Bringing clinical trials into the new age with blockchain

The COVID-19 pandemic has sparked digital transformation across the pharmaceutical industry; however, the shift to reliance on software and cloud technologies has only heightened concerns about data integrity and security. While these are vital across the entire sector, keeping patient data safe while implementing decentralised or hybrid trial protocols is of critical importance.

With the increasing emergence of decentralised trials and adoption of technologies to facilitate them, European Pharmaceutical Review’s Hannah Balfour interviewed Rama Rao, the Chief Executive Officer of Bloqcube^®, to learn about how blockchain can benefit drug development.

Bloqcube has developed a clinical trials software system that uses blockchain technology, but what is blockchain?

“Blockchain is, in simple terms, a transaction record. It is a record that is immutably stored and linked up cryptographically, so that there is a single source of truth over a period of time thus engendering trust. As a result, the record can be relied upon by multiple parties, in the absence of any other processes,” explained Rao.

Blockchain-based systems use a distributed ledger driven computer network to store time-stamped data entries, known as transaction records. When an entry is made, each node in the network processes and verifies the record and archives the change. Over time, the system builds up a chronological trail of all the transactions that have ever been recorded.

As a result of the data being spread across a large network of databases in replicate copies, rather than a single repository, the information is much less vulnerable to hack, infringe or steal. In addition, the verification steps ensure the stored data is kept intact and immutable, protected against falsification, ‘beautification’ or invention. These properties make it a desirable platform for storing and processing sensitive data, such as patients’ medical records, clinical trial data, patients’ identities, stakeholders’ credentials or even novel compound libraries.

How can transaction records benefit clinical trials?

Rao explained: “Using a blockchain-based system enables you to look at records years after the fact and know that the data that is held in that block of that chain has full integrity and has not been tampered with. This is particularly important when it comes to regulatory processes or when cause-effect analyses are performed to resolve issues.

“Additionally, blockchain systems have the benefit of being used in a decentralised way. In effect, that means that, in tomorrow’s world, clinical trials could be run in a patient’s home and retain strong governance mechanisms. This also levels the playing field, so whether you are in rural Africa, India or Latin America, or in a major hospital in New York, Paris or London you should be able to achieve similar scientific results and the same level of data integrity.”

Diving deeper:

Enhancing recruitment

Rao explained that there is a paradox in recruiting patients for trials: “while there is a high desire to recruit from the trial sponsors and investigators, there is a low connectivity rate of patients to trials”. He noted the 2019 report that found only eight percent of US cancer patients participate in clinical trials as an example.¹ To overcome these issues, which have only been compounded with restrictions and fear surrounding the potential for viral transmission at healthcare facilities during the pandemic, trials must be able to go to the patient, ie, they ought to be decentralised. However, robust governance cannot be compromised, said Rao, and this is where blockchain comes in to provide an algorithmic mechanism of trust.

Enabling full decentralisation

In its simplest form, decentralisation means that no single power has exclusive control over the data or its processing. In the context of blockchain, this is achieved because the data is also distributed, ie, it is stored at each individual node in the network and not a single location. In terms of clinical trials, decentralisation means that it is not happening at a single central site; instead, it may be a multi-centre trial or be using connected technologies to enable participants and investigators to report remotely – while remaining within the overall structure of scientific and regulatory controls.

Trial decentralisation is one of the primary practices implemented to ensure continuation of clinical research during the pandemic. As a result, electronically submitted patient reported outcomes (ePRO) and many other remote solutions have become increasingly accepted. These approaches not only produce a vast quantity of data, as does a typical trial, but also require robust governance, as in many cases participants may not attend regular face-to-face follow ups with medical professionals.

The security of the data held in a blockchain-based system, and the technology’s ability to be scaled by adding more nodes, enables data to be entered remotely and safely shared between patients, (suitably pseudonymised if needed), stakeholders and sites, thereby facilitating decentralised trials.

When combined with Self Sovereign Identity (SSID) both the control of the identity of the individual, their storage and access rights would be securely controlled to the benefit of the trial stakeholders.

Supporting governance with real-time decision making

“Another benefit of blockchain is that it can present data to multiple people at the same time; this is the beauty of its decentralised distributed ledger structure. For instance, say there are four physicians monitoring a trial – one is based in London, another in New York, the third in Frankfurt and the last in Zurich.

“Through a blockchain-based system they would all receive the data simultaneously and in real time. This is critical for decision making in trials, as there may be, amongst others, two broad results that require quick action. Either there are serious adverse events, and the trial has to be stopped quickly, or the product may be performing so well that it would be unethical to continue. In the pandemic world, when people cannot physically meet, this solution allows quick action and near real-time decision making, regardless of restrictions,” stated Rao.

Facilitating integration

“The industry spends almost a hundred billion dollars a year setting up and running clinical trials. There is anything from 4,000 to 5,000 new trials started on clinicaltrials.gov each year, run by multiple companies. This complexity is augmented by the presence of various intermediaries, such as contract research organisations (CROs) who work in conjunction with the owners of the product, or the owner of the trial, to deliver the result. As such, there is a huge number of players all looking at the problem in different ways and this complexity increases year on year – it is partly why products cost so much time and money to get into the market.

