Blockchain Papers

Niraj Vyas

<p class="abstract">Drug development is a complex and resource intensive endeavor. The average cost of developing a new drug, has been estimated to be $2 to $3 billion. However, the success rate of clinical trials is very low around and is estimated to be between 3-5%. The common reasons for failure of clinical trials include failure to demonstrate efficacy or safety, budgeting and financing, failure of subjects meeting protocol eligibility criteria, poor investigator site selection, patient withdrawals and dropouts. Considering the growing demands to get better and affordable treatment options, there needs to be fundamental shift required in drug development and specifically the clinical trials oversight processes to mitigate risks and reduce failures. The International Council for Harmonisation in the E6 R2 addendumhas now provided guidelines for adaptation of risk based approach to trial conduct and monitoring to implement mitigation strategies for potential risks which might derail the conduct of the trail. The industry is steadily gearing up to put together the required processes, systems and teams to align to the new ways of working. However with the changing landscape of drug development which includes novel therapies like gene therapy, remote/decentralized trials, growing use of wearable technologies, esource, electronic health record/electronic medical records interoperability, implementation of artificial intelligence and machine learning algorithms, the future of risk based approach towards managing clinical trials is going to be very different from what we see now. This paper explores the impact of these new developments on the future of risk based monitoring in clinical trials.</p>

Ilhaam A. Omar, Raja Jayaraman, Khaled Salah, Ibrar Yaqoob · 5 authors

Blockchain technology has disclosed unprecedented opportunities in the healthcare sector by unlocking the true value of interoperability. Specifically, the striking features of blockchain technology, such as data provenance, transparency, decentralized transaction validation, and immutability can help to compensate for stringent data management issues (e.g., patient recruitment, persistent monitoring, data management, and data analytics and accurate reporting) in clinical trials (CTs). Although several research studies show that blockchain solutions help to improve patient retention, data integrity, privacy, and ensure CTs compliance with regulatory policies, a comprehensive survey on this topic is lacking. In this survey, we provide insights into the adoption of blockchain technology in CTs. We categorize and classify the literature by devising a meticulous taxonomy of the decentralized tasks of CT and practices based on indispensable parameters. Furthermore, we provide insights on works in progress towards deploying blockchain solutions in CTs. Finally, we identify and discuss several challenges that hinder the successful implementation of blockchain technologies in CTs.

Sebastian Porsdam Mann, Julian Savulescu, Philippe Ravaud, Mehdi Benchoufi

Recent advances in medical and information technologies, the availability of new types of medical data, the requirement of increasing numbers of study participants, as well as difficulties in recruitment and retention, all present serious problems for traditional models of specific and informed consent to medical research. However, these advances also enable novel ways to securely share and analyse data. This paper introduces one of these advances-blockchain technologies-and argues that they can be used to share medical data in a secure and auditable fashion. In addition, some aspects of consent and data collection, as well as data access management and analysis, can be automated using blockchain-based smart contracts. This paper demonstrates how blockchain technologies can be used to further all three of the bioethical principles underlying consent requirements: the autonomy of patients, by giving them much greater control over their data; beneficence, by greatly facilitating medical research efficiency and by reducing biases and opportunities for errors; and justice, by enabling patients with rare or under-researched conditions to pseudonymously aggregate their data for analysis. Finally, we coin and describe the novel concept of prosent, by which we mean the blockchain-enabled ability of all stakeholders in the research process to pseudonymously and proactively consent to data release or exchange under specific conditions, such as trial completion.

Tomonobu Hirano, Tomomitsu Motohashi, Kosuke Okumura, Kentaro Takajo · 9 authors

BACKGROUND: The integrity of data in a clinical trial is essential, but the current data management process is too complex and highly labor-intensive. As a result, clinical trials are prone to consuming a lot of budget and time, and there is a risk for human-induced error and data falsification. Blockchain technology has the potential to address some of these challenges. OBJECTIVE: The aim of the study was to validate a system that enables the security of medical data in a clinical trial using blockchain technology. METHODS: We have developed a blockchain-based data management system for clinical trials and tested the system through a clinical trial for breast cancer. The project was conducted to demonstrate clinical data management using blockchain technology under the regulatory sandbox enabled by the Japanese Cabinet Office. RESULTS: We verified and validated the data in the clinical trial using the validation protocol and tested its resilience to data tampering. The robustness of the system was also proven by survival with zero downtime for clinical data registration during a Amazon Web Services disruption event in the Tokyo region on August 23, 2019. CONCLUSIONS: We show that our system can improve clinical trial data management, enhance trust in the clinical research process, and ease regulator burden. The system will contribute to the sustainability of health care services through the optimization of cost for clinical trials.

