research paper on blockchain in healthcare

SYSTEMATIC REVIEW article

Exploring applications of blockchain in healthcare: road map and future directions.

• 1 School of Computing Science and Engineering, VIT Bhopal University, Bhopal, Madhya Pradesh, India
• 2 Department of Computer Science and Engineering (AI&ML), Vardhaman College of Engineering, Hyderabad, Telangana, India
• 3 Department of Artificial Intelligence Systems, Lviv Polytechnic National University, Lviv, Oblast, Ukraine

Blockchain technology includes numerous elements such as distributed ledgers, decentralization, authenticity, privacy, and immutability. It has progressed past the hype to find actual use cases in industries like healthcare. Blockchain is an emerging area that relies on a consensus algorithm and the idea of a digitally distributed ledger to eliminate any intermediary risks. By enabling them to trace data provenance and any changes made, blockchain technology can enable different healthcare stakeholders to share access to their networks without violating data security and integrity. The healthcare industry faces challenges like fragmented data, security and privacy concerns, and interoperability issues. Blockchain technology offers potential solutions by ensuring secure, tamper-proof storage across multiple network nodes, improving interoperability and patient privacy. Encrypting patient data further enhances security and reduces unauthorized access concerns. Blockchain technology, deployed over the Internet, can potentially use the current healthcare data by using a patient-centric approach and removing the intermediaries. This paper discusses the effective utilization of blockchain technology in the healthcare industry. In contrast to other applications, the exoteric evaluation in this paper shows that the innovative technology called blockchain technology has a major role to play in the existing and future applications of the healthcare industry and has significant benefits.

1. Introduction

Blockchain technology has been around for at least 20 years. It wasn't until recently that academics and businesses began to consider it strongly. This paper aims to highlight blockchain technology's existing and future applications in the healthcare industry through a thorough analysis. The authors wanted to highlight projects from the scientific and commercial sectors. This article may alternatively be seen as a concise summary and annotation of the idea behind the potential connections between healthcare and cryptocurrency and blockchain technology.

The blockchain's core value is closely related to trust and decentralization. A distributed database called blockchain supports transactions between unreliable entities, instead of having banks or another brokerage firm it acts as a middleman as is the case with traditional transactions, people and organizations may deal directly with one another. Because of this, it is anticipated that the blockchain will alter how people conduct international payments. It is crucial to investigate the potential benefits that this new technology might bring to the healthcare industry. It is clear that instead of just financial transactions, this effort will focus on healthcare data applicability and operations in general.

One of the biggest sectors, healthcare accounts for more than 10% of the GDP of developed nations. The expense of providing effective healthcare services is rising, and patient data is fragmented which calls for the need to protect patient data and deliver effective services to be expanding whereas patient data is scattered, and sharing this private information may occasionally be subject to the practice of authorization management. Data is sometimes unavailable and inaccessible; all such problems in healthcare may be resolved with the help of blockchain. Distributed ledger technology is the foundation of blockchain technology, where transactions occur amongst peers rather than through a central authority. Decentralized transactions will be used throughout none of the entities can change any of the transactions once they have been added since they are all immutable which offers security and privacy for the transactions. A single location may be used to store patient data as a result, diagnosing a patient will be simple. IoT and blockchain can be utilized for real-time patient monitoring. As patient claims are properly monitored by health insurance companies, records are kept in a ledger that cannot be changed after it has been added. Blockchain has a wide variety of features that allow its implementation in a variety of applications. Decentralized storage and authentication are one of the key characteristics of blockchain. There are three main types of blockchain: public, private, and federated. Table 1 lists different types of blockchains. Anyone may participate in and validate public transactions on a public blockchain. The public is in charge of maintaining this kind of blockchain. Public blockchains include, for example, (1) Ethereum, (2) Bitcoin, (3) Bit shares, (4) Waves, and (5) Dash. Government agencies are in charge of maintaining private blockchains. Transactions are internally vetted and not accessible to the public. The consortium maintains federated blockchains, the third form of blockchain. This blockchain may or may not make transactions public. Federated blockchains include B3i, EWF, and Corda R3 as examples.

Table 1 . Blockchain types.

Blockchain has started to infiltrate a variety of different industries over the past few years, including finance and banking, capital markets, trade finance, business, real estate, media, government organizations, etc. The area where blockchain has enormous potential is healthcare. Data security, data access, data sharing, and interoperability are the top needs in the healthcare industry. Confidentiality and security are fundamental needs of the healthcare sector to protect patient medical information. In this digital age, cloud storage has become the most popular way to exchange and retrieve data, but since it is shared across a network, there is a danger of virus attacks and even a chance that personal information may be compromised. The constraints of healthcare requirements include data sharing, data access, data transmission, authenticity, and interoperability.

An EHR system (electronic health records) has replaced the conventional manual filing method, although it is expensive and labor-intensive. Following the introduction of EHR cloud-based systems to address the problems with EHR systems, however, these cloud-based systems still fell short in terms of encryption, data confidentiality, interoperability, and security standards. Every challenge the healthcare industry has, from interoperability to data security and transmission, might be addressed by blockchain technology.

Blockchain technology has several characteristics that include immutability, transparency, distributed ledgers, data security, authentication, and decentralization. This highlights why and how this technology is becoming increasingly popular across all industries, but especially in those like healthcare where issues with legitimacy, dependability, and security are especially problematic. The blockchain architecture is seen in Figure 1 and consists of three layers: an application layer, a transaction layer, and a network layer. Users will communicate with one another using blockchain applications in the application layer, and immutable transactions will be carried out in the transaction layer and on a global ledger. At the network layer, information exchange will take place on a P2P network.

Figure 1 . Architecture of blockchain.

2. Motivation

It is now well acknowledged and perhaps even evident that blockchain will most likely significantly disrupt the healthcare sector. Nevertheless, the authors tried to define the amount of relevance anticipated in as many ways as possible, to measure it, and to quickly characterize it in general terms.

In order to start with peer-reviewed papers, a search at Scopus was made in January 2022 for publications that had both “blockchain” and “healthcare” in their “Article” or “Abstract” or “Keyword” sections. This search returned a total of 1,776 documents ( Figure 2 ). Figure 3 shows their distribution according to their country of origin, scientific field, keyword, and year of publication. The authors can clearly see the apparent quick growth in the number of relevant publications, as well as an intriguing keyword distribution where some keywords (like “security” and “privacy”) do not occur as frequently as expected. It is important to note that interest has extended globally, in addition to China and the USA. On January 2023, the authors ran the same query and received 2,828 documents in response. According to this, there are around three articles about blockchain technology in healthcare every day.

Figure 2 . Publications per country over years.

Figure 3 . Publications in subject area and keywords.

A similar search at Solulab turned up the 18 projects financed by independent companies under their Research and Innovation initiative. The acronyms for these R & D projects are provided below, followed by their titles, and they are ranked by Solulab according to how closely they adhere to the keywords. Presents a visual representation of the chronological distribution of these initiatives. These projects' time distribution is graphically shown in Figure 4 .

Figure 4 . Time distribution of projects.

BurstIQ : The organization uses blockchain to enhance the sharing and utilization of medical data.

SoluLab : Solulab uses blockchain to strengthen healthcare cybersecurity and to increase the sharing and use of medical data.

Medicalchain : The blockchain-based infrastructure used by Medicalchain keeps track of the source and safeguards patient identification.

Guardtime : Blockchain technology is used by Guardtime in cybersecurity applications, including healthcare.

Avaneer Health : Avaneer is a startup that seeks to use blockchain technology to improve healthcare efficiency. It is supported by Aetna, Anthem, and Cleveland Clinic. This is accomplished by utilizing a public ledger to provide improved claims processing, safe healthcare data transfers, and upgrade provider directories.

Chronicled : The usage of the Chronicled blockchain network ensures the secure delivery and thorough examination of drug supplies.

ProCredEx : ProCredEx has created a decentralized record system for healthcare credential information, ensuring that the data cannot be altered and remains permanently trackable. This enhances the effectiveness of intricate datasets, allowing for data customization to meet specific organizational requirements and the secure sharing of this data with authorized collaborators.

Robomed : Robomed captures patient data via blockchain and securely distributes it to the patient's healthcare professionals.

Patientory : The blockchain platform used by Patientory makes it possible to store and send sensitive medical data securely.

Doc.ai : The company uses artificial intelligence to decentralize medical data on the blockchain.

Encrypgen : It is now simpler to locate, share, save, and purchase genetic information because of the company's blockchain technology.

Coral Health : Coral Health uses blockchain to streamline administrative procedures, speed up the delivery of treatment, and enhance patient outcomes. The startup establishes faster connections between doctors, scientists, lab workers, and public health authorities by incorporating patients' records into DLT. To ensure that information and treatments are correct, Coral Health also uses smart contracts between patients and medical experts.

Embleema : Embleema is a tool for regulatory analytics and virtual experiments intended to accelerate the drug development process. Users are encouraged to provide their digital consent for the safe, unaltered acquisition of their medical data, which is subsequently recorded on the blockchain of Embleema and examined.

Blockpharma : Blockpharma provides a method to combat medication fraud and counterfeiting. Patients may find out whether they are taking fake medications using the company's app by scanning the supplier base and validating all points of shipping. Using a blockchain-based supply chain management system, Blockpharma claims it can screen out the 15% of medications that are fake worldwide.

Tierion : The blockchain of Tierion verifies all documentation, data, and pharmaceuticals to maintain a complete record of ownership. The company maintains evidence of ownership throughout a medical supply chain using timestamps and credentials.

FarmaTrust : The blockchain solutions from FarmaTrust may be used to manage prescriptions, validate the legitimacy of medical equipment, and protect patient data when they schedule vaccines and diagnostic tests. For example, the firm offers a service that prevents fraudulent pharmaceuticals from entering the supply chain and an app that allows customers to verify that their medications are authentic.

Nebula Genomics : Nebula Genomics is utilizing distributed ledger technology to eliminate extra fees and intermediaries in the genetic research industry. Annually, companies in the biotech and drug industries spend billions of dollars to get genetic data from other sources. While contributing to the development of a substantial genetic library, Nebula Genomics invites users to sell their encrypted genetic data securely.

3. Background and concepts

In 2008 Satoshi Nakamoto implemented the cryptocurrency named Bitcoin based on the web white paper ( 1 ). This cryptocurrency works on open source technology and on the decentralized network in simple terms all nodes are connected mutually, and these nodes have the authority to leave and rejoin the network on demand and later receives the authentic record i.e., Proof of Work (PoW) referred to as the blockchain ( 1 ). To rejoin the network, they had to perform certain large computations to show evidence of their authentic members. PoW describes and gives proof of what happened when the particular nodes left the network. In cryptocurrency there may be a threat of a Sybil attack and this situation can be solved by claiming PoW from all nodes of the network which verifies transactions. The working of PoW can be understood by understanding the block of the bitcoin structure. The network consists of nodes that are nothing but participants and all of them have an identical ledger copy and these blocks of information are attached ( 2 ). These blocks consist of transaction data of both sender and receiver, the extent of the transaction, and hash value. Hash values are used to link the blocks, therefore Blockchain is a series of blocks tailored together as illustrated in Figure 5 . It reflects, how blocks are linked together in blockchain. The order of blocks linked together will be determined by PoW consensus in Bitcoin. Bitcoins are chained using hashing. Changing the hash value will lead to the invalidation of a block. To validate, the block hash value needs to be recalculated. Bitcoin as being public blockchain technology is susceptible to security and privacy threats; this property is not acceptable for healthcare systems where data privacy is concerned. Bitcoin along with throughput is most desirable for building healthcare applications ( 3 ).

Figure 5 . Representation of blocks in blockchain. Blockchain blocks include transaction details, including sender and recipient information, transaction size, and hash value. Blockchain is made up of a collection of interconnected blocks that are linked together using hash values.

Blockchain is best characterized by a decentralized, immutable ledger that records data. It enables entities to communicate with one another without the requirement for a centralized, reliable middleman. The blockchain contains blocks of data, comprising sets of information that grow consistently. Once integrated into the blockchain, these blocks are linked to the preceding and subsequent blocks through cryptographic procedures. All parties can read, write, and modify these data records/blocks in the blockchain's original form. Decentralized transactions and data processing are made possible. These characteristics have made blockchain very popular for a variety of uses. Blockchain also supports smart contracts, fully independent contracts that may be executed without a central authority. As of right now, Ethereum is the blockchain that facilitates smart contracts.

3.1. What is blockchain?

3.1.1. key characteristics.

Blockchain is decentralized, so nobody has full control over the data that is uploaded to it. Instead, a P2P network utilizing different consensus mechanisms approves the data that is uploaded to the blockchain. Persistence is another essential component of blockchain technology. Due to the distributed ledger's massive node storage, it is highly challenging to remove anything after it has been published onto the blockchain. Additionally, a lot of blockchains make use of the desirable potential anonymity (or pseudonymity) characteristic. By linking each block in a chain of blocks by containing the hash of the one before it, blockchains offer traceability and transparency. The Merkle tree-based organization of the blocks' transactions enables independent root-to-transaction verification ( 4 , 5 ).

3.1.2. Type of blockchains

Blockchains come in three basic forms: consortium, public, and private. They have a wide range of characteristics that influence who is able to read from, write to, and access data on the blockchain. All users have access to the data on a public chain, and anybody may contribute and make changes to the consensus and the core software. The two biggest cryptocurrencies, Bitcoin and Ethereum, which are categorized as public permissionless networks, are among the several cryptocurrencies that utilize the public blockchain. Because only a small number of carefully chosen groups of businesses have access to observe and take part in the consensus process, a consortium blockchain may be perceived as being somewhat centralized. A decentralized network that is frequently centralized makes up a private blockchain. A few nodes can connect to the network, and they are often under the supervision of one central authority ( 4 , 6 , 7 ). The definition and classification of the many blockchain types discussed here are still subject to debate. There is currently no widespread agreement on what defining characteristics and consensus procedures are necessary to refer to a piece of technology as “blockchain” ( 8 ). For the creation of decentralized applications, there are currently available blockchain frameworks and platforms (Dapps). The most well-known blockchain development platforms to date are Ethereum (decentralized platform) and Hyperledger (framework), both of which let programmers add new blockchain apps to current blockchains and construct new test nets using their protocols ( 9 ).

