EMA recommendation paper: Safety, data integrity key to decentralized trial conduct

The European Medicines Agency (EMA), European Commission (EC), and Heads of Medicines Agencies (HMA) recently acknowledged the growing role of decentralized elements in the conduct of clinical trials and offered recommendations for their use, with a focus on ensuring trial participant safety and data integrity.

Clinical trials of medicine products already have adopted several decentralized elements, including electronic diaries, wearables, phone calls, and online appointments. However, the appropriate use of these elements is dependent on the type of clinical trial, the trial population, the disease being treated, the trial participant’s condition, the type of medical product, as well as the product’s characteristics and stage of development, the agencies wrote in a recommendation paper issued on 13 December 2022.

“We have seen that decentralized clinical trials can work in a pandemic setting because they have to. Let’s make sure that we can serve the patients in peace time also,” Emer Cooke, EMA executive director, said during the Accelerating Clinical Trials in the EU (ACT EU) multi-stakeholder meeting on decentralized clinical trials in October 2022, prior to the release of the recommendation paper.

Officials who worked on the development of the paper noted that it is not a guideline and may not always be harmonized with the national provisions of EU member states, which are listed in an appendix. “It is a recommendation paper, and it is a first step towards a harmonized approach, and we are expecting that we’ll update that as knowledge and experience evolve,” said Ditte Zerlang Christensen of the Danish Medicines Agency (DKMA) at the ACT EU meeting.

The paper emphasized the rights, safety, and dignity of trial participants. When assessing whether decentralized trial elements are appropriate, sponsors and investigators should engage potential trial participants, patients, and patient organizations early in the process to gain input on the design, development, and implementation of the clinical trial. For instance, patients could provide their experience of living with a condition and help assess the feasibility of appointments by videoconference instead of in person (RELATED: DIA: Experts offer advice on conducting decentralized trials, Regulatory Focus 24 June 2022).

Investigators and healthcare professionals also should be involved in clinical trial design, according to the recommendation paper, to help troubleshoot the impact of less personal contact with trial participants and how to accomplish data collection and ensure the quality and integrity of the source data.
 
The agencies also noted that the shifting of burden for trial procedures from investigators to participants should be weighed against the potential benefits of using decentralized element in the trial.

Sponsors planning trials with decentralized elements that could be considered to support marketing authorization need to ensure they are generating reliable and robust data, according to the recommendation paper.

“The data is required to meet the same expectations as those from trials with on-site procedures,” the agencies wrote. Sponsors are “strongly encouraged” to seek scientific advice for trials with decentralized elements and qualification advice when new methods or endpoints are planned.

Additionally, any IT devices or technologies that are used in a clinical trial should be fit for purpose for reliable data collection and handling, and any use of a computerized system or capture of electronic clinical data should be compliant with the guideline on computerized systems and electronic data in clinical trials (EMA/226170/2021), according to the paper. That guideline is currently being revised.

The recommendation paper also outlined responsibilities of the sponsors and investigators, considerations for oversight of incoming data and handling of source data, the informed consent process, the delivery and administration of investigational medicinal products at a trial participant’s home, trial-related procedures at home, and trial monitoring. The paper does not address General Data Protection Regulation (GDPR) specific requirements.

Recommendation paper on decentralized trial elements