Pharma Focus Asia

Powering Decentralised Drug Development

Enabling downstream disruptive technologies to generate high fidelity output

Frank Leu, Founder and Managing Member, BioPharMatrix LLC

Decentralised clinical trials are the latest and rapidly growing trend in conducting clinical trials through leveraging improved disruptive digital technologies and remote data collection methods. Blockchain oracle is the keystone technology, upstream from disruptive technologies, such as machine learning (ML) and artificial intelligence (AI) that can significantly enable and enhance decentralised clinical trials' efficiency, transparency, and security.

The Decentralised Drug Development (DDD) process involves coordinating various vendors and pulling together contract research organisations (CRO) to operate seamlessly to achieve developmental milestones from conception to market. Currently, there are inefficient legacy technologies and non-digital methods used together during pre-clinical drug development to meet the Investigational New Drug application requirements set by the Federal Drug Administration (FDA). However, the scrutiny of drug candidates' toxicity and efficacy in humans during its clinical trial is becoming more intensive as data fidelity, security, and data/information immunity are critical attributes required for the FDA’s final approval. Recently, during human clinical trials, the evolution of moving away from centralised to decentralised developments are means to eliminate bottleneck restraints and delays as the decentralised method allows flexibility in patient recruitment and could reflect a much better geographical representation of a diverse patient background. For instance, for rare disease drug development, this could facilitate the trial’s ability to collect as many patients in the shortest amount of time possible as there is no geographical barrier. In this article, I will focus on the discussion of Decentralised Clinical Trials (DCT) and how these most expensive and often the least efficient phases of drug development could get a turbo boost from implementing disruptive technologies. This discussion will further focus on the requirements of the Blockchain Oracle (BO) and how it could power the rest of the blockchain architecture and provide high fidelity and immutable data collection for ML and AI training.

Running a DCT involves conducting a clinical trial with the use of digital technology, remote devices, and customised approaches for data gathering, participant monitoring, and trial process management. DCTs offer several advantages, such as increased patient participation and reduced logistical burdens as opposed to centralised trials. Here is an outline of key steps for running a decentralised clinical trial:

1 Define your trial’s questions and objectives. It is also very important to develop a detailed clinical trial protocol that outlines the study design, inclusion/exclusion criteria, endpoints, and data collection methods;

2 Upon submission of an Investigational New Drug (IND) application or Investigational Device Exemption (IDE), continue to establish close communication with the regulatory agency (i.e. FDA in the United States) to make sure your proposed DCT execution complies with local regulatory requirements;

3 Pick and choose and adopt technology that can digital tools for data collection, information transfer, patient recruitment, and monitoring. Automating and integrating electronic informed consent (eConsent), wearable devices, mobile apps, and telehealth platforms;

4 Recruit and screen participants remotely via digital communications/advertising and online platforms to recruit patients that accurately meet the study criteria;

5 To facilitate and make a decentralised trial workable, eConsent procedures needed to be put in place to validate participants’ consents were informed. Most importantly, participants need to be aware that throughout the study, their consent can be given electronically;

6 Use a real-time monitoring system to track patient progress and safety remotely. Data can be detected and collected remotely using digital tools, wearables, and patient self-reported outcomes;

7 In addition, maintain regular and informed communications with participants to keep them engaged and prevent participant dropout;

8 In the event of an adverse event, establish a procedure and system that participants can immediately notify relevant authorities;

9 In site-less trial management, coordinate trial activities, data collection, and patient interactions remotely. Define various decentralised trial platforms or clinical trial management systems (CTMS) for centralised control;

10 Timely and accurate distributions of investigational products and supplies to participants’ locations. Construct and put in place an effective remote system monitoring and management of the supply chain;

11 Implement a robust data transfer among stakeholders, however, the integrity of participants’ data and sensitive information have to be protected with security and privacy safeguards in place to be in compliance with local data privacy regulations (e.g., GDPR, HIPAA);

12 Analysing collected data and prepare interim and final study reports for local regulatory submissions;

13 Once submitted, engage the regulatory authorities in a transparent manner, maintain open and free communication throughout the trial. Promptly submit required documentation and updates as required;

14 Ensure trial results are completed with quality assurances that are ready for regulatory inspections and audits; Enabling the trial to come to a closure in accordance with the predefined criteria, submitting final reports to local regulatory agencies for approval;

15 Publish and share clinical trial results via journals, conferences, or clinical trial registries and continue to monitor participants for any long-term safety or efficacy concerns as posttrial follow-up.

