Representing the first major overhaul of GCP guidelines in twenty years, ICH E6 (R2) delivers a GCP that reflects modern-day responsibilities for outsourced clinical trials incorporating new technologies. The effective date issued by the European Medicines Agency passed on 14th June 2017. Canada has confirmed it will implement the addendum fully in April 2018, whilst the US, Japanese, and Swiss regulators are expected to announce implementation dates for their adoption of the addendum shortly.
The addendum consists of 26 items added to address the gaps and concerns of GCP regulatory inspections relative to the areas of sponsor/investigator responsibilities and risk-based monitoring approaches, in-light of rapid technological and process changes in the industry.
From the Sponsor and CRO perspectives, the impacted areas for clinical research conduct include quality management, trial management, data handling, record keeping, monitoring, and non-compliance. A key message is that organisations should move away from fixed interval monitoring visits at set time points and adopt a quality and risk-based management approach to monitoring. This requires Sponsors and CROs to be able to identify and leverage critical data points to flag when an on-site monitoring visit is necessary, as well as moving away from a 100% source data verification strategy. To achieve this, Sponsors must implement a quality management system that supports a risk-based monitoring strategy (see Section 5.0). Further clarifications relating to responsibilities in the areas of contract research organisations (5.2), trial management, data handling, record keeping (5.5.3), monitoring (5.18.3), and non-compliance (5.20) are also now included.
From the clinical research site perspective, the revised guidelines now cover the investigators obligations relating to delegation and oversight of third parties (Section 4.2), and the collection and maintenance of essential documents at the site (Section 4.9). Sites can also now expect a shift in how study monitors interact with them, with more remote contact and on-site visits when warranted by critical data points as opposed to regular visit intervals.
Relevant for Sponsors, CROs, and site staff, Section 8.1 now addresses practices for records for essential and source documents irrespective of the type of media used, reflecting modern methods of storing and managing trial master files and other key documentation. This section also outlines requirements for document identification, version history, search and retrieval, data control, access, replacements of originals, and requirements for certified copies.
Done correctly, the adoption of a quality-based risk-management approach will force discussions and evaluations of risk from the outset. It will push the industry towards proactive risk-management done in a structured way. Ultimately, ICH E6 R2 encourages the implementation of improved and more efficient approaches to clinical trial design, conduct, oversight, recording, and reporting, while ensuring that human subject protection and data integrity are maintained. This can only be viewed as a positive thing!
One of the key potential challenges for Sponsors and CROs will be aligning to the new guidelines without full confidence in their quality management system and critical data point strategy. Trying to run both methodologies together runs the risk of putting an additional burden on all involved. It will be essential for Sponsors, CROs, and sites to invest in training to familiarise all functions with the new guidelines, so that they can define a clear roadmap about how they will put the structures in place to support clinical trial management in-line with ICH E6 (R2).
Note: Longboat’s ICH GCP (E6) R2 training is listed on Transcelerate's website of GCP providers who meet the Transcelerate GCP training minimum criteria.
If you want to learn more about how Longboat can support consistent training delivery and compliance across all stakeholders involved in the successful delivery of your clinical trial, we'd love to talk to you!