This Q&A document provides guidance and support to sponsors regarding the key scientific and operational aspects of managing complex clinical trials under the EU Clinical Trials Regulation (EU CTR).
Complex clinical trials are non-conventional trials characterised by elements that make their design, conduct, analysis, or reporting complex. Such trials can be conducted in any clinical development phase, offering added value such as early development decisions. They are especially valuable when they can expedite evidence generation, benefiting public health and supporting marketing authorisation. Their diverse nature requires careful planning, balancing their benefits against their complexities—where the primary focus remains on data robustness and the rights, safety, dignity, and well-being of participants.
This Q&A document offers guidance and support to sponsors regarding the management of complex clinical trials in the EU. It covers scientific aspects, planning, setup, submitting for Clinical Trial Authorisation (CTA), conduct, reporting & transparency, analysis & interpretation, and submitting for marketing authorisation under the EU Clinical Trials Regulation (EU CTR).
1. Important considerations for the planning and conduct of complex clinical trials
2. Which additional considerations are needed for the design and conduct of master protocol studies?
3. How to describe and explain Bayesian approaches in complex clinical trials?
4. What are the considerations for planning, collection, and use of control data from within a complex clinical trial for regulatory purposes?
5. Which principles apply, and which regulatory pathways should be consiered when using biomarkers and biomarker assays in compelx clinical trials and consequently applying for marketing authorisations?
6. Safety, rights, and well-being of participants
7. Transparency (balance with integrity) and communication between regulators, sponsors, and investigators
Important notice: This document 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).