Blockchain technology can be adopted to improve the efficiency, transparency, and security of the entire decentralised clinical trial process mentioned above. There are thousands of blockchain projects under development, creating some of the most exciting and innovative technologies to enable Web 3.0, which is an online universe that allows the internet to be as decentralised as possible and places control of information/data back to users’ control. Running a decentralised clinical trial requires careful planning, technology integration, and adherence to regulatory guidelines. Collaboration with experienced clinical trial experts, data scientists, and regulatory professionals is essential for success in this rapidly expanding field.

A blockchain could only be used properly in a decentralised clinical trial if the methods and devices used to track and collect data have been properly designed with a chosen blockchain oracle platform. A blockchain oracle is a trusted source of external data that feeds information into a blockchain smart contract. The chosen blockchain oracle would then be integrated with the wearable devices placed on the clinical trial participants to collect patient data and store it on the drug development blockchain. The oracle would also monitor the patient data for certain events, such as when a participant reaches a certain milestone or when a safety event occurs. In a decentralised clinical trial, this can be crucial for verifying off-chain data such as patient electronic health records (EHRs), lab results, and other relevant information.

The blockchain oracle can also be used to manage clinical trial data, such as participant eligibility, randomisation assignment, and data collection schedules. This can help to ensure that clinical trials are conducted efficiently and ethically. Oracles can be used to trigger smart contracts embedded in the blockchain to automatically advance to the next phase and/or distribute incentives to participants who have reached certain milestones in the trial. The blockchain oracle ensures the integrity and reliability of data in a DCT via feeding accurate and immutable information/ data for downstream disruptive technologies, such as ML and AI training.

The first step in constructing a functional blockchain to power DCT is to choose a blockchain platform that supports smart contracts and oracles of choice. Ethereum is a popular choice, but other platforms like Binance Smart Chain, Polkadot, or Tezos may also be suitable. Next, define and develop smart contracts that will be used in your decentralised clinical trial. These contracts should outline the rules and conditions of the trial, including data verification and storage. Selecting a reliable oracle provider, such as Chainlink is a widely used oracle service in the blockchain ecosystem. You'll need to integrate their services into your blockchain platform. Once integrated, identify the external data sources that the oracle will need to access for your clinical trial. These could include medical records systems, laboratory databases, or other sources of relevant clinical data. Integrate these clinical data into selected oracle and convert them into your smart contract code. The oracle will then fetch data from external sources and provide it to your smart contract when needed. A data verification mechanism will then need to be implemented within the smart contract. The data from the oracle should be cross-checked for accuracy and reliability, methods such as cryptographic hashing, digital signatures, or other methods to ensure the integrity of the data. Once the data verification method is set in place, set-up triggers in the smart contract initiate the oracle to fetch and feed data into the blockchain when specific conditions are met. For example, when a new clinical trial participant submits their health data, the oracle can be triggered to verify and store this data on the blockchain. Once data is stored on the blockchain, it is imperative to ensure that sensitive patient data is handled securely and with utmost strict privacy measures. Compliance with data protection regulations such as HIPAA (in the United States) or GDPR (in the European Union) is critical. Before deploying a decentralised clinical trial solution on the chosen blockchain platform, first thoroughly test your smart contract and oracle integration. Conduct security audits to identify vulnerabilities and address them before deploying the solution. Once deployed, one needs to continuously monitor the data feeds from the oracle to ensure accuracy and reliability throughout the trial. Stakeholder’s data accessibility will need to be set up considering how participants researchers, and other stakeholders can access and interact with data stored on the blockchain. A user-friendly interface or applications will be extremely crucial for this purpose. In the end, it is extremely crucial to ensure your decentralised clinical trials comply with all relevant regulations and ethical standards, especially in the healthcare sector.

In conclusion, by integrating a blockchain oracle into a decentralised clinical trial, you can enhance the trustworthiness and transparency of your trial's data, potentially improving the overall integrity and efficiency of the trial while maintaining the security and privacy of data/patient information.

--Issue 53--

Author Bio

Frank Leu

FRANK LEU is the founding managing member of BioPharMatrix LLC, providing intelligence in the areas of innovative processes and platforms for biotech, pharmaceutical, and life sciences. Frank has over two decades of experience in drug discovery and development. Frank has over a hundred speaking presentations and publications on the discovery, bio-ventures, and disruptive technologies for drug discovery and development processes.

magazine-slider-imageMFA + MMA 20244th Annual Cleaning Validation 20242nd Annual Pharma Impurity Conclave 2024CPHI Korea 2024CHEMICAL INDONESIA 2024World Orphan Drug Congress Europe 2024INALAB 2024Thermo Fisher - Drug Discovery and the impact of mAbsAdvanced Therapies USA 2024ISPE Singapore Affiliate Conference & Exhibition 20242024 PDA Aseptic Manufacturing Excellence Conference2024 PDA Aseptic Processing of Biopharmaceuticals Conference