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IEEE TRANSACTIONS ON ENGINEERING MANAGEMENT
Technical, Temporal, and Spatial Research
Challenges and Opportunities in Blockchain-Based
Healthcare: A Systematic Literature Review
Leili Soltanisehat , Reza Alizadeh , Haijing Hao , and Kim-Kwang Raymond Choo , Senior Member, IEEE
Abstract—Blockchain can be used to build a peer-to-peer, secure,
and smart transaction system. As a horizontal technology that
has changed several fields of industry, blockchain has tremendous
potential to transform healthcare systems as well. In this article,
a systematic review is conducted to critically evaluate 64 articles
on blockchain-based healthcare systems, published between 2016
and January 2020 in 21 conferences, 33 journals, and ten online
sources. The aim of this article is to answer three main questions.
First, what are the applications of blockchain in the healthcare
systems, and what are the structures and challenges of applying
blockchain to a specific healthcare domain? Second, what are the
technical, temporal, and spatial aspects of the currently developed
blockchain applications for different healthcare domain? Third,
what are the future research directions in designing and imple-
menting blockchain-based healthcare systems? Statistical facts
about the technical aspects of these 64 articles show that most
of the proposed blockchain-based healthcare systems use private
blockchain and Ethereum platforms; furthermore, the majority
of the authors are affiliated with research institutions in the USA
and China. We also discuss potential future research directions,
e.g., integrating the blockchain in artificial intelligence based so-
lutions, cloud-computing-based solutions, and parallel blockchain
architecture.
Index Terms—Blockchain, security, smart healthcare, spatial
analysis, temporal analysis.
I. INTRODUCTION
EALTHCARE systems are designed to meet our health-
H care needs, and the need for efficiency grows even more
pronounced as our population ages and becomes more mo-
bile [1]. For example, the recent outbreak of the 2019 novel
coronavirus (2019-nCoV, also referred to as SARS-CoV-2 and
Manuscript received March 20, 2020; revised June 30, 2020; accepted July
24, 2020. Review of this manuscript was arranged by Department Editor D.
Meissner. (Corresponding author: Leili Soltanisehat.)
Leili Soltanisehat and Reza Alizadeh are with the School of Industrial and
Systems Engineering, University of Oklahoma, Norman, OK 73019-0390 USA
(e-mail: leili.soltanisehat@ou.edu; reza.alizadeh@ou.edu).
Haijing Hao is with the Department of Computer Information Systems, Bent-
ley University, Waltham, MA 02452-4713 USA (e-mail: hhao@bentley.edu).
Kim-Kwang Raymond Choo is with the Department of Information Systems
and Cyber Security, University of Texas at San Antonio, San Antonio, TX 78249
USA (e-mail: raymond.choo@fulbrightmail.org).
Color versions of one or more of the figures in this article are available online
at https://ieeexplore.ieee.org.
Digital Object Identifier 10.1109/TEM.2020.3013507
0018-9391 © 2020 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission.
See https://www.ieee.org/publications/rights/index.html for more information.
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1
COVID-19)1 demonstrates the importance of real-time infor-
mation sharing (e.g., patient data and symptoms) and telehealth.
Recent trends in healthcare systems have shifted from patient-
centered and hospital-centered healthcare toward eHealth (elec-
tronic healthcare), mHealth (mobile healthcare), and uHealth
(universal healthcare). While mobile and ubiquitous Internet of
Things (IoT) devices (e.g., Internet of Medical Things (IoMT)
devices) have contributed to more agile, efficient, and cost-
effective processes, they have also brought new sets of chal-
lenges [2].
One of the most important challenges in the electronic and
ubiquitous healthcare is the security of IoT devices (broadly
defined also to include mobile devices) and the underpinning
healthcare information infrastructure. With the evolution of IoT
and the pervasiveness of healthcare devices and applications
(apps), a significant amount of medical data is recorded and
transferred hourly, daily, weekly, and so on. Existing healthcare
systems face challenges such as interoperability, long processes,
delays in process and diagnosis, delays in sharing information,
the high cost of operation and processes, time-consuming
insurance processes and costs, privacy, security, data ownership,
and control [2], [3].
Blockchain [4], a relatively new decentralization mechanism,
provides robust solutions for security and efficiency challenges
existing in healthcare systems. The idea of applying a blockchain
in healthcare domains is a result of the necessity for secu-
rity and interoperability in healthcare. Example advantages
of blockchain for the healthcare system include secure data
sharing [5], the consensus in changes, deletion, addition, and
decentralized and immutable records modification of records
[6]. There are a number of building blocks and related concepts
in blockchain-based systems, such as smart contracts [7] and
consensus protocols [8]. For instance, different types of con-
sensus algorithms have been designed for different blockchain
systems [9], and example consensus algorithms include proof
of work (PoW) [8], proof of concept (PoC) [10], proof of stake
(PoS) [11], proof of space [12], proof of activity [13], practical
Byzantine fault tolerance (PBFT) [14], and redundant Byzantine
fault tolerance (RBFT) [15].
1 [Online]. Available: https://www.cdc.gov/coronavirus/index.html (last ac-
cessed on Jun 29, 2020).
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2 IEEE TRANSACTIONS ON ENGINEERING MANAGEMENT