Hans H. Jung, Franz Pfister

1. Introduction to Subject: Participation in Research Trial1.1 Relevance of the Subject Conducting clinical studies includes an obligation to publish results to participants, sponsors, colleagues, and the public (Antes, 2009). ClinicalTrials.gov lists over 304,000 studies with locations in 208 countries (ClinicalTrials, 2019). The German Register of Clinical Trials (Deutsches

Nicholas Mamo, Gillian M. Martin, Maria Desira, Bridget Ellul · 5 authors

Dynamic consent aims to empower research partners and facilitate active participation in the research process. Used within the context of biobanking, it gives individuals access to information and control to determine how and where their biospecimens and data should be used. We present Dwarna-a web portal for 'dynamic consent' that acts as a hub connecting the different stakeholders of the Malta Biobank: biobank managers, researchers, research partners, and the general public. The portal stores research partners' consent in a blockchain to create an immutable audit trail of research partners' consent changes. Dwarna's structure also presents a solution to the European Union's General Data Protection Regulation's right to erasure-a right that is seemingly incompatible with the blockchain model. Dwarna's transparent structure increases trustworthiness in the biobanking process by giving research partners more control over which research studies they participate in, by facilitating the withdrawal of consent and by making it possible to request that the biospecimen and associated data are destroyed.

Mehdi Benchoufi, Doug Altman, Philippe Ravaud

Quality of clinical research is undermined by severe misconducts, errors, frauds, which are detrimental to the trust it should arouse. In this perspective article, we show how Blockchain may trace and control processes of Clinical Trials preventing from the above issues or at least discourage them since they would become traceable and opposable. Then, we propose a short and doable program where, amidst the complex stream of events that a Clinical Trials consist of, we select sensitive and misconduct-prone steps that could dramatically benefit from Blockchain, through either simple core features as traceability and incorruptibility of its data registration, or through more refined automation tools called Smart Contracts.

Wendy Charles, Natalie Marler, Lauren Long, Sean T. Manion

As clinical research moves toward real-world data capture with increased data sharing, there is a growing need for patient-centered technologies that ensure data authenticity and promote researcher and patient access. Blockchain is one of an emerging set of distributed ledger technologies with the potential to offer both research data transparency and trust, while offering robust security measures. As blockchain-based systems are being developed for clinical research applications, these systems may be required to follow state and federal research regulations, such as ethical protections for human participants and data privacy. Blockchain developers and research organizations alike are struggling to identify and interpret these regulatory requirements. Further, regulatory agencies and policymakers have not yet provided blockchain stakeholders with clear guidelines to achieve compliance. This article provides an introduction to the clinical research and health information privacy regulations in the United States as well as data design standards and electronic signature laws. We also offer recommendations for blockchain developers, researchers, and research organizations for achieving compliant blockchain solutions in clinical research.

Wang Zhong

In most regions of China, Electronic Medical Record (EMR) systems in hospitals are developed in an uncoordinated manner. Medical Insurance and Healthcare Administration are localised and organizations gather data from a functional management viewpoint without consideration of wider information sharing. Discontinuity of data resources is serious. Despite the government's repeated emphasis on EMR data integration, little progress has been made, causing inconvenience to patients, but also significantly hindering data mining.This exploratory investigation used a case study to identify bottlenecks of data integration and proposes countermeasures. Interviews were carried out with 27 practitioners from central and provincial governments, hospitals, and related enterprises in China. This research shows that EMR data collection without patients' authorization poses a major hazard to data integration. In addition, non-uniform information standards and hospitals' unwillingness to share data are also significant obstacles to integration. Moreover, friction caused by the administrative decentralization, as well as unsustainability of public finance investment, also hinders the integration of data resources.To solve these problems, first, a protocol should be adopted for multi-stakeholder participation in data collection. Administrative authorities should then co-establish information standards and a data audit mechanism. Finally, measures are proposed for expanding data integration for multiplying effectiveness and adopting the Public-Private Partnerships model.

