Risk-Based Monitoring: Understanding The Future Of Clinical Trial Monitoring

By Lynn King, senior director, clinical operations, TKL Research

While risk-based monitoring (RBM) has been a popular discussion topic among the clinical research community for quite some time, sponsors and researchers have been slow to implement adaptive strategies. RBM moves away from the traditional approach of frequent on-site visits and 100 percent source data verification (SDV) toward a combination of activities, including centralized data collection and monitoring.

The goal of traditional monitoring approaches is to ensure patient safety and quality data, and a properly designed RBM strategy can support and even enhance this practice while more efficiently using resources. This article explores alternative monitoring strategies and offers guidance for implementation in an effort to clarify the confusion surrounding RBM.

Alternative Monitoring Strategies

Although the FDA guidance, “A Risk-Based Approach to Monitoring,” has been final for almost two years, much of this industry is struggling with how to implement practices that align with key elements of the recommendations.

To help understand the guidance, there are first a few terms important to understand:

• Source data verification is the process of confirming accuracy and validity by comparing reported information to the original records to make sure data is reliable and that the study can be reconstructed.
• A targeted monitoring strategy includes a reduced SDV approach that focuses on critical data, patient visits, and/or selected patients, depending on the risk-benefit profile of the trial. Predefined triggers are used in this method to determine necessary on- and off-site attention.
• Risk-based monitoring aims to allocate resources based on risk and need instead of equally distributing resources. The goal of RBM is to increase monitoring efficiency without compromising patient safety or data quality.

Frequent on-site monitoring with 100 percent SDV is no longer the recommended method for monitoring all trials, but many organizations still hesitate to transition to RBM from traditional methods. The FDA recognizes that an approach focused on the specific risks for each specific clinical trial is more likely to ensure the safety of the patient than routine visits and 100 percent SDV. Handling every single risk the same way has proven to be inefficient, and, therefore, risks should be prioritized to be managed correctly. After all, monitoring does have a large effect on a trial’s bottom line; limited resources must be allocated in ways that maximize benefits.

Considerations For Implementing An RBM Strategy

At the beginning of a study, each clinical trial should be assessed for alternative monitoring strategies based on a number of factors, including what’s being studied, protocol complexity, and experience with similar trials. Risk assessment will serve as the foundation for all successive steps in the RBM strategy. Assessment involves:

• Defining the data and processes critical to patient safety and data quality
• Identifying the risks and creating processes to minimize them
• Setting indicators and thresholds that will trigger an investigation and/or corrective action

Implementing RBM can be challenging, but it’s not impossible if certain steps are taken. To achieve success, sponsors, CROs, and sites should consider:

• Identifying areas of greatest risk based on previous experience with similar trials and developing metrics to quantify potential risks
• Assigning roles for staff, along with providing written operational instructions
• Creating decision trees for responses based on failure events
• Mapping the relationships between clinical and operational data

• Composing a monitoring plan to coordinate activities between the members of the project team
• Implementing training on RBM strategies for all team members

Whoever is in charge of designing or maintaining a risk mitigation model must be familiar with multiple tools and techniques available. A standard model may include a failure modes and effects analysis to analyze potential failures and causes to prioritize risk; fault tree analysis using a causal diagram to find possible failures in a system; and risk ranking and filtering to evaluate risk factors to produce a relative risk score that can then be prioritized.

Centralized Monitoring vs. On-Site Monitoring

RBM offers the advantages of centralized monitoring. Centralized monitoring is a remote evaluation carried out at a location other than the clinical investigational site(s). Trial staff can perform data checks, review data for inconsistencies, and complete regulatory reviews and updates, and, once problems arise, determine whether an on-site visit is necessary.

While centralized monitoring allows for much of the study oversight and review to be done remotely, there is still value in being on site. Centralized monitoring should supplement, though not always replace, on-site monitoring, especially for certain sites that pose higher risk. In person, a monitor can thoroughly examine all documents to ensure each patient has met eligibility criteria, review informed consent documentation, assess the site’s understanding of the study and protocol, review regulatory documentation, and ensure regulatory compliance.

A Successful Plan

First and foremost, communication pathways must be strong among all team members, and each member must also have a clear understanding of their roles and expectations from the beginning. The clinical monitoring plan must be concise, yet thorough. Information must be study-specific and processes must be developed to gather, analyze, and act on data throughout the trial. If electronic data collection is part of your clinical monitoring plan, you must have the appropriate technological capabilities to capture, monitor, and transfer data.

Looking Into The Future

RBM is one solution to combat the continually rising costs of conducting effective clinical research. By shifting costs away from on-site visits and 100 percent SDV toward centralized data collection and monitoring, limited resources and budgets can be better utilized to ensure data quality. While the challenges of moving toward an alternative monitoring approach have slowed industry-wide implementation, the future looks bright for RBM. Progress is being made and discussion among key players is becoming more prevalent.