Blockchain and its implications for Clinical Research
Many people are aware of Bitcoin and other cryptocurrencies but are unaware, perhaps, of how and why they were and are being developed. Cryptocurrencies all rely on the use of decentralised ledger technology, or blockchain, thus avoiding the necessity for a “middle man” or central authority to regulate the value and flow of currency, such as the Bank of England. Much has been written as to the desirability or otherwise of cryptocurrencies, and the author doesn’t intend to explore those issues here!
In essence, blockchain is a decentralised database. It is shared, and immutable – once altered, the database cannot be changed further without the consent of all sharing parties. But why is this desirable?
“Transactions take place every second — orders, payments, account tracking. Often, each participant has his own ledger — and, thus, his own version of the truth. Having multiple ledgers is a recipe for error, fraud and inefficiencies. The goal is to see a transaction end-to-end and reduce those vulnerabilities.”[i]
Simply put, the more the data is recorded separately, the more the opportunities for innocent error[ii]:
By using the decentralised blockchain technologies[iii]:
Rather than intermediaries such as retail banks, suppliers and customers maintaining their own ledgers, the transaction itself forms part of the blockchain – the transaction cannot take place without being logged. What improvements could this technology bring to the clinical trials industry?
In a recent article[iv], Alex Alves proposes the following potential uses throughout the pharmaceutical sector:
- Regulatory Issues
- Supply Chain
- The data management of Clinical Trials
In addition to his proposals, there are implications in the tracking and assurance of informed consent procedures, version control of other essential documents, and in fact any transactional activity taking place between trusted parties involved in the clinical trial, e.g. investigators, sponsors, regulatory bodies, ethics committees…and patients.
Blockchain, Supply Chain and Regulatory Affairs
“In the European Union, the Falsified Medicines Directive specifies that pharmaceutical products must be serialised so they can be tracked by February 2019. Similarly, the Drug Supply Chain Security Act was introduced in the US in 2013 by the FDA. This is much like the Falsified Medicines Directive, stipulating that by 2023 there must be an electronic system tracking certain drugs through the supply chain in the United States (FDA, 2017; Lo, 2017).”[v]
Although not directly related to CTs, electronic tracking is already in use in the transfer of IMP supplies, and the relationship between manufacture, shipping, QP and site can be considered a prime candidate for blockchain ledger technology, allowing both tracking and confirmation of shipments.
Blockchain and Data Management
“It’s been many years since I have trusted anything I read in a medical or psychiatric journal. There is an enterprise wide positive bias; findings never seem to replicate; benefits are hyped; harms are hidden.”[vi]
Allen goes on to apportion blame for this state of affairs:
“Drug companies bear most of the blame — the research they sponsor is shoddy and market driven. Scientists are also to blame when they torture data so much it will confess to anything. Medical journals are to blame when they publish positive findings from lousy studies and reject negative results from well done studies. And journalists are to blame when they uncritically accept phony claims.”[vii]
Timothy Nugent et al agree: “The scientific credibility of findings from clinical trials can be undermined by a range of problems including missing data, endpoint switching, data dredging, and selective publication. Together, these issues have contributed to systematically distorted perceptions regarding the benefits and risks of treatments.”[viii] They conducted a pilot study to “… show that blockchain smart contracts provide a novel technological solution to the data manipulation problem, by acting as trusted administrators and providing an immutable record of trial history.”
They conclude that their trial “should help to increase trust in the data they hold and the credibility of trials findings, allowing medical professionals to make better-informed decisions that have the potential to reduce both patient risk and the financial strain placed on health services that data manipulation issues contribute to.” [ix]
Blockchain and Informed Consent
It has been found that one of the main reasons for not enrolling in a clinical trial is mistrust in the system or sponsor:[x]
“A majority of the mistrust in this process stems from prior knowledge of fraud in the proceedings. For example, prior knowledge of the Tuskegee experiments showed negative correlation with willingness of certain African American patients to participate in clinical trials. “Other examples of misconduct include the 2007 case regarding the clinical trial on the safety and effectiveness of oral telithromycin and amoxicillin/elavulanic acid in outpatients”. A survey on 717 adults in the United States found mounting distrust in clinical research staff in 2007, when user fee rates at drug manufacturers surpassed $1,000,000. This lack of trust often hinges on consent signing prior to participation in the Clinical Trial proceedings.”[xi]
The use of blockchain technology allows the sponsor, investigator, patient, IRB/IEC and regulator to have absolute confidence that informed consent has been thorough, accurate and complete.
The image above shows how the tracking of consent is controlled by all parties, thus ensuring that accurate information is captured, timestamped and next to impossible to alter. This is turn can be used within other blockchains to trigger randomisation, release of IMP, access to medical records etc.
In conclusion, blockchain technology offers efficiencies and reassurance of data integrity, quality and ethical standards. It provides simplicity and reliability to all contractual transactions and allows the sort of transparency, both of process and trial results that the industry wishes to see – the question is whether or not the industry is sufficiently dynamic to take the opportunities that are presented, or as with eCRF and eTMF systems, provide blocks and delays to the adoption of such technology. It does not come without some elements of risk. The tech is not suitable for everything, but the natural conservatism of the industry must be a concern – it is important that public trust and regulatory scrutiny can be leveraged to ensure adoption.
by Douglas Stewart
[viii] Nugent T, Upton D and Cimpoesu M. Improving data transparency in clinical trials using blockchain smart contracts [version 1; referees: 3 approved]. F1000Research 2016, 5:2541 (doi: 10.12688/f1000research.9756.1)