TABLE I
COMPARISON BETWEEN THIS ARTICLE AND EXISTING LITERATURE REVIEWS AND SURVEYS

2
Internet of Medical Things.

This article aims to depict the technical, temporal, and spatial
development of blockchain-based healthcare research by analyz-
ing recent progress in designing and implementing blockchain-
based systems in various healthcare domains, comprehensively.
The technical analysis focuses on the features of the developed
blockchain-based system, such as the applications of the devel-
oped system, the blockchain used, and the consensus algorithm
used. The spatial analysis focuses on applications that are more
popular in a specific country(ies) and/or region(s). Finally, the
temporal analysis reveals the estimated timeline during which
blockchain penetrated each healthcare research domain.
Table I represents a comparison between this article and ex-
isting literature review (also referred to as the literature survey)
articles on blockchain studies in healthcare. The first 11 columns
represent the technical applications, which are described by
each of the existing review papers. The next three columns
show articles that have analyzed the spatial and temporal
evolution of blockchain-based healthcare applications as well as
their technical features in various healthcare domains. The next
columns show the number of surveys that each review article an-
alyzed, along with the period when those surveys are published.
The last four columns show the papers that describe the future
directions of research on blockchain-based healthcare, including
regulations of blockchain, cloud-based blockchain, and artificial
intelligence (AI) in blockchain. A number of challenges were
also identified in these works: level of scalability, security, and
privacy issues in a blockchain; the need for powerful com-
putational infrastructures; lack of healthcare operators’ skills
and knowledge about blockchains; lack of regulations; risk due
to immutability feature of a blockchain; and the challenges in
quantifying the cost of applying a blockchain. These challenges
are explained extensively in Section IV of this article.

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SOLTANISEHAT et al.: TECHNICAL, TEMPORAL, AND SPATIAL RESEARCH CHALLENGES AND OPPORTUNITIES 3

Fig. 1. Article search procedure (last updated on February 10, 2020). Note: During the exclusion stage, articles that are not published in the English language,
not relevant to the healthcare application domains, or only theoretically address the applicability of blockchain in general, are omitted.

Fig. 2. (a) Interdependencies between eight applications of blockchain in healthcare. (b) Main layers in architecting blockchain-based healthcare systems.

II. REVIEW DESIGN
Blockchain has been explored as a potential solution to ad-
dress existing security and efficiency challenges faced by health-
care systems [23], [30]. Specifically, this article will provide
an overview of investigated blockchain applications in various
healthcare environments, as well as the associated challenges
and future directions for the development of blockchain-based
healthcare systems. The three research questions (RQs) are as
follows.
RQ1: What are the applications of blockchain in the healthcare
systems, and what are the structures and challenges of applying
blockchain to a specific healthcare domain??
RQ2: What are the technical, spatial, and temporal aspects of the
currently developed blockchain applications for different healthcare
domain?
RQ3: What are the future research directions for designing and
implementing blockchain-based healthcare systems?
In order to answer the above RQs, we perform a comprehen-
sive systematic literature search through the major academic
publisher databases, including Scopus, PubMed, Springerlink,
ScienceDirect, IEEEXplore, and ACM Digital Library. The
bibliographic databases are searched for the blockchain concept
within health-related fields such as insurance, supply chain,
patient-centric model, electronic medical record (EMR) or elec-
tronic health record (EHR), organ transplantation, blood do-
nation, identity management, medical trial, and neuroscience.
Boolean operators OR and AND are used to combine the search
keywords “blockchain,” “healthcare,” and a third word deter-
mining the specific application of blockchain, for instance,
“data management.” The literature search was last updated on
February 10, 2020. Fig. 1 shows a flow diagram of the search
procedure applied for this article.
A. Application Domains
In this article, we summarize blockchain applications in
healthcare in six main domains [31]–[40]: medical data man-
agement, interoperability, and consolidated healthcare, pharma-
ceutical supply chain (PSC), organ transplantation and blood
donation, clinical trial and medical research, health insurance,
and others. In fact, some of the identified categories share similar
processes and applications of blockchain. For instance, data cir-
culation among different parties such as medical care providers,
doctors, and patients is a must in all domains; further, all should
have an efficient data management system. Similarly, in the
PSC and organ transplantation processes, the IoMT devices
are used to update the blockchain network. Fig. 2(a) shows the
interdependencies between the identified healthcare domains.

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4 IEEE TRANSACTIONS ON ENGINEERING MANAGEMENT

Fig. 3. Summary of publications’ statistical findings for total articles versus technical articles.

Fig. 4. Statistical findings on the technical features of a blockchain-based platform.

