4/27/2021
Photo by Philipp Katzenberger on Unsplash
There has been an increase in the complexity of clinical trials over the last decade. Add to that the support for including more diverse populations who may have additional underlying conditions (FDA Guidance document “Enhancing the Diversity of Clinical Trial Populations”), and this leads to an increase in the number of safety events reported. Unfortunately, there is a trend for reporting all serious adverse events, which leads to mix of safety events that are meaningful and linked to the investigational product with those which add extra burden and are not meaningful.
The FDA released a guidance document in 2009 “Adverse Event Reporting to IRBs — Improving Human Subject Protection” to clarify when safety reporting is required according to the regulations and to help differentiate the adverse events that must be reported to an IRB and which need not be. Additionally, the FDA guidance document, “Safety Reporting Requirements for INDs” originally released in 2012 and updated in 2020, clarifies how it should receive IND safety reports of serious adverse reactions that have a reasonable possibility of being associated with the use of the investigational product. The guidance points out that sponsors frequently were reporting serious adverse reactions that were explained by something other than the investigational product, such as the underlying disease.
Overinterpretation of the regulations on reporting safety events leads to overburdening already busy clinical sites. Safety reporting is one of the more time consuming tasks that a site can do for a clinical trial and it is frequently not compensated for the additional time. Sponsors and CROs who push for all serious adverse reactions to be reported in a suspected unexpected serious adverse reaction (SUSAR) report can also create a situation where meaningful data can become difficult to locate.
As a reminder, the FDA provides these clarifications of the definitions in the guidance:
Suspected adverse reaction means any adverse event for which there is a reasonable possibility (meaning there is evidence to suggest a causal relationship between the drug and the adverse event) that the drug caused the adverse event. A suspected adverse reaction implies a lesser degree of certainty about causality than adverse reaction.
Teams should assess if their internal processes define “reasonable possibility” in the manner the FDA intends to avoid overburdensome tasks for the site and for the FDA review. This in turn helps all stakeholders focus on meaningful safety information and other important clinical trials tasks. Following the regulations as they are intended rather than overinterpreting them reduces the costs and time to complete as well as improves the quality of the data.
- The Clinical Pathways Team
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