Recommendation paper on decentralised elements in clinical trials

This recommendation paper aims to facilitate the appropriate use of decentralised elements in clinical trials in the European Union / European Economic Area by providing detailed, practical guidance while maintaining participant safety, rights, dignity and data reliability. 

It emphasises a risk proportionate approach as described in International Council for Harmonisation guideline E8 and the recommendations on risk proportionate approaches for Clinical Trial Regulation 536/2014: decentralised elements should not increase risk to participants and must allow generation of reliable data for publication and regulatory decision making. 

The paper offers a regulatory and ethical framework for planning decentralised or hybrid designs and documenting risk assessments in protocols and related documents. It provides concrete recommendations on oversight, task delegation, informed consent (including electronic methods), investigational medicinal product delivery, home procedures, data management and monitoring that can be translated into standard operating procedures and trial specific plans. 
It also gives practical support for multinational trials through the national provisions overview, helping teams anticipate where certain decentralised elements may need additional discussion with Member States.

The paper highlights the need to engage patients, patient organisations and investigators early and meaningfully when designing trials with decentralised elements, including weighing any transfer of burden to participants or sites against potential benefits.

The document is organised into seven main chapters plus an appendix:

• Introduction, scope and general considerations: defines decentralisation, reiterates adherence to Clinical Trial Regulation 536/2014, Good Clinical Practice, Good Manufacturing Practice, Good Distribution Practice, General Data Protection Regulation and medical device legislation, and sets expectations for documented risk–benefit assessments when decentralised elements may affect safety or data integrity.
• Clinical trial oversight – roles and responsibilities: explains how sponsor and investigator responsibilities remain unchanged even when service providers such as home nurses or technology vendors are involved; requires clear task delegation, contracts, qualification and training of service providers, and robust communication plans and emergency contact routes.
• Informed consent process: covers remote informed consent interviews (for example video or telephone), digital information leaflets and informed consent signatures, including national rules on electronic signatures and documentation of consent.
• Delivery and home administration of investigational medicinal products: provides considerations for direct to patient delivery, storage at home, administration, and alignment with Good Distribution Practice.
• Trial related procedures at home: addresses when procedures may be performed by healthcare professionals or trial participants outside the site and how to maintain safety and oversight.
• Data collection and management, including source data: describes expectations for defining and handling source data, using computerised systems and ensuring compliance with the guideline on computerised systems and electronic data in clinical trials.
• Trial monitoring: sets out principles for monitoring trials with decentralised elements, including risk based and remote monitoring approaches and management of increased data volumes from digital tools.

An appendix summarises current national provisions for topics such as investigational medicinal product home delivery, involvement of external healthcare providers and remote consent for each Member State, for guidance only. Sponsors remain responsible for checking detailed national requirements, particularly in cross border trials, and are encouraged to seek scientific advice from the European Medicines Agency Scientific Advice Working Party, national competent authorities or through simultaneous national scientific advice.