The ICH plans announced at the start of this year to further revise ICH-GCP – so called “GCP renovation” – set out a strategy to first revise ICH E8, “General considerations for clinical trials” before commencing with a further and more substantial revision of ICH-GCP (E6). This seems like a sensible approach, but given the fact that relatively little is known about E8, in this article I want to look at this guideline more closely.
The E8 guideline was finalised 20 years ago. It is a very high-level document setting out a framework for rational drug development rather than focusing on how to conduct individual trials. It presents two distinct approaches to classify the different stages of a drug development plan. The first of these is a classification based upon the objective of the trial, with four categories starting with human pharmacology, followed by therapeutic exploratory, then therapeutic confirmatory and, finally, therapeutic use. The second classification is based upon the sequential phases of drug development from phases one through to phase four. The guideline also shows the overlap between these two different classifications.
The second part of the guideline presents an overview of the different steps required to conduct a trial. The five steps outlined are; objective, design, conduct, analysis and reporting and for each of these references are provided for more specific ICH guidelines. The guideline has an accompanying annex that lists all of the ICH guidelines that are referenced.
In summary, the high-level nature of E8 will mean that any revision is likely to have little, if any, impact on how individual trials get done. Instead, any changes to E8 will be at the level of drug development plans although it is difficult to foresee how much scope there is for significant revision. This all means that any revision to E8 is likely to be modest. Instead, the fundamental changes that are needed to how trials get done will require a complete revision of the ICH-GCP (E6) guideline to focus on those few key principles for how to do a randomised trial well. This substantial revision to ICH-GCP (E6) is what we are focusing on at MoreTrials.