Introduction
December 2022, The European Commission (EC), the Heads of Medicines Agencies (HMA) and the European Medicines Agency (EMA) have published recommendations that aim to facilitate the conduct of decentralised clinical trials (DCTs) while safeguarding the rights and well-being of participants as well as the robustness and reliability of the data collected. This is an outcome of their joint initiative to Accelerate Clinical Trials in the European Union (ACT EU).
What are Decentralized clinical Trials:
Decentralized Clinical Trials (DCTs), also known as “direct-to-participant” or “virtual” studies, involve the use of technology such as telemedicine, wearable devices, and virtual health care interfaces to collect data and communicate with patients remotely. This reduces the need for traditional research facilities and intermediaries. In fully decentralized trials, all aspects of the trial, including recruitment, medication administration, and data collection, are conducted remotely, with minimal in-person contact between the study team and patients. Many clinical trials for drug approval now incorporate decentralized elements, and DCTs often combine traditional trial design with decentralization of patient interactions.
What are the advantages of DCT:
DCTs can improve the logistics of conducting clinical trials by making it easier to recruit and retain participants. The use of remote monitoring and data collection in DCTs can remove barriers to participation, such as the cost of travel, difficulty in taking time off work, and mobility issues related to medical conditions. Additionally, DCTs may also increase participation from groups that are traditionally underrepresented in clinical trials, such as the elderly, low-income individuals, those living in remote areas, and ethnic minorities. This may also lead to faster recruitment and more representative results.
Traditional clinical trials rely heavily on trained intermediaries, such as study coordinators, research assistants, and medical staff, to collect and compile data. In contrast, DCTs use partially or fully virtual methods for data collection. A partially virtual intermediary may still require some direct interaction with the patient, such as having the patient enter information about side effects into a research platform. A fully virtual data collection system would collect data automatically, for example, by transmitting data from a wearable device to the research platform, without any interaction from the patient or research intermediary. This can lead to the need for smaller investigative teams, lower costs for sponsors, and fewer inconveniences for patients, which can increase their willingness and ability to participate in the study, resulting in outcomes that better reflect the safety and efficacy behavior of the study drug in a “real-world” environment.
Traditionally, clinical trials have been conducted at specific clinical trial sites, to which patients had to travel to. The aim of DCTs is to make it easier for patients to participate in clinical trials by reducing the need to travel to central trial sites. This approach has the potential to make clinical trials available to a wider demographic of participants and reduce drop-out rates.
Challenges with conducting DCT trials:
One of the main advantages of centralized studies over DCTs is that drug distribution and management is simpler. In centralized studies, drugs are shipped to a single location and managed centrally, whereas in DCTs, drugs must be shipped to multiple locations and potentially directly to patient homes. This requires proper storage facilities and measures to prevent unauthorized access, detect tampering, track temperature, and record drug administration. Additionally, local laws must be taken into consideration, which may vary by state. The complexity of decentralized drug shipping and management in DCTs can introduce greater complexity and risk to the trial, both for the participants and the integrity of the trial.
One of the major challenges of DCTs is protecting patient privacy when using connected devices and transmitting data through connection services. DCTs require reliable cybersecurity systems to safeguard private patient data stored and transmitted. Traditional trials typically use locally managed data systems that are firewalled, but in DCTs, patients may interact with multiple health care providers using multiple electronic health record systems, creating challenges for central data amalgamation from multiple EHRs that may not communicate effectively with each other.
Accelerate Clinical Trials in the European Union (ACT EU) initiative:
ACT EU is a collaboration between the EC, HMA and EMA that seeks to transform how clinical trials are initiated, designed and run. The initiative was launched in January 2022 and aims to further develop the EU as a focal point for clinical research, to promote the development of high-quality, safe and effective medicines, and to better integrate clinical research in the European health system. ACT EU will strengthen the European environment for clinical trials, whilst maintaining the high level of protection of trial participants, data robustness and transparency that EU/EEA citizens expect.
The recommendations include an overview of national provisions for specific decentralised clinical trial elements to be used in clinical trials. They were put together by the European medicines regulatory network with experts from regulatory bodies responsible for the authorisation of clinical trials, members of ethic committees, good clinical practice inspectors, methodology experts and representatives of patient organisations. Drafting of the paper was coordinated by the clinical trials coordination group (CTCG).
These recommendations under ACT EU are a first and important step towards clarifying the use of decentralised clinical trials in the EU/EEA by the European medicines regulatory network. They are expected to evolve as knowledge increases and experience is gained. In particular, the overview of national provisions will be updated on a continuous basis.
Additional Initiative by other agencies:
DCTs initiatives have been supported by other agencies. The first entirely web-based trial, under an Investigational New Drug application, was carried out by Pfizer in 2011 in the REMOTE (Research on Electronic Monitoring of Overactive Bladder Treatment Experience) trial. During REMOTE, no in-person site visits occurred at all and the study investigators used internet recruitment, online questionnaires, electronic diaries, and home delivery of the investigational drug. The Clinical Trials Transformation Initiative (CTTI), was cofounded by the Food and Drug Administration (FDA) and Duke University in 2007 to identify and promote quality and efficacy of clinical trials and has recently issued recommendations for DCTs.
Sources:
https://www.ema.europa.eu/en/news/facilitating-decentralised-clinical-trials-eu