3.1.3. Consensus algorithms

The procedure for approving data records on the decentralized ledger is a crucial component of blockchain technology. A distributed consensus method that checks the data entries accomplishes this. For this, a variety of consensus techniques have been put out and used; the three most popular ones are shown in Table 2 and are given below:

Table 2 . Comparison of consensus mechanisms.

Proof of Work (PoW): PoW is the consensus system that is most closely connected to the blockchain because it is a part of Bitcoin. The process confirms the transaction and creates a new block for the blockchain. Miners compete in this procedure to finish the network transaction first. Competing is involved in mining. Miners receive incentives for successfully confirming a new block. This idea is supported by evidence of the significant electricity needed for Bitcoin mining, which is currently comparable to the requirements of a small nation ( 10 ).

Proof of Stake (PoS): With PoS, the node that will serve as an approving node is chosen based on its stake in the blockchain. When it comes to cryptocurrencies, a person's balance in a certain currency represents their investment. The “richest” node may, however, unjustly gain from this. Many hybrid PoS systems have been put out as a solution to this problem, where the approving node is selected using a mix of the stake and some randomization. The second-largest cryptocurrency, Ethereum, plans to transition to Proof of Stake from Proof of Work ( 4 ).

Practical Byzantine Fault Tolerance (PBFT): The underlying protocol of PBFT is a Byzantine agreement mechanism. This consensus procedure can't be used in a public blockchain since every node in PBFT must be known to the network, which places limitations on its use. Pre-prepared, prepared, and commit are the three separate stages of the PBFT consensus process. A node must get two-thirds of the votes from the other nodes in order to pass through the three phases. PBFT is now used by Hyperledger Fabric ( 11 , 12 ).

3.1.4. Smart contracts

Smart contracts are supported by blockchain infrastructures like Ethereum. These are executed automatically contracts with clauses that are written clearly into the source code. Smart contracts operate independently of any third parties or middlemen since they are automatically implemented based on these set clauses. A blockchain transaction may activate this smart contract feature, and the healthcare industry seems like an appealing use for it ( 7 ).

3.2. Significance of blockchain in healthcare industry

Healthcare is a problem-driven, people- and data-intensive industry, and access to, updating, and trust in the information generated by its operations are essential for the sector's overall operations. According to a classification of healthcare operations into accident and emergency, health problem-solving, clinical decision-making, realization, and evaluation of knowledge-based care ( Figure 6 ), it is essential to have a multidisciplinary team of healthcare professionals who treat patients with the best knowledge, technologies, and skills. To help students learn and develop their skill sets, the healthcare industry must work with educational institutions to give them access to patients and a training environment. In exchange, educational institutions give the industry skilled staff.

Figure 6 . Map of healthcare industry.

The healthcare sector faces a number of challenges, including data fragmentation, security and privacy issues, and interoperability problems caused by the usage of numerous standards in healthcare systems. By assuring secure and impenetrable data storage through a distributed ledger system, enabling secure data sharing to improve interoperability, and protecting patient privacy through data encryption, blockchain technology presents a potential solution. In the context of blockchain, various technologies have been implemented to address these issues, such as electronic health records (EHRs), health information exchanges (HIEs), and federated learning. While blockchain has great potential, it is important to understand that it is not a cure-all, and the healthcare sector is still exploring a variety of methods and technologies to meet its changing demands.

Health institutions must assist with access to experts, informants, test subjects, and samples when working with organizations and businesses for research and engineering purposes. Health institutions are required to help in the design, planning, execution, and analysis of the studies while taking part in prospective clinical trials. In exchange, the research and engineering organizations offer the healthcare industry the most recent information, practices, and technology. Therefore, the operations of health institutions are closely linked to those of organizations that educate health professionals and conduct biomedical research and engineering ( Figure 6 ). The efficient sharing of patient-related information and evidence, along with reimbursement processes, necessitates the exchange of data between different institutions. It's crucial to safeguard the sensitive data patients entrust to healthcare organizations. Ensuring patients' privacy while sharing data with other entities in the healthcare network requires measures like access control, maintaining data origin, preserving data integrity, and enabling interoperability. The traditional way of implementing access control assumes a level of trust between data owners and the entities holding the data. These entities often manage access restrictions. To enhance the health of individuals and communities through collaborative data access, exchange, and utilization, a variety of information systems, devices, or applications need to seamlessly connect within and across organizational boundaries in a coordinated manner.

Data provenance refers to the origins and historical records of data sources. It can enhance transparency and reliability in electronic health records (EHRs) and foster consumer confidence in EHR software. According to Courtney and Ware, data integrity encompasses data quality and its expected standards. This means that meeting or surpassing these standards directly impacts data reliability. The demand for real-world data from businesses and research units is increasing within healthcare institutions. Simultaneously, the public's trust in healthcare organizations is waning due to instances of unlawful data sharing, widely publicized breaches, and private information theft. Another constraint is the existence of healthcare system mispractices that exploit the same trust level, involving issues like counterfeit medications, fraudulent personnel, and patients. Given this overall scenario, a reassessment and adoption of alternative strategies are imperative ( 13 , 14 ).

4. Related works

In this study, the keywords such as “Blockchain in healthcare,” “healthcare record(s),” “healthcare system(s),” “healthcare and system and record(s),” “healthcare and blockchain,” and “healthcare and blockchain” were used to search the Scopus and Google Scholar databases for EHR-related literature. By limiting the inclusion of the research in these influential review publications, this manuscript provides a concise overview. In this study, the word “Healthcare” is used instead of “Healthcare,” as “Health care” refers to an industry or system that enables individuals to access the medical care they require ( 12 , 15 , 16 ).

People have expressed a desire to save their medical records as new technologies have emerged. For instance, research revealed that 87% of the health data that US citizens have gathered for themselves and their families are physical copies and that 42% of US citizens have done the same ( 17 ). EHR systems include several restrictions (like security) that make it challenging for users to exchange information. Rezaeibagha et al. ( 16 ) took into account the implications of security and privacy on EHR systems in their assessment of healthcare systems. They recognized a number of important aspects that affect information security and privacy, including encryption and scaling techniques, laws and regulations applicability, agreement and choice mechanisms, and integration and sharing of information. In the latest review to investigate the effectiveness of EHR systems, Afrizal et al. ( 18 ) explored the perspective of both individuals and an organization. Their research revealed organizational limitations, such as a lack of teamwork, inadequate executives, and a shortage of competent personnel. Aside from that, each person had their own limitations, such as a lack of computational resources and apprehension about novel technologies.

Modern technologies reduce the aforementioned restrictions. For instance, there are various ways to use blockchain to reduce hurdles in electronic health record systems ( 19 ). Blockchain is a distributed ledger technology that records network member transactions using immutable, reliable, and encrypted data ( 20 ). A system is referred to as a completely distributed system when no individual authority manages transaction operations that require the computing labor of several machines ( 21 ). UN's sustainable development goal may be greatly enhanced and achieved using blockchain, particularly in the healthcare sector ( 22 ). EHRs are one example of a public sector function that can be modernized with blockchain ( 23 ).

Zhang et al. ( 19 ) investigated the application of blockchain in healthcare systems using health scenarios that highlighted a patient-centric strategy in a framework for safe data sharing. They proposed adopting blockchain in seven different areas, including clinical documentation, patient-supervised cancer information, telemedicine treatment, patient verification, and health insurance disputes. In order to show how blockchain is related to patients' information-sharing behavior, authors focused on their health data. Even though Zhang et al. emphasized the benefits of utilizing it in health record administration, very few current works have offered a foundation for employing blockchain for patient health records. Homans et al. ( 24 ) built a blockchain-based management information system for electronic health records to solve security and privacy concerns. The ledger, database, committer, “orderer,” endorser, and client were suggested as the six components that make up the framework. Fan et al. did not concentrate on the concepts of privacy labor and digital money and left them for future investigations.

Griggs et al., Fan et al. ( 25 ), added to the work done by Fan et al., using Homans ( 24 ), by introducing a private blockchain to address privacy concerns in blockchain usage. Public and private blocks come in two varieties. A block is a complete record of every completed and pending transaction. A private blockchain can be a useful option in healthcare administration, according to Griggs et al., given the serious security issues surrounding personal information. Reduced opt-in rates might be the outcome of privacy problems in EHR systems.

The study proposes “PeNLP Parser,” a tool developed to extract and visualize exact geographic information about maternal, neonatal, and pediatric healthcare from unstructured data. The application extracts pertinent data and geolocations from the unstructured data using Natural Language Processing (NLP) techniques. By employing PeNLP Parser, healthcare providers and researchers can efficiently access and visualize essential geo-location data, enhancing their ability to make informed decisions and improve maternal and child healthcare services ( 26 ).

An integrated ontology is presented in the study by Patience et al. to aid in decision-making in the Maternal, Newborn, and Child Health (MNCH) sector. Context awareness is a feature of the ontology that enables it to take a variety of situational circumstances into account while offering decision help. By utilizing the integrated ontology, which can effectively analyze and understand data relevant to maternity, newborn, and child health to provide insightful analysis and suggestions for healthcare professionals and policymakers, the study seeks to improve decision-making processes in MNCH ( 27 ).

Sharma et al. ( 28 ) used the technique of the soft system to present qualitative evidence demonstrating that the usage of EHRs assisted with blockchain can increase patient engagement opt-in rates. They worked on the PHC strategy, which consists of a number of separate EHRs that are meant to be available to everyone in order to advance the healthcare system. They demonstrated how their suggested blockchain-based approach may boost patient and doctor trust in the sharing of medical records, while also enhancing the security and privacy of trustless PHC platforms.

The prospective impacts of blockchain on HIE were taken into account by Esmaeilzadeh et al. ( 29 ) their findings demonstrated that consumers are particularly planning complete blockchain-based privacy protection tools. Shahnaz et al. ( 30 ) provided a framework to reduce the scalability issue in the usage of blockchain in order to enable the adoption of blockchain in EHR. Blockchain-based healthcare systems have both beneficial and detrimental effects on patients and healthcare professionals, which presents new study opportunities ( 31 ).

The use of blockchain technology in the healthcare industry administration has lately been the subject of a number of studies, although its exact function in healthcare systems is yet unknown ( 32 ). To the best of the authors' knowledge, this is the only study to date that systematically examines the correlation between the intention of patients to share medical information and blockchain technology through mediating effects. The role of external incentives and security/privacy in the information system of a healthcare practitioner is also not well understood conceptually.

5. Applications of blockchain in healthcare

Blockchain technology possesses the potential to enhance the healthcare sector by prioritizing the patient within the system and enhancing the safeguarding, security, and seamless exchange of health information. In essence, the healthcare industry could undergo a substantial transformation through the widespread implementation of blockchain, resulting in comprehensive improvements in safety, security, and openness across all operations. Blockchain has the ability to improve things in this specific industry. It may perform a range of tasks, including controlling epidemics and safely encrypting patient data. Finally, by enabling secure data sharing between multiple healthcare systems with patient authorization, blockchain may enhance digital health ( Figure 7 ).

Figure 7 . Emerging healthcare blockchain uses cases.

5.1. Electronic health records

Blockchain technology could be employed to exchange and store patients' EHR. It may offer a supporting system for the exchange of health information that is safer, more transparent, and traceable. With the use of this technology, several data management systems that currently function in isolation might be linked to creating an EHR system that is both interconnected and functional. Therefore can patients and healthcare professionals easily access health information stored on the blockchain. It may be summed up in four easy steps:

1. The patient is examined by the doctor, who also registers the patient's report, lab findings, prescribed medications, and important comments in their current health information system. The patient's government-approved and accepted approved ID-related data fields are then transmitted to the blockchain using APIs. Here, a transaction is established.

2. Each transaction on the blockchain is verified and given a unique public key that would be stored on the blockchain.

3. Using the patient's decryption key, doctors and healthcare organizations may use APIs to build a query that retrieves the encrypted patient data.

4. Patients can give their doctor or the healthcare institution authorization to decrypt their data by giving them the private key, which serves as a password. The information is nonetheless encrypted for those without a secret key.

Asaph et al. introduced a decentralized system for managing medical records, aimed at handling electronic medical records (EMRs). In this system, MedRec provides patients with a comprehensive and reliable log of their medical history. This log is easily accessible and empowers patients with a better understanding of their medical past and any modifications to it, thus restoring their control over their medical information. The authors established a mechanism for patients to initiate sharing of their data across different medical entities using blockchain-based permission management.

MedRec's architecture enables specific permissions to be granted with a focus on maintaining confidentiality at a very detailed level. Additional constraints, such as setting time limits on viewing rights, can be placed within the various metadata segments that constitute a single medical record. These constraints can be independently communicated through smart contract provisions. By utilizing blockchain technology, the ledger ensures a transparent and traceable record of all medical interactions involving patients, doctors, and regulatory bodies ( 33 ).

5.2. Genomic data exchange platform

Platforms built on the blockchain aim to solve some of the biggest problems with governance, including the exchange of genetic data. The ultimate objective is to guarantee that organizations and people may exchange data with privacy-preserving algorithms that make it easier to adhere to moral and legal obligations. Even though most new platforms are still in their infancy, they might be regarded as advantageous since they provide fresh solutions to the governance issues associated with the sharing of genetic data. Notably, Blockchain represents more than a mere technological foundation; it introduces a novel approach to overseeing open networks that leverages the advantages of decentralized systems, market dynamics, and consumer genetics. As a result, the primary innovation in this context surpasses technological aspects, although it is facilitated by them. Networks built on blockchain hold the potential to amplify data volume while introducing fresh ownership models and fostering active user participation in data-sharing governance. Especially in the realm of blockchain-based solutions, there's the potential to automate data access control processes, thus enhancing transparency and the availability of genetic data. Similarly, the incorporation of smart contracts could significantly bolster the enforcement of access agreements. This effort is noteworthy as it instills confidence among researchers and data custodians that subsequent data uses will adhere to the specified terms and conditions ( Table 3 ).

Table 3 . Applications/delivery functions of blockchain in healthcare.

Furthermore, effective implementation of the Blockchain-driven solution has the potential to reshape cultural norms around data sharing. This could result in a shift away from the dominance of public and commercial genetic test providers in controlling the dissemination of genetic information. This shift would empower patients and individuals to play a more influential role in the data-sharing landscape. Blockchain technology holds the capacity to establish novel shared resources that bridge the gap between market-driven dynamics and public resources. To initiate this transformation, substantial efforts in education, incentive design, ownership structure, and collaborative governance may be required. The aim of blockchain-based platforms is to empower patients and citizens to have agency over their data and participate in data sharing. Nonetheless, it's important to note that legal frameworks are still essential for the success of Blockchain-based solutions.

