ICH’s long-awaited E8(R1) guidelines have been finalized, and the guidelines are now awaiting implementation by the FDA and other regulatory agencies.

Together with E6(R3), which is considerably further behind and is expected to come out in draft form in early 2022, the guidelines seek to make quality a central component and concern in clinical trials. ICH E6 — Good Clinical Practice focuses on the responsibilities of sponsors, investigators and other clinical trial stakeholders, while ICH E8 — General Considerations for Clinical Trials addresses broader principles of quality in clinical trials (CenterWatch Weekly, Sept. 6).

E8(R1) is a revision that modernizes the original E8 guidelines adopted by the FDA way back in 1997. The modernized version lays out the concept of risk-based quality management (RBQM).

Importantly, it delves into quality by design, which entails focusing on “critical-to-quality factors” to ensure data generated are reliable, study participants are protected and risks are managed based on their importance. In identifying a basic set of factors that are paramount to ensuring the quality of the study, sponsors should use an approach that establishes a culture of open dialogue, focuses on essential study activities and engages stakeholders in the design of the study. A feasibility assessment and periodic reviews of critical-to-quality factors should also be conducted.

There is also a section that discusses key components of trial designs: patient population; treatment; the control group and response variable; methods to reduce bias; statistical analysis; and data sources. This section, the guidelines say, is meant to help identify critical-to-quality factors that are needed to meet the trial’s objectives while also allowing for a flexible design and efficiency in running the trial. While its focus is on interventional studies, it’s also relevant to observational studies and is expected to apply to new data sources and trial types developed in the future.

The E8(R1) guidelines also offer quality principles and approaches for study conduct, safety monitoring and study reporting.

Read the full final guidelines here: https://bit.ly/2Yr5hsj.