If it isn’t documented, it didn’t happen. This mindset has shaped the way clinical monitoring activities, both on-site and remote, are reported and standardized. But as centralized monitoring becomes the norm, how can Sponsors and CROs apply this philosophy to a model built on data-driven oversight?
Frédéric Blais, PhD, Director of Central Monitoring at CluePoints, shares how teams can effectively document risk signals and corrective actions to satisfy inspectors and regulatory bodies and help study teams “rebuild the story” of a trial. The goal? To fully realize the potential of Risk-Based Quality Management (RBQM).
Table of Contents
The Adoption of Risk Based Monitoring (RBM)
Documenting the Risk Signal Journey: From Detection to Resolution
Risk Signal Management: A Structured Approach to Investigation & Mitigation
From Signal Detection to Team Review
Ensuring Traceability with the Signal & Action Tracker
Clarity & Collaboration in Field Actions
Risk Signal Management in Action
Why Root Cause Matters
Documentation: The Other Half of the Equation
Leveraging CluePoints’ Audit Trail Tools
Bringing Confidence & Clarity to Centralized Monitoring
The Adoption of Risk-Based Monitoring (RBM)
Since the release of the ICH E6 (R2) addendum in 2016, which reinforced the importance of risk-based approaches in clinical research, an increasing number of organizations—particularly mid-sized pharmaceutical and small biotech companies—have adopted Risk-Based Monitoring (RBM) as part of their clinical trial strategy.
They’ve discovered that RBM’s value extends well beyond regulatory compliance. By enabling Sponsors and CROs to concentrate on the most critical data for each specific study, RBQM not only enhances patient safety but also facilitates more efficient trial execution, ultimately increasing the likelihood of operational success.
The COVID-19 pandemic further accelerated adoption. With social distancing and lockdown measures in place, many study teams were forced to shift toward centralized monitoring in order to maintain continuity across ongoing and planned trials.
Organizations already embracing centralized monitoring understand that thorough documentation is foundational to Good Clinical Practice (GCP). For years, they’ve worked within structured systems that log and manage both on-site and remote monitoring activities through tools like the Clinical Trial Management System (CTMS).
Yet, centralized monitoring brings a new perspective to data oversight and a new standard for documentation. To realize its full potential, sponsors must evolve their record-keeping practices to capture the nuances of data-driven decision-making and ensure transparency at every stage of the trial.
Documenting the Risk Signal Journey: From Detection to Resolution
Centralized monitoring enables study teams to compare patients, sites, regions, and countries to uncover patterns and detect outliers. These statistical observations often serve as early indicators of potential issues related to participant safety or data quality.
However, identifying a signal is just the beginning. Regulatory authorities expect more than just analysis; they require complete transparency and traceability throughout the entire risk signal journey. To remain compliant, teams must:
• Document Every Step: All actions must be recorded from initial signal detection to final resolution. This includes the analysis performed, the decisions made, and the rationale behind each decision.
• Demonstrate Consideration & Accountability: It must be clear that every signal was thoroughly reviewed, with documented evidence of any corrective or preventive actions taken.
• Monitor the Impact: Actions taken in response to a signal should be closely tracked to ensure effectiveness. The journey is only complete once the signal is formally closed, with supporting documentation to show how the issue was resolved.
This meticulous documentation satisfies regulatory expectations and strengthens trial integrity by fostering proactive, data-driven oversight and reinforcing a culture of accountability.
Risk Signal Management: A Structured Approach to Investigation & Mitigation
At CluePoints, a risk signal refers to a statistically meaningful observation detected within the assessed clinical trial data. These signals are not definitive evidence of a problem, but potential indicators that warrant further investigation into patient safety or data quality.
From Signal Detection to Team Review
The signal management process begins when Data Analysts from CluePoints, the Sponsor, or the CRO compile all detected signals into a comprehensive Risk Signal Report. This report is then distributed to Clinical Operations and relevant stakeholder groups.