In architecting the structure of every blockchain-based health-
care system, the following four main layers should be considered
[19] [as shown in Fig. 2(b)]:
1) stakeholders, known as parties involved in developing,
running, and deploying a blockchain-based system;
2) specific application domain in healthcare applied to the
blockchain thus far;
3) blockchain-based architecture for each application;
4) electronic data, which are shared and circulated into
blockchain-based systems for specific application domain
in healthcare.
B. Statistical Findings
In this article, we reviewed 123 articles, published between
2016 and 2020, to understand the applications of blockchain in
solving the current challenges in different healthcare domains.
Findings show that healthcare has attracted much attention to
not only explain the theoretical foundations but also to develop
practical platforms for blockchain-based healthcare systems. We
found eight main categories and five subcategories of blockchain
applications in healthcare. From the 123 articles, 23 articles
conducted the literature review or survey, and 36 articles theo-
retically explained the applicability of blockchain in healthcare,
whereas 64 articles have developed a blockchain-based platform
or architecture for the specific healthcare domain (named here
as application papers).
As shown in Fig. 3, almost half of the application articles (33
out of 64) are published in peer-reviewed journals. There is no
significant difference between the number of articles published
each year from 2016 to 2019. Also, a majority of the application
articles (36 out of 64) are published by the first authors affiliated
with a research institution in the USA and China, respectively.
Fig. 4 shows a summary of the technical features of
blockchain-based applications developed by the application

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SOLTANISEHAT et al.: TECHNICAL, TEMPORAL, AND SPATIAL RESEARCH CHALLENGES AND OPPORTUNITIES
Fig. 5. Spatial–temporal research map of blockchain-based healthcare.
articles. Most of the application articles are focused on EHR and
medical research/clinical trial domains, respectively. PoW, PoC,
and RBFT are the three most popular consensus algorithms used
by the developed applications. Furthermore, most of the models
have used private blockchain in their design. The Ethereum
platform and Hyperledger are used for the implementation of the
designed blockchain-based systems in most of the application
articles.
The spatial and temporal analysis (see Fig. 5) of the literature
shows the first applications of a blockchain designed for solving
data-management problems, including security and privacy is-
sues. The need for highly secured interoperability and confiden-
tial and accurate medical data directed the research path toward
developing blockchain-based architectures in various domains,
including clinical trials and medical research, PSCs, and organ
transplantation systems. Development of the IoT and the need
for medical device security inspired researchers to deploy the
advantages of a blockchain in securing medical devices and
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5
wearables. With the fast development of AI and cloud computing
applications in different industrial fields, the future direction of
a blockchain can be geared toward resolving many of its current
challenges, including scalability, data storage, and necessary
computational power.
III. BLOCKCHAIN APPLICATION IN HEALTHCARE
A. Electronic Medical Data Management
The past few years have witnessed a significant increase in
the amount of healthcare data being generated. These data are
being generated not only from healthcare providers, in the form
of electronic healthcare record systems and patient history (con-
ventionally stored locally), but also from personal healthcare
and fitness devices (usually wearable IoMT) [41]. Currently, the
major challenges faced by healthcare data management are data
fragmentation, security, interoperability, and incompatibility of
EMRs. Individual solutions exist to tackle these problems, such
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6 IEEE TRANSACTIONS ON ENGINEERING MANAGEMENT

TABLE II
BLOCKCHAIN-BASED SYSTEMS FOR EHR/EMR MANAGEMENT

3
Delegated Proof of Stake.
4
Byzantine Fault Tolerance.

as patient health care smart cards [42]. This solution may help
with availability and compatibility to some extent; however,
serious security concerns remain. The blockchain-based data
management system will ease patient identification, as data are
assigned to addresses, not patients, and patients’ control keys to
the address. This method addresses the issues of security, data
provenance, privacy, and interoperability [43], [44]. By omitting
the central data management system, blockchain-based systems
also allow patients to be truly in charge of their data and who they
choose to share it with, thus preventing misuse of information.
In terms of the need for data storage, blockchain can benefit
from cloud storage capacity with the recompenses of decent
sharing, fast transmission, low cost, abundant storage capacity,
easy admission, and dynamic association [19].
Table II lists important blockchain-based platforms that have
been designed for data management in the healthcare domain.
Generally, these systems manage authentication, confidentiality,
and accountability of data. Further, they incentivize medical
stakeholders to contribute to the system as blockchain “miners.”
Also, the choice of blockchain type, consensus algorithms, and
their efficiency depend on the type of data and its specific
application [20].
B. Interoperability and Consolidated Healthcare
The adoption of the EHR system has two main benefits, i.e.,
prevention of duplicative records and medical processes and
enhancement of the quality of care, both by sharing patients’
healthcare information among practitioners. These two benefits
of sharing EHRs in the healthcare domain are integrated and
known as “interoperability” [67]. Current EHR systems are
based on an isolated credential validation architecture; fur-
ther, they suffer from problems such as 1) heterogeneities in
hardware and software solutions in the EHR systems and 2)
heterogeneities in the structure, purpose, and deployment of
EHR in terms of variable healthcare systems existent in different
geographical locations [68]. While in current systems, no single
trusted source of available identity exists to aggregate patient’s

