In the two decades since ICH E6 was first drafted, clinical trials have become more complex with respect to trial design, use of technology, adoption of decentralized approaches, and the quantity of data collected.
The ICH developed guidelines on multiple subjects. Guideline E6 covers 3 specific areas:
- Protection of human subjects
- Ensuring quality of data
- Providing a standard compliance guide for clinical researchers
For years, E6 has been pivotal in the success of trials around the world, but so much has changed since 1990, and the pace of change is increasing more quickly than ever. This has been magnified in 2020 in particular, as CROs and Sponsors have had to rapidly adapt in light of the COVID-19 pandemic and its impact on clinical trial operations.
E6(R2) is not fully designed to address emerging technologies, innovations in trial design, the diversity of data sources, testing facilities, and service providers, or to address other emerging complexities of the current clinical trial climate in light of COVID-19. Consequently, referring to the current E6 provisions can result in a failure to take full advantage of these technological innovations and new practices.
The application of the current standard to new technologies is challenging. Thanks to the revolution of technological advancements and efficiencies in the past 5 years, coupled with the ability to generate and instantly share vast quantities of data to multiple platforms, there are new questions and concerns about data security and patient privacy. As a result, E6 is in review again.
E6(R3) is being developed to provide guidance that is applicable to different clinical trial designs and to encourage more Sponsors and CROs to focus on risk-based approaches to the design and conduct of clinical trials with a focus on technologies.
As of June 2020, after a public web conference held by the FDA and CTTI, work on E6 (R3) is underway. It is expected to be a complete rewrite of E6 (R2). New topics will include decentralized clinical trials and guidance on how to incorporate real-world data in an appropriate and timely matter.
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The proposed rewrite will include more specific discussions and refinement to E6 principles in the context of different trial types and data sources in the annexes as described below:
- Annex 1 - Interventional clinical trials. Will include the use of unapproved or approved drugs in a controlled setting with prospective allocation of treatment to participants and collection of trial data.
- Annex 2 - Additional considerations for non-traditional interventional clinical trials. Will include designs such as pragmatic clinical trials and decentralized clinical trials, as well as those trials that incorporate real world data sources.
The proposed revision to ICH E6 will primarily benefit progressive researchers who are using, or exploring the use of, more diverse trial types and ensure that data sources employed support the relevant regulatory requirements for drug development. It is an exciting recognition of how technology is changing the industry and how multiple tools and methods can be used to collect data. As we continue to move towards decentralized or hybrid approaches that rely on virtual elements, E6(R3) will provide much needed guidance to ensure the 3 fundamental areas of E6 are maintained.