In part 1 and part 2 of this series, we explained how blockchain technology can be leveraged to enhance the integrity, auditability, and exchange of data in clinical trials. In this article, we will cover how smart contracts can be used to automate clinical trial activities and improve protocol compliance.
This is the final article of a three-part series on blockchain in clinical trials, and was adapted from the Triall whitepaper (which you can download by following this link). Triall’s mission is to enable a future of smarter, safer and more-efficient clinical trials by delivering blockchain-enabled solutions for clinical trial professionals.
Blockchain has become famous with the rise of cryptocurrencies but offers a unique set of other possibilities. The technology can be used to promote efficient and secure exchange of data across organizational boundaries and data systems. Blockchain is said to minimize or in some instances eliminate the need for middlemen or third-party intermediaries, who often drive costs or increase the risk of errors or security breaches.
In part 1 and part 2 of this series, we covered how blockchain can function as a tool in promoting data integrity, traceability, and auditability. We also addressed the use of Decentralized Identifiers (DIDs) for a new and revolutionary means of decentralized identity and access management. In this article, we’ll focus on smart contracts and the role they can play in automating some of the critical workflows, processes, and procedures found in clinical research. But before we dive into this topic, let’s first have another look at the learning points from the previous articles.
Key learning points from the previous articles
- Clinical trials require efficient communication of sensitive information among many different specialty stakeholders.
- Over the past decade, trials have become increasingly complex, digitalized and data-heavy, with data coming from a growing number of different sources, such as sensors, wearables, and mobile devices.
- Blockchain technology offers a means to promote data integrity, auditability, and traceability in clinical trial recordkeeping and data management.
- The technology can also act as a gatekeeper in connecting currently siloed data repositories and ultimately will help clinical researchers to make faster and better-informed decisions regarding trial management, monitoring, and resource allocation.
- To fully reap the benefits of this technology, blockchain should be implemented in conjunction with ‘traditional’, time-proven technologies, while following industry best practices and quality guidelines
The first clinical trial on the blockchain
Did you know Triall is the world’s first organization to apply blockchain technology in a live and running clinical trial? Read about it here.
Work smarter, not harder: a case for automation
Acquiring and sustaining a competitive advantage in a dynamic field such as the clinical trial industry requires more than just the modernization of existing technologies and processes. By levering automation, clinical trial stakeholders can work smarter and adapt faster to an ever-changing and highly-regulated environment. Automating (repetitive) workflows, procedures, and processes can increase staff productivity and work quality by complementing existing skillsets and by helping redirect focus on those aspects requiring the highest level of attention, such as patient safety. Automation and digitization can optimize processes and increase efficiencies while decreasing the change of human error, thereby promoting quality, compliance and more-effective decision-making. This can be of immense value to an industry that’s constantly under pressure to deliver a steady and efficient influx of novel medical solutions to society.
Smart contract for instantaneous business transactions
The concept of smart contracts, first introduced by computer scientist and lawyer Nick Szabo in 1994, has become increasingly popular with the rise of blockchain. A smart contract is a computer protocol that executes itself according to a set of predetermined conditions and without the involvement of a third party. Smart contracts enable instantaneous business transactions, eliminate enforcement costs and leave no room for ambiguity. They have the potential to lower the costs associated with setting up agreements and settling disputes, while reducing opportunities for deceitful behavior among contracting parties.
Implemented on a blockchain, smart contracts can be seen as computer programs that enable decentralized automation that is facilitated, verified and enforced by the conditions set out on the blockchain ledger. These programs cannot be manipulated and the (data) transactions resulting from an executed contract are irreversible. For this reason, smart contracts have to be coded in an explicitly detailed way and necessitate an extremely high level of precision, thereby forcing parties to be as transparent and open about their terms and conditions as possible.
It follows that smart contracts are heavily rule-based and require the encoding of all possible outcomes. They are therefore not always secure or cost-effective and, at this point in time, not yet suitable for automating complex arrangements that leave room for ambiguity. Furthermore, as the conditions set out in a contract often relate to activities in the physical world, there should be a reliable link between the physical and digital realm (something known as the Oracle problem). Moreover, while physical activities and objects are subject to a certain geographic location and therefore jurisdiction, decentralized smart contracts are not. This raises issues of enforceability in current legal frameworks. Yet, the promises of smart contracts are manifold, and this definitely holds true for clinical trial consortia.
