Italy Clarifies the Conduct of Decentralised Clinical Trials

Thu, 26 Sep 2024 04:14:09 GMT

The new guidance goes beyond decentralised elements

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.

Switzerland Aligns with the EU CTR

Fri, 26 Jul 2024 16:23:07 GMT

The clinical trials legislation in Switzerland undergoes a major change

A critical appraisal of the Swiss Federal Act on Research involving Human Beings (Human Research Act, HRA) and associated Ordinances conducted in 2019 revealed, among others, that Switzerland might lose attractiveness for clinical trial conduct if it did not align with the international legislation, in particular with the EU Clinical Trials Regulation (Reg. (EU) No. 536/2014, also known as the EU CTR).

Following this analysis, the Swiss authorities have made revisions to the four Ordinances to promote transparency, to harmonise the requirements for sponsors and to keep up with digitalisation advancements like e-consent. The revised legal texts have been published on 7 June 2024.

Looking at the clinical trials framework, among the EU CTR concepts that have been adopted in the Clinical Research Ordinance (ClinO) are the following:

Increased transparency in publishing clinical trials and posting a summary of results within 1 year from the end of trial
Reporting of key study milestones like the start and end of trial, early termination and trial restart
Safety reporting requirements and timelines
The expiry of the trial authorisation if no participant is included within 2 years
The longer archiving period for clinical trial master file, albeit only for 20 years as opposed to 25 years under the EU CTR.

What has not been taken over from the EU CTR are the following aspects, that have posed difficulties to sponsors and investigators so far:

The notoriously tight deadlines to respond to Requests for Information (RFIs) in relation to clinical trial applications
The reporting timelines for the milestones above, which will be 30 days under the ClinO.

Other changes include the openness towards and clarity around the requirements for e-consent or the redefinition of research categories (A, B and C).

The transitional provisions are staggered and complex, reminding us again of the EU CTR. For example, the reporting requirements become applicable as early as 1 November 2024, however they are optional until 31 October 2025. The publishing of the summary of results within 1 year of completing the trial under ClinO is applicable from 1 March 2025.

Further guidance, templates and exact list of required documents for submission are expected from the Swissmedic and swissethics later on.

Latest Regulatory News and Insights

Italy Clarifies the Conduct of Decentralised Clinical Trials

The new guidance goes beyond decentralised elements

Switzerland Aligns with the EU CTR

The clinical trials legislation in Switzerland undergoes a major change