CLINICAL OPERATIONS & OUTSOURCING Risk assessment in clinical trials THOMAS TREMBLAY, RN BSN, VICE PRESIDENT OF CLINICAL DEVELOPMENT AT TREFOIL THERAPEUTICS T 1 2
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he first step for sponsors to effectively oversee clinical investigations starts with identifying the associated risks.
To this end, the FDA released a guidance document entitled ‘Oversight of Clinical Investigations - A Risk-Based Approach to Monitoring’ (RBM, FDA 2013). I recall the anticipation (and trepidation) within the industry regarding this guidance and the
concerns among stakeholders about its potential impact on our clinical trial implementation and monitoring practices. However, it is notable that many sponsors have not fully embraced the guidance provided by the Agency. It is important to recognise that all Guidance for Industry documents reflect the FDA’s current perspectives on the topic.
Table 1: Key points in Oversight of Clinical Investigations - A Risk-Based Approach to Monitoring Point
RBM Page
“This guidance assists sponsors of clinical investigations in developing risk-based monitoring strategies and plans for investigational studies…”
“This guidance makes clear that sponsors can use a variety of approaches to fulfill their responsibilities for monitoring.”
“Effective monitoring of clinical investigations by sponsors is critical to the protection of human subjects and the conduct of high-quality studies.”
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...the number and complexity of clinical trials … create new challenges to clinical trial oversight.”
“FDA encourages sponsors to develop monitoring plans that manage important risks to human subjects and data quality and address the challenges of oversight in part by taking advantage of the innovations in modern clinical trials.”
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“A risk-based approach to monitoring does not suggest any less vigilance in oversight of clinical investigations. Rather, it focuses sponsor oversight activities on preventing or mitigating important and likely risks to data quality and to processes critical to human subject protection and trial integrity.”
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A survey conducted through the Clinical Trials Transformation Initiative has shown that for major efficacy trials, “companies typically conduct on-site monitoring visits at approximately 4- to 8-week intervals, 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.”
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“There is a growing consensus that risk-based approaches to monitoring, focused on risks to the most critical data elements and processes necessary to achieve study objectives, are more likely than routine visits to all clinical sites and 100% data verification to ensure subject protection and overall study quality.”
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“Sponsors should prospectively identify critical data and processes that if inaccurate, not performed, or performed incorrectly, would threaten the protection of human subjects or the integrity of the study results.”
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“The identified risks should be assessed and prioritized by considering the following: • the likelihood of errors occurring • the impact of such errors on human subject protection and trial integrity • the extent to which such errors would be detectable Sponsors should use the results of the risk assessment in developing the monitoring plan.”
Adapted from Oversight of Clinical Investigations - A Risk-Based Approach to Monitoring” (FDA 2013) 26 | Outsourcing in Clinical Trials Handbook 1 1
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