Smart contracts in clinical trials
Smart contracts open up the way for new forms of automation, with the blockchain functioning as an overarching layer that governs data exchange between different off-chain repositories. In this scenario, the often confidential or personal data itself remains in its private repositories, which could be a secure cloud environment or on-premise server. Integrating immutability of data with DIDs for digital identity management and smart contracts for automated workflows is a powerful combination. For clinical trials, smart contracts can be used to govern data transactions within a clinical trial consortium, by implementing and enforcing the rules set out in the clinical trial agreement and protocol as well as those in individual contracts and standard operating procedures (SOPs). The following paragraphs will explain this in further detail.
Smart contract automation – streamlined and trustless collaboration in clinical trial activities
Protocol compliance: a crucial but challenging process
Throughout a trial, sponsors, contract research organizations (CROs), sites and regulators need to interact and collaborate in a broad range of trial-related activities, such as study approval, site monitoring, data management, safety reporting, regulatory filing, medical writing, and research dissemination. These activities are conducted according to the schedule and rules set out in the clinical trial protocol. It can, however, be difficult to ensure that everyone adheres to the clinical trial protocol at all times. Adding to this is the fact that a single clinical trial has an average of 2,3 protocol amendments over its lifetime. Any amendments to the clinical trial protocol have to be communicated to all involved stakeholders, who then have to adopt and comply with the new protocol version. Implementing and communication these amendments can be burdensome and creates room for error. Protocol deviations and violations resulting from the above can decrease research data integrity and can negatively affect patient safety and wellbeing.
Enforcing and monitoring protocol compliance using smart contracts
Smart contracts can function as a valuable tool in enforcing protocol compliance and at the same time can track key activities in real-time, thereby reducing the change of finding protocol deviations and violations later on in the trial. These contracts help enforce procedural rules in key activities such as collecting informed consent, enrolling patients and reporting safety events. They can determine what data is required at each point in the chain and may help ensure that data entries are complete, immutable and viewable to anyone with the right permissions. Moreover, in the case of protocol amendments, smart contracts can help enforce the updated set of rules of the new protocol version. In doing so, they automate part of the monitoring responsibilities, often accountability of the involved CRO, detecting and registering any occurring protocol violations over the course of the clinical trial. Collecting and reporting these violations in a timely manner is essential for the correct interpretation of the trial’s results. This process will also create a transparent, traceable and immutable event log for regulatory agencies.
Placing smart contract-gated workflows into context
Smart contracts can verify if data is collected according to timeline and if specific conditions have been met prior to data entry, thereby promoting data integrity and enforcing data coherence across research sites. To illustrate, a smart contract-gated workflow could only allow the collection of patient data after informed consent has been obtained and registered for that patient on the most current protocol version (patients have to reconsent for newer versions) and after it’s sure the patient satisfies the inclusion criteria. This would eliminate the enrollment of patients that are ineligible to participate or situations where researchers start data collection before the informed consent form is signed correctly.
Timeliness of payments
Smart contracts could also play a role in the budget agreements laid out in the clinical trial agreement and individual contracts. Uncertainty and delays with regards to payment are a persistent burden to the industry as many clinical trial stakeholders often don’t have an effective way of tracking and managing their payments. This can be a burden to clinical trial sites, who often only have a couple months of operating cash on hand, and is considered to be one of the key reasons for turnover among site staff. Moreover, delayed payments can be particularly burdensome to patients who are left unsure when they will be reimbursed for participating in the clinical trial. As the industry is currently struggling to retain patients throughout the full length of a trial (the average drop-out rate is 30%), certainty and timeliness of payments can be a significant step towards improving patient engagement.
Smart contract-enabled automated payments
When integrating blockchain with an online payment solution, smart contracts can enable automated payments between sponsors, CROs, and Sites based on specific trial milestones (e.g. first patient recruited) and the collection of data sets as soon as this information is registered on the blockchain ledger. As such, smart contract-enabled automated payments will reduce manual administrative work, further streamlining clinical operations. Moreover, this approach facilitates trust between trial stakeholders, knowing payments will automatically arrive according to the agreed terms and timeline. Again, to safeguard privacy and security, such a solution will work in conjunction with the DID-enabled digital identity infrastructure explained earlier.
Blockchain holds the potential to revolutionize the way clinical trial stakeholders interact and exchange data. Smart contracts can enforce protocol compliance for key clinical trial activities, especially those that require data entry in accordance with a predefined set of rules and conditions. This will promote data integrity and consistency across all involved stakeholders, leading to better and faster decision-making in trial management, monitoring, and budgeting. Nevertheless, blockchain and its smart contract capabilities are not a panacea to all persistent issues currently experienced by the industry. As with all technologies, humans remain an integral part of the process, and careful steps should be taken to avoid code corruption, mitigate risks and assure the overall quality and compliance of the technical solutions.