Decentralised clinical trials (DCTs) have been hailed as the next paradigm in clinical research. Pushed by COVID-19 lockdowns and restrictions, DCTs promise a way of working that is more suited to our increasingly digital and interconnected world. The benefits offered by DCTs have been frequently reported over the past three years and include, among others, access to a wider patient pool, improved patient convenience, and more flexible data collection.
As we now enter the post-pandemic era, many stakeholders are weighing the balance of this new operating model. Are DCTs a logical evolution of the traditional centralised trial model or merely an industry response to lockdown-induced clinical trial disruption? And if DCTs are indeed here to stay, how will technology continue to shape our clinical operations in and outside of the clinic? To address these questions, we will take a closer look at the DCT terminology, the concept of decentralisation, and the impact of both existing and emerging technologies on clinical operations.
Decentralised, virtual, remote?
The growing popularity of DCTs has resulted in a wildfire of different terminology where the terms decentralised, virtual, hybrid, remote and at-home trials are often used interchangeably. This can be confusing to clinical operations leaders interested in adopting this new model. Adding to this ambiguity, DCTs also lack a clear definition, with definitions ranging from fully decentralised trials to studies that incorporate one or more DCT components.
A more useful way to look at DCTs is to plot clinical trials on a centralised-decentralised continuum with studies becoming more decentralised as they adopt a growing number of DCT components. As most stakeholders are now adopting a ‘digital-first’ approach, on-site visits will only apply when specialised equipment and/or medical staff are needed. In practice, this means DCTs are all about combining the best of both worlds—the digital and the physical realm.
A closer look at decentralisation
Now that we have a better grip on DCT terminology, it is time to further examine decentralisation. As a concept, decentralisation can be viewed from different angles. From a data capture and patient management perspective, clinical trials have clearly become more decentralised. This shift started two decades ago, with the introduction of eClinical tools such as ePRO and eConsent in the early 2000s. Fast forward to today, the set of available tools has become increasingly sophisticated. We can use wearables for remote patient monitoring, social media for patient recruitment, and video conferencing for virtual visits. Combined with Direct-to-Patient supply chains and at-home nursing, these tools allow us to effectively migrate many study procedures outside the walls of the clinic.
However, when looking at decentralisation from the perspective of data exchange or data ownership, clinical trials are still very centralised. Study data is almost always captured for the purpose of one study only, with the sponsor as its sole owner. This practice goes against major industry trends such as patient empowerment, which centers around providing patients with more ownership and control. Moreover, it also hampers the re-use of clinical trial data outside the context of a single study in accordance with the FAIR data principles (making data Findable, Accessible, Interoperable, and Reusable).
What if patients could own their data? And what if patients could choose to make their data available for future research purposes? Empowering and evolving patients in this way may help to increase recruitment and retention rates. With an average patient dropout rate of 30% across studies and with the ever-increasing costs of drug development, novel approaches in this area are certainly welcome. However, if we are to unlock data from its centralised siloed repositories and consider redistributing its ownership, we require a new stack of eClinical tools. A combination of technologies and standards that provide a cybersecure, privacy-preserving, and interoperable infrastructure for data exchange.
Blockchain: a decentralised record-keeping system
One of the most prominent emerging technologies underpinning such an infrastructure is blockchain. This technology allows us to decentralise the way we store, manage, and retain data. Blockchain acts like a decentralised record-keeping system—a database that is kept online by a network of different computer servers. Moreover, everything stored on blockchain is immutable (i.e., cannot be altered), thereby preventing data corruption and manipulation of any kind. Let’s touch upon some of the unique benefits offered by blockchain in combination with more traditional eClinical infrastructure.
Verifiable data for end-to-end data integrity and data re-use
Integrated with an EDC and eTMF solution, blockchain can be used to generate a system-independent and immutable audit trail of clinical trial data and documents. Through a process called hashing, we can create a unique digital fingerprint (hash code) for each newly generated trial-related data object or document. These hash codes are subsequently stored and timestamped on the blockchain and allow clinical research professionals, auditors, and inspectors to indisputably verify that data was present at a certain point in time and that it has not been altered since.
The resulting audit trial offers several unique features. Firstly, the audit trail is privacy-preserving since hash codes do not disclose personal identifiable information or any other form of sensitive confidential information. Secondly, anything stored and timestamped on the blockchain is immutable, meaning malicious actors cannot tamper with the data. Thirdly, the audit trial offers superior interoperability since it lives independent of the eClinical systems used to store and manage data. This means you can verify the integrity of data throughout its entire lifecycle, even after the applied eClinical solutions have long been retired.
Blockchain therefore allows us to secure clinical trial data integrity end-to-end—from the moment it is generated until the end of the full retention period (and beyond for that matter). In practice, this means we can de-risk the likelihood of both intentional and unintentional data manipulation by making trial-related data, documents, and processes tamper-resistant. We can for instance prove and verify a priori hypotheses for the study protocol, appropriate consent management prior to data collection, and unaltered data after database lock. But more importantly, we can promote the re-use of clinical trial data after study completion and across existing organisational boundaries, since the system-independent audit trail allows us to verify the integrity of data regardless of its storage location.