There are crucial scenarios where self-regulation might fall short, such as when assigning value to specific genetic datasets and determining ownership rights. To ensure that regulations align with the best interests of scientific advancement, society, and innovation, a thorough evaluation of the broader impact of such regulations within the realm of biomedical research is of utmost importance ( 104 ).

5.3. Medical imaging

Many scientists have been working on creating a feasible method for storing and distributing medical images in the realm of healthcare in recent years. The use of centralized cloud-based data centers in current practices raises privacy problems when exchanging information across a network, increases maintenance expenses, and necessitates vast storage capacity. The chain of transactions on the blockchain simply contains a list of the key owners who are authorized to view each research; no medical pictures are kept there. The image recipient must issue a signed request to the URL endpoint of the imaging source that generated the research before the actual image transfer can take place. Any person or organization that the owner (patient) who has granted permission to obtain this specific imaging study may be considered the requesting entity. The authors made use of the already existing work by the Integrating the Healthcare Enterprise (IHE) effort, which has established the ITI-43 transaction as a standard form for document retrieval across domains. The image source certifies the validity of the signature, confirms that the repository Unique ID specifies its own public key, confirms that the hashed UID matches to a study it previously released for the patient, and confirms—via the blockchain—that the patient has authorized the requester access to these images. If every requirement is met, the source sends back an ITI-43 response that includes the imaging study. To avoid eavesdropping, the request and the response are both sent via a secure channel at the transport layer ( 62 , 105 ).

5.4. Pharmaceutical and drug discovery

Pharmaceutical research and development encompass a comprehensive journey, spanning multiple years dedicated to drug discovery, drug development, and regulatory approval within the pharmaceutical supply chain. However, drug counterfeiting occurs when drug producers and regulatory agencies conceal, lack control over, or use obsolete information on the supply of pharmaceuticals. This information results in the production, marketing, and use of fake pharmaceuticals. In situations like these, when data security and privacy protection are top priorities, blockchain is the most appropriate technology. It demonstrates the reliability of medical treatment for the people and the safety of pharmaceuticals sold on the market by utilizing current, genuine digital technologies. When considering the potential uses of blockchain technology in the sector, the pharmaceutical supply chain offers a convincing example: Pharmaceutical drugs are created and produced in specialized facilities before being routinely distributed to wholesalers and eventually patients. A possible way to improve medication research and secure the dependability of the pharmaceutical supply chain is through the incorporation of blockchain technology. The whole drug development process is facilitated and managed by this technology thanks to features like distributed ledgers, smart contracts, asset transfers, and proof of work ( Table 4 ).

Table 4 . Applications of blockchain in healthcare and related technology used.

Despite its potential benefits, the influx of counterfeit and substandard pharmaceuticals into the legitimate supply chain poses a significant threat to public health. However, blockchain technology holds the promise of mitigating these risks and improving current systems. As the acceptance of blockchain technology becomes widespread, its capacity to revolutionize intercompany interactions is evident. While industries are only beginning to grasp its potential implications, it's essential to recognize that its applications span beyond specific sectors.

The full extent of the impact this transformative technology will have on the global landscape will become apparent over the years. As blockchain technology gains traction, its potential to reshape business interactions becomes increasingly apparent.

5.5. Remote patient monitoring in IoT

The utilization of the Internet of Things (IoT) and Blockchain advancements has found extensive application in various domains, such as remote patient monitoring (RPM). There has been swift development in crafting wearable medical devices within the IoT framework, equipped with diverse functionalities that facilitate the collection and analysis of live sensory data from patients. Data from IoT devices is gathered, analyzed, and stored centrally. However, there may be a number of drawbacks to this centralization, such as single-point failure, data manipulation, privacy concerns, etc. Blockchain's decentralized design can be used to solve these issues. Consequently, using IoT and blockchain to create a smart RPM system is a viable option. RPM is effective for treating a wide range of medical diseases, including diabetes, pediatrics, prenatal care, hypertension, and post-operative treatment. Patients can monitor their health at home with medical tools including blood pressure cuffs for hypertension, pulse oximeters for blood oxygen monitoring, glucometers for blood sugar levels, ECG machines for heart patients, and activity trackers. When one of these devices is attached to a patient, the health readings are automatically taken. The readings are then sent to the healthcare professionals who may monitor for health trends, and changes in conditions, and even be alerted when a patient's condition is likely to deteriorate using danger warnings.

5.6. Parallel Healthcare systems

The authors provided a paradigm for ACP-based Parallel Healthcare systems (PHSs) to improve the precision of diagnosis and efficacy of treatment. PHS uses computerized testing to analyze and evaluate a variety of medical prescriptions, simulating real-world healthcare systems to represent and reflect patient conditions, infections, and prescriptions. Healthcare operations for both humans and machines use real-time advancement as well as data-driven decision support in system arrangement. Additionally, they combined the recently developed blockchain-based PHS, which utilizes a consortium blockchain to interconnect patients, hospitals, healthcare organizations, and societies for critical health data interchange, medical record review, and accessibility to treatment ( 84 ).

5.7. Medical body sensor network

In addition to concurrent wireless technologies like wireless personal area networks, WBANs, and WPANs offer a lot of promise in healthcare monitoring systems to assess particular vital data and also to give location-based data (WPANs). A high incidence of both diagnostic and therapeutic studies is being driven by the expanding selection of wearable and subcutaneous medical equipment and their incorporation with wireless sensors. The development of Wireless Body Area Networks has been facilitated by the growing use of wireless networks and the ongoing shrinking of electrical invasive/non-invasive devices (WBANs). A WBAN allows for continuous patient health monitoring without interfering with the patient's regular daily activities. Numerous technologies have demonstrated their effectiveness in enabling WBANs applications by meeting their unique quality of service (QoS) needs, such as remote monitoring, biofeedback, and assisted living. It might be difficult to choose the best technology for a medical application because there are so many technologies that are now accessible.

5.8. Personal Health Records

A Personal Health Records (PHR) is a medical file where a patient manages their own health records as well as other information related to their healthcare. It is an electronic tool that enables people to manage their healthcare information securely. A patient may maintain and share their health information via an electronic PHR, which is secure software. Information entered by the patient from other sources, such as pharmacies and healthcare providers, may also be included. The medical professionals who assisted in the treatment processes might be held accountable for the patient's disease. PHRs can be stored electronically or using a computer program. The sort of information that each individual may access can be managed by users using PHR.

PHR aims to provide an accurate, online-accessible summary of a patient's medical history. Lab reports, patient-reported outcomes, and other information could be included in the PHR. The phrase first appeared in usage between 1956 and 1978. It was first used in paper-based and digital systems.

People think that PHR and EHR are similar. However, this is not true. Doctors maintain an electronic health record (EHR). Hospitals, pharmacies, and doctors' offices can all create personal health records. Its main goal is to give patients the tools they need to manage their information. PHR calls for all the tools necessary for you to manage your health with the guidance of your doctors. It includes information such as doctor's names, medicine allergies, family history, sickness dates, and extra dosages.

5.9. Drug supply chain

At the moment, counterfeit drugs are pharmacology's primary problem. Health Research Funding estimates that 10%–30% of medicines in underdeveloped nations are bogus. The effects that counterfeit pharmaceuticals cause are not just different from those of traditional drugs; they also have distinct consequences on human health. According to the World Health Organization, around 30% of the medications marketed in Africa, Asia, and Latin America are unfortunately fake. In underdeveloped nations, where one in every ten medicines could be fake or don't follow drug standards, this issue is regrettably becoming worse. Monitoring drug safety has become more difficult as a result of the rise of online pharmacies. These medications run via a more convoluted, dispersed supply chain, making it more challenging to detect fakes and providing possibilities for fake pharmaceuticals to penetrate the real supply chain. Concern over the security of the drug supply chain has increased within the public health community, a process that affects everyone. Public health, a process that involves everyone, has grown more concerned about the safety of the drug supply chain. Transparency might make medication supply chain surveillance and inspection considerably more effective and accessible. Laws and regulations pertaining to blockchain are currently being developed because the technology is in its genesis stage. Even blockchain technology itself is evolving (e.g., “smart contracts,” “Blockchain 2.0”), therefore more regulatory effect analyses and system simulation stress testing will be required in the future, along with engagement with key stakeholders, to undertake the cost-benefit analysis.

5.10. Fraud detection

The healthcare industry and public entities are very concerned about medical insurance fraud. The cost of healthcare fraud was reported as a loss to health insurance companies in the United States on an annual basis in the tens of billions. The patient's health is in danger from some types of fraud. This happens because the mechanism used to manually process medical insurance claims frequently fails to consider some stakeholders' consent throughout the assertion validation procedure. Blockchain is a peer-to-peer decentralized technology that can enable the secure, open, and unchangeable validation of medical claims.

Blockchain will be applied to Electronic Health Information (EHR) to address issues of security and privacy; by integrating blockchain with EHR, patients can effectively manage and save their records. Dissemination of patient data will be handled confidentially by blockchain using the blockchain medical records can be securely audited. With the blockchain, clinical data sharing will be securely and effectively managed with the help of blockchain. Blockchain enables IoT to provide a range of services, including Remote Patient Monitoring. Blockchain-based Remote Patient Monitoring will be maintained confidently. Health insurance companies are adapting blockchains to monitor false insurance claims made by patients. Various applications of blockchain and related technologies are listed in Table 2 . Applications and delivery functions are listed in Table 5 . Blockchain will be used in the pharmaceutical industry to address challenges like:

• Clinical data sharing.

• Supply chain of drugs.

• To manage clinical trials.

• Prescription management etc.

Table 5 . Blockchain frameworks in the healthcare domain.

6. Use cases of blockchain-assisted decentralized applications

Blockchain technology is still in its adolescence stages, and even when prototype apps are created, they may serve just experimental or least functional objectives. However, some publications give implementation information for programs that have been created for specific use cases. Examples of such apps for the EMR use cases are, Hyperledger Fabric-based Healthchain ( 118 ), Acile ( 119 ), and MedRec ( 33 ), both of which were created on the Ethereum platform and Other instances include MeDShare ( 96 ), BlockHIE ( 88 ), FHIRChain ( 81 ), and MedBlock ( 25 ).

The administration of the pharmaceutical and drug supply chain, biomedical education and research, handling health insurance claims, and remote patient monitoring are examples of other blockchain use cases that have been discussed. However, there are also potential blockchain use cases that are still conceptual and do not yet have prototypes, such as the usage of blockchain in legal medicine ( 120 ).

7. Constraints of blockchain-assisted decentralized apps

The development of blockchain-assisted applications has been slowed by a variety of issues, including interoperability, security and privacy, scalability, speed, and patient involvement. Due to the lack of an open standard, it may be challenging for applications made by different manufacturers or on technology to interact with one another. This creates an interoperability dilemma. Consider taking a look at the other RPM apps: one was programmed on the Ethereum network, and the other was on the Permissioned Blockchain platform. Information exchange between these two systems would be difficult because, despite the encryption mechanisms used, it may still be possible to determine a patient's identity on a public blockchain by correlating enough data that are pertinent to that patient, blockchain-assisted healthcare apps have received criticism for their lack of security and privacy. Additionally, there is a chance that security flaws brought on by hostile deliberate attacks launched against the healthcare blockchain by criminal groups or even governmental entities might compromise patients' privacy. Various cryptocurrencies' blockchain networks have allegedly been the victim of many hacks. The private keys utilized by the blockchain for the cryptographed data are also prone to hacking, which might give unapproved individuals permission to the stored medical data. How well the immutability aspect of blockchain will function with the “right to be forgotten” clause of the EU GDPR, which specifies that users have the right to request the complete deletion of their personal data, raises further doubts. When a patient's clinical history is wiped away, it may be problematic since data once synced on the blockchain may not be altered or changed because of its immutability. Blockchain-based healthcare systems have major scalability challenges, especially in light of the amount of data involved. It is not advisable to put a vast quantity of biological data on the blockchain since doing so will always result in a severe performance hit. There is also the question of speed, since processing with blockchain may result in significant delays. For instance, the current validation technique used by the Ethereum blockchain platform involves participation from each network node. This results in a sizable processing lag, particularly when the input file is substantial. The management of medical records on the blockchain presents another challenge, particularly the inclusion of patients. It's likely that patients won't be able to or desire to get engaged in the processing of their medical data, primarily individuals of younger or elder age.

8. Addressing challenges

There are several constraints and limitations over how blockchain can be implemented in health IT systems, and many methods are being put up to get around these restrictions. For example, it is advised that encrypted health data be stored “off-chain,” with just a limited amount of knowledge about the medical record and how to access it, in contemplation of the scalability issue. Thus, the “right to be forgotten” concern raised by the GDPR is similarly addressed. Although the connection to the medical data stored upon that distributed ledger cannot be unpublished, the particular medical data retained off-chain may be removed permanently. This countermeasure has a number of disadvantages, along with a gradual decrease in the built-in redundancy of the blockchain, which increases data availability. To better safeguard the data and maintain patient privacy, healthcare apps use permissioned blockchains, such as the consortium blockchain, instead of the permissionless, public blockchain. Additionally, by utilizing a strong software development strategy and all existing security safeguards during code development, many security vulnerabilities may be addressed. There are procedures in place on blockchains with permits for the healthcare sector that enable the rectification of transactions that go completely bonkers.

9. Future research

The application of distributed ledger technologies like blockchain in the healthcare industry is still in its premature stage, thus researchers must develop more proofs-of-concept and prototypes. This will aid scientists in their efforts to comprehend and advance technology as it pertains to healthcare systems. It is necessary to construct and test a number of the suggested principles, concepts, methods, and architectural designs in order to examine their merits and drawbacks. To check interoperability across diverse blockchain applications, open standards are necessary. Currently, the focus is on evaluating the capabilities of blockchain prototypes to demonstrate principles. Prior to blockchain becoming fully operational in healthcare systems, open protocols for compatibility must be developed. Researchers must immediately begin researching the issues with interoperability and standardization practices. Currently, there is a standards body (ISO/TC 307) where researchers may propose their concepts.