Eric Venner, Mullai Murugan, Walker Hale, Jordan M Jones · 7 authors

MOTIVATION: Clinical genome sequencing laboratories return reports containing clinical testing results, signed by a board-certified clinical geneticist, to the ordering physician. This report is often a PDF, but can also be a paper copy or a structured data file. The reports are frequently modified and reissued due to changes in variant interpretation or clinical attributes. MATERIALS AND METHODS: To precisely track report authenticity, we developed ARBoR (Authenticated Resources in a Hashed Block Registry), an application for tracking the authenticity and lineage of versioned clinical reports even when they are distributed as PDF or paper copies. ARBoR tracks clinical reports as cryptographically signed hash blocks in an electronic ledger file, which is then exactly replicated to many clients. RESULTS: ARBoR was implemented for clinical reporting in the Human Genome Sequencing Center Clinical Laboratory, initially as part of the National Institute of Health's Electronic Medical Record and Genomics (eMERGE) project. CONCLUSIONS: To date, we have issued 15 205 versioned clinical reports tracked by ARBoR. This system has provided us with a simple and tamper-proof mechanism for tracking clinical reports with a complicated update history.

Daniel R. Wong, Sanchita Bhattacharya, Atul J. Butte

Monitoring and ensuring the integrity of data within the clinical trial process is currently not always feasible with the current research system. We propose a blockchain-based system to make data collected in the clinical trial process immutable, traceable, and potentially more trustworthy. We use raw data from a real completed clinical trial, simulate the trial onto a proof of concept web portal service, and test its resilience to data tampering. We also assess its prospects to provide a traceable and useful audit trail of trial data for regulators, and a flexible service for all members within the clinical trials network. We also improve the way adverse events are currently reported. In conclusion, we advocate that this service could offer an improvement in clinical trial data management, and could bolster trust in the clinical research process and the ease at which regulators can oversee trials.

Olivia Choudhury, Noor Fairoza, Issa Sylla, Amar K. Das

The cost of conducting multi-site clinical trials has significantly increased over time, with site monitoring, data management, and amendments being key drivers. Clinical trial data management approaches typically rely on a central database, and require manual efforts to encode and maintain data capture and reporting requirements. To reduce the administrative burden, time, and effort of ensuring data integrity and privacy in multi-site trials, we propose a novel data management framework based on permissioned blockchain technology. We demonstrate how our framework, which uses smart contracts and private channels, enables confidential data communication, protocol enforcement, and and an automated audit trail. We compare this framework with the traditional data management approach and evaluate its effectiveness in satisfying the major requirements of multi-site clinical trials. We show that our framework ensures enforcement of IRB-related regulatory requirements across multiple sites and stakeholders.

StanislawPeter Stawicki, SagarC Galwankar, Sebastian Clarke, Iain Craig · 11 authors

