The recent update to the ICH GCP E6 guidelines calls for sponsors to adopt a formal approach to quality management which embraces technology and leverages access to real-time information to drive a more structured approach to risk. In light of this change, a natural question that may arise is: How should I incorporate this into my Clinical Monitoring Plan (CMP)? And, what are the critical components that need to be addressed with respect to risk-based monitoring (RBM)?
Here are some thoughts….
Over the past two decades, the complexity of clinical trials has grown dramatically. The increasingly global nature of clinical studies has created new challenges to clinical trial oversight, including variability in investigator experience, site infrastructure, and standard of care.
RBM aims to allocate study resources based on risk, need, and each investigative site’s unique challenges. According to the U.S. Food and Drug Administration (FDA) guidance on a risk-based approach to monitoring, RBM strategies and plans focus sponsor oversight on the most important aspects of study conduct and reporting, rather than routine visits to all clinical sites and 100% source data verification (SDV). The fundamental objective of RBM is to strategically utilize available resources to ensure patient safety and data integrity, and the benefits include improved efficiency, lower costs, and superior data quality.
Any comprehensive RBM strategy should address the following five basic elements:
- What are the critical data and processes?
- How will the risks be assessed and identified?
- How will the risks be measured and evaluated?
- How will the risks be actioned and communicated?
- How will the risk-based process be kept current and updated?
Let’s take these one at a time.
- Critical Data and Processes: Not all data are created equal and not every activity is critical. Data and processes that are critical to managing risk in the study should be clearly identified and linked to the appropriate risk for which it is intended.
- Risk Assessment: A thorough a priori evaluation of known risks, along with their likelihood of occurrence, their potential impact, and the methods by which they will be assessed, should be conducted.
- Risk Measurement: Every identified risk should have a clear methodology for how the risk will be measured and how occurrence of the risk will be detected. This includes defining appropriate components of automated risk detection (i.e., thresholds, triggers, and profile checks), as well as manual reviews (e.g., checklists).
- Risk Actioning: This should specify how the risks, once detected, will be actioned including the role and process of central monitoring, impact on SDV levels, how the SDV levels will be managed, and how the risks will be communicated and closed.
- Risk Review: The process of risk identification and mitigation is by its very nature dynamic. We start with risks known a priori and incorporate learnings and findings that take into account emerging knowledge and experience throughout the conduct of a trial. As such, this element of the RBM strategy specifies and explains the process by which the risk assessment and mitigation methodology will be updated in a regular manner to reflect new information, learnings, and findings throughout the life of a clinical trial.
A robust RBM software application should allow you to create, manage, and maintain all of the above elements within the system, as well as provide functionality that facilitates their implementation. Effective RBM solutions help sponsors distill large amounts of data quickly so they can focus on key risks, make more informed decisions, and facilitate continual improvement in trial conduct and oversight.
Download our white paper Best Practices for Implementing Risk-Based Monitoring into the Clinical Trial Process to learn more about finding and adopting the right RBM solution.
 International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. Guideline for Good Clinical Practice E6 (R2), November 9, 2016. Available at http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R2__Step_4_2016_1109.pdf.
 U.S. Food and Drug Administration. Guidance for Industry: Oversight of Clinical Investigations—A Risk-Based Approach to Monitoring. Available at https://www.fda.gov/downloads/Drugs/Guidances/UCM269919.pdf.