Medidata Welcomes ICH GCP (E6) Revision 3 Draft Publication for Consultation

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) was founded in 1990, and since then has acted as an agent of harmonization of global drug development. ICH’s mission is to “achieve greater harmonization worldwide to ensure that safe, effective, and high-quality medicines are developed and registered in the most resource-efficient manner.”

ICH works on this mission through the creation of quality, safety, efficacy, and multidisciplinary guidelines. Efficacy guideline number E6 is Good Clinical Practice, (GCP), which is critical to all clinical research operations. GCP was first adopted in 1996 and has since undergone one revision (R2) in 2016. Now, in May 2023, the draft GCP Revision 3 (R3) is open for public consultation.

The release of the draft R3 of the GCP guideline marks a step forward in the modernization of clinical research and patient centricity. The participant terminology of GCP also changes, as ICH now refers to “trial participants”, rather than “subjects”, highlighting the recognized role that participants play as stakeholders in the research process. 

The document leverages a “media neutral” approach to outlining the fundamental principles of clinical research, as the aim is for the GCP R3 text to “remain relevant as technological and methodological advances occur”. This updated approach provides insight into the reason behind the revision, which the MHRA summarizes as being “to address the application of GCP to new trial designs, technological innovations, and to strengthen a proportionate risk-based approach of its application for clinical trials of medicines to support regulatory and healthcare decision making.” 

The draft outlines Annex I which covers interventional clinical trials. Annex II will be in development soon and cover additional considerations for non-traditional, interventional clinical trials. 

The ICH GCP (E6)R3 principles have been revised to reflect the new strategy that allows for flexibility to adapt to evolving trial approaches while preserving the fundamental principles of ensuring the rights, safety, and well-being of participants and data quality with a risk-based approach tailored to the specific trial. 

There are substantial updates to the investigator-oriented section 2, including a new addition to include eConsent options. Section 2.12 on records also outlines the various ways in which the investigator should ensure the integrity of data. 

One of these novel approaches has involved industry work on making decentralized clinical trials accessible to the participants who would benefit from this opportunity through collaborative projects and regulatory engagement. It’s promising to see the result of the industry’s work culminating in ‘trials with decentralized elements’ being referenced as an example of trial design options.

Medidata & ICH GCP (E6)R3

An area that Medidata has been very forward thinking in and deeply engaged in is global acceptance of eConsent and transparency of the regulatory landscape. As such, it’s a positive addition to see that the informed consent process is defined as one that “may involve a physical signature or an electronic signature” and remote consent is considered as an option where appropriate. In section 1.1.2, which outlines which information should be reviewed by the IRB/IEC (institutional review board/ independent ethics committee), subsection (d) includes in the list not only all of the “information to be provided to the trial participant(s)”, but also “a description of the media through which such information will be provided”.

The sponsor section shines a light on the ICH principles on agreements in section 3.6, which outlines the relationship between the sponsor and service providers—a list that now includes CROs. The monitoring section 3.11.4 also opens the possibility to conduct certain on-site monitoring activities remotely with the trial design and monitoring strategy in mind. 

Centralized monitoring is woven into the monitoring section and is portrayed in R3 as an essential aspect of the monitoring process, unlike the prior R2 reference to it being used in exceptional circumstances. Data handling section 3.16.1 further solidified the requirement for data flow maps to be pre-specified for trials, which has been previously mentioned in GCP Symposia meetings and inspired the ACRO DCT data flow maps project by the ACRO DCT Working Party which Medidata chairs.

ICH GCP (E6)R3 also brings a completely new section to GCP, section 4 on Data Governance, with emphasis on data life cycle elements, such as metadata, audit trail data corrections, data transfer, exchange and migrations, and computerized systems and their security and validation. 

As part of the Accelerating Clinical Trials in the EU initiative (ACT EU), the EMA hosted a stakeholder workshop on the ICH GCP (E6)R3 draft—a welcomed opportunity to engage with industry colleagues and the EMA on the R3 document in July 2023. The workshop summarized the GCP renovation, details of the public consultation, and break-out sessions allowed for the industry voice to be heard at this early stage by regulators. 

Medidata has been consistently dedicated to playing an active part in the industry effort to connect clinical research with the potential of novel technologies and scientific approaches to foster collaboration-powered innovation.

Our fast-evolving world is full of potential to integrate novel approaches to improve existing science and it’s encouraging to see global regulatory authorities effectively and thoughtfully positioning the life sciences industry in such a way that the fundamental guiding ethical and quality principles persist in a future-proof manner with respect to the novel and emerging way of conducting research.