Self-Sovereign Identity: the next paradigm in digital identity management
In addition to leveraging blockchain for its unique audit trail capabilities, we can also leverage this technology for identity and access management. This particular use case has given rise to the concept of Self-Sovereign Identity (SSI), a novel approach to digital identity management where users have full control over their personal data.
SSI is a cornerstone of the next generation internet—often referred to as ‘Web3’. It answers to growing privacy concerns and cybersecurity threats, functioning as a logical follow-on to privacy regulations such as the GDPR, which set the stage for redistributing data ownership and control to ensure a uniform and harmonised level of personal data protection. In the context of healthcare, SSI also ties in perfectly with rising levels of health literacy and health consumerism, which have made patients increasingly autonomous in their health-related decisions.
Put simply, SSI puts people in control of their own data. With interoperability as one of its core principles, SSI-enabled identity solutions often leverage the built-in security and privacy protection features of today’s smart mobile devices such as facial recognition, data encryption, and single sign-on. They allow users to identify themselves, sign documents, and selectively disclose data with other entities over the internet. SSI is truly unique because it eliminates the need for third-party intermediaries in any of these processes. To illustrate, nowadays many websites offer the ‘Sign in with Google’ option. This feature, although convenient, provides Google with information about when, where, and how you interact across the web. In the case of SSI, users are empowered with their self-owned identity, meaning third-party companies are not informed of their every action.
Self-Sovereign Identity and clinical research
SSI is a natural fit for increasingly digital and decentralised clinical trials. Firstly, it offers better security against cyberattacks since it removes the need for storing all sensitive data in a single centralised server that might be prone to hacking. Secondly, it enhances privacy as it minimises personal data use by providing patients with granular control over what data properties they want to disclose and with whom. Thirdly, it provides a single interoperable solution for identity and access management that can be used across disparate eClinical systems and devices.
In practice, an SSI infrastructure can be applied across various clinical trial processes. One example is dynamic consent, where patients can use their self-owned identity to provide, update, and revoke consent throughout a study as well as post-study for future research purposes. Another example is eRecruitment, where patients can use their self-owned identity to manage and maintain a privacy-preserving patient profile that includes features for selectively disclosing screening data and/or willingness to participate in future studies. It’s important to note that, in both these cases, patients directly interact with the corresponding investigator (or other authorised individual), meaning a third-party intermediary is not needed for information transfer. Moreover, patients leverage the built-in security and privacy protection capabilities of their smartphone, using features such as facial recognition and single sign-on to digitally sign a consent form or to authorise access to specific data properties.
However, these examples only scratch the surface of what is possible. Health or fitness data generated by a wearable device can be directly linked to the patient’s self-owned identity and the same applies to other forms of patient-level data. In other words, SSI allows us to connect patient identities to clinical trial data in a secure and privacy-preserving way, even as this data moves across different systems. The blockchain serves as an overarching interoperability layer linking each data asset to its data provider while automatically logging each data transaction in an immutable audit trail.
SSI thus provides a unique avenue for empowering patients and enabling more patient-centric clinical research. It allows us to redistribute and decentralise data ownership by providing patients with shared (also ‘fractional’) ownership over their data contributions to a clinical trial. In this way, SSI has the potential to promote patient recruitment, engagement, and retention. It promises a power shift from sponsor to patient and might finally allow us to reshape the patient’s role from subject to collaborator.
Near future or distant reality?
While we still have a long road ahead towards industry-wide adoption of such an infrastructure, blockchain and SSI are not as novel as they might sound. Over the past 5 years, we’ve seen the rise of numerous enterprise-ready blockchains as well as tremendous developments in the SSI space by renowned standard bodies such as the World Wide Web Consortium (the standards organisation once involved in launching the internet).
Similar to the rise of eClinical solutions, the set of available blockchain and SSI tools is becoming more sophisticated by the year and there are several lessons learned that we can apply in this next wave of decentralisation. For starters, we ought to remember that any shape or form of decentralisation is not simply a matter of doing things digitally. To illustrate, the introduction of eClinical tools in the early 2000s enabled new decentralised ways of data capture and patient management. Prominent examples include real-world data collection using wearables or remote patient onboarding using eConsent. These cases demonstrated that best practices applied to the clinical trials of today cannot simply be copied to the clinical trials of tomorrow, especially not when the technology at hand introduced a new way of working.
The keyword is interoperability
Luckily, we don’t need to completely reinvent the wheel. The hallmark of decentralised technologies and concepts like blockchain and SSI is that they are designed to work with existing eClinical solutions and infrastructure. The blockchain and SSI infrastructures under development today are almost always based on open standards with interoperability as a cornerstone principle. This is a must-have feature for successful adoption, especially in an industry that has long been plagued by interoperability constraints and fragmentation.
Rethinking the status quo
The decentralisation of data exchange and data ownership will most likely have a profound effect on clinical research as we know it today. We will have to rethink the status quo and redefine the roles of sponsors, sites, and patients in the clinical trial arena. Being successful will require buy-in from all these stakeholders on one end and new regulatory frameworks and guidance on the other end. Therefore, stakeholder education, industry-wide validation, and adapting regulation will be key drivers of adoption.