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TABLE III
BLOCKCHAIN-BASED SYSTEMS FOR THE PSC
medical records, blockchain can be a new solution that supports
data integrity, privacy, interoperability [68], [69], and at-scale
consolidation in any information exchange among healthcare
professionals, patients, their proxies, and healthcare providers.
Since blockchain records are immutable and accessible to all
participants in a patient’s network, recovery contingencies are
unnecessary [68]. This fact will provide advantages for patients
and healthcare providers. Patients will realize the value of their
healthcare data; they also have control of their EHR [70]. Health-
care providers can also leverage patients’ data to improve health
and wellness with improved clinical and financial outcomes
based on complete EHR.
Different research projects have focused on developing
blockchain-based frameworks to improve interoperability in
different healthcare domains [70]–[72]. Examples of developed
blockchain applications include GemOS Blockchain [73], KON-
FIDO [74], iWellChain [75], and HGD [70]. While a blockchain
provides many benefits for improving interoperability in health-
care systems, it also faces several challenges that should be ad-
dressed, including regulatory and legal compliance, scalability,
verification speed, and available infrastructures [55].
C. Pharmaceutical Supply Chain
The PSC is one of the largest divisions in healthcare, which
is more complex and delicate compared with regular supply
chains. Since pharmaceutical products have a sensitive produc-
tion process and lifecycle and are sensitive to the preservation
condition, they require a more accurate management system.
The globalization of the PSC, on the other hand, has introduced
new challenges such as the criminal trade of counterfeit medicine
[76]. Therefore, the complexity of the PSC increases the demand
for transparency and traceability of a product’s lifecycle [77].
Designing a blockchain-based PSC [78], [79] includes key
requirements, e.g., a unique product identifier, product tracing
protocol in the shared ledger, product verification protocol,
detection, and response recording protocol, Food and Drug
Administration (FDA) notification protocol, and the product
and transaction information’s shared ledger [3]. The blockchain-
based supply system features two layers of the structure [80]: 1)
back-end, which is the blockchain network and the smart con-
tract containing the rules, authorizations, and responsibilities,
which are confirmed by all parties before being embedded in
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7
the blockchain; 2) front-end, which consists of recording devices
and sensors for measuring the pharmaceutical product condition.
This will ensure automatic enforcement for the implementation
of smart contract rules in the supply process.
Different startups such as Everledger, Blockverify, Prove-
nance, IBM Blockchain, Blockpharma, FarmaTrust, Modum,
OriginTrial, T-Mining, the LinkLab, VeChain, Walton, and
Chronicled are among several companies working on making
global supply chains more secure, transparent, and efficient
using blockchain. Recently, Hyperledger is collaborating with
Accenture and other blockchain pioneers, to fight the spread
of counterfeit drugs using blockchain [81], [82]. The BlockRx
token project is another blockchain-based platform for the PSC,
which is led by iSolve, Intel, and YourEncore companies [83].
Table III lists recent blockchain-based systems developed by
different companies for the PSC management.
D. Organ Transplantation and Blood Donation
According to organ donor statistics [89], the number of people
in the organ transplantation list continues to be much greater
than the number of donors and transplants. Despite advances in
technology and medicine, along with augmented consciousness
of organ donation, there continues to be a breach between supply
and demand. In the donation process, a scarce resource must
be obtained, matched to a recipient, and complete a journey of
transactions from extraction to the implant. Various factors and
verification processes are critical to ensure the transplantation
success, including authentic data circulation, the organ’s origin
verification, organ supply chain verification, interoperability
between donation institutes, hospitals, laboratories, and other
donor or donor family, registrar offices, transportation hubs, drug
stores, etc. These factors can be magnified if the global scale for
organ transplantation is considered.
According to [90], applying a blockchain to the organ trans-
plantation system has three advantages. First, it ensures the im-
mutability of medical records that prevent corruption and abuse.
Second, it increases the traceability and transparency of data
from different parties in the donation and transplantation pro-
cess. Third, it creates trustworthy interaction between different
parties in the process with omitting the central control. Since the
blockchain ensures transparency and real-time transaction, it re-
places manual article records, redundant and duplicate electronic
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8 IEEE TRANSACTIONS ON ENGINEERING MANAGEMENT
Fig. 6. Blockchain-based organ donation system. Source: [90] and [92].
TABLE IV
BLOCKCHAIN-BASED SYSTEMS FOR ORGAN TRANSPLANTATION AND BLOOD DONATION
5
Proof of Match.
records, and any incompatible and inefficient transaction system
in the organ transplantation supply chain [91]. The process of
organ transplantation within the blockchain system is depicted
in Fig. 6. At any point, if a contradiction with the regulation of
the donation and transplant system happens, the system will stop
the process of organ transplantation to save the recipient’s life.
The transparency in the blockchain system helps all parties in
the donation process have the same information and view of the
organ’s status, location, and availability for the right recipient at
the right time.
Blood donation is also another transplantation type, which is
critical for helping patients with medical emergencies or specific
diseases (e.g., cancer, leukemia, blood disorders). A blockchain
can create a smart system that helps hospitals and health centers
to query and fulfill their requests for blood stocks from nearby
centers in a short time [93]. Table IV lists two studies on
developing blockchain-based systems for organ transplantation
and blood donation.
Zouarhi [90] proposed Kidner as a worldwide, decentralized
matching system for kidney transplantation. Zaremba et al.
[92] proposed a blockchain-based system that facilitates an
open social blood bank. Other current projects include KanCoin
[93] and Dhonor [93]. Although a blockchain can facilitate
and speed up the donation processes, the scalability of the
blockchain-based database remains questionable. On the other
hand, the transformation from the current centralized system
to the blockchain-based system has cultural, time, trust, and
regulatory challenges.
E. Insurance
Insurance companies are good candidates for blockchain
since multiple parties need to share data, update data, and
verify records and incidents. In addition, intermediaries in the
insurance system add costs and complexity, time sensitivity,
and transaction interdependence to the process [94]. Depend-
ing upon blockchain-based health data collection and policy
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execution, blockchain can be leveraged to health insurance
in different ways. These include cost-effective insurance pro-
cesses; online insurance exchanges; improved reliability of in-
surance providers and customer experience; less fraud in medical
reports and claims to the process by providers, claimants, or
applicants; near-real-time health status monitoring; and more
dynamic pricing by insurers and reduced redundancy in medical
reports [24], [95]. On the other hand, blockchain-based identity
verification systems will also decrease the need for overloaded
data entry in the case of signing or renewing insurance rules. Pa-
tients will control their medical data for sharing with healthcare
providers and insurance companies [96].
While healthcare organizations are typically concerned
with the Health Insurance Portability and Accountability Act
(HIPAA) and associated regulations, a blockchain can pro-
vide a secure solution for medical data sharing and storage
in health insurance processes [39]. Table V features studies
on the blockchain-based insurance platform. Despite several
advantages of a blockchain in the insurance industry, regula-
tion challenges have hindered the development of this kind
of platform. On the other hand, current insurance industries
should align with the new systems on specific design points
to increase their interoperability. Privacy is the other challenge
when revealing selective information to counterparties, insurers,
and brokers in the system is necessary [96].
F. Medical Research/Clinical Trial
Considering numerous healthcare stockholders as well as
all documents whose PoE and origin should be verified, the
clinical trial has a complex flow of heterogeneous data and
metadata circulations. Problematic issues, e.g., endpoint switch-
ing, selective publications, missing data, data dredging, etc.,
can undermine findings from clinical research. These issues
affect the perceptions regarding the integrity of the research,
the validity of the benefits and risks of medical treatments, and
the reproducibility of medical research [46]. Therefore, it is
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SOLTANISEHAT et al.: TECHNICAL, TEMPORAL, AND SPATIAL RESEARCH CHALLENGES AND OPPORTUNITIES 9

