Over the last few years, the FDA has intensified its focus on risk management (RM) as a central component of quality management systems. But what is RM exactly when it comes to clinical trials and GCP?

The intent of E6 requirements is to engage teams in managing risk proactively, preventing mistakes that lead to issues with data integrity or patient safety. Current approaches to risk management in clinical trials are often ineffective. Despite an organization’s best efforts at including risk management in their quality improvement efforts, quality issues persist, and error prevention is inconsistent because the current tools are static with limited ability for searching, reviewing and reporting information. 

As a result, ICH E6 (R2) guidance (and to an even greater degree, R3) shows that the ICH and the regulators who adopt its recommendations are pushing sponsors increasingly to be more proactive in managing clinical trial risk.

ICH E6 (R2), the current revision specifies that:

• “Sponsors should implement a system to manage quality throughout all stages of the trial.
• “The methods used to assure and control the quality of the trial should be proportionate to the risks inherent in the trial and the importance of the information collected.
• “The quality management system should use a risk-based approach.” (1)

New ICH E6 (R3) guidance increases the focus on risk even further:

• “The Sponsor should adopt a proportionate and risk-based approach to quality management, which involves incorporating quality into the design of the clinical trial and identifying those factors that are likely to have a meaningful impact on participant’s rights, and well-being and the reliability of the results.” (2)

Changing The Mindset – From A Reactive to Proactive Approach
Traditional RM approaches are often anchored in the analysis of issues after they’ve already occurred. Beginning with the problem (like a critical audit finding, an FDA letter, or costly mistakes), traditional approaches work backward, using methods like RCA and CAPAs to identify “risk” after the damage is done.

While CAPAs can improve quality “the next time,” it can be too late for the current trial. ICH E6 (R3) guidelines require sponsors to shift their focus toward the prevention of errors, rather than relying heavily on the investigation of issues that occur when risk is not anticipated and addressed proactively.

Involving Front-line Staff in Proactive Planning
While RM is certainly a critical part of a quality management system, it is most frequently conducted primarily by the Quality Management or QA team, who have limited tools to engage with the people closest to a trial’s risk and its likely consequences: the clinical and operational staff who are responsible for design, planning and execution of the trial.

Front line personnel have real-world knowledge and experience that allows them to foresee potential issues and often valuable ideas that can help prevent them. Their input should be a central component of any RM program – but capturing, managing and utilizing that input in a consistent, structured manner is a challenge.

Using Better Tools for The Task At Hand
When it comes to ICH E6 (R2), the following are required: (3)

• Critical Process and Data Identification
• Risk Identification
• Risk Evaluation
• Risk Control
• Risk Communication
• Risk Review
• Risk Reporting

Current tools used to capture and manage risk in clinical trials are often inadequate to satisfy the intent of E6 guidelines, and to effectively improve trial quality. Risks are often captured in spreadsheets or other static documents that don’t address all of the critical components of the risk management process (see above) as defined by ICH and associated regulations.

Frankly, these options were never optimized for such a complex task. Without a way to manage all elements of the process in one place, risk management becomes cumbersome, time-consuming and fragmented, sapping team motivation and participation in serious risk management activities. These burdens result in a diminished focus on managing trial risks proactively and a lack of visible results in preventing issues.

As a result, documented and filed risk assessments don’t accomplish the goal of minimizing the risk through improved planning and oversight. With the current scenario, RM becomes a static process performed by a siloed quality management team vs. a dynamic process that engages teams across departments where they have much better visibility and technical expertise in each area where risk resides in a clinical trial.

“Fire Prevention” over “Fighting Fires”
A software platform, like QI Path, can be a cost-effective solution for managing risk effectively across the entire drug development continuum, from pre-clinical development through clinical trials and CMC. Such a platform can help with your RM needs for a pharma company developing a pipeline of drug products or a CRO running clinical trials across multiple sites, countries and geographies. Designed with QbD and Risk-Based Quality Management (RBQM) principles in mind, such technology can streamline RM planning and satisfy all of the components of ICH E6 requirements:

• Cross functional teams can be engaged quickly and easily to gather their perspective and communicate on specific risks in one place, and take action if required.
• Complex operational processes and associated risks can be quickly mapped and visualized from different perspectives such as by site, by drug class, department, or country.
• Risks can be actively monitored with dashboards.
• Mitigating actions can be mapped to specific risks and monitored.
• Risks can be actively reviewed and reported seamlessly for internal and regulatory purposes.
• With the right platform in place, not only does risk management become far more effective, but it takes significantly less time, resulting in Quality teams that have more “eyes and ears” helping to monitor and manage risk ensuring product quality, patient safety, and clinical trial data integrity.

About the Author
Jonathan Vaught, Ph.D, is the CEO of QI Path. The company combinesconsulting and software to help pharma organizations get out in front of risk proactively to drive better outcomes. QI Path helps organizations shift from a reactive, response-based risk approach to a forward-facing, proactive stance. Find him on LinkedIn.

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Citations

1) FDA. March 2018. E6(R2) Good Clinical Practice: Integrated Addendum to ICH E6(R1) Guidance for Industry. Page 29.

2) ICH. May 2023. E6(R3) GOOD CLINICAL PRACTICE (GCP). Page 34.

3) FDA. March 2018. E6(R2) Good Clinical Practice: Integrated Addendum to ICH E6(R1) Guidance for Industry. Page 29-30.