This Q&A document provides guidance and seeks to support sponsors, clinical trialists and applicants regarding scientific aspects and the planning, set-up, submission for obtaining CT authorisation (CTA), conduct, reporting and transparency, analysis and interpretation of complex clinical trials (CCTs) under the EU Clinical Trials Regulation (EU CTR) as well as their use in submissions for marketing authorisation. It complements and should be used together with relevant EU and ICH guidelines, in particular E6, E8, E9, E10, E16, E19, E11A and E20 (when available).

For the purpose of this document, the nomenclature follows the EU CTR, relevant ICH guidance, CTFG Recommendation Paper on the Initiation and Conduct of Complex Clinical Trials (2019) and international common use as appropriate. Additional non-binding terminology conventions are described in the glossary to facilitate alignment between different sources of information and ensure consistent meaning.

This document aims to address challenges sponsors may face as regards scientific and operational aspects of CCTs and to encourage considering choices in development and implementation as early as possible, in order to generate useful evidence and inform clinical and regulatory decisionmaking. This document also refers to additional resources providing guidance for CCTs throughout the medicinal product lifecycle.

The document is planned to be updated with evolving experience. 

Operational aspects related to the Clinical Trials Information System (CTIS) are not addressed in this Q&A.

The scope of this document is to provide guidance and support for complex clinical trials which are defined as being non-conventional in the sense that they have elements, features, methods or combination thereof, including novel approaches, that confer complexity of their designs, conduct, analyses or reporting.