EU Recommendations on Decentralised Clinical Trials: Everything You Need to Know / LS Law

13th February 2023

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.

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.

Decentralisation is enabled by the advancement of digital tools, telemedicine and more mobile and local healthcare. It includes aspects such as home health visits, remote monitoring and diagnostics, direct-to-patient shipment of study drugs and electronic informed consent.

The 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.

We’ve put together some of the key takeaways from the guidelines.

The Evolution of Decentralised Clinical Trials

The COVID-19 pandemic highlighted the importance and usefulness of digital tools and decentralised procedures in a healthcare setting and in clinical trials. The above context and trend highlighted the need to provide further recommendations on the introduction of decentralised elements in the conduct of clinical trials in the EU/EEA, regardless of any health crisis. It is acknowledged that certain decentralised elements in clinical trials have been adopted for some time and that not all of these elements are likely to have a significant impact on scientific validity, data integrity, benefit-risk ratio or the protection of trial participants’ rights.

Clinical Trials With Medicinal Products

Clinical trials with medicinal products have already adopted many decentralised elements such as electronic diaries, wearables, phone calls and online appointments. How decentralised elements are used in clinical trials depends on many factors including the type of clinical trial, the trial population, the disease being treated, the condition of the trial participant, the type of medicinal product, its characteristics and development stage.

The guidelines suggest these elements should be considered individually and in combination when planning for and implementing the use of decentralised elements. In addition, the following general considerations should be taken into account:

*The rights, safety, dignity and well-being of the trial participants should be protected and prevail over all other interests.

*The implementation of decentralised elements in the conduct of a clinical trial should not result in increased risks to the safety, rights, and well-being of trial participants.

*Particular emphasis should be placed on compliance with the General Data Protection Regulation.

*Sponsors and investigators should engage potential trial participants, patients or patient organisations in a meaningful participatory process that involves them in an early and sustained manner in the design, development and implementation of the clinical trial.

*Early participant involvement in the design of the clinical trial is likely to increase scientific value.

How to Design a Decentralised Clinical Trial

When developing a clinical trial with decentralised elements, investigators/healthcare professionals should be involved in the design, development, and implementation of the clinical trial, according to the guidelines.

Trials with decentralised elements should be designed to generate reliable and robust data. Regarding regulatory decisions supporting marketing authorisation, the data is required to meet the same expectations as those from trials with on-site procedures.

IT devices / technologies which are developed and utilised should be fit for the purpose of reliable data collection and handling in accordance with the protocol. A contingency plan should be in place to minimise the impact of any risk, for example malfunction of a digital tool or disruption of a planned decentralised visit, for identified critical quality decentralised elements.

Who Should Hold Responsibility for a Decentralised Clinical Trial?

The clinical trial specific tasks as described in the protocol are ultimately the responsibility of either the investigator or the sponsor, it points out in the guidelines. To maintain the investigator’s responsibility regarding the medical care and safety of the trial participant and to ensure that the sponsor has adequate oversight over the conduct of the clinical trial, effective lines of communication should be established, documented and shared with all relevant parties, including trial participants, investigators, sponsor and any service providers.

All parties involved should have access to the information required to fulfill their roles and responsibilities related to the conduct of the clinical trial at any time. Trial participants, investigators and service providers involved in the trial should receive training on how to use the digital tools employed in the trial, to ensure proper data collection, review, and transmission.

How to Deal with Data in a Decentralised Clinical Trial

Decentralised clinical trials are characterized by an extensive shift of data collection from the investigator/investigator site to the trial participants and/or their caregiver and/or service providers (e.g. home nurses). Direct data capture by electronic systems (e.g. electronic Case Report Forms (CRFs), ePROs, wearables etc.) may occur, for instance, at the clinical trial site or off-site locations. According to ICH E6, the data recorded during the clinical trial should be credible, reliable and verifiable. In addition, the data protection requirements according to the GDPR should be adhered to.

What is the Consent Process?

An important aspect of a clinical trial is that the potential trial participants give their voluntarily informed consent to participate. To give consent, the potential participant needs adequate information. Informed consent is not only of ethical and legal importance: good communication between the investigator and the trial participant is beneficial for mutual trust and may promote trial compliance. Therefore, when considering the appropriateness of conducting the informed consent process in a remote manner, to use digital information leaflets, and/or to use electronic methods for the signature of the informed consent form, several aspects have to be thoroughly assessed. These include the design of the clinical trial, the characteristics of the trial population, and the risks, burdens and potential benefit related to participating in the clinical trial. The entire procedure for obtaining informed consent, i.e. the selection, the evaluation of the eligibility, and the actual informed consent process, should be described step-by-step in the clinical trial application to ensure appropriate ethical review.

How Should Confidentiality be Managed?

The reliability and confidentiality of the method used should be ensured. As a general principle, the communication channel used for the informed consent interview should be encrypted to protect the confidential information that will be discussed. The use of different kinds of media may enhance the trial participant’s comprehension of the trial. However, when considering the use of electronic methods, the sponsor should also be aware that its use may unintentionally discriminate against participants who cannot or prefer not to use such technology.

At Life Science Law we have a team of regulatory affairs experts with experience in the development of new therapeutic products and the regulatory process to be followed to place medicinal products on the market across the globe. This includes the design of interventional and non-interventional studies and the preparation of Clinical Trial Agreements, Investigational Medicinal Product Dossiers, and Investigational New Drug applications for clinical trials. For more information contact us.

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