TABLE V
BLOCKCHAIN-BASED SYSTEMS FOR INSURANCE

TABLE VI
BLOCKCHAIN-BASED SYSTEMS FOR MEDICAL RESEARCH/CLINICAL TRIALS

necessary to increase the quality of medical research from both
patients’ and researchers’ perspectives [100].
Using cryptographic validation and timestamp mechanism,
blockchain can benefit the clinical trial processes by build-
ing reliable and traceable clinical studies, securing design and
data sharing in community-driven medicine, protecting pri-
vacy, controlling the clinical trial phases using smart contracts,
and ensuring a patient’s consent for a clinical trial using the
proof-of-concept mechanism [100], [101]. Table VI lists studies
on developing the blockchain platform for the clinical trial
application.
G. Other Applications
1) Internet of Medical Things: In all of the aforementioned
domains of healthcare, wearable electronic devices, which are
known as the IoMT, are used for managing and transferring
medical data and information [109], [110]. Increasing the use of
mobile applications, consumer medical electronics, and wear-
ables and AI has influenced the interoperability level in the
healthcare domain. However, it has also raised security and
confidentiality concerns due to the limitations of centralized
institutes for access to patient data. Several type of research
has combined the concepts of data encryption, accessibility,
encrypted keys, and digital identity for designing a framework
for managing the IoMT [111]. Griggs et al. [112] developed
a private blockchain grounded on the Ethereum protocol for
managing data transformation among medical electronic devices
and sensors. Linn and Koo [113] provided a conceptualized
framework for depicting the role of blockchain in reducing
fraud and security risks associated with IoMT. Zhao et al. [114]
introduced a blockchain-based architecture for body sensor net-
works for recording and sharing health information.
2) Neuroscience: The concept of a blockchain mechanism
can be applied to AI for integrating the human thinking process
and neural devices, whereas some neuroscience concepts can be
applied to blockchain mechanisms such as consensus protocols
[115]. The neural devices will receive brain signals via sensors,
computing chips, and wireless communication and then translate
them into commands that define the mental state [28].
Neurogress is a Geneva-based company that is focusing on
combining machine learning and AI with building a neurosys-
tem for accurately controlling robotic arms, drones, and other
smart electronic devices via human thinking [28]. Netcome, a
neurotechnology company based in California, is focusing on
developing a process called “aldehyde-stabilized cryopreser-
vation” for preserving and recreating brain signals stored on
blockchain [115]. Obviously, blockchain can improve the re-
search on digitalizing human brain thinking augmentation and
simulation. Such blockchain thinking is proposed as an input-
processing-output computational system [115] that enables the
connection between AI and human enhancement for further
medical research development.
3) Patient-Centric Healthcare: Several studies developed
the blockchain platform for specific healthcare processes, which
allows patients to be the primary owners of medical records and
processes [5], [116]. In such processes (known as patient-centric
healthcare processes), patients are among the main decision-
makers in these processes, which include data sharing. For
example, Chen et al. [61] proposed a medical data management
system based on a blockchain, thus providing patients ownership
of their own medical records. Liu et al. [117] developed a