10. Conclusion

Blockchain technology has evolved since it was first used in Bitcoin to become a general-purpose technology with uses in many other sectors, including healthcare. The authors conducted a systematic review, employing the systematic mapping study methodology, to create a comprehensive overview of relevant research. This was done to gain insights into the current status of blockchain technology utilization in the healthcare sector. The study aimed to achieve several specific objectives: identification of healthcare applications utilizing blockchain technology, examination of exemplary apps developed for these applications, exploration of challenges and limitations linked to blockchain-based healthcare apps, analysis of the methodologies employed in creating such apps, and identification of potential avenues for future research. Through a meticulous search and selection process, the team identified 136 papers. These papers were subsequently scrutinized by the authors to address the research inquiries at hand.

The study we conducted revealed various healthcare applications for blockchain technology, including governing electronic medical records, overseeing the pharmaceutical and drug supply chain, advancing biotech research and education, enabling remote patient monitoring, and facilitating healthcare information analytics. To achieve these goals, different blockchain development approaches such as permissioned blockchains, off-chain storage, and smart contracts have been employed.

However, further investigation is necessary to refine, evaluate, and fully grasp the potential of blockchain technology in the healthcare sector. There is also a need for additional research to support ongoing endeavors aimed at resolving challenges related to scalability, latency, interoperability, confidentiality, and security in the implementation of blockchain-based healthcare solutions.

Data availability statement

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

Author contributions

SS and YS focused on Blockchain and its practical applications. YH, MJ, and OV dedicated their efforts to the effective implementation of blockchain in the healthcare sector. All authors have reviewed and approved the final version of the manuscript for publication.

Acknowledgments

We, as the authors, express our gratitude to our esteemed reviewers for their accurate and concise suggestions, which greatly contributed to the optimal presentation of the material. The realization of this work became possible solely through the unwavering determination and bravery of the Ukrainian Army.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Author disclaimer

The viewpoints presented in this paper are exclusively those of the researchers and do not necessarily reflect the perspectives of their associated institutions, or the viewpoints of the publishing entity, the editorial team, and the reviewers. The publisher does not provide a guarantee or endorsement for any product discussed in this article or for any claims made by its manufacturer.

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Keywords: blockchain, distributed public ledger, healthcare, electronic health record, personal health record, medical health insurance

Citation: Singh Y, Jabbar MA, Kumar Shandilya S, Vovk O and Hnatiuk Y (2023) Exploring applications of blockchain in healthcare: road map and future directions. Front. Public Health 11:1229386. doi: 10.3389/fpubh.2023.1229386

Received: 26 May 2023; Accepted: 23 August 2023; Published: 15 September 2023.

Reviewed by:

Copyright © 2023 Singh, Jabbar, Kumar Shandilya, Vovk and Hnatiuk. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Olena Vovk, olena.b.vovk@lpnu.ua

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Blockchain Technology in Healthcare: A Systematic Review

Affiliations.

• 1 Department of Electrical, Computer and Software Engineering, University of Ontario Institute of Technology, Oshawa, ON L1G 0C5, Canada. [email protected].
• 2 Department of Electrical, Computer and Software Engineering, University of Ontario Institute of Technology, Oshawa, ON L1G 0C5, Canada. [email protected].
• 3 Department of Electrical, Computer and Software Engineering, University of Ontario Institute of Technology, Oshawa, ON L1G 0C5, Canada. [email protected].
• PMID: 30987333
• PMCID: PMC6627742
• DOI: 10.3390/healthcare7020056

Since blockchain was introduced through Bitcoin, research has been ongoing to extend its applications to non-financial use cases. Healthcare is one industry in which blockchain is expected to have significant impacts. Research in this area is relatively new but growing rapidly; so, health informatics researchers and practitioners are always struggling to keep pace with research progress in this area. This paper reports on a systematic review of the ongoing research in the application of blockchain technology in healthcare. The research methodology is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and a systematic mapping study process, in which a well-designed search protocol is used to search four scientific databases, to identify, extract and analyze all relevant publications. The review shows that a number of studies have proposed different use cases for the application of blockchain in healthcare; however, there is a lack of adequate prototype implementations and studies to characterize the effectiveness of these proposed use cases. The review further highlights the state-of-the-art in the development of blockchain applications for healthcare, their limitations and the areas for future research. To this end, therefore, there is still the need for more research to better understand, characterize and evaluate the utility of blockchain in healthcare.

Keywords: blockchain; healthcare; systematic review.

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Research Article

Blockchain technology in healthcare: A systematic review

Roles Data curation, Methodology, Writing – original draft

Affiliation Department of Computer Science, National College of Business Administration & Economics Lahore, Multan, Pakistan

Roles Conceptualization, Data curation, Supervision, Writing – original draft

* E-mail: [email protected]

Affiliations Department of Computer Science, National College of Business Administration & Economics Lahore, Multan, Pakistan, Department of Computer Science, University of Management and Technology, Lahore, Pakistan

Roles Conceptualization, Formal analysis, Writing – review & editing

Roles Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Writing – original draft

Roles Data curation, Funding acquisition, Methodology

Roles Conceptualization, Formal analysis, Methodology, Writing – original draft

Roles Data curation, Formal analysis, Writing – review & editing

Roles Conceptualization, Data curation, Resources

• Huma Saeed, 
• Hassaan Malik, 
• Umair Bashir, 
• Aiesha Ahmad, 
• Shafia Riaz, 
• Maheen Ilyas, 
• Wajahat Anwaar Bukhari, 
• Muhammad Imran Ali Khan

• Published: April 11, 2022
• https://doi.org/10.1371/journal.pone.0266462
• Peer Review
• Reader Comments

Blockchain technology (BCT) has emerged in the last decade and added a lot of interest in the healthcare sector. The purpose of this systematic literature review (SLR) is to explore the potential paradigm shift in healthcare utilizing BCT. The study is compiled by reviewing research articles published in nine well-reputed venues such as IEEE Xplore, ACM Digital Library, Springs Link, Scopus, Taylor & Francis, Science Direct, PsycINFO, Ovid Medline, and MDPI between January 2016 to August 2021. A total of 1,192 research studies were identified out of which 51 articles were selected based on inclusion criteria for this SLR that presents the modern information on the recent implications and gaps in the use of BCT for enhancing the healthcare procedures. According to the outcomes, BCT is being applied to design the novel and advanced interventions to enrich the current protocol of managing, distributing, and processing clinical records and personal medical information. BCT is enduring the conceptual development in the healthcare domain, where it has summed up the substantial elements through better and enhanced efficiency, technological innovation, access control, data privacy, and security. A framework is developed to address the probable field where future researchers can add considerable value, such as data protection, system architecture, and regulatory compliance. Finally, this SLR concludes that the upcoming research can support the pervasive implementation of BCT to address the critical dilemmas related to health diagnostics, enhancing the patient healthcare process in remote monitoring or emergencies, data integrity, and avoiding fraud.

Citation: Saeed H, Malik H, Bashir U, Ahmad A, Riaz S, Ilyas M, et al. (2022) Blockchain technology in healthcare: A systematic review. PLoS ONE 17(4): e0266462. https://doi.org/10.1371/journal.pone.0266462

Editor: Pandi Vijayakumar, University College of Engineering Tindivanam, INDIA

Received: November 8, 2021; Accepted: March 21, 2022; Published: April 11, 2022

Copyright: © 2022 Saeed et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting information files.

Funding: The author(s) received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist.

Introduction

Healthcare is a system that includes 3 main components: (i) Main suppliers of services for medical treatment, For instance, doctors, nurses, technicians, and hospital administrations (ii) Emergency related services [ 1 – 4 ], and (iii) Health and health-oriented service users, specific patients. In the current study, to encourage, preserve or restore the health of beneficiaries, we examine the health maintenance to include technology-based remotely controlling services increased by constituent service providers [ 5 – 9 ]. In the medical field, every year, there are more security and privacy breaches, in 2017, more than 300 breaches were reported, and up to 37 million records were affected during 2010–2017 [ 10 , 11 ]. The growing digitization of medical care has advanced the acknowledgment of issues about secure storage, accessing of patients’ medical records, ownership, and medical data from associated sources [ 12 – 16 ]. Blockchain is recommended as a method of addressing critical issues faced by healthcare, for instance, protected sharing of health records and adherence to data privacy laws [ 17 – 19 ].

Blockchain is a particular type of database that can be managed by the network of authenticated members or nodes [ 13 ] and stores immutable information blocks that can be strongly exchanged without interference by third parties [ 10 ]. With cryptographic signatures and the use of consensus algorithms which are implemented as key enablers in their application, data is stored and registered [ 20 ]. The capability of preserving data is a major aim for using the BCT particularly in healthcare [ 21 ], which is subject to massive sharing and dissemination of a significant amount of data [ 7 ]. In different stages, the development of blockchain technology, as well as its application in various contexts, had been materialized. The first phase of blockchain development was focused on cryptocurrencies, while the second focused on the use of smart contracts in industries like real estate and finance [ 11 , 22 ]. The 3rd generation of evolution concentrated on employing blockchain in non-financial areas including government, culture [ 23 ], and healthcare space [ 22 , 24 ]. Also, powered by revolutionary technical features such as data immutability [ 25 ], with the introduction of artificial intelligence, blockchain technology is having its 4th generation of evolution [ 26 ]. This asserted diversity in Blockchain’s application spectrum can be attributed to its ability to build decentralized [ 27 ] and trustless transaction environments [ 28 ]. As blockchain can tackle serious issues, such as automated claim authentication [ 9 ] and public health management [ 29 ], the healthcare sector is a prime choice for the application of blockchain technology [ 30 – 32 ]. This technology allows patients to keep personal data and determine with whom this can be shared, thus resolving current data ownership, and sharing issues [ 28 , 33 ]. At the same time, it allows recorded data to be integrated, modified, shared safely, and retrieved on time by relevant authorities using consensus protocols [ 31 ]. This is a significant benefit of the use of this technology in the healthcare system, as existing procedures need third parties to store the data [ 10 ]. Finally, because of possible human error, blockchain could potentially add accountability to data management processes [ 34 ] further decreasing the risks of mishandling or misusing recorded data [ 31 ]. Given the optimistic connotations of the effects of blockchain on social and business change, in contrast to previously defined expectations, it appears to be a discussion regarding its basic and derived advantages. A recent study indicates that while organizations will make substantial investments in the future in adopting blockchain-based technology due to a widespread perception that the advantages could be over-hype, they will probably accept a cautiously pragmatic approach [ 35 ]. It can be said that this technology has yet to fulfill its expectations [ 36 ], a fact that can be due to the prevalent adoption of block chain, particularly about regulatory barriers, to certain challenges [ 31 ]. The general public and specific users, for instance, patients or physicians are not acquainted with the way blockchain works, the technological features, or its advantages for data processing is another significant obstacle in promulgating the implementation of blockchain [ 35 ]. Suggest that it may take a considerable time for this technology to establish all anticipated stages of business transformation mainly because of the organizational, social, and implementation challenges, for example, security issues or governance reasons [ 22 , 31 ]. This could also be exacerbated by general confusion regarding the use of blockchain regarding legal enforcement and regulations of the government. Current research focuses on supporting blockchain operational growth and speed-up its prevalence by overcoming these barriers.

However, previous studies have made little attempt to comprehensively summarize the existing knowledge by using SLRs [ 9 – 13 ]. For example, bibliometric techniques were used by [ 10 ] to provide a summary of blockchain research patterns and components related to the implementation of blockchain in the field of healthcare. In [ 9 ] the different blockchain platforms have been developed to deploy blockchain in healthcare. The study [ 11 ] addressed different examples of the implementation in the healthcare of blockchain technology, the problems, and their potential solutions. In diverse contexts where this technology was implemented [ 12 ], addressed design choices and tradeoffs made by the researchers. The research studies of [ 13 , 14 ] have discussed the Blockchain-based applications throughout numerous industries and addressed many contexts of use for this technology in a broad manner. Recently [ 14 ] reviewed 39 studies to present an overview on common channels and other areas where blockchain technology is utilized for healthcare enhancement. Although these systematic literature reviews have a contribution to the extent of knowledge, their emphasis has been mainly on synthesizing or delineating blockchain technology patterns and areas [ 10 , 11 , 13 , 14 , 16 ]. However, researchers will get benefit from a concentrated discussion on the implications of its adoption [ 15 ], along with concrete obstacles and areas for progress for advancing the field, due to the reach and diversity of previous blockchain studies [ 11 ]. Through assimilating existing information and describing focus areas that require considerable academic attention, review-based research will assist in meeting these needs [ 11 , 16 – 19 ]. As a result of this necessity, we perform an SLR on the blockchain technology application. This SLR presents a valuable overview of ongoing research, gaps in current knowledge, and future avenues of research as well. The contribution of this study is in two ways, this research adds to the emerging blockchain literature in healthcare. First regarding their implementation areas, restrictions, and recommendations, it offers an advanced and thematically ordered classification of previous literature. Second, we propose a synthesizing process according to the results of the SLR to detail possible topics that need academic attention to further update the existing body of literature.

The present study is organized as follows: In Section 2, we provide a thorough description of the research method utilized to search, screen, and select the literature. In Section 3, we present relevant review works that have been conducted in the field of health care using blockchain technology and discuss all the papers that have been selected, focusing on their main findings, and highlighting research gaps for future research. Finally, in Section 4we conclude this study.

Methodology

SLRs always provide a thorough understanding of literature as it presents a complete and systematized review meeting all standard protocols in it [ 18 , 37 – 39 ]. SLRs also help in the understanding of current information gaps and, as a result, the discovery of potential research avenues [ 19 ].

Research questions

• RQ1 : What is the advanced profile used for the employment of blockchain in the healthcare domain? The purpose of this research question is to identify the number of research papers issued every year, the average citation received on research papers yearly, and academic contribution on the subject by Journals, publishing houses, and community.
• RQ2 : What are the major healthcare domains where blockchain technology has been implemented? The purpose of this question is to identify the contexts in which blockchain technology has shown significant outcomes in healthcare.
• RQ3 : What are the existing problems and constraints raised by the previous studies in the healthcare field using blockchain technology? The motivation behind this question is to identify existing problems and issues of blockchain technology in the healthcare field based on results, limitations, and conclusions of previous research studies.
• RQ4 : What are the potential healthcare avenues that would benefit from blockchain technology implementation? The purpose of this question is to identify growing gaps and prospects of the future research agenda

Research objectives

• RO1 : Establishing an archive of work that relates a wide topic about Blockchain in healthcare and offers an open dataset about Blockchain for all other researchers.
• RO2 : Identify a more focused set of studies that have used blockchain technology in healthcare applications.
• RO3 : Identify problems and constraints discussed in the healthcare field using blockchain technology.
• RO4 : Characterize existing solutions in the field of blockchain in healthcare and clarify the similarities and differences between them using a characterization framework.

