ICH E6(R3) gets most of the attention, but ICH E8(R1), the guideline on general considerations for clinical studies finalized in 2021, explains where quality begins. E8(R1) describes quality by design: identifying what matters most, engaging stakeholders and building studies that are fit for purpose. E6(R3) describes how that quality is protected during conduct. Sponsors who read one without the other miss half the picture.
What is ICH E8(R1)?
It is a modernized guideline covering the general principles of clinical study design and planning across study types. It introduces quality by design and critical-to-quality factors, encourages engagement with patients and investigators, and discusses the appropriate use of different data sources.
How do E8(R1) and E6(R3) fit together?
E8(R1) focuses on design and planning: deciding what the study must achieve and what could threaten it. E6(R3) focuses on conduct and oversight: managing those risks proportionately while the study runs. They share the language of critical-to-quality factors, and E6(R3) explicitly builds on quality-by-design thinking. Together, they describe a continuous line from protocol concept to final report.
What does quality by design mean in practice?
Identifying, before the protocol is final, the factors that are critical to participant protection and reliable results. Designing the protocol to protect those factors. Removing complexity that doesn't serve the study's objectives. Consulting patients about burden and investigators about feasibility. And planning data collection that is fit for purpose rather than exhaustive.
Why do sponsors overlook E8(R1)?
Good clinical practice training focuses on E6. E8 can seem academic. And in many organizations, study design belongs to scientists while conduct belongs to operations, so neither group feels fully responsible for connecting the two guidelines.
How can a sponsor put E8(R1) to work?
Review draft protocols against its principles. Hold a critical-to-quality workshop before finalization. Ask patients and site staff about burden. Bring feasibility input into design discussions. And document the rationale for key design choices, so later teams, regulators and inspectors can see how quality was built in.
What is the payoff?
Fewer avoidable amendments, less data collected for no purpose, more reliable results and a clearer story for inspectors about why the study was designed the way it was. For an emerging sponsor with limited budget, avoiding unnecessary complexity is not just good practice. It is good economics.
Where should E8(R1) appear in your process?
In your protocol development SOP, your protocol review checklist and the agenda of your design meetings. When quality-by-design questions are built into how protocols are written, they stop depending on whether the right person happens to be in the room.
Keep reading: Running a Critical-to-Quality Workshop That Changes the Protocol
