Italy Clarifies the Conduct of Decentralised Clinical Trials

Italy is the 4th most popular European Union destination for conducting clinical trials after Spain, France and Germany, as per the latest ACT EU report (Monitoring the European clinical trials environment, August 2024).

This is why the recent guideline from AIFA (Agenzia Italiana del Farmaco) on regulatory simplification and elements of decentralisation for conducting clinical trials of medicinal products in Italy may be of special interest to a high number of sponsors and investigators, even more so when patients may be hindered from taking part in clinical trials because they live far from the investigative site, they have mobility issues or the protocol foresees a high number of visits.

The guideline, released on the 21st of August 2024, confirms full applicability of the recommendations issued at EU level on this topic and complements the Italy-specific provisions available already in the ACT EU Recommendation paper on decentralised elements in clinical trials, where this national guidance was anticipated to clarify how certain aspects contained (or not prohibited) in the European standards and guidance documents can be applied at national level.

The document is also setting the stage for the imminent update of the Good Clinical Practice guidelines, ICH E6 (R3).

The most interesting provisions of the Italian guideline are the following:

• Persons accompanying trial participants may benefit from reimbursement of expenses (accommodation, transportation) if participants are unable to travel alone. Along the criteria for reimbursement, the methods for this process are recommended to be included in the informed consent and/or information to participants. Importantly, participants should not have to pay in advance, but be provided with travel tickets or be allowed to make reservations instead.
• Compensation for loss of earnings: the eligibility in Italy is wider than what is expressly stated by the Regulation (EU) no. 536/2014 (EU CTR) in articles 31-33, and healthy volunteers are also included. This is, of course, subject to Ethics Committee assessment.
• The delivery or dispensing of IMPs to clinical trial participants can also be made directly to the participant's address, through the hospital pharmacy, delegated territorial pharmacy, warehouse or service provider, in justified cases and taking a risk-based approach. This topic does not fully cover the missing answers in the ACT EU Recommendation Paper from 2022, i.e. concerning cross-border delivery from other EU Member States.
• The costs related to IMPs, auxiliary medicinal products (AxMPs) and ancillary supplies must, of course, not be borne by the participant as per Article 92 of the EU CTR. However, the Italian guidance goes even further and clarifies an aspect that has been known to cause confusion among clinical trial sponsors even under the old Directive 2001/20/EC framework: the term "not borne by the subject" must be interpreted broader, so that no cost of IMP, AxMP, medical device or procedure foreseen by the trial protocol must be charged to the NHS or to the trial site either (for commercial trials only). Moreover, direct supply by the sponsor is preferred to direct purchase by the investigative site. These aspects should be clarified during feasibility at the site and be specified in the clinical trial agreements with the institution.
• Clinical trials in indications relevant to public health can also be conducted outside hospital facilities, for example in residential health facilities or public institutions.

The guideline can be found here on the AIFA website, exclusively in Italian at the moment.

Such clarifications from other Member States (especially those who did not provide their take on national provisions in the overview from the ACT EU Recommendation Paper) would indeed be welcome, to promote the implementation of decentralised clinical trial elements even further and make it easier to conduct and take part in clinical trials in Europe.