Research strategy

Nine databases—IEEE Xplore, ACM Digital Library, Springs Link, Scopus, Taylor & Francis, Science Direct, PsycINFO, Ovid Medline, MDPI—are recognized by previous studies as standard data sources of research papers about health informatics [ 40 ]. Reviewed papers have been outlined for understanding the research status of applying blockchain in health care. For the right database search the three keyword combinations existed as—“blockchain and Healthcare”, or “medical Health” or Medical Management or Health Management. The above keywords were extracted from an article of previous literature i.e. SLRs) using similar keywords such as blockchain and medical healthcare.

Study selection

The selection process aimed to find the articles that are the most relevant to the objective of this SLR. If there was the same paper in more than one source, as per our research, it was considered only once. The content of the papers chosen for the final sample was evaluated [ 39 , 41 ] to make sure that the findings of the present SLR produced clear results and that is not biased. For reaching a consensus of final inclusion or exclusion, two of the researchers finalized the evaluation. After completing this, the discrepancies of individual assessments were addressed through discussion. A third author was engaged in analysis and debate in situations where the two writers did not find consensus. After the papers were found, the first move was to delete redundant titles and those which are not connected in scrutiny. The standards for inclusion were limited to the hunt for String, and a study conducted by at least one of the following criteria for exclusion (EC) is omitted:

Inclusion criteria (IC`s).

• IC1 : Studies are released any time on or before August 2021.
• IC2 : Studies are limited to the journal, conference, report, workshop, and symposium articles only.
• IC3 : Availability of complete texts in digital databases.
• IC4 : Proposed models or frameworks present.

Exclusion criteria (EC).

• EC1 : Exclude duplicated studies.
• EC2 : Eliminate preview, book chapters, magazines, thesis, monographs, and interview-based articles.
• EC3 : Exclude studies based on quality evaluation criteria.
• EC4 : Studies written in a language other than English.

The choice of papers was based on clear above discussed criteria for inclusion and exclusion. Below Fig 1 has been developed through the aspiration from the PRISMA diagram [ 42 ]. Fig 1 shows the study selection process.

• PPT PowerPoint slide
• PNG larger image
• TIFF original image

https://doi.org/10.1371/journal.pone.0266462.g001

Results and discussion

This section describes the outcomes related to the systematic study RQs discussed above. 51 research studies have been selected to illustrate the outcomes of each RQs. Publication and other selection biases are a potential threat to validity in all SLR and we cannot exclude the possibility that some research studies were missed resulting in reduced precision and the potential for bias. Therefore, we made significant efforts in finding all eligible research articles, and conference proceedings from different well-reputed databases and by contacting experts in the BCT area through social media platforms. We believe that our work provides a significant contribution to the role of blockchain technology in health care.

Selection results

Our search identified 1177 records, of which 1126 were screened as shown in Fig 1 . 51 research articles were included in this SLR. The list of selected papers with descriptions of the overall classification results are discussed below.

RQ1: What is the advanced profile used for the employment of blockchain in the healthcare domain?

This SLR addresses the achieved descriptive records about the number of articles that have been published each year, publication source, the average citation received on research papers yearly (see Table 1 ). To complete this SLR, we have examined published surveys, systematic literature review (SLR), systematic reviews (SR), and research papers related to blockchain in healthcare, and published in the field of blockchain from 2018 to 2021. The number of highest citation research articles with the most citations is shown in Table 1 .

https://doi.org/10.1371/journal.pone.0266462.t001

Fig 2 demonstrates the number of articles published each year from 2018–2021. The four obvious outliers are existing from 2018 to 2021. In 2018, 24 articles were published, 16 articles were published in 2019, 9 articles were published in 2020 and 2 articles were published in 2021.

https://doi.org/10.1371/journal.pone.0266462.g002

The authors of the reviewed articles were found to be affiliated with institutes located across 17 countries. Five countries, China (number of articles = 12), USA (number of articles = 6), South Korea (number of articles = 4), Brazil (number of articles = 3) and India (number of articles = 3), cumulatively represented 65% of the sample (see Fig 3 ).

https://doi.org/10.1371/journal.pone.0266462.g003

In addition, the analysis of author indexed keywords conducted by using word cloud showed that the main emphasis of article related to “blockchain”, “technology”, “data”, “healthcare”, “sharing”, and “medical” which are graphically illustrated in Fig 4 .

https://doi.org/10.1371/journal.pone.0266462.g004

RQ2: What are the major healthcare domains where blockchain technology has been implemented?

In this part, we will discuss a review of the fundamental principles of blockchain. BCT is used in medicine, especially in managing the information in healthcare that particularly is important in the healthcare area as this technology involves the sensitive data of patients. This sector is important to society because innovations in this field will enhance the quality of people’s life. Following this logic, the computation can help to mitigate the effects of certain problems in this field. Informatics, for example, helps in the automation of medical records by ensuring more reliable data sharing, log management, and other applications. One of the first and most popular blockchain applications in healthcare is the exchange of health records. Information related to health is difficult to disclose because it is labeled as confidential information and includes patients’ details. Among the key works in the literature that discuss this application of blockchain technology are: [ 85 , 86 ]. The characteristics of blockchain-based architectures for the sharing of electronic healthcare records can vary. The features of blockchain-based systems for the exchange of electronic healthcare records may vary. One of the most well-known structures in the literature is discussed in the work of Azaria et al. [ 86 ]. Several recent papers in the literature have cited this as a framework for the development of other similar architectures. Some of these systems are inspired by Azaria et al. [ 86 ] cited in [ 30 , 79 , 87 , 88 ]. Voting is a formal statement of an individual’s or a group’s opinion or choice, whether positive or negative. Traditional voting methods, on the other hand, are centralized and are known to have security and efficiency flaws. The study [ 89 ] examines blockchain-based voting systems in depth and categorizes them based on a variety of characteristics e.g., the types of blockchain used, the consensus approaches used, and the scale of participants. Artificial intelligence (AI) is now the core technology for a wide range of applications, from self-driving cars to smart cities. One of the most crucial pillars of social and economic stability is smart healthcare, which is an integral part of smart cities. The research study [ 90 ] focused on designing a human-in-the-loop-aided (HitL-aided) scheme to protect patient privacy in smart healthcare. Profile matching technology can facilitate the sharing of medical information across patients by matching similar symptom traits. However, because the symptom attributes are linked to sensitive information about patients, their privacy will be compromised during the IoMT matching process. To accomplish fine-grained profile matching, the study [ 91 ] provides a verifiable private set intersection scheme and used a re-encryption technique to preserve patients’ privacy. Technologically advanced countries are exploring or implementing smart homes, it is convenient but risky. Most of the existing solutions are generally based on a single-server architecture, which has limitations in terms of privacy, integrity, and confidentiality. While blockchain-based solutions may alleviate some of these problems, they still face some significant obstacles. Lin et al. [ 92 ] developed a revolutionary safe mutual authentication method for use in smart homes and other applications. MedRec will be the first sharing architecture to be discussed, which uses a blockchain-based system to store electronic medical records. The MedRec considers resolving issues as data access response time, interoperability, and increased data quality in healthcare research [ 86 ]. It is worth looking into the resources that were used to create MedRec’s architecture, since it implements a private P2P network (Permission block chain), as well as using Ethereum’s smart contract platform, to make it easier to monitor and track network state transitions. One of the MedRec architecture’s hallmarks is that it provides patients with a consulting agency that has records of their healthcare background, enabling them to remain informed about health decisions. Another difference is that they enable the standardization of health data since they are adaptable and provide open data standards in a variety of formats. This architecture takes a novel approach to the use of health data management systems by enhancing security and establishing a common language for data exchange for research purposes [ 86 ]. While Azaria et al. [ 86 ] also plan to perform experiments and analyses with a diverse community of users. In summary, MedRec is a realistic choice for exchanging healthcare information that can be used to combine patient care, hospital care, and physician care. As a consequence, the reported data can help to minimize discrepancies among different systems of hospitals. As stated by [ 85 ], the method introduces the topic of cloud computing, which could help in creating new architectures for sharing healthcare records via blockchain, resulting in safer and more secure healthcare systems for clinical use. The authors propose a cloud-based architecture that uses a blockchain-based data system to connect a network of communication nodes. The paper [ 85 ] shows how to handle the exchange of healthcare information using a blockchain architecture, which employs the principles of intelligent contracts and, immutable bookkeeping. The major roles of BCT in sharing health information, remote care with IoT, security, and privacy, and supply chain are depicted in Fig 5 .

https://doi.org/10.1371/journal.pone.0266462.g005

The list of blockchain-based healthcare methods is discussed in Table 2 .

https://doi.org/10.1371/journal.pone.0266462.t002

RQ3: What are the existing problems and constraints raised by the previous studies in the healthcare field using blockchain technology?

Even though blockchain is a multidisciplinary concept with challenges and limitations, it can be applied to a variety of areas [ 88 ]. Researchers in this field are working to overcome or mitigate the negative effects of these factors. The following are some of the problems (i.e. technological challenges) that blockchain technology faces when used in healthcare [ 22 , 88 , 97 , 98 ].

1) Throughput.

If the number of transactions and nodes in the network grows, more checks will need to be performed, possibly causing a network bottleneck. When dealing with healthcare systems, high throughput is a challenge because unless there is fast access, it might adversely affect a diagnosis which could save someone’s life [ 64 ], correspondingly recognizing that the suggested framework focuses on identifying inconsistencies will possibly not perform well when datasets are unlabeled. Issues including specifications for continuous updates by the used system [ 59 ], keyword set size [ 75 ], network set-up and disk space needed based on the blockchain type, such as Ethereum software, employed to the framework can all affect a framework’s scalability and performance quality [ 25 , 99 ]. Similarly [ 48 ], suggests that integrating certain features into established systems, e.g. making global smart deals, can offset higher performance-related costs. Furthermore, a small number of studies have suggested that performance-related problems can be connected to the node management in a suggested system.

2) Latency.

Validating a block takes about 10 minutes; this can be harmful to system security services since successful attacks may occur during that time. Healthcare networks are complex and should be accessed at all times, as any delay may negatively affect the analysis of an exam.

3) Security.

When a party has control of 51 percent of the voting power, this can adversely affect the computing power of the network. This is a serious issue that needs to be addressed because a harmed healthcare system will lead to healthcare organizations losing their reputation.

4) Resource Consumption.

Since the mining process consumes a lot of energy, using this technology could result in a significant loss of resources. Since multiple devices are required to track patients in a healthcare setting, energy costs are high; however, the use of blockchain may result in high computing and energy costs. Managing these expenses is a challenge for businesses.

5) Usability.

Since these systems are so complicated, usability is a challenge as well to deal with. Additionally, an API must be developed (Application Programming Interface) Users would enjoy the user-friendly features. Since not all health practitioners have the same level of education, As IT professionals, we should be able to use frameworks that are easy and effective.

6) Centralization.

Even though blockchain has a decentralized design, certain implementations tend to concentrate the miner, which decreases network stability. Because this central node is insecure and may be hacked, hostile attackers can get access to the data it holds [ 25 ].

7) Privacy.

It is common to suppose that the Bitcoin framework allows blockchain to make sure the privacy of its nodes. The results of [ 25 ], on the other hand, contradict this assumption. Furthermore, strategies to provide this functionality to blockchain-based systems are needed [ 25 ]. Due to privacy laws and regulations, blockchain-based systems have to conform to the General Data Protection Regulation (GDPR). Our research also indicates those users’ reservations about the safe and ethical utilization of data could be a major barrier to blockchain adoption in healthcare systems. The existing issues are primarily associated with blockchain technology’s technological limitations, such as the protection of individual nodes [ 53 ], the degree of safety permitted through cryptographic elements implemented with the system [ 70 ], besides the preservation of confidential data whereas requesters complete their computations [ 100 ]. However, certain research has drawn attention to more socially relevant issues regarding sharing of public data [ 73 ] and users’ confidence in governments [ 49 , 74 ]. Such issues may also be linked to the suggested framework protection from the perspective of users for example users’ management and misuse of permitted personal keys/codes [ 46 ].

8) Constraint.

Prior studies have identified constraints, which can be divided into four categories. These dimensions mean that such constraints extend beyond technical boundaries (costs of designing, implementing blockchain systems, data analysis for system assessment, and framework constituent elements) to include certain social facets also such as trust in the administration, infrastructure of technology in a country.

This set of constraints is specifically concerned with the time, capital, and economic expenses of putting a system of blockchain into action. For example [ 50 ], discuss resource constraints in IoT, while [ 28 ] discuss the costs of arranging dispersed app in the deployment of blockchain. Additional expenses that have been established as constraints and limitations in previous research include the linear increase in protocol costs based on the characteristics and attributes of the entities involved, such as patients [ 54 ], increased operational overhead for the patient, and access latency for the requester [ 69 ], the exchange and implementation costs depend upon inconstant inputs in size and length of a string [ 67 ]. The issues related to time are further listed as one of the limitations, i.e. the spent time in finding smart contracts globally [ 48 ], increased time consumption [ 57 ], transmission timing [ 53 ], the time needed for the data receiver to seek the required data in shared storage [ 68 ], and higher overall execution time [ 21 ].

RQ4: What are the potential healthcare avenues that would benefit from blockchain technology implementation?