Technological progress is reshaping multiple domains of human activity, from financial transactions to medical care.[1] This paradigm shift represents a global movement that will transform our lives for generations to come.[2] The democratization of decision-making capacity, including consensus-based mechanisms for transaction verification, will enable global implementation of projects that were previously not feasible because of the requirement for centralized control.[34] Blockchain represents a decentralized ledger technology that operates by consensus and serves to democratize decision-making processes and to disintermediate traditionally understood intermediaries.[1] According to Deutsche Bank forecasts, by mid-2020's, approximately 10% of the worldwide gross domestic product could be regulated by blockchain-based solutions.[5] It is estimated that more than $400 billion will be invested in this technology in 2019 to advance its capabilities.[6] Within this broader context, it is important to understand that cryptocurrencies and financial transactions constitute only one small aspect of the blockchain concept, which also incorporates areas like verification, transparency, encryption, and maintenance of data integrity.[378] Blockchain technology appears to be following a fairly typical pattern of adoption, with multiple early entrants into the increasingly crowded and competitive cryptocurrency space and the fast-growing sphere of blockchain-based applications.[91011] It is the latter that will help truly define, and be responsible for the societal impact of, “the era of distributed ledgers” that is under way.[1112] The primary goal of the strategic global partnership between Litecoin Cash Foundation (LCCF, https://litecoinca.sh/) and OPUS 12 Foundation, Inc. (O12FI, http://www.opus12.org/), is to leverage our collective resources to establish early leadership in the development and implementation of practical, real-life, blockchain-based solutions in academic and clinical medicine.[11314] The practicality of the dual blockchain utilization, featuring both currency and application layers, becomes apparent with the realization that the need for ongoing data processing relies on constant verification and encryption activity throughout the entire network of blockchain nodes.[113] Thus, the approach selected by the LCCF-O12FI consortium creates significantly more synergy than a single-track approach based on subcomponent strategy. Within this context, the technology provides not only a “digital wallet” functionality for currency exchange, but also different blockchain-based use cases incorporating academic and medical information. In one example, cell phones are ubiquitous in low- and middle-income countries (LMIC) whereas electronic health records are not. Older, less costly cell phone technology would suffice as only SMS capability is needed to utilize blockchain or cryptocurrency, enabling broad access to the populations of LMICs. Blockchain can support information exchange across disparate data types, while providing digital payments on a global scale and across borders. The functional dimension of introducing the primary currency feature of Litecoin Cash (LCC) cryptocurrency has the potential to bring tremendous benefits to the areas of the world where banking services (and infrastructure) are severely underdeveloped, yet basic components for the successful adoption of cryptocurrencies clearly exist (e.g., limited internet access and mobile devices capable of supporting blockchain transactions). Much like entire regions of the world that essentially “bypassed” landline-based telephony following the introduction of cellular networks, many localities stand to “bypass and leapfrog” traditional banking, and progress directly to distributed ledger technologies.[151617181920] There is growing recognition of the role of microeconomies and the critical need for efficient, dependable, accessible, safe, and scalable financial transactions and infrastructures, especially in low-resource regions, a topic that was recently recognized with a Nobel Prize in Economics.[2122] Of note, this does not necessarily preclude traditional banking firms from participation; however, they will need to adapt to new competitive pressures across economic realities for which high-resource environment models are not optimized. Ability to appropriately scale current blockchain capabilities will be critical to such implementations.[32324] Blockchain-based mechanisms also allow for crossover of monetary value from various loyalty cards and rewards programs, similar to currency exchange between different nations. Such reward points (mileage, car rental, and hotel stay) can then become an alternative subsidy for healthcare services. This can, for example, help establish a modernized barter system where a patient could use their “frequent flyer miles” to pay for medical costs, exchanging their reward points for “health care coins” through an intermediary exchange market. Institutions, such as nongovernmental organizations, could turn “flyer miles” used to shuttle staff between locations into vaccine and medical equipment purchases. Further, direct and real-time transparent payment for services in healthcare could lead to a reduction of both “intermediary” insurance companies and inefficiencies in the system. This streamlining would result in substantial healthcare savings, translating to lower costs, more access for patients, and decreased overhead with increased revenue for clinics, hospitals, and providers. Security of the blockchain (including various “side chains” and “layers”) is of paramount importance to ensuring trust and wider mainstream adoption of this technology.[252627] The inherent risk in the concept of distributed ledger “democratization” is the possibility of emerging inequality due to maldistribution of infrastructure responsible for the maintenance and ongoing operations of the blockchain.[2829] Within this broader topic area, our group previously described the risk of ill-intended, third-party actors to project massive bursts of “hashing power” and effectively take over the blockchain for a limited duration of time.[1] This, in turn, allows such destructive actors to “double spend” cryptocurrency output to the detriment of the broader populace.[114] To effectively prevent the risk of the blockchain being “hijacked,” the LCCF Developer Team devised an innovative paradigm of agent-based mining (e.g., the creation of new cryptocurrency) that helps ensure democratization of the LCC generation/transaction process while providing sustainable, long-term security of the distributed ledger.[14] Another significant advantage of this prototype mining technique is that it is not based on technologies that are becoming increasingly energy and resource inefficient, thus not requiring ever greater amounts of energy to generate diminishing amounts of block rewards (e.g., “coins”). The synergy between secure mining processes and the need for the highest possible levels of distributed ledger security creates a unique environment for the development of blockchain-based educational and medical applications. Our joint implementation framework of blockchain-based application layer includes clearly stated and reasonably achievable milestones, each defined within the broader contexts of adoption readiness and resource availability. Parallel to these developments will be the phased introduction of LCC as a voluntary medium of exchange for various international medical programs (IMPs) collaborating within our global network of institutions, providers, and clinical sites.