The Guide to Ensuring the Quality and Integrity of Clinical Trials

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GSK Case Study: “The QTL We Switched Off”

RBQM is easy to design. It’s harder to live with—especially when a Quality Tolerance Limit (QTL) stays red week after week.

In this newly released free chapter from “Risk-Based Quality Management: Practical Guide for Clinical Research Professionals (2nd Edition)”, Artem Andrianov and Johann Proeve share a real-world inspired case (anonymized) originally rooted in a story from GSK’s centralized monitoring leadership: a global Phase III inflammation trial where a rescue-medication QTL turned into constant “red,” triggered alert fatigue, and was quietly switched off.

Why this case resonates with every RBQM leader

Because it captures a pattern many teams recognize:

  • Rescue medication use was correctly linked to a CtQ factor and encoded in governance and planning.
  • But it stayed “red” continuously, generating repetitive governance discussions and little actionable direction—classic alert fatigue.
  • The QTL wasn’t recalibrated—it was silenced. No formal re-baselining, limited documentation,

And later, when regulators asked the obvious questions (“What did you do when it breached? Why did it disappear?”), the organization no longer had a coherent narrative of control.

The core lesson: RBQM maturity is governance, not perfection

This case is not a critique of QTLs. It’s a critique of how organizations treat them when reality collides with assumptions.

A mature RBQM response, as the chapter outlines, looks like this:

  1. Re-examine the definition: is the parameter clinically meaningful and realistically calibrated?
  2. Look for patterns, not a single red/green: trends, regional distributions, severity strata, site clusters.
  3. Re-baseline formally and document: QTLs can evolve—they must never vanish silently.

Why rescue medication is a “double risk”

Rescue medication is not only a statistical nuisance. It’s:

  • a patient safety signal (e.g., steroid toxicity),
  • and an interpretability/HTA signal (it can mask efficacy or dilute “steroid-sparing” narratives), even if balanced between arms.

Download the free PDF chapter

If you’re building RBQM governance, implementing ICH E6(R3)-aligned oversight, or trying to avoid “checkbox RBQM,” this case will feel uncomfortably familiar—in a good way.

Download the free chapter (PDF) and use it as a discussion starter in your next RACT/QbD workshop, Central Monitoring forum, or inspection-readiness review.

RBQM Practical Guide Free Chapter – Case Study

Key takeaway: When a QTL is always red, the answer is rarely “switch it off.” More often, it’s an invitation to learn—about the disease, the protocol, and site behavior—and to build a discipline of continuous control.