“Blockchain can optimise the number of intermediaries and the performance of repetitive tasks that enable trials to take place, for instance by replacing traditional tasks with smart contracts and e-consent forms. This holds a lot of onus, as it allows us to move away from siloed systems into integrated systems. Having a unified platform with multiple capabilities is one very strong feature of a blockchain-based clinical process,” explained Rao.

He added that one of the major issues in clinical trials is that both patients and physician typically do not get paid rapidly: “There is a white paper by the Society of Clinical Research Sites in the US, which talks about how people typically get paid after four or five months.² That puts a huge stress on the ability of sites to operate and run a trial, and also the patient – the least we can do is pay them for what they do as quickly as possible.”

He stated that blockchain is helping overcome this. For instance, the proprietary system Bloqcube has built automates and speeds up payment processes. Rao explained that in future they hope to develop the system further, so it can use central bank digital currencies (such as the electronic pound, euro or dollar) rather than current processes. Through this he stated that, in future, payments could be made to patients or physicians minutes after they perform a task, such as remotely recording an outcome. “This would benefit multiple players, simplify processes and also encourage patient recruitment, by ensuring they are reimbursed rapidly.”

“The beauty of the blockchain-driven system is that it can integrate multiple systems and enable that sort of automation,” Rao said. This echoes what is being projected across the entire pharmaceutical industry; through digitalisation, platforms will become increasingly unified, rather than continuing to rely on the fractioned and siloed legacy systems that have been implemented in dribs and drabs as problem fixes over the past decades.

Are there any limitations on the use of blockchain in clinical trials?

Rao stated: “Just like any technology, it is not a magic bullet. It needs to be used with some degree of care and concern. One of the considerations with blockchain is the distributed aspect and the scale at which replication takes place. Limitations arise in blockchain networks once you start scaling up in terms of data volumes, such as if you were to enrol 20,000 patients and replicate the data across 1,000 sites, primarily because of the capabilities of current technology. However, while some data limitations exist now, that may not necessarily be the case in the future, as technologies continue to evolve.

“Additionally, blockchain systems require good wi-fi connectivity, so if this is an issue, such as in a rural community, then implementing such systems can become a challenge.”

How could blockchain and other technologies revolutionise drug development?

“When you look at the computer sciences industry, they have what is called Moore’s Law; essentially the cost of computing is decreasing exponentially while the power of computing is increasing exponentially. This is why there is the same amount of computing power in our phones today as was used to put the man on the moon in 1969.

“However, in the drug development industry, and clinical trials in particular, we have Eroom’s Law operating. It is the exact reverse of Moore’s Law; our costs are increasing exponentially, while the power is getting more fractionated, siloed and decreasing.” He continued to explain that we therefore must discover a way to reduce the cost of clinical trials and drug development, to be able to deliver medicines at a reasonable price to patients. “Because the current price of medication is really unsustainable; when I started in the industry 28 years ago it cost roughly about $250 million to build a drug from start to finish – now it is close to $2.6 billion.”

“The complexities of having numerous stakeholders all looking at clinical trials from various angles is just one of the reasons medicines are so expensive. The technologies that are being implemented now, such as blockchain, that the pandemic has helped to promote, are majorly changing the industry and have the potential to do this,” enthused Rao.

What other applications are there for blockchain in the pharma industry?

The application of blockchain that excited Rao the most was its possible application in track and trace supply chain management. He gave two examples of its potential to revolutionise this field:

1. If a drug is contaminated for some reason, with a blockchain-driven digital certification of the drug it should be faster to ascertain where that contaminant appeared and what ingredient or process caused it than with current procedures.
2. Preventing counterfeiting. Having a single source of truth, such as the blockchain record, can be hugely beneficial in stopping counterfeit medications from entering the supply chain. He gave COVID-19 vaccines as an example: they are hugely expensive but in essence the vials contain a white to off white liquid. Now that they are being sent across the world, what is to stop hackers partially filling vials from approved vaccines with water and selling them on? It could be hugely damaging to companies if their vaccines stop working and to peoples’ lives and, according to Rao, difficult to figure out where the issue may be coming from with current processes, if hacked. So, a blockchain-driven digital solution to track the vials could make the supply a lot more secure.

Conclusions

Overall, Rao presented blockchain as an innovative solution for secure trial decentralisation. The primary benefits for the application of blockchain in clinical trials included its ability to enable real-time decision making and robust governance, despite geographical divides; encourage recruitment; enhance and optimise the running of trials, minimize manual or repetitive tasks through the usage of smart contracts and ensure data integrity. He also acknowledged that the technology, being so new to this industry, has limitations and that further development will be needed to optimise its use.

References

1. Unger J, Vaidya R, Hershman D, Minasian L, Fleury M. Systematic Review and Meta-Analysis of the Magnitude of Structural, Clinical, and Physician and Patient Barriers to Cancer Clinical Trial Participation. JNCI: Journal of the National Cancer Institute [Internet]. 2019;111(3):245-255. Available from: https://doi.org/10.1093/jnci/djy221
2. Society for Clinical Research Sites (SCRS). Financial Barriers to Site Sustainability, Patient Experience and Overall Trial Success [Internet]. 2021. Available from: https://myscrs.org/downloads/download-id/9887/