Blockchain consists of a sequence of blocks connected with cryptographic techniques. The immutability of this is one of the most attractive characteristics to many industries. The data that is added to the blockchain is irreversible, consequently, allowing for the creation of a consensus-based, verifiable, and accurate data ledger. That creates blockchain especially well-suited to tasks wherever integrity of data is critical; ProvChain [ 101 ], an infrastructure based on this technology in giving chain-of-custody to the database, is a functional example of this immutability. There are many blockchain implementations, including Bitcoin, a cryptocurrency token based on the blockchain; and Ethereum, a cryptocurrency token based on blockchain. Ethereum [ 102 ], a blockchain ledger with Turing-complete computer-generated device that allows smart contracts to implement code on this; and JP Morgan’s Juno [ 103 ], an Ethereum fork that uses the particular consensus mechanism called Quorum, along with several other blockchain implementations. The execution of blockchain varies due to ways in their consensus approaches. Bitcoin, for example, employs the HashCash [ 104 ] Proof-Of-Work algorithm, which is a deliberately slow system intended to avoid denial-of-service attacks. As a vote against the blockchain’s agreement, every Bitcoin miner authenticates this blockchain system by conducting that algorithm. Ethereum includes Ethash, which is an algorithm called Proof-of-work based on the Dagger-Hashimoto algorithm, as described in the Ethereum Yellow Paper [ 103 ]. However, shortly Ethereum is likely to advance in an algorithm named Casper. It will consider the excess requirement of energy in Proof-of-work [ 105 ]. The implementation of smart contracts separates Ethereum from Bitcoin. The smart contract is one of the snippets of code that run on each blockchain node. These are self-executing contracts in which all members of the blockchain are bound by the agreement. In the same way, as a standard contract does, they influence advantages, responsibilities, also punishments related to contract-related conduct. It could be utilized to model the HIPAA healthcare personal health information (PHI) workflow to satisfy audit and regulatory standards, likewise, done inside Patientory since they resemble conventional paper contracts and rules [ 106 ]. A new type of blockchain trust model, trust in the consortium, is also emerging. Microsoft recently released the Coco framework, which enables the creation of blockchain-agnostic consortiums [ 107 ]. Above mentioned models are based on a pre-defined group of trustworthy parties. It can be among various clinics or in the UK, NHS Trusts, third parties, and manufacturers of devices. By implementing smart contracts only on the hardware of trusted partners, without requiring miners, a consensus can be generated. It turned out in remarkably improved results, through a Coco-optimized blockchain case capable of processing 1600 transactions in a second, taking the blockchain system very close to the major payment processors. Coco also supports a variety of trusted execution environments, including Windows Virtual Secure Mode, Arm Trust Zone, and Intel Guard Extensions to name a few.

1) Clinical trials.

Managing trial subject consent and clinical trials itself is an area in which blockchain can potentially improve the accountability, audit ability, and transparency of researchers and practitioners in the medical field. By keeping the unchangeable log of a patient’s approval, officials could control the standard of clinical trials easily, making sure it complies with informed consent regulations of the country. It is especially important because a forged informed consent form is one of the common types of clinical fraud. It involves falsifying patient consent and editing records, implying that authentication of trial subjects is essential for avoiding it. That kind of setup may be improved by implementing a smart contract system that stops clinicians to use the data of patients unless a key is issued by the end of an auditable process of smart contract that requires permission in each step in the trial, as proposed by Benchoufi, Porcher, and Ravaud. This procedure should also allow the patient’s consent to be revoked. Executing the clinical trial of blockchain consent log provides the subjects with data ownership while also having a trail of audit for regulators, medical professionals, and researchers. The role of BCT in clinical trials is graphically represented in Fig 6 .

https://doi.org/10.1371/journal.pone.0266462.g006

2) Sharing the data.

Sharing information is regarded as the most significant opportunity for improvement in healthcare; however, it too poses a significant challenge in privacy. Sharing the data using BCT is presented in Fig 7 . Powles and Hodson [ 108 ] use DeepMind’s case study teamwork with the Royal Free London NHS Foundation Trust to address the need for transparency in how patient data is being shared with third parties. Regardless of the good impact on diagnosis/treatment of patients by the product suite of Google, one of the significant issues addressed in the previous case study was a lack of patient consent. On the other hand, Sleep Apnea American Association, and IBM [ 109 ] were collaborating to solve major healthcare challenges to examine sleep apnea (with IBM’s Watson supercomputer at home) in thousands of Americans, with informed and clear patient consent. That was critical to implementing the national standard for interoperability in the healthcare system of IT. Which was emphasized by Wachter and Hafter through a white paper in UK NHS in comparison to the US healthcare sector that emphasized the significance of interoperability in permitting patient Electronic Health Records (EHRs) over various clinics, such as various trusts that do not maintain a separate system to get access on these records built by different vendors.

https://doi.org/10.1371/journal.pone.0266462.g007

In a report of Harland Simon on a project justifying RFID tagging in NHS Cambridge shire, about 15% loss of assets annually, resulting in a substantial cost to repurchase the items that hospitals previously have. Furthermore, as per GE Healthcare [ 110 ] report, nurses spend an average of 21 minutes per shift searching for misplaced devices as stated by, defining any device under $5000 as consumable and to again purchase if any device is lost, suggesting significant cost in the sector. Published by Harland Simon, another study reported that [ 111 ], by adopting radio frequency identification (RFID) standards for tracking of medical devices, NHS Forth Valley in Scotland had saved nearly £400,000 in cost avoidance by not having to buy the important devices which would have been lost by the medical system. Tracking of Drugs has been a completely different issue than tracking of devices because a major concern is counterfeits of drugs here. According to WHO’s report, In the US up to 10% supply of Pharmaceutical products is counterfeit. In the United States, the Food and Drug Administration (FDA) recently approved the utilizing the RFID to track pharmaceuticals between the supply side to the patient. It enables the whole sequence kept supervised, to make sure that pharmaceuticals were purchased from a legitimate source. Pfizer was the first pharmaceutical company to use RFID “e-pedigree” to ensure that patients and doctors could trust the source and capabilities of their flagship medicine, Viagra, after identifying it as one of their most counterfeited drugs. Because of the use of low-cost passive RFID tags and barcodes, the system enabled the pharmacists and wholesalers to check the authenticity of their Viagra through a simple RFID scanner at a low rate than Pfizer.

3) Records of patients.

Blockchain is having the potential to significantly disrupt health services and place data in the patient’s hand. The specific intriguing steps are in MedRec [ 86 ], which provides doctors and patients with an immutable log of a health record as shown in Fig 8 . That has a different approach to incentivize miners by providing access to anonymized data about health in exchange for network maintenance. MedRec maps Patient-Provider Relationships (PPRs) using Smart Contracts when the contract displays a reference list having relationships between nodes on the Blockchain-system. This too places PPRs in the patient’s hand, empowering them in accepting, rejecting, or modifying relations with health service providers for example doctors, insurers, and hospitals, etc. Blockchain-system allows for interoperability in the health system by providing a decentralized ledger of accepted facts in healthcare records to which all health service providers are having access. It implies that while user interfaces may differ, the central ledger would be the same across all service suppliers. A challenge that exists relates to the current state of health records across providers, which contain significant amounts of the same information under different identifiers that may not be linked. This causes replication, and as the blockchain system increases in size, it is reduced in performance. The level of data duplication in all records will necessitate replication to maintain a reasonably performant system with unique, anonymized identifiers to identify the patient in all kinds of service. Adopting the blockchain health record is a business challenge in and of itself. The important thing is that medical records will not start from zero because they would have to replace the current setup, and that is challenging. Furthermore, the sheer volume of data generated in the healthcare sector is ever-growing, with Kaiser Permanente estimated to have between 26 and 44 petabytes of data on its 9 million members from EHRs and other medical data in 2014. The data volume which is logged and referenced would mainly exacerbate the scalability issue.

https://doi.org/10.1371/journal.pone.0266462.g008

4) Drug tracking.

Another opportunity is tracking the drugs using a blockchain system as shown in Fig 9 , which takes advantage of its immutability in the development of tracking and a chain of custody from manufacturer to patient. Chronicled is a technology startup company that is working on its product, Discover, that develops a chain of custody model that shows the manufacturing place of a drug, the places it had been since then, and when it was disbursed to patients, hence reducing the pharmaceutical theft and fraud. That enables the health professionals in meeting existing standards of the pharmaceutical supply chain, along with focusing on interoperability among healthcare professionals. The Counterfeit Medicines Project has been launched by Hyperledger, the Open-Source Blockchain Working Group, to address the issue of counterfeits of medicines. The origins of counterfeit medicines would have been tracked and thus eliminated from the chain of supply. One benefit of tracking drugs by blockchain-system over conventional methods is the inherent decentralization of trust and authority in the technology’s principles; whereas chief authorities could have bribed or faked, it is much more difficult to bribe a consensus of those on the blockchain. As a result, an existing standard in pharmaceuticals tracking in industry, ePedigree, which already employs RFID and a traditional database, is transitioning to its blockchain application. If medicines/drugs could be tracked and developed at the point of manufacture using blockchain’s inherent anti-tampering capabilities, that will remove the counterfeited pharma products engaging in the supply chain.

https://doi.org/10.1371/journal.pone.0266462.g009

5) Device tracking.

Tracking of medical devices is one aspect of Block chain in disrupting healthcare, from manufacturing to decommissioning. The monetary benefit generated through tracking of assets is clear; NHS East Kent Hospital discovered 98 infusion pumps they had no idea they still owned across three sites as concluded through the case study of Harland Simon [ 111 ] in which active RFID trackers were implanted. Because of this single case study, they saved $147,000 at $1,500 per person. The use of blockchain in conjunction with this technology allows for an immutable ledger that not only shows the current location of the device, also the location of the lifecycle, along with the serial number, distributors, and the manufacturer linked with the device, assisting with regulatory compliance. Deloitte identified the competency among the potential game-changers for blockchain in the domain of healthcare in a white paper. According to an IBM study, 60 percent of government stakeholders in healthcare believed the integration of medical devices and asset management as the most likely area of disturbance in industry. The blockchain-based system has various advantages above conventional products of location tracking. This immutability and tamper-proof properties of the Blockchain are the most obvious. This prevents a malicious user from changing or deleting a device’s location history. This is especially important given that theft of devices and shrinkage has been a major issue in the United States and the United Kingdom. This immutability, in addition to preventing traditional theft, also protect devices from being lost and reordered, that have incurred high cost in terms of both actual equipment cost and care provided. The setup must not add significantly to the workload of staff, nurses, or workers because that requires tapping the device only using a mobile phone and further entering the device location. Whereas the use of blockchain on the Internet of Things (IoT) is still in its early stages, Huh states a method to communicate the devices using an Ethereum blockchain and public key system of RSA. Likewise, the device while it stores on blockchain its public key also stores the associated private key on the device.

This study aimed to conduct an organized analysis of previous literature about the employment blockchain in healthcare for a better understanding of their current and probable state. The four key research problems are defined for this reason. RQ1 was presented with summing up top writers, publishers, publication houses, and designs of publication patterns of this subject. Furthermore, it included an existing outline of research about employing blockchain in the healthcare space. The comprehensive description of the reviewed articles is discussed in Table 3 . RQ2 was designed to help researchers better understand how blockchain can be used, it is responded by defining particular themes and sub-themes that reflect key aspects in employing blockchain in this sector. RQ3 further discussed its shortcomings and obstacles that previous researchers had encountered. We were able to recognize the research gap in the existing literature and responded to this question by summarizing its main research themes and existing limitations. RQ4 concentrated on the key aspects where future investigation can provide valuable insight. The fourth research question is addressed by combining findings through emerging differences, shortcomings, and previously proposed guidelines.

https://doi.org/10.1371/journal.pone.0266462.t003

Conceptual evolution

According to the findings of the study, research in healthcare’s blockchain was largely focused on enhancing more creating new ideas and concepts that help researchers to derive multi-domain [ 59 ] also practicable blockchain in healthcare implementations. The viability of employment [ 99 ] is being established and evaluated across three sub-themes of research: design creation, applications on benefit-based, and developing predictive competencies.

Concept development

The findings of the analysis indicate that new proofs and algorithms have received a lot of attention, such as proof of data primitiveness [ 62 , 112 ], proof of familiarity [ 74 ], and simpler workload for proof of work; [ 54 ]. Studies have also focused on testing new variables and components in architecture systems, as well as improving frameworks that enable blockchain execution by including them. Consider cryptosystems based on attribute [ 72 ], approach the Stackelberg game [ 63 ], sibling intractable functions [ 70 ], and homomorphic computations for more efficient frameworks [ 77 ]. Further [ 113 ], suggested a new scheme (BBDS) based on blockchain to protect data transactions and maintain privacy [ 57 ]. Used fog computing estimation efficiency as well as reliable models for human pursuit acknowledgment to support remote e-health controlling [ 51 ]. To eliminate a single point of failure, they are focused on incorporating several time sources into their technique. Finally, this research has centered on how to boost the efficiency of already established algorithms and structures based on the blockchain.

Benefit-based application

Blockchain has been used in healthcare research to extract concrete benefits by identifying and testing new technology avenues. It involves work in upgrading the technical advantages of employing blockchains, such as advanced image processing [ 60 ], effective behavior recognition [ 57 ], and Internet-of-Things synchronization (IoT) devices [ 51 ]. Furthermore, the majority of studies in this category have centered on the use of blockchain technology to establish specific benefits of healthcare, e.g. mutual decision making in the medical field [ 74 ]. Blockchain adoption, for example, is being suggested to have positive implications while managing clinical trials [ 73 ], DNA data transmission [ 61 ], preventive healthcare, biomarker growth, and discovery of drugs are all examples of remote patient monitoring [ 50 , 53 , 64 ].

Advancing decentralization

Existing research is also considering promoting key advantages of blockchain technology throughout healthcare environments for encouraging justice and also efficient decentralization [ 76 , 114 ]. For instance [ 63 ], produced an efficient framework for promoting maximization of revenue maximization along with fair decentralized trade, considering that [ 48 ] stated the need for trade-offs for mining benefits. Researchers in previous literature already described blockchain’s prospects in developing transparency in exchanging the data [ 56 ], such as utilizing upright client roles [ 21 , 30 ]. By doing this, we can say that previous research about the increasing use of blockchain-based technology in the medical space is focused on spreading decentralization along with its related advantages.

Advancement in technology

Current studies have contributed substantial progress in terms of advancement and refinement of blockchain for the development of targeted deployment, particularly in the healthcare space. We suggested previous research that is classified in this theme be directed regarding the three main topical issues based on our review:

Developing intelligent healthcare ecosystems

The introduction of blockchain technology programs into healthcare environments has piqued the interest of some academics [ 45 ]. Such integrations can pave the way for the development of intelligent healthcare systems [ 100 ]. For example [ 47 ], argues that blockchain adoption will aid in the development of a more efficient e-health ecosystem. Prior research has also suggested frameworks for developing blockchain-based e-health [ 56 ] and telemedical information systems [ 33 ], which could help healthcare providers, expand the scope of their services in the future.

