The ICH E6(R3) guideline for Good Clinical Practice from the International Council for Harmonization (ICH) is designed to foster a culture of quality as clinical research methods evolve. ICH E6(R3) does not ask clinical research professionals to memorize new terminology or adopt more templates. It requires something more subtle and more challenging—to be intentional about decisions. The rationale behind these decisions then needs to be explained based on what matters most: participant safety and data reliability.
“That shift sounds simple, but in practice, it changes how we think about everything from trial design to day-to-day oversight,” says Leslie Sam, BA, CSSBB, CQIA, President of Leslie Sam and Associates. “Terms introduced or emphasized in ICH E6(R3)—Critical to Quality (CtQ) factors, Quality by Design (QbD), fit-for-purpose, data governance—are often treated as standalone concepts. However, the guideline does not present them that way. It describes how they connect, and how they shape decisions across the trial lifecycle.”
“The starting point is clarity around what is truly critical,” adds Sam. “When CtQs are identified early, they anchor design choices and help teams distinguish what must be tightly controlled from what can be more flexible. That clarity is what enables QbD to function as intended—not as a document or exercise, but as a way of thinking that informs real decisions.”
Beyond the Buzzwords: Oversight, Quality by Design, and Risk-Based Thinking
Join Leslie at ACRP 2026 [April 24-27; Orlando, Fla.] as she examines practical strategies and thinking to implement oversight, Quality by Design (QbD), and risk-based thinking in day-to-day trial decisions. View complete schedule.
Sam explains, “Those early design decisions directly influence oversight. When risks are understood and prioritized, oversight becomes focused and defensible rather than broad and reactive. Not every activity requires the same level of scrutiny, and not every data point deserves equal attention. The challenge—and the expectation—is to know where to pay particular attention. Fit-for-purpose is not a program, but a way to decide what deserves rigor, what deserves monitoring, and what deserves flexibility. Fit-for-purpose thinking shows up in practical ways: what data are collected, how often information is reviewed, which signals require escalation, and where flexibility is acceptable without compromising safety or reliability. These are judgment calls—and they are central to how oversight is demonstrated.”
“Data governance plays a quiet but critical role in this ecosystem, not as a system or an information technology deliverable alone, but allowing teams to trust the data they’re reviewing, see trends across sources, and confidently explain how decisions were made and acted upon,” concludes Sam. “One of the most persistent misconceptions about ICH E6(R3) is that it raises the bar for perfection. In fact, it raises the bar for intentionality and rationale. You don’t need to get every decision right. You do need to be able to explain why you made the decision you did—based on risk, impact, and intent.”
Edited by Jill Dawson