[30] The initial step in the strategic LCCF-O12FI collaboration will be the development of a cryptography-based “Secure ID” (SID) that will serve as the foundation for the future developments. This SID will contain each user's unique identifying information, accessible only to the end-user (incorporating various best practices in cyber security such as 2-factor or multisource verification), and shareable for viewing and information verification only with end-user's designees. The SID will also serve as a “Secure Key” to access other, downstream blockchain-based applications including “Academic Activity Logger” (AAL) and “Credentialing Document Repository” (CDR). We will now discuss the development and implementation of AAL and CDR. The AAL will be the first step toward the integration of blockchain technology into real-life academic international medicine (AIM) applications. Powered by the global LCC network, the AAL will help record and track activities by faculty members, facilitating the categorization and quantification of academic efforts into the following subtypes: (a) teaching, (b) clinical medicine, (c) community/government interactions, (d) research, and (e) other/miscellaneous. Each entry will include the activity date/time/duration as well as basic description, with a number of generic entries available through a drop-down menu. Activities entered by academic faculty will then be analyzed periodically and will serve as a basis for resource mobilization and allocation. Access to the AAL will only be possible using the SID, thus making the AAL a logical extension and a springboard for subsequent LCC blockchain-based implementations. On this foundation, the CDR and ultimately a “basic electronic medical record” (BEMR, see below) will be constructed. Although the task of constructing a high-fidelity, immutable, and accurate ledger of academic activities will not be easy, certain steps can be taken to minimize the likelihood of “false claims.” Much like the blockchain-based cryptocurrency paradigm, a secure mechanism for consensus building and data verification can be constructed. Such a “network of trust” (NOT) is technically workable and analogous to how “pretty good privacy” keys were distributed at signing parties attended by people known to each other, and also similar to the way “secure socket layer” certificate authorities work.[3132] For example, if Party A's certificate is signed by some Party B who is trusted by Party C, Party C can trust Party A's certificate, etc. The next developmental step in our strategic plan will be the implementation of the CDR, where provider credentials will be securely uploaded and stored in decentralized fashion. These documents will follow predefined credentialing requirements by most institutions globally such as record of college education/graduation, professional school record/diploma, professional licensing/verification/certification, and any additional elements deemed important to the safe conduct of AIM efforts globally. Uploading of credentialing information will be voluntary, and access to this information will only be possible with the permission of the record owner, utilizing his or her unique SID. Optimally, this important credentialing instrument will help providers verify their identity, education, and qualifications, and ensure that appropriate standards are followed by all stakeholders. The end-result will be the provision of safe and efficient care to the patients worldwide. Similar to the academic activity verification process, there will be important challenges to consider before successfully implementing the global CDR. In principle, there will need to exist some form of “data onboarding” authority. This should be performed by a “verification agent” (e.g., independent organization/group) with equivalent authority to that which it takes to set up a legitimate record of specific type (e.g., a medical school diploma and medical board specialty certification). In terms of identity verification, for example, the level of diligence required is similar to that already present in “know your customer” legislation. The case for verifying professional credentials would be similar, including the process of independent data validation and certification. Again, this is technically possible with a NOT arrangement as mentioned above; however, there will be obvious limitations inherent to the workability of credential verification similar to traditional efforts already in place. If a practitioner is claiming to possess credentials from some credentialing provider, only that particular provider really has (and only should have) the authority to confirm that. At the same time, there must also be a mechanism to revoke trust and to hardwire time-defined recertification processes based on the expiry of records currently on file. The final step in the strategic LCCF-O12FI collaboration will be the development of a super secure, BEMR that could be deployed in low-resource environments, utilizing rudimentary portable device technology, and containing fundamental health information for each end-user. Much like the SID, information stored on the BEMR would be owned by the end-user and could be shared with healthcare providers only with the end-user's consent, requiring SID as the “Secure Key” to unlock information. We recognize the substantial challenges in the global implementation of this concept, especially with regards to the enormity of healthcare-related data (often from multiple systems and sources), the need for privacy, timely and accurate access, and verification of data. Other potential shortcomings, at this time, include the need for further development of the technology, limited availability of expert knowledge, significant gaps in public awareness, along with growth-related issues of scalability, security, and user adoption.[6] Nonetheless, it is our hope that the lessons learned from other blockchain application layers will serve as the foundation for successful development, evolution, and adoption of BEMR.[1] There are many other considerations related to blockchain technology implementations in healthcare. Although full discussion of such a broad topic is beyond the scope of this manuscript, certain key ramifications must be discussed in the context of the proposed O12FI-LCCF initiatives. Blockchain technology may be an important tool for increasing transparency of how charities collect and allocate funds, propelling a much leaner system that will benefit intended recipients to a much greater degree.[1] This application of the blockchain technology will help verify the integrity of an organization's operations such as the transparency regarding the proportion of contributions distributed to medical and educational causes versus the overhead. In turn, the public, philanthropic donors, and potential collaborators will be able to make more informed choices regarding where their contributions can be allocated most efficiently. Pharmaceutical companies may utilize blockchain to keep track of medications manufacturing and shipment, supply, expiration, and possible points of contamination.[33] By extension, similar technological approaches could be useful for tracking opiates in this age of epidemic prescription drug abuse.[34] In such cases, blockchain would make it easier to investigate and determine the source of access as the supply chain would become much more transparent. Various built-in data verification and safety features could also be used to prevent duplication of medications from different providers and other hazards that occur with polypharmacy. Furthermore, the same tracking approaches could be used to secure food supply chains and safeguard against disease outbreaks.[35] Contaminated food products could be quickly and more efficiently traced to specific farms, processing or packaging plants for immediate identification, and removal from circulation. When combined with potential applications for AIM and global health equity, blockchain-based applications could help catalyze further innovation. First, they can enable universal access to financial resources by removing third-party intermediaries and offering transparent, secure, and accountable means for AIM financing.[36] Next, they could help facilitate multilateral financing mechanisms dedicated to health system development and strengthening.[136] In addition, they could reduce fraud and corruption through the use of immutable, tamper-proof transaction ledgers.[136] Finally, entire new capital markets for healthcare data could be created, providing better access (and opportunities) to patients, institutions, governments, researchers, and other key stakeholders.[136] Additional benefit offered by any token with fixed or “capped” supply as a medium of international exchange – subject to harmonization with region-specific laws and regulations – is the noninflationary character of such cryptocurrency. This, in turn, may help provide end-users with a protective mechanism against inflation and loss of monetary value – a phenomenon experienced across many LMICs.[3738] In conclusion, the global partnership between OPUS 12 Foundation (including its allied partners and subsidiaries) and LCCF provides a unique platform for the parallel development of both global currency support framework and medical/educational application layer for the academic international medical community.