Improvements to the blockchain architecture on a technical level

The majority of this field’s study has concentrated on improving the efficiency of architectures and developed systems by technological improvements for example utilizing smaller data block sizes [ 74 ] and reducing transaction propagation delay [ 68 , 74 ]. Some attention has also been given to problems that have previously been described as possible roadblocks to the successful implementation of blockchain architectures. Memory and CPU specifications [ 77 ], as well as accurate node recognition, are among the problems considered in research, grouped under this theme [ 71 ]. The efficacy of potential solutions to the above problems has been illustrated in several cases by network and algorithm comparison studies [ 21 , 30 , 74 ]. However, we believe that this theme will continue to progress in the future, necessitating a parallel emphasis on comparative analyses to determine the most powerful networks and algorithms.

Building predictive capabilities

A similar pattern can be seen in blockchain technology’s use in healthcare as it enters the fourth step in development with the rising integration of AI [ 26 ]. IoT [ 50 ], sensors [ 47 ], wireless body area networks [ 53 , 64 ], big data [ 49 ], edge computing [ 76 ], and cloud technology have all recently been incorporated through blockchain-based device architecture [ 59 ]. Researchers are using such technologies to help them develop systems based on blockchain having predictive capacities for enhancing medical information systems and diagnostics [ 61 , 75 ]. Prescription fraud avoidance [ 47 ], verifiable data generation [ 77 ], and automatic claim resolution [ 47 ] have all been investigated previously using such frameworks [ 72 ]. Furthermore, studies have centered on using blockchain-based technology in supporting providers of health care services with other tasks, e.g data collection on population-level [ 46 ] and user identity description [ 28 ].

Enhancement of efficiency

Several researchers in previous literature have attempted to determine how blockchain-based implementation would improve the efficiency of healthcare processes [ 34 , 59 , 79 , 82 ]. According to this study, scholars’ attention has been drawn to two facets of performance improvement: structures and processes.

Prior research has focused on improving the efficiency of technological aspects of the processes that are needed to run a blockchain-based healthcare system. Prior research has also focused on developing systems for timely alerts [ 72 ] and adverse event reporting [ 73 ]. Some research has centered on increasing the computational processes efficiency [ 57 ] and thorough evaluation of suggested architectures [ 60 ] to ensure that its architecture gives far efficient processing as compared to conventional architectures [ 71 ]. Furthermore, studies have proposed changes in blockchain systems to resolve the alleged risks related to time management, data management, and managing related costs. For example, reviewed research has established mechanisms for reducing the cost of implementation after setting up initially [ 74 ], lowering storage costs [ 65 ], and making maintenance and storing files of any size is easier [ 62 , 112 ].

According to our analysis of the current literature, several steps have been applied to enhance the blockchain-based healthcare framework holistically. For example, research has focused on improving system interoperability [ 27 , 49 ], managing inter-institutional access rights [ 63 , 99 ], and data management [ 28 , 46 , 63 , 64 , 99 ]. Enhancing machine scalability [ 113 ] and efficiency have also received scholarly attention [ 60 , 65 ]. Researchers have concentrated their efforts on designing integrated service-oriented architectures [ 56 ] and enhancing the generalizability and flexibility of blockchain systems that have been implemented [ 21 , 27 , 30 ].

Management of data

According to the results, we can conclude that managing the data and medical records is getting more scholarly attention. Existing research has endorsed the blockchain’s utilization for medical data management [ 27 , 48 , 54 , 55 , 69 , 70 , 99 , 115 ]. Furthermore, by integrating heterogeneous forms of data [ 27 , 69 , 100 ], blockchain can aid in the development of an application system of information to manage such PHRs [ 59 , 64 ]. We define three main aspects of current research in this field based on the SLR.

Data privacy

Previous research about data security implications of this technology in medical care has focused on handling the privacy of data by maintaining permitted access to the data. According to the study, access control management [ 76 ] has gotten a lot of attention [ 45 , 46 ]. Because of the requirement of protecting the privacy of confidential data by greater transparency, access control, and immutability, this problem is particularly important in healthcare [ 55 ]. Prior research has developed a framework based on blockchain to guarantee the delivery of effective services [ 115 ], user-centric [ 114 ], and access to patient PHRs and other medical data that is safe and encrypted in response to this vital need e.g. [ 45 , 50 , 54 ].

Data protection

Another main concern discussed in studies on the blockchain aspects of data management in healthcare is the avoidance of unauthorized access and the preservation of data confidentiality to ensure data safety. The majority of the studies that were examined focused on preventing unauthorized access [ 66 ] and preventing eavesdropping [ 71 ]. Several methods have been proposed to achieve this aim, including efficient authentication [ 65 ], biometric authentication [ 49 ], user verification [ 55 ], and the use of dual signatures [ 63 ].

Data handling

Prior research has addressed the need for legally and legally compliant collection, sharing, and controlling of healthcare data to some extent. According to our findings, few research studies have recognized the importance of monitoring enforcement [ 100 ], let alone the criteria and targets for compliance [ 63 , 67 , 75 ]. However, the importance of data integrity has received a lot of attention [ 56 , 69 , 70 ]. Prior research has looked at issues like authentic data mobilization [ 46 , 77 ], double storage expenditure [ 68 ], and eternal data protection [ 68 , 112 , 116 , 117 ]. Along with the growing inter-institutional adoption of blockchain, researchers have transformed their attention to the issue of storing and maintaining sensitive data [ 67 ] from a variety of sources, including medical devices [ 52 ] and health insurance [ 77 ]. A few studies have concentrated on the assistance of cross-institutional sharing of data [ 67 ], as well as changes in data sharing quality and flexibility [ 69 ]. Additionally, previous studies have addressed the need for data processing improvements (e.g. [ 77 ]). Some steps for inducing these changes have been suggested in the reviewed studies, such as the successful incorporation of diverse data from various sources of data [ 99 ] and the integration of smart contracts [ 48 ]. These themes specify that past studies in that area have focused on (i) improving technological features, (ii) managing medical databases, also (iii) identifying unique capabilities in the medical field, where blockchain could make remarkable contributions. Based on emerging trends, it can be said that scholarship in this field is still transforming, with existing facets of healthcare being recognized as possible recipients of using blockchain as a result of technological advancements.

Research framework for future synthesis

This analysis and review helped in the framework development which was created with the research gaps identified in existing recommendations suggested in previous research. The research model includes 5components that would aid in the development of the healthcare ecosystem based on blockchain, for future research. The research framework for the BCT-based healthcare system is depicted in Fig 10 .

https://doi.org/10.1371/journal.pone.0266462.g010

Data sources.

Personal and medical health records are created and managed by the patients using mobile devices, healthcare service suppliers, and pharmaceutics is one of these associated industries., research and insurance [ 32 , 47 , 70 ]. These serve as the foundation of the blockchain architecture and need management by legitimate and regulatory rules. This technology might aid in the development of authorized databases that information can be retrieved by inter-institutional authorities in collaboration with the required agencies to aid in patient treatment and medical decision-making [ 21 , 30 ]. Because of the incorporation of newer technologies, such as smart patient tracking devices [ 53 ], to increase the comprehensiveness of medical databases, future research should concentrate on handling those data sources.

System architecture.

With advances in blockchain technology, the system’s architecture will undergo important changes and refinement in terms of the components incorporated into the system of blockchain. Such as using Permissioned consortium blockchain [ 28 ] or platforms other than Ethereum [ 68 , 77 ], could improve current blockchain deployment architectures in the healthcare ecosystem. Also, future research should concentrate on creating techniques for managing system architectures that have been established, particularly the challenging circumstances that can have an impact on the performance and efficiency, for instance, node management [ 74 ] and techniques of key distribution [ 67 ].

Blockchain technology strategic implementation.

In the case of increasing integration of information and communication technology and blockchain over healthcare ecosystems, researchers should have focused on the elements which could impede and assist in the widespread application of blockchain technology. According to our findings, we believe that organizations should think about whether or not, by identifying the key issues throughout this study, blockchain technology might prove a potential source of creating or enhancing value. Strategic problems like resource constraints [ 50 ] and technical problems like performance uncertainty [ 56 ] and system requirements are these examples [ 99 ]. Considering these problems might help scholars to develop blockchain architectures that can offer better functional utility and productivity in terms of resource and output management. This can also guide health system administrators and personnel to adopt a holistic and strategic approach to the potential inclusion of blockchain as an essential component of a company’s value chain.

Beneficiaries.

Databases built on the blockchain can provide trustworthy information to particular beneficiaries in the sector of healthcare, such as patients who keep ownership of their information. Authorities including doctors, pharmacists, medical researchers, and insurance firms are also beneficiaries. Patients may authorize them to use medical information for a range of purposes, plus collaborative medical decision-making [ 63 ], medical informatics and diagnosis (S.J. [ 61 ]), and fraud prevention [ 47 ]. Because of the blurring of the borders between the health system, wellness sectors, and mobile phones, researchers must recognize such beneficiaries ensuring data is accessed by the relevant authority. Moreover, the important thing is maintaining the integrity of data following ethical and legal bindings. As a result, scholars must concentrate to understand the perspective of the user about the perceived advantages and costs of engaging in a blockchain system. It can assist to identify and remove obstacles in the widespread application and use of blockchain.

Ethical & legal consideration.

Blockchain applications are addressing critical issues for example authentication, interoperability, and safe sharing of medical data [ 49 , 118 – 120 ]. Regardless of the increased emphasis on the blockchain, the acceptance of such concerns may be regarded as a remarkable barrier to its extensive adoption. More emphasis should be placed on regulatory compliance [ 100 ] and ethical recommendation for issues like control of ownership and access of patient data [ 99 ]. We propose that future scholars take a multidisciplinary approach to determine avenues for resolving ethical and legal compliance issues in multi-national or cross-institutional contexts for blockchain adoption. We also argue that there is a need to positively impact the public and appease regulatory agencies by deliberating and highlighting the critical benefits derived by using technology based on blockchain.

Directions for future research

According to the SLR, we provide a brief summarization of the thematic problems that would require attention from future researchers:

Deployment of holistic view.

In case it is critical to find solutions to security and performance-related problems, like interoperability [ 67 ] and access-control [ 68 ], we argue that scholars must take a broader view of blockchain adoption. This is critical to creating holistic, legally, and ethically compliant [ 21 , 30 ], robust data management, and authentication procedures in e-health ecosystems [ 33 ]. Furthermore [ 36 ], argues that context variables like people and culture may play an important role in the development of new technologies. Eventually, we suggest testing blockchain-based electronic health ecosystems in cross-institutional and cross-national contexts to build tailored context-based healthcare solutions in collaborating with different organizations inside the healthcare space, such as research medical centers [ 60 ].

Optimization of the architecture.

Scholars might focus on improving the efficiency and performance of proposed designs to account for the higher transaction rates which may be expected if blockchain is integrated into healthcare operations in the future [ 113 ]. That can be accomplished by dealing with network congestion [ 69 ], scalability [ 99 ], throughput [ 76 ], and bandwidth issues [ 22 ].

Data protection & legal compliance.

Addressing data, plus user privacy and legal problems will be an important area of future research [ 21 , 30 , 53 ]. These can be directly tackled by designing blockchain protocols in handling healthcare records that can be enforceable by smart-contract [ 36 ] and compliant with data and privacy protection regulations, for example, Health Insurance Portability and Accountability Act [ 31 , 36 , 53 ].

Other technologies integration.

For improved functionality, deployment of block-chain might be advantageous by the technology with business processes in healthcare [ 36 ]. For example, researchers can concentrate to advance the incorporation of edge computing, AI, and ML through blockchain health service ecosystems in developing an improved anticipatory analytic model to provide customized health treatment and diagnostics (e.g. [ 52 , 63 , 64 ]). Furthermore, research may aim to improve accessibility, remote control, and emergency services via the integration of sensors based on IoT. Furthermore, we propose two additional potential directions for future scholars to extend the existing scope of academic boundaries in this sector. First of all, it proposes the requirement to understand the implications of blockchain deployment in more niches in healthcare, but related fields i.e. managing the digital rights of users’ [ 13 ], drug prescription management [ 11 ], and prescription fraud prevention [ 47 ]. Furthermore, the research could be conducted to investigate the implications of blockchain usage across the whole health system supply and value chain. It can help scholars better understand user-related interoperability problems and additionally enables creating standard protocols to use systems working under the blockchain.

This research study is designed to understand completely the application of blockchain in the domain of healthcare. To achieve this goal, SLRs were conducted on nine highly regarded databases using particular protocols to pick out relevant articles for review. The outcomes were used, to sum up, current knowledge on applications of blockchain in the specific sector of medical care, but to also summarize past and the present academic research theme trends in this field. Future research possibilities have been showcased in the form of a synthesized framework created by combining insights from existing restrictions, suggestions, and emerging gaps in current knowledge observed throughout this review.

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Title: a confirmation rule for the ethereum consensus protocol.

Abstract: A Confirmation Rule, within blockchain networks, refers to an algorithm implemented by network nodes that determines (either probabilistically or deterministically) the permanence of certain blocks on the blockchain. An example of Confirmation Rule is the Bitcoin's longest chain Confirmation Rule where a block is confirmed (with high probability) when it has a sufficiently long chain of successors, its siblings have notably shorter successor chains, and network synchrony holds. In this work, we devise a Confirmation Rule for Ethereum's consensus protocol, Gasper. Initially, our focus is on developing a rule specifically for LMD-GHOST, the component of Gasper responsible for ensuring dynamic availability. This is done independently of the influence of FFG-Casper, which is designed to finalize the blocks produced by LMD-GHOST. Subsequently, we build upon this rule to consider FFG-Casper's impact, aiming to achieve fast block confirmations through a heuristic that balances confirmation speed with a trade-off in safety guarantees. This refined Confirmation Rule could potentially standardize fast block confirmation within Gasper.

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Generative A.I. Arrives in the Gene Editing World of CRISPR

Much as ChatGPT generates poetry, a new A.I. system devises blueprints for microscopic mechanisms that can edit your DNA.

The physical structure of OpenCRISPR-1, a gene editor created by A.I. technology from Profluent. Credit... Video by Profluent Bio

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By Cade Metz

Has reported on the intersection of A.I. and health care for a decade.

• April 22, 2024

Generative A.I. technologies can write poetry and computer programs or create images of teddy bears and videos of cartoon characters that look like something from a Hollywood movie.

Now, new A.I. technology is generating blueprints for microscopic biological mechanisms that can edit your DNA, pointing to a future when scientists can battle illness and diseases with even greater precision and speed than they can today.

Described in a research paper published on Monday by a Berkeley, Calif., startup called Profluent, the technology is based on the same methods that drive ChatGPT, the online chatbot that launched the A.I. boom after its release in 2022 . The company is expected to present the paper next month at the annual meeting of the American Society of Gene and Cell Therapy.

