1. INTRODUCTION AND SCOPE
This document provides recommendations for sponsors regarding the authorisation and conduct of complex clinical trials. The document describes the current perspective of the Clinical Trials Facilitation and Co-Ordination Group (CTFG) on these trials and outlines the major issues that sponsors should address in the process of initiating and conducting complex clinical trials in the EU/EEA.
The document highlights differences between complex clinical trials and conventional clinical trials particularly with regard to clinical trial applications (CTAs) and requests for substantial amendments. These recommendations should be read in conjunction with current legislation regulating clinical trials.
Marketing authorisation applications are outside the scope of this guidance.
2. COMPLEX CLINICAL TRIALS – DEFINITIONS AND CONCEPTS
2.1. Descriptions and concepts of complex clinical trials
For the purpose of this guidance, a clinical trial is considered to have a complex clinical trial design if it has separate parts that could constitute individual clinical trials and/or is characterised by extensive prospective adaptations such as planned additions of new Investigational Medicinal Products (IMPs) or new target populations. In this document, the separate parts of a complex clinical trial design will be designated ‘sub-protocols’ and may be described by sponsors in separate protocols or within a common protocol as
study cohorts or arms depending on the context.
Sub-protocols are characterised by sub-protocol-specific statistical analyses and are thus considered independent parts of the clinical trial design. In comparison, a study ‘arm’ will be used to describe study cohorts where statistical analyses depend on other cohorts such as comparison to a common control arm. Each sub-protocol may be composed of one or several arms…