Quinn DuPont

This article investigates ethical research risks associated with cryptocurrencies and the related family of digital "value" technologies. It provides an empirical analysis of innovation and recommends guiding principles for ethical research and development. Ethical research risks are identified through 1) an analysis of research methods and ethics disclosure practices in published empirical research; and 2) a survey of academic research practices and researcher opinions. These data identified multiple research ethics issues. It was discovered that most researchers have extensive and undisclosed industry relationships, have undisclosed conflicts of interest arising from token ownership, and report low use of institutional review or ethics guidelines, among other issues. Three novel research risks-conflicts of interest, risky methods, and disclosure-are then introduced and compared to the risks of conventional research. It is argued that these technologies introduce ethical risks and opportunities beyond their sector. These findings suggest a new class of ethical and normative research practice, comparable to fields such as bio-or nanotechnology ethics. Based on these analyses, eight principles for ethical research are described, with practical lessons for the researcher.

Yan Zhuang, Lincoln Sheets, Zon‐Yin Shae, Yin-Wu Chen · 6 authors

Patient recruitment for clinical trials is known to be a challenging aspect of clinical research. There are multiple competing concerns from the sponsor, patient and principal investigator's perspectives resulting in most clinical trials not meeting recruitment requirements on time. Conducting under-enrolled clinical trials affects the power of conclusive results or causes premature trial termination. The Blockchain is a distributed ledger technology originally applied in the financial sector. Its features as a peer-to-peer system with publicly audited transactions, data security, and patient privacy are a good fit for the needs of clinical trials recruitment. The "Smart Contract" is a programmable self-executing protocol that regulates the blockchain transactions. Given current recruitment challenges, we have proposed a blockchain model containing multiple trial-based contracts for trial management and patient engagement and a master smart contract for automated subject matching, patient recruitment, and trial-based contracts management.

David M. Maslove, Jacob Klein, M. Kathryn Brohman, Patrick Martin

BACKGROUND: Blockchain technology is emerging as an innovative tool in data and software security. OBJECTIVE: This study aims to explore the role of blockchain in supporting clinical trials data management and develop a proof-of-concept implementation of a patient-facing and researcher-facing system. METHODS: Blockchain-based Smart Contracts were built using the Ethereum platform. RESULTS: We described BlockTrial, a system that uses a Web-based interface to allow users to run trials-related Smart Contracts on an Ethereum network. Functions allow patients to grant researchers access to their data and allow researchers to submit queries for data that are stored off chain. As a type of distributed ledger, the system generates a durable and transparent log of these and other transactions. BlockTrial could be used to increase the trustworthiness of data collected during clinical research with benefits to researchers, regulators, and drug companies alike. In addition, the system could empower patients to become more active and fully informed partners in research. CONCLUSIONS: Blockchain technology presents an opportunity to address some of the common threats to the integrity of data collected in clinical trials and ensure that the analysis of these data comply with prespecified plans. Further technical work is needed to add additional functions. Policies must be developed to determine the optimal models for participation in the system by its various stakeholders.