Much as ChatGPT learns to generate language by analyzing Wikipedia articles, books and chat logs, Profluent’s technology creates new gene editors after analyzing enormous amounts of biological data, including microscopic mechanisms that scientists already use to edit human DNA.

These gene editors are based on Nobel Prize-winning methods involving biological mechanisms called CRISPR. Technology based on CRISPR is already changing how scientists study and fight illness and disease , providing a way of altering genes that cause hereditary conditions, such as sickle cell anemia and blindness.

Previously, CRISPR methods used mechanisms found in nature — biological material gleaned from bacteria that allows these microscopic organisms to fight off germs.

“They have never existed on Earth,” said James Fraser, a professor and chair of the department of bioengineering and therapeutic sciences at the University of California, San Francisco, who has read Profluent’s research paper. “The system has learned from nature to create them, but they are new.”

The hope is that the technology will eventually produce gene editors that are more nimble and more powerful than those that have been honed over billions of years of evolution.

On Monday, Profluent also said that it had used one of these A.I.-generated gene editors to edit human DNA and that it was “open sourcing” this editor, called OpenCRISPR-1. That means it is allowing individuals, academic labs and companies to experiment with the technology for free.

A.I. researchers often open source the underlying software that drives their A.I. systems , because it allows others to build on their work and accelerate the development of new technologies. But it is less common for biological labs and pharmaceutical companies to open source inventions like OpenCRISPR-1.

Though Profluent is open sourcing the gene editors generated by its A.I. technology, it is not open sourcing the A.I. technology itself.

The project is part of a wider effort to build A.I. technologies that can improve medical care. Scientists at the University of Washington, for instance, are using the methods behind chatbots like OpenAI’s ChatGPT and image generators like Midjourney to create entirely new proteins — the microscopic molecules that drive all human life — as they work to accelerate the development of new vaccines and medicines.

(The New York Times has sued OpenAI and its partner, Microsoft, on claims of copyright infringement involving artificial intelligence systems that generate text.)

Generative A.I. technologies are driven by what scientists call a neural network , a mathematical system that learns skills by analyzing vast amounts of data. The image creator Midjourney, for example, is underpinned by a neural network that has analyzed millions of digital images and the captions that describe each of those images. The system learned to recognize the links between the images and the words. So when you ask it for an image of a rhinoceros leaping off the Golden Gate Bridge, it knows what to do.

Profluent’s technology is driven by a similar A.I. model that learns from sequences of amino acids and nucleic acids — the chemical compounds that define the microscopic biological mechanisms that scientists use to edit genes. Essentially, it analyzes the behavior of CRISPR gene editors pulled from nature and learns how to generate entirely new gene editors.

“These A.I. models learn from sequences — whether those are sequences of characters or words or computer code or amino acids,” said Profluent’s chief executive, Ali Madani, a researcher who previously worked in the A.I. lab at the software giant Salesforce.

Profluent has not yet put these synthetic gene editors through clinical trials, so it is not clear if they can match or exceed the performance of CRISPR. But this proof of concept shows that A.I. models can produce something capable of editing the human genome.

Still, it is unlikely to affect health care in the short term. Fyodor Urnov, a gene editing pioneer and scientific director at the Innovative Genomics Institute at the University of California, Berkeley, said scientists had no shortage of naturally occurring gene editors that they could use to fight illness and disease. The bottleneck, he said, is the cost of pushing these editors through preclinical studies, such as safety, manufacturing and regulatory reviews, before they can be used on patients.

But generative A.I. systems often hold enormous potential because they tend to improve quickly as they learn from increasingly large amounts of data. If technology like Profluent’s continues to improve, it could eventually allow scientists to edit genes in far more precise ways. The hope, Dr. Urnov said, is that this could, in the long term, lead to a world where medicines and treatments are quickly tailored to individual people even faster than we can do today.

“I dream of a world where we have CRISPR on demand within weeks,” he said.

Scientists have long cautioned against using CRISPR for human enhancement because it is a relatively new technology that could potentially have undesired side effects, such as triggering cancer, and have warned against unethical uses, such as genetically modifying human embryos.

This is also a concern with synthetic gene editors. But scientists already have access to everything they need to edit embryos.

“A bad actor, someone who is unethical, is not worried about whether they use an A.I.-created editor or not,” Dr. Fraser said. “They are just going to go ahead and use what’s available.”

Cade Metz writes about artificial intelligence, driverless cars, robotics, virtual reality and other emerging areas of technology. More about Cade Metz

Explore Our Coverage of Artificial Intelligence

News  and Analysis

Eight daily newspapers owned by Alden Global Capital sued OpenAI and Microsoft , accusing the tech companies of illegally using news articles to power their A.I. chatbots.

The spending that the tech industry’s giants expect A.I. to require, for the chips and data centers , is starting to come into focus — and it is jarringly large.

The table stakes for A.I. start-ups to compete with the likes of Microsoft and Google are in the billions of dollars. And even that may not be enough .

The Age of A.I.

A new category of apps promises to relieve parents of drudgery, with an assist from A.I . But a family’s grunt work is more human, and valuable, than it seems.

Despite Mark Zuckerberg’s hope for Meta’s A.I. assistant to be the smartest , it struggles with facts, numbers and web search.

Much as ChatGPT generates poetry, a new A.I. system devises blueprints for microscopic mechanisms  that can edit your DNA.

Could A.I. change India’s elections? Avatars are addressing voters by name, in whichever of India’s many languages they speak. Experts see potential for misuse  in a country already rife with disinformation.

Which A.I. system writes the best computer code or generates the most realistic image? Right now, there’s no easy way to answer those questions, our technology columnist writes .

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Healthcare Trends 2024 Pdf . 10 biggest trends revolutionizing healthcare blockchain delivering the. However, it will remain vulnerable to headwinds,.

Healthcare finance trends for 2024 by commercehealthcare® presents the bank’s annual outlook on major factors. Healthcare technology trends for 2024 and beyond.

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First steps toward a whole-body map of molecular responses to exercise

by Coydon Ireland, Pacific Northwest National Laboratory

Research definitively confirms that muscle-moving, calorie-burning activity slows the advance of disease, improves cognitive function, boosts the immune system, and reduces rates of mortality from all causes.

Scientists are now going even deeper into the effects of exercise on humans and other mammals by investigating the impacts of exercise at the molecular level. They aim to uncover, at the smallest scales, the impacts of exercise and to better understand how the body works in states of health and disease.

Molecules are clusters of atoms. They represent the smallest unit of a chemical compound that can take part in a chemical reaction. Such chemical reactions in proteins, carbohydrates, lipids (fats), and nucleic acids—the "omics" (cellular components) that control the inner workings of every organ system.

Exercise appears to change these molecular workhorses in ways that are poorly understood. Identifying such changes, however, holds out the promise of clinical benefits for all humans, regardless of age, sex, body composition, or fitness level.

The genesis of MoTrPAC

In late 2016, to find out more about exercise-induced changes at the molecular level , the National Institutes of Health Common Fund began supporting expanded research into mapping the smallest details of how exercise helps maintain healthy tissues and organ systems. That led to establishing a national group of collaborative experts called the Molecular Transducers of Physical Activity Consortium (MoTrPAC).

From the start, Pacific Northwest National Laboratory (PNNL)—under the direction of biochemists Josh Adkins and Wei-Jun Qian—has been among MoTrPAC's nationwide centers of expertise in animal and human exercise, biomolecular analyses, and bioinformatics.

The consortium's biomolecular analysis centers use an omics approach to analyze genes, proteins, or other biomolecules at a whole-body level. Ultimately, the goal of MoTrPAC is to create a molecular map of exercise responses in both human and animal models. From muscle to molecule, such a map would help reveal how exercise affects health.

"The ability to see broad molecular responses across organs in the body is particularly intriguing," said Qian of molecular mapping. "Such knowledge could be a strong motivating factor for exercising."

An emphasis on proteomics

PNNL's main role in MoTrPAC is to investigate exercise-induced changes in proteins and post-translational modifications (PTMs). Proteins are made of amino acid chains that fold into three-dimensional structures and that then regulate tissue and organ structure and function. PTMs are processing events that alter protein functions by chemically modifying specific amino acids within a given protein. Studying changes in all detectable proteins and their PTMs in a sample is called proteomics.

"We've been central to the study design of the consortium from the very beginning, with an emphasis on proteomics," said Adkins. He acknowledged a critical partner: Steven Carr and his proteomics group at the Broad Institute, a research center directed by Harvard University and the Massachusetts Institute of Technology.

A mapping challenge

In a 2020 perspective overview in the journal Cell , Adkins and PNNL biomedical scientist James Sanford joined with other co-authors to describe molecular "cross talk," a kind of chemical telegraph prompted by exercise among a variety of tissues. The study also outlined the importance of mapping such molecular exchanges.

The Cell paper also introduced the idea of a public MoTrPAC dataset to help find the hidden mechanisms behind the benefits of exercise. It is now thriving and growing. One of the lead analysts for the dataset is PNNL chemist Paul Piehowski.

For Adkins, Qian and others on PNNL's MoTrPAC team, proteomics research depends on instruments at the Environmental Molecular Sciences Laboratory (EMSL), a Department of Energy Office of Science user facility located on the PNNL campus. EMSL's capabilities include an array of high-end orbitrap mass spectrometers. They produce analyses that help identify and quantify proteins and other molecules from a variety of tissue types and samples.

MoTrPAC "is huge in scope," said Adkins. "PNNL's scale of operation allows us to do something of this size with very high quality and high operational reproducibility." He called the PNNL-EMSL role in MoTrPAC "a tour de force for a proteomic study. Few on this scale have been done before."

A first major paper

MoTrPAC researchers nationwide contributed to a May 2, 2024, study in the journal Nature . This first major paper to come out of the consortium provides the first whole-organism map of molecular responses to endurance exercise training.

The experiment's model organism was the rat. Male and female rats of the same species ran on motorized treadmills for 1-, 2-, 4-, and 8-week periods. For controls, researchers used sedentary, untrained rats, matched for sex with their exercising counterparts.

Within 48 hours of each training interval, researchers collected samples of whole blood, plasma, and 18 solid tissues and dispersed them to omics centers like PNNL for intensive analysis.

Of the numerous samples, said Adkins, "We want to understand the integration of organ systems." Molecular responses in the body to endurance training are system-wide, say authors of the Nature paper—a conclusion confirmed by integrating tissue samples in a range of omics analyses.

Other results were finer tuned. Exercise enhances liver health and metabolism, for instance. It also remodels and strengthens the structure of the heart, improves pathways related to gut integrity (gut health is linked to inflammation throughout the body), enriches immune pathways, and reduces inflammation in the lungs and small intestine. Importantly, the authors relate, the sex differences observed in training responses highlight how important it is to include both sexes in exercise research.

The rat–human problem

Translating rat data into conclusions relevant to humans is challenging. However, rats are the preferred animal model because rat–human skeletal muscle and organ system signaling patterns are similar. So are exercise-induced glucose metabolism and cardiac responses. In addition, the large tissue masses of rats provide better samples than mice for multiomics analysis.

"These data will help us bring knowledge from the rat into the human sphere," said Adkins.

To help close the rat–human data gap, the MoTrPAC consortium has an exercise-response experiment underway that records molecular responses to endurance training and resistance training across a cohort of 2,000 adult human volunteers.

Insights, with more on the way

The recent Nature paper provides what Adkins called "a landscape view" of multi-center national MoTrPAC research. At the same time, other studies in progress are taking narrower and more detailed views of consortium data. PNNL's Sanford is part of a research team showing how multiomics help identify key gene regulatory programs that come into play during exercise.

The Sanford team is looking at thousands of observed molecular alterations. They included how exercise regulates gene expression related to mitochondrial changes, heat shock responses, immune regulation, and other molecular processes.

Sanford has also joined PNNL biostructure and function biochemist Gina Many and PNNL data scientist Tyler Sagendorf in an analysis of the running-rats data to investigate sexual dimorphism in white adipose tissue responses .

White adipose is a storage and secretory organ system linked to the development of obesity, cardiovascular disease, type 2 diabetes, cancer, and other conditions. This fat type also has important effects on the immune system and other biological processes that maintain systemic health.

So far, the analysis seems to demonstrate that in rats there are "profound" differences in white adipose tissue response between the sexes. While physical training benefits rats of both sexes, only male rats respond to exercise by losing white adipose tissue. In female rats , exercise prevents them from gaining fat mass.

Such narrowly focused investigations use the MoTrPAC dataset to look for insights on how exercise affects individual tissues or specific biological processes.

One MoTrPAC investigation underway, for instance, looks at how exercise affects gene transcription. That's the process of copying information from a strand of DNA onto a molecule called messenger RNA (mRNA), which relays genetic information to the areas of cells where proteins are made. Another example of research in progress deals with the impact of exercise on mitochondrial response. Mitochondria, present in mammalian cells, regulate energy production and stress response.

Every smaller study based on separate facets of MoTrPAC data, said Adkins, "is one piece of a greater vision." That vision is the consortium's: to map the body's molecular changes after exercise .

Journal information: Nature , Cell

Provided by Pacific Northwest National Laboratory

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Immigration's Effect on US Wages and Employment Redux

In this article we revive, extend and improve the approach used in a series of influential papers written in the 2000s to estimate how changes in the supply of immigrant workers affected natives' wages in the US. We begin by extending the analysis to include the more recent years 2000-2022. Additionally, we introduce three important improvements. First, we introduce an IV that uses a new skill-based shift-share for immigrants and the demographic evolution for natives, which we show passes validity tests and has reasonably strong power. Second, we provide estimates of the impact of immigration on the employment-population ratio of natives to test for crowding out at the national level. Third, we analyze occupational upgrading of natives in response to immigrants. Using these estimates, we calculate that immigration, thanks to native-immigrant complementarity and college skill content of immigrants, had a positive and significant effect between +1.7 to +2.6\% on wages of less educated native workers, over the period 2000-2019 and no significant wage effect on college educated natives. We also calculate a positive employment rate effect for most native workers. Even simulations for the most recent 2019-2022 period suggest small positive effects on wages of non-college natives and no significant crowding out effects on employment.

We are grateful for Rebecca Brough for her research assistance and suggestions. The views expressed herein are those of the authors and do not necessarily reflect the views of the National Bureau of Economic Research.

MARC RIS BibTeΧ

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