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10
blockchain-based structure for the sharing of x-ray medical
images in a highly secure manner. Badré et al. [39] developed a
decentralized patient assignment system is a blockchain-based
system that allows patients to be part of the decision-makers
in the patient referral system. Lo et al. [75] also developed a
blockchain-based framework, known as the iWellChain DApp
framework, to make the medical referral processes automatic
and paperless and to facilitate well-organized reimbursement
[75].
4) Identity Verification: In the current system, the patient’s
identity is verified based on personal, government, and financial
records. However, using the cryptographic public and private
key in blockchain, identity verification can be stored and utilized
in perpetuity. Each authority in the healthcare network plays a
specific role in the network and can be verified for a specific
action. As an example, Ancile [105] is a blockchain-based ar-
chitecture developed for identity management and access control
to electronic medical data.
5) Uncategorized Applications: Besides the well-studied ap-
plications of blockchains in healthcare domains, related subdo-
mains can be investigated more in-depth in the future. These
domains include, but are not limited to, the dental industry
[118], medication prescriptions [5], public health surveillance
[119], pervasive social network systems [120], telesurgery [121],
home-based healthcare services [122], and leveraging genomic
data [16].
IV. DISCUSSION
A. Challenges of Blockchain-Based Healthcare Systems
Blockchain can solve several challenging issues in transac-
tion systems via its decentralization mechanism, cryptographic
algorithms, and immutable audit trail mechanisms. Transac-
tions in the blockchain system can be done peer-to-peer with
significantly lower cost (without a central control as a single
point of failure) and higher data provenance, availability, and
security. Since every transaction on the blockchain is validated,
recorded, and timestamped, the history of transactions can be
traced [4]. Despite the advantages, blockchain faces several
challenges when implemented in the real world. The merits and
limitations of each of the developed blockchain-based healthcare
systems are summarized in [22], [24], [123], [124], and [125].
Table VII summarizes the most important challenges that exist
in the blockchain-based healthcare system in all our considered
healthcare domains.
B. Future Research Directions
The applied research in the literature is mostly about the
design and preparation of a blockchain platform. However,
understudied areas remain, which require more investigation to
solve the current challenges before applying the blockchain-
based system to real-world networks. For this goal, new inves-
tigations in AI, big data, and cloud computing can be combined
with the decentralized concept of blockchain. Also, the fewer
concerns in blockchain-based systems, the easier the regulation
and standardization of such systems.
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IEEE TRANSACTIONS ON ENGINEERING MANAGEMENT
1) Combination of Blockchain With AI and Data Analytics:
Combining blockchain with AI techniques (including machine
learning and deep learning) and data analytics can help rev-
olutionize medical treatment decisions, medical research, and
clinical trials [24]. Combining blockchain and AI to improve
data management and medical treatment decision-making in
healthcare appears to be understudied [39], [134]–[137]. How-
ever, the accuracy and validity of the prediction remain debatable
[137], and requires more in-depth investigations.
One of the important challenges in applying blockchain and
AI in healthcare is the language or cultural differences of EHR
systems across the world. Translation of medical reports from
one language to another language is a challenge in medical
research and clinical trials. However, if a global system records
and interprets reports for similar diagnosis and treatment, AI
techniques such as natural language processing and other (big)
data analytics solutions can facilitate more effective transla-
tion or interpretation of medical terms coming from doctors
of different countries. A blockchain without data analytics can
ensure integrity, reliability, and accessibility of medical reports,
although it cannot ensure their interpretation. On the other hand,
data analytics is not a foolproof technique; further, it is only an
adequate approximation of the interpretations of medical reports
and diagnosis [137], [138]. One of the advantages of aggregating
data analytics and blockchain is to detect similarities between
two documents in a large volume of medical reports inside the
blockchain. This will reduce the need for more storage and
computational power as well as increase the validity of reports
while keeping them tamper-proof [130], [139].
2) Parallel Blockchain-Based Healthcare Organizations:
Another research direction for blockchain-based healthcare
systems is designing and implementing decentralized parallel
healthcare organizations (DPHOs) as a combination of par-
allel healthcare systems and a blockchain’s decentralized au-
tonomous organizations [135] for unifying different healthcare
domains. All healthcare parties, including patients, hospitals,
health organizations, medical researchers, healthcare communi-
ties, and health insurance companies, will partake in the “coown-
ership, coconstruction, and cosharing” of the DPHO ecosystem
as a member. The combination of parallel blockchain [140],
healthcare systems, and big data will enable a powerful medical
treatment decision-support tool.
3) Combination of Blockchain With Cloud Computing: One
of the important challenges of a blockchain is the massive
amount of data that is generated and saved into each network
node. An increasing number of nodes and transactions will
intensify this challenge; further, IoT devices do not have enough
computational and storage capacity [141]. Therefore, one of the
future directions could be decreasing the amount of produced
data or increasing the available storage capacity along with the
ongoing research about optimizing the mining process in terms
of consumed energy, time, and resources as well as using new
technology in IoMT devices to improve computational power
and speed.
Several researchers have studied the applicability of cloud
computing in healthcare domains [142]. Some studies also
developed healthcare systems for more efficient and secure
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SOLTANISEHAT et al.: TECHNICAL, TEMPORAL, AND SPATIAL RESEARCH CHALLENGES AND OPPORTUNITIES 11

