"Are you ready for ICH E6(R3)?" is an easy question for a CRO to answer, and the answer is almost always "Yes." The more useful conversation starts with one more word: how? ICH adopted the final E6(R3) guideline on 6 January 2025, so most providers now have updated policies. Whether you are selecting a CRO or working with an existing partner, these six questions can move the discussion from policy to practice.
How will you support our oversight, beyond reporting your activity? Ask what information you will receive, when it will arrive, and how it will help you make decisions. Ask which issues trigger escalation right away rather than waiting for the next governance meeting.
How will you translate this protocol's risks into the delivery model? Ask how the factors most critical to participant protection and reliable results will shape monitoring, quality controls, and staffing, and where the approach will differ from the CRO's standard model.
What evidence shows that the systems used for our trial are fit for purpose? "The platform is validated" is a starting point. Ask about the configurations built for your study, the interfaces between systems, how changes are controlled, and who maintains the validation documentation.
How will you distinguish an isolated deviation from a systemic problem? Ask how deviations are assessed, how trends are spotted across sites, and when findings reach the sponsor.
How will you know a CAPA worked? Ask who owns the root-cause analysis behind each corrective and preventive action, and what will demonstrate that it was effective. Closing an action and preventing recurrence are two different outcomes.
What happens when you subcontract work? Ask which activities move to another provider, how responsibilities are documented, how that provider's performance is overseen, and how its issues come back into your governance process.
These are practical discussion prompts that put R3's expectations for risk-proportionate quality management, service-provider oversight, and fit-for-purpose systems into operational terms. For each answer, ask for a recent example, an accountable owner by name, and the evidence your study team would actually see.
A policy tells you what an organization intends to do, and the operating model tells you how it will happen. When we support sponsors through CRO selection at ABRA Clinical Consulting, the most useful question is often the simplest one: "Show us how this will work on our study."
