Revision 2 of ICH GCP caused confusion to those of us who work with non-interventional studies. The glossary claimed that a ‘clinical trial’ was synonymous with a ‘clinical study’ (Section 1.12 of ICH GCP(R2)). This works if you conduct clinical trials (they are a type of clinical study), but not if you conduct non-interventional studies, which are a type of ‘clinical study other than a clinical trial’ (Article 2.2(4) of Regulation EU/536/2014).

The (draft) Revision 3 of ICH GCP, makes it clear “This guideline applies to interventional clinical trials of investigational products that are intended to be submitted to regulatory authorities. This guideline may also be applicable to other interventional clinical trials of investigational products that are not intended to support marketing authorisation applications in accordance with local requirements.”

Also, the new definition of ‘clinical trial’ provided in the Glossary, removes any confusion regarding clinical trial vs clinical study.

Clinical Trial = Any interventional investigation in human participants intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of an investigational product(s); and/or to identify any adverse reactions to an investigational product(s); and/or to study absorption, distribution, metabolism and excretion of an investigational product(s) with the object of ascertaining its safety and/or efficacy.

The emphasis in ICH GCP(R3) is on ‘interventional’ investigations, although the term ‘intervention’ is missing from the Glossary…as well as most national clinical trial regulations. This may cause trialists some difficulties in the coming years when asked ‘what makes my non-interventional study…interventional?’

This revision to the clinical trial definition and explicit emphasis on ‘interventional clinical trials’ is a positive (constructive) move in the context of real world evidence as it removes the previously unnecessary confusion caused by revision 2 (i.e., clinical trial = clinical study).

The concept paper for Annex 2 was published on 28 April 2023, with the draft expected in 12 – 18 months. Annex 2 is of relevance to RWE because it will include additional considerations on how GCP principles may be applied across a variety of trial designs and data sources, where applicable. This will include:

1. Decentralised elements, where some or all trial-related activities occur at locations other than traditional clinical trial sites, and data collection may occur remotely.

2. Pragmatic elements, reflecting trials that closely resemble routine clinical practice.

3. Real-world data (RWD) sources [not including observational studies], for example, the use of registries, electronic health records (EHR), hospital data, pharmacy and medical claims data or wearables

Next? Is it time for similar harmonised guidelines for ‘non-interventional studies’?