TABLE VII
MOST IMPORTANT CHALLENGES IN THE BLOCKCHAIN-BASED HEALTHCARE SYSTEM DESIGN

6
General Data Protection Regulation.

data management in healthcare utilizing cloud computing [143],
[144]. A combination of cloud computing and blockchain makes
distributed cloud architecture that provides secure, cheap, and
demand-full admittance to heterogeneous healthcare infrastruc-
tures in an IoT network. This will also increase the accuracy
and effectiveness of medical treatment decisions due to the
availability of big data and fast decision-making [145], [146].
Few studies, to the best of our knowledge, have developed
blockchain-based systems in cloud environments for specific
applications in healthcare [51], [147]; however, combining cloud
computing with blockchain applicable to healthcare domains
still needs more investigation in terms of design and modeling,
efficiency analysis, cost-benefit analysis, regulations, etc. [148],
[149].
4) Blockchain-Based Healthcare Regulations and Standard-
ization: Currently, developers and researchers are moving to-
ward the design stage. However, some barriers derived from
the lack of standards and legal control makes using designed
systems more challenging. There is still a regulatory challenge
for clarifying the terms of use and instruction for all parties
involved in the real-world systems [150]. Besides, cross-border
sharing of EHR, where there are diverse and often contradictory
jurisdictions, may diminish the benefits of blockchain data shar-
ing. Thus, one of the important future directions is to develop
a compliance code, including unified regulations, standardiza-
tions, and cross-border policies for applying a blockchain to each
specific healthcare domain [17], [129]. Also, regulatory barriers
like HIPAA are required to ensure the appropriate use of data
while they can delay developmental efforts [137]. In this regard,
another future research direction could be to develop a standard
user-friendly interface that complies with customer expectations
and standard protocols. This field of research can be a trending
research direction, as several governments, including those in
Canada, USA, UEA, and Estonia, [151] have supported and
involved themselves in expanding blockchain-based healthcare
systems.
5) Considerations of Blockchain-Based Healthcare System
Development: With the development of research on combining