Within seven to ten days of the report’s release, the Sponsor or CRO typically convenes a cross-functional meeting, drawing on diverse expertise from internal departments. The purpose of this meeting is to:
• Assess each signal to determine whether it represents a real issue or a benign variation.
• Brainstorm all plausible causes behind the statistical observation.
• Assign an appropriate mitigation status and define next steps for investigation or action.
Ensuring Traceability with the Signal & Action Tracker
To create a robust audit trail, CluePoints provides clients with a Signal & Action Tracker. This tool enables study teams to:
• Document the assigned mitigation status: Alert, Watch, Standby, or Closed.
• Record the rationale behind each decision.
• Outline any required follow-up actions.
This centralized documentation ensures transparency, accountability, and readiness for audits or inspections.
Clarity & Collaboration in Field Actions
When a signal is marked as Alert, requiring immediate intervention, it’s critical for the study team to clearly communicate expectations to downstream personnel—usually the Clinical Research Associate (CRA). In such cases:
• The CRA may be tasked with conducting further investigation at the implicated site.
• Communication with the site must remain open and neutral. Signals are potential concerns, not evidence of misconduct.
• The CRA should use open-ended, root cause-oriented questions to fully understand the site’s working practices, avoiding assumptions or premature conclusions.
Assuming the most obvious cause or dismissing a signal without deep analysis undermines the process. A root cause-focused approach is essential to implementing effective, targeted corrective actions.
Risk Signal Management in Action
Consider a common example: a risk signal flags delayed data entry into the Electronic Data Capture (EDC) system. At first glance, the study team or CRA might assume this stems from a lack of awareness of the protocol’s timing requirements, prompting a recommendation for staff retraining. But that assumption may miss the mark.
In reality, the delay could be due to other root causes, such as a technical malfunction in the EDC system or the absence of the site’s designated data entry personnel, with no backup assigned. In such scenarios, retraining would fail to resolve the issue and could waste time and resources.
Why Root Cause Matters
This is why a structured, open-minded, and fit-for-purpose discussion is critical. By approaching each risk signal from multiple angles and inviting diverse perspectives, study teams can:
• Avoid jumping to conclusions based on surface-level observations.
• Identify the true root cause of the issue.
• Select corrective and preventive actions (CAPAs) that are both effective and sustainable.
Documentation: The Other Half of the Equation
Root cause analysis is only half the story. In the eyes of regulators, if a risk signal review isn’t documented, it didn’t happen.
Every step must be carefully recorded, from signal identification to analysis, resolution, and follow-up. This demonstrates compliance with GCP and builds confidence in the integrity of the study’s data and oversight processes.
Leveraging CluePoints’ Audit Trail Tools
As centralized monitoring becomes more widely adopted, maintaining the same level of documentation rigor as traditional on-site methods is essential for compliance and building trust in trial oversight.
One of the CluePoints platform’s most powerful features is its robust audit trail capability, anchored by the Signal & Action Tracker. This centralized tool enables sponsors and CROs to:
• Record each risk signal and its assigned mitigation status (e.g., Alert, Watch, Standby, Closed).
• Document the rationale behind each decision, ensuring that every action is traceable and justifiable.
• Log the specific actions required by the study team and capture feedback from CRAs, closing the loop on investigation and resolution.
This comprehensive documentation framework empowers inspectors and regulatory authorities to easily follow the entire risk signal journey from identification and analysis to resolution and closure.
By unifying the signal management process within a single, transparent system, CluePoints helps study teams fully leverage centralized monitoring to uphold data integrity, patient safety, and regulatory compliance while operating with greater efficiency and confidence.
Bringing Confidence & Clarity to Centralized Monitoring
Centralized monitoring is a strategic advancement in how clinical trials are managed, measured, and made compliant. Our platform is purpose-built to support this transformation, providing the tools and frameworks study teams need to detect, investigate, and resolve risk signals with precision and transparency.
We’re proud to support the evolution of modern clinical trial oversight, and we’re here to help you lead the way. Connect with an expert now and download our Ultimate Guide to RBQM for more information.