Zeeshan Jan, Allan Third, Michelle Bachler, John Domingue

Peer-reviewing holds a significant importance in the process of scientific publishing. The process of peer-reviewing has been criticized for its defects, but research communities have faith in it, and hence, it is perceived as the backbone of scientific publishing. The process needs improvements in a number of ways, i.e, establishing trust in the pro- cess, preventing abuse, bringing transparency in the process and keeping the integrity of data intact. Moreover, the activity of peer-reviewing is carried out without any formal incentives. We present considerations in refreshing peer-review, and our approach to experiment in this space.

Mahsa Shabani

Blockchain-based platforms are emerging to provide solutions for technical and governance challenges associated with genomic data sharing. Providing capabilities for distributed data stewardship and participatory access control along with effective ways for enforcement of the data access agreements and data ownership are among the major promises of these platforms.

David M. Maslove, Jacob Klein, M. Kathryn Brohman, Patrick Martin

<sec> <title>BACKGROUND</title> Blockchain technology is emerging as an innovative tool in data and software security. </sec> <sec> <title>OBJECTIVE</title> This study aims to explore the role of blockchain in supporting clinical trials data management and develop a proof-of-concept implementation of a patient-facing and researcher-facing system. </sec> <sec> <title>METHODS</title> Blockchain-based Smart Contracts were built using the Ethereum platform. </sec> <sec> <title>RESULTS</title> We described BlockTrial, a system that uses a Web-based interface to allow users to run trials-related Smart Contracts on an Ethereum network. Functions allow patients to grant researchers access to their data and allow researchers to submit queries for data that are stored off chain. As a type of distributed ledger, the system generates a durable and transparent log of these and other transactions. BlockTrial could be used to increase the trustworthiness of data collected during clinical research with benefits to researchers, regulators, and drug companies alike. In addition, the system could empower patients to become more active and fully informed partners in research. </sec> <sec> <title>CONCLUSIONS</title> Blockchain technology presents an opportunity to address some of the common threats to the integrity of data collected in clinical trials and ensure that the analysis of these data comply with prespecified plans. Further technical work is needed to add additional functions. Policies must be developed to determine the optimal models for participation in the system by its various stakeholders. </sec>

Hao Dai, H. P. Young, Thomas J S Durant, Guannan Gong · 8 authors

The governance of data used for biomedical research and clinical trials is an important requirement for generating accurate results. To improve the visibility of data quality and analysis, we developed TrialChain, a blockchain-based platform that can be used to validate data integrity from large, biomedical research studies. We implemented a private blockchain using the MultiChain platform and integrated it with a data science platform deployed within a large research center. An administrative web application was built with Python to manage the platform, which was built with a microservice architecture using Docker. The TrialChain platform was integrated during data acquisition into our existing data science platform. Using NiFi, data were hashed and logged within the local blockchain infrastructure. To provide public validation, the local blockchain state was periodically synchronized to the public Ethereum network. The use of a combined private/public blockchain platform allows for both public validation of results while maintaining additional security and lower cost for blockchain transactions. Original data and modifications due to downstream analysis can be logged within TrialChain and data assets or results can be rapidly validated when needed using API calls to the platform. The TrialChain platform provides a data governance solution to audit the acquisition and analysis of biomedical research data. The platform provides cryptographic assurance of data authenticity and can also be used to document data analysis.

Edward Meinert, Abrar Alturkistani, Kimberley Foley, Tasnime Osama · 9 authors

BACKGROUND A blockchain is a digitized, decentralized, distributed public ledger that acts as a shared and synchronized database that records cryptocurrency transactions. Despite the shift toward digital platforms enabled by electronic medical records, demonstrating a will to reform the health care sector, health systems face issues including security, interoperability, data fragmentation, timely access to patient data, and silos. The application of health care blockchains could enable data interoperability, enhancement of precision medicine, and reduction in prescription frauds through implementing novel methods in access and patient consent. OBJECTIVE To summarize the evidence on the strategies and frameworks utilized to implement blockchains for patient data in health care to ensure privacy and improve interoperability and scalability. It is anticipated this review will assist in the development of recommendations that will assist key stakeholders in health care blockchain implementation, and we predict that the evidence generated will challenge the health care status quo, moving away from more traditional approaches and facilitating decision making of patients, health care providers, and researchers. METHODS A systematic search of MEDLINE/PubMed, Embase, Scopus, ProQuest Technology Collection and Engineering Index will be conducted. Two experienced independent reviewers will conduct titles and abstract screening followed by full-text reading to determine study eligibility. Data will then be extracted onto data extraction forms before using the Cochrane Collaboration Risk of Bias Tool to appraise the quality of included randomized studies and the Risk of Bias in nonrandomized studies of Interventions to assess the quality of nonrandomized studies. Data will then be analyzed and synthesized. RESULTS Database searches will be initiated in September 2018. We expect to complete the review in January 2019. CONCLUSIONS This review will summarize the strategies and frameworks used to implement blockchains in health care to increase data privacy, interoperability, and scalability. This review will also help clarify if the strategies and frameworks required for the operationalization of blockchains in health care ensure the privacy of patient data while enabling efficiency, interoperability, and scalability.

