A new guidance document released by the US Food and Drug Administration on 6 August 2013 calls on sponsors to develop centralized risk-based monitoring strategies for clinical trials involving medical products with the ultimate goal of enhancing protections for human subjects while simultaneously improving the quality of clinical trial data.
The guidance, Oversight of Clinical Investigations, A Risk-Based Approach to Monitoring, isn't focused on any one type of product in particular; rather, it applies to pharmaceutical, biologics, medical devices and combination products, making clear that sponsors may utilize a "variety of approaches to fulfill their [monitoring] responsibilities" of clinical trials.
And while a variety of approaches are available, FDA's guidance lists several it says would "reflect a modern, risk-based approach that focuses on critical study parameters and relies on a combination of monitoring activities to oversee a study effectively," such as the use of centralized monitoring.
That sort of approach is becoming increasingly necessary, FDA explained, as clinical trials become increasingly complex and geographically dispersed thanks to outsourcing trends. At the same time, new technologies are making is easier than ever to keep track of these trials through electronic monitoring, allowing more greater and more efficient oversight.
The challenge, then, is getting clinical trial sponsors to use this technology and adopt best practices to ensure the safety of patients and the efficient allocation of trial resources.
A Focus on Monitoring Trials
Though the related challenges are myriad, FDA's guidance focuses primarily on monitoring, "one aspect of the processes and procedures needed to ensure clinical trial quality and subject safety," and one critical to ensuring whether the study is being conducted as intended by the sponsor. While FDA notes that monitoring alone isn't sufficient to ensure trial quality, it is nevertheless an integral part of any quality risk management system.
Survey data obtained by FDA shows a range of monitoring methods. Many companies, and particularly those engaged in clinical investigations, conducted on-site monitoring to verify clinical data at least every four to eight weeks, "at least partly because of the perception that the frequent on-site monitoring visit model, with 100% verification of all data, historically has been FDA's preferred way for sponsors to meet their monitoring obligations." Outside of industry, some academic and government groups only monitor trial sites in person once every two or three years in order to qualify or certify the site itself.
Moving Away from On-Site Monitoring
In still other large-scale trials, no regular on-site monitoring is used in favor of alternative monitoring methods, suggesting "that use of alternative monitoring approaches should be considered by all sponsors, including commercial sponsors, when developing risk-based monitoring strategies and plans."
"Several publications suggest that certain data anomalies (e.g., fraud, including fabrication of data, and other non-random data distributions) may be more readily detected by centralized monitoring techniques than by on-site monitoring," FDA adds later in the guidance. As a result, the guidance states that FDA "encourages greater use" of centralized monitoring practices compared to historical trends that emphasized on-site monitoring.
"Sponsors who plan to use centralized monitoring processes should ensure that the processes and expectations for site record keeping, data entry, and reporting are well-defined and ensure timely access to clinical trial data and supporting documentation," FDA added, noting that on-site monitoring should still be conducted from time to time.
The guidance goes on to list a plethora of considerations sponsors should take into account, most notably the risks to human subjects, and how that should inform the type, frequency and practices of monitoring the trial.
Oversight of Clinical Investigations, A Risk-Based Approach to Monitoring
Federal Register Notice