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ICH E6(R3) – Are people asking the wrong questions already?

Updated: Nov 9, 2021

“How do you identify the critical thinkers in your organization?”

This question came from a recent webinar on E6(R3) Quality by Design. Specifically, it was referring to section 3.3.1, Establishing a Culture that Supports Open Dialogue, which says “Create a culture that values and rewards critical thinking…”

As the panellists responded, it struck me that they were answering the wrong question. Surely a better question would be “How do you make everyone in your organization a critical thinker”?

As an example, take risk assessment and risk management, activities at the core of E6(R2). We often see organizations where risk management is handled by a small team (one or two people at the centre). We also see clinical trial risks being treated like project management risks, i.e. when an issue comes up, it’s dealt with, documented and the team moves on. There’s no communication or lessons learned fed back into the trial. If Risk-Based Quality Management (RBQM) is done properly, then there should be both regular risk reviews, and reviews whenever a risk occurs to understand the nature and cause of that risk and whether any change needs to be made to our risk management approach.

Importantly, both upcoming regulatory changes, E6(R3) and E8(R1) talk about stakeholder engagement. It would therefore seem sensible to include more people, not less, in risk identification, especially during protocol development and early quality management planning. Clearly you may want to engage people who have relevant experience, insights, or vested interests (e.g., sites, CRAs, statisticians, data scientists, patients). Sometimes it may be sensible to invite someone who doesn’t have any direct involvement to bring a ‘fresh pair of eyes’ to provide an unbiased perspective and avoid ‘groupthink’.

Which brings us back to our question: “How do you make everyone in your organization a critical thinker”? Here’s a very simple way. Get everyone involved to ask themselves (and others) the following five simple questions:

  • What could possibly go wrong?

  • How would we know if it was going wrong?

  • What could we do to prevent it happening?

  • If it does go wrong, what would we do to fix it?

  • Who would need to know?

If you just start asking everyone related to your clinical trial those questions, and ask them often, it will become a habit and it will quickly spread. Not only will other people start asking those questions (and more) for themselves, but the smart ones will also start preparing their answers in advance. At that point critical thinking starts to become part of the culture.

Not every risk raised will be relevant, but your trial team will quickly become proficient at filtering and focusing on the most important ones. This gives you a great starting point for risk evaluation and will be the backbone of your strategic monitoring plan. This sort of early, cross-functional critical thinking is setting your trial up for the best possible chance of success. Now that’s a habit worth forming.


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