Vaso Rahimzadeh

Clinical research and health information data sharing are but ripples in a growing wave of reimagined applications of distributed ledger technologies beyond the digital marketplace for which they were originally created. This paper explores the use of distributed ledger technologies to facilitate single institutional ethics review of multi-site, collaborative studies in the dataintensive sciences such as genetics and genomics. Immutable record-keeping, automatable protocol amendments and direct connectivity between stakeholders in the research enterprise (e.g., researchers, research ethics committees, institutions, funders and regulators) comprise several of the conceptual and technological advantages of distributed ledger technologies to research ethics review. This novel-use proposal dovetails recent policy reforms to research ethics review across North America that mandate a single ethics review for any study that takes place across more than one research site. Such reforms in the United States, Canada and Australia replace prior institution-by-institution approval mechanisms that contributed to significant research delays and duplicative procedures for collaborative research worldwide. While this paper centers on the Common Rule revision in the United States, the single ethics review mandate is a noteworthy example of regulation evolving in parallel with advances in the dataintensive sciences it governs. The informational exchange capacities of distributed ledger technologies align well with the procedural goals of streamlining the ethics review system under the new Common Rule ahead of its official implementation on January 19, 2020. The ethical, legal and social implications of applying such technologies to ethics review will be explored in this concept paper. Namely, the paper proposes how administrative data from research ethics committees (REC) could be protected and shared responsibly, as well as interinstitutional cooperation negotiated within a centralized network of research ethics committees using the blockchain. Keywords: Blockchain, Data Sharing, Ethics Review, Governance, IRB, Research, Single Mutual Recognition

Kenneth Colon

Over the past decade, there have been many innovations in new payment and care delivery models and technology, from telemedicine to artificial intelligence (AI) to blockchain. These innovations, however, must be used in tandem to drive real change. We review each of these innovations and propose a model for how they can be combined to be greater than the sum of their parts. In doing so, we can create a global, decentralized health system that truly puts patient care at the center, while supporting and further enabling the clinicians who make this care possible, to deliver higher quality care at a fraction of the cost. Keywords: Artificial Intelligence, Behavioral Health, Blockchain, Collaborative Care, Decentralization,Direct Primary Care, Ethereum, Integration, Payment Models, Telemedicine, Virtual Assistants

Mehdi Benchoufi, Philippe Ravaud

Reproducibility, data sharing, personal data privacy concerns and patient enrolment in clinical trials are huge medical challenges for contemporary clinical research. A new technology, Blockchain, may be a key to addressing these challenges and should draw the attention of the whole clinical research community.Blockchain brings the Internet to its definitive decentralisation goal. The core principle of Blockchain is that any service relying on trusted third parties can be built in a transparent, decentralised, secure "trustless" manner at the top of the Blockchain (in fact, there is trust, but it is hardcoded in the Blockchain protocol via a complex cryptographic algorithm). Therefore, users have a high degree of control over and autonomy and trust of the data and its integrity. Blockchain allows for reaching a substantial level of historicity and inviolability of data for the whole document flow in a clinical trial. Hence, it ensures traceability, prevents a posteriori reconstruction and allows for securely automating the clinical trial through what are called Smart Contracts. At the same time, the technology ensures fine-grained control of the data, its security and its shareable parameters, for a single patient or group of patients or clinical trial stakeholders.In this commentary article, we explore the core functionalities of Blockchain applied to clinical trials and we illustrate concretely its general principle in the context of consent to a trial protocol. Trying to figure out the potential impact of Blockchain implementations in the setting of clinical trials will shed new light on how modern clinical trial methods could evolve and benefit from Blockchain technologies in order to tackle the aforementioned challenges.