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12
AI, cloud computing, and blockchain, many other doors will
open to various domains, including healthcare research. Along
with the ongoing research, there are necessary steps to take while
developing blockchain-based healthcare applications, including
the following.
1) Analyzing the main characteristic of the specific
blockchain-based system in the healthcare domain: To
analyze the scalability, efficiency, resiliency, data security
and privacy, shortcomings, and any specific and probable
outcome from the blockchain application in a thematic
area. Also, future research needs to use real-world data sets
for increasing the validity and verification of the proposed
architectures [22].
2) Risk analysis on the application of the blockchain lo-
cally and globally: To assess the resiliency of the pro-
posed blockchain-based system against application-free
and application-dependent attacks. This is due to the nov-
elty of the technology, competitive threats, and opportuni-
ties, intellectual property of any new platform, risk analy-
sis of regulatory change, and assessing and scheduling the
strategic landscape [150].
3) Tradeoff analysis of blockchain applications: To make a
comparison with current and future alternatives, develop
the scenario planning, and create an optimum design of the
blockchain-based system for each thematic area [129].
4) Smart contract development: To analyze the performance
of the smart contract in each specific healthcare domain
should be analyzed in terms of the inclusion of details,
speed of implementation, and updating the blockchain
systems [4].
5) Other implications: Less-investigated healthcare domains,
e.g., telesurgery, dental services, and home-based health-
care services, could be further investigated in terms of
applicability to real-world systems, challenges, and tech-
nical requirements.
V. CONCLUSION
Blockchain is a new decentralized architecture that can trans-
form traditional centralized industries toward a secure and
trustable system. The existing security, privacy, and interoper-
ability issues in current healthcare systems have increased the
potential of applying blockchain to this domain. The EHR is
the main area in which blockchain can be applied to solve data
management and identity management (in terms of accessibility)
issues. In many other healthcare domains, blockchain can be
applied to improve the efficiency and quality of the processes at
a lower cost.
Several types of research have studied the applications of
blockchain in different healthcare domains. Researchers have
stepped out beyond the theoretical explanations and developed
a blockchain-based architecture for specific healthcare domains
and tested the efficiency of their proposed architecture. For in-
depth analysis, in this article, the authors inspected 123 publica-
tions, which were selected based on the inclusion and exclusion
criteria prompted by our RQs. We identified six main domains,
i.e., electronic medical data management, interoperability and
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IEEE TRANSACTIONS ON ENGINEERING MANAGEMENT
consolidated healthcare, PSC, organ transplantation and blood
donation, clinical trial and medical research, health insurance,
and another category. From 123 reviewed articles, 64 articles
were recognized for their proposed design and implementation
of blockchain-based systems. The temporal analysis revealed
that data management and interoperability are the first domains
that received the most attention from researchers. The spatial
analysis showed that most of the proposed designs were de-
veloped by researchers from the USA and China. Further, the
technical analysis showed that most of the proposed designs used
the private blockchain from the Ethereum platform. A number of
future research opportunities were also identified and discussed,
which hopefully will inform the design of the next generation
blockchain-based systems.
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Leili Soltanisehat received the B.Sc. degree in in-
dustrial engineering and the M.Sc. degree in socio-
economic systems engineering from Bu-Ali Sina Uni-
versity, Hamadan, Iran, in 2011 and 2013, respec-
tively, and the master’s degree in engineering man-
agement and systems engineering from Old Domin-
ion University, Norfolk, VA, USA, in 2018. She is
currently working toward the Ph.D. degree in indus-
trial and systems engineering with the University of
Oklahoma, Norman, OK, USA.
She has authored and coauthored a number of pa-
pers that appeared in conferences, and journals, including the IISE Transactions
on Healthcare Systems Engineering, Journal of Energy Policy, Energy Sources,
Part A: Recovery, Utilization, and Environmental Effects, Foresight, Iranian
Economic Review, IISE Annual Conference and Expo, IEEE International Con-
ference on Blockchain, and INFORMS. Her research interests include operation
research, modeling and simulation, data analytics, and blockchain.
Reza Alizadeh received the B.Sc. degree in industrial
engineering from the Urmia University of Technol-
ogy, Urmia, Iran, in 2011, and the M.Sc. degree in
technology foresight from the Amirkabir University
of Technology, Tehran, Iran, in 2013. He is currently
working toward the Ph.D. degree in industrial and sys-
tems engineering with the University of Oklahoma,
Norman, OK, USA.
He has authored and coauthored a number of
papers that appeared in conferences, edited books,
and journals, including the Journal of Technological
Forecasting and Social Change, Journal of Energy Policy, Foresight, Iranian
Economic Review, Journal of Intelligent Manufacturing, Journal of Energy
Policy and Planning Research, International Journal of Global Warming, In-
ternational Journal of Environmental Research, Scientia Iranica Transactions
E: Industrial Engineering, Energy Sources, Part A: Recovery, Utilization, and
Environmental Effects, Sustainability, and Artificial Intelligence in Engineering
Design and Manufacturing. His current research interests include data analytics,
energy and climate policy, technology foresight, data envelopment analysis,
performance assessment, decision-making under uncertainty, simulation-based
design, surrogate modeling, network analysis, and cloud-based design.
 This article has been accepted for inclusion in a future issue of this journal. Content is final as presented, with the exception of pagination.
16
Haijing Hao received the Ph.D. degree in information
systems management from Carnegie Mellon Univer-
sity, Pittsburgh, PA, USA, in 2012.
She is currently an Associate Professor with the
Computer Information Systems Department, Bentley
University, Waltham, MA, USA. Her research inter-
ests include healthcare information systems, online
doctor reviews, new technology adoption, Bayesian
learning models in technology implementation, etc.,
which have been published on Information Systems
Research, International Journal of Medial Informat-
ics, Journal of Medical Internet Research, Knowledge-Based Management,
International Journal of Healthcare Information Systems and Informatics, etc.
Dr. Hao’s dissertation was awarded the William Cooper Dissertation Award:
Social Influence on Information Technology Adoption and Sustained Use in
Healthcare: A Hierarchical Bayesian Learning Method Analysis.
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IEEE TRANSACTIONS ON ENGINEERING MANAGEMENT
Kim-Kwang Raymond Choo (Senior Member,
IEEE) received the Ph.D. degree in information se-
curity from Queensland University of Technology,
Brisbane, QLD, Australia, in 2006.
He currently holds the Cloud Technology Endowed
Professorship at The University of Texas at San An-
tonio (UTSA), San Antonio, TX, USA. In 2015, he
and his team won the Digital Forensics Research
Challenge organized by Germany’s University of
Erlangen-Nuremberg.
Dr. Choo was the recipient of the 2019 IEEE Tech-
nical Committee on Scalable Computing Award for Excellence in Scalable
Computing (Middle Career Researcher), 2018 UTSA College of Business Col.
Jean Piccione and Lt. Col. Philip Piccione Endowed Research Award for Tenured
Faculty, British Computer Society’s 2019 Wilkes Award Runner-Up, Best Paper
Awards from 2019 EURASIP JWCN, IEEE TrustCom and ESORICS 2015,
Korea Information Processing Society’s JIPS Survey Paper Award (Gold) 2019,
IEEE Blockchain 2019 Outstanding Paper Award, Inscrypt 2019 Best Student
Paper Award, Fulbright Scholarship in 2009, 2008 Australia Day Achievement
Medallion, and British Computer Society’s Wilkes Award in 2008. He is also a
Fellow of the Australian Computer Society and Co-Chair of IEEE Multimedia
Communications Technical Committee’s Digital Rights Management for Mul-
timedia Interest Group.