CGMs) by adding Internet of Things (IoT) capabilities to them that allow for monitoring patients remotely and warning them about potentially dangerous situations. To motivate users to add new data to the system, an incentive system based on a digital cryptocurrency can be devised to reward the users that contribute to the system by providing their own data. It is a meaningful attempt to control chronic diseases. Furthermore, in the 5G environment, the blockchain-based cloud system is supposed to take full charge of data transfer, storage and processing. By combining all the previously mentioned technologies, we can build a healthy database for developing a complete medical ecosystem.

Principle findings
The results of this narrative literature review suggest that blockchain is an innovative technology that has great potential in healthcare. Prior reviews included conceptual papers, industry reports, and empirical research that primarily focused on technology, business or patient care. In this paper, we demonstrated the use of blockchain in managing medical data, confirming the traceability of the supply chain, and in anticounterfeiting electronic prescriptions and clinical and biomedical research.
We also demonstrated the important role that blockchain played during the COVID-19 outbreak, which provides a reference for the prevention of major infectious diseases in the future. The integration and application of new technologies and blockchain were explored, attempting to describe a blueprint of the interconnected ecosystem in healthcare.
From a practical point of view, the application of EMR exchange appears relatively mature. For example, in 10 studies, there were some related systems, such as the ACTION-HER [22], HealthChain [25], Healthcare Data Gateway [28], Guardtime [29], and MeDShare [30], which were based on blockchain and used for preservation and exchange of health data. In five studies However, some concerns were also identified when applying blockchain to healthcare. The first was the interoperability issue. When encountering a problem requiring cooperation, it is necessary for blockchain-based service providers and users to connect seamlessly, but the standards among different institutions are not unified. There still exist great differences in the supervision modes of blockchain across countries. In the European Union, individual countries may be willing to use blockchain technology for public plans, but it is not clear how blockchain projects meet the General Data Protection Regulation (GDPR) privacy standards within the European Union [1,2,3,4,99,100,101]. The general standard of blockchain will accelerate the industry to reach an agreement on blockchain and contribute to the formation of a large-scale ecosystem of social blockchain [102][103][104][105][106][107]. The second is efficiency issues. With the amount of data growing exponentially, the blockchain database has higher requirements for network speed, and the efficiency of data dissemination and real-time acquisition of data will be affected. More reasonable frameworks need to be designed to avoid blockchain efficiency problems across sectors. Then, security issues must be taken into consideration. It is not clear whether blockchain is truly the solution for all issues regarding highly sensitive data. The decentralized networks may be subject to 51% of attacks when there are fewer honest nodes than malicious nodes in the network, and the entire network will be taken over by malicious attackers. The last but not least is the related regulatory policies. Regulatory policies are important factors for the stable development of blockchain. Decentralization is one of the advantages of blockchain, but after diluting government regulations, blockchain may have an impact on the existing electronic health system of a country [1,2,3,[100][101][102][103][104][105]. Therefore, related policies need to be introduced systematically as soon as possible.

Limitations
The results of this review must be interpreted with caution due to multiple limitations. First, the findings of this scoping review are mainly intended for healthcare entities and are not as applicable to other domains, such as business and marketing. Second, for practical reasons, the search strategy was restricted to studies reported in the English language, which could have overlooked other benefits and threats reported in other studies in languages other than English. Third, for the variety of application scenarios of blockchain in the medical field, we cannot demonstrate every aspect of principle and framework in detail.

Conclusions
With the continuous improvement and development of new technologies, blockchain may become increasingly closely integrated with the contemporary development of the financial sector and health industry. Since each country and region has different attitudes towards this technology, we need to conduct in-depth exploration and research on the blockchain according to our own situations.
In medical applications, many start-up companies are actively exploring, promoting the development of blockchain in the fields of post transaction settlement, smart contracts, supply chains and identity authentication. From the theoretical perspective, blockchain based theoretical foundations have been established for enhancing trust in an intelligent medicine environment. In the future, the issuance of digital currency will change the traditional economic transaction mode, and the introduction of blockchain will reshape the value exchange system, increase trust and privacy, and efficiently complete economic transactions and medical records [108]. Although countries and regions around the world have diverse attitudes towards the blockchain and there still exist skeptical attitudes towards it, these will not affect the research and further development of this technology. Throughout this work, we have also highlighted the principles and major challenges concerning distributed ledger technology. The great value of blockchain-based healthcare systems will gradually emerge in the coming years. In future work, technical personnel and researchers need to cooperate and incorporate the blockchain into the design of the medical framework. In this paper, we demonstrated all the potential scenarios of blockchain technology for patients and healthcare providers, which provides large samples for further research. This is just the beginning of the blockchain, and its development will be more like a marathon than a sprint.

Figures
PRISMA flow diagram outlining the review process.
Framework structure and classification of blockchain.