FDA updates Covid-19 clinical trials guidance to address serious adverse events
The FDA last week updated its guidance on conducting clinical trials amid the coronavirus disease pandemic to address how and when sponsors and application holders should report serious adverse events (SAE).
The latest update to the guidance comes just days after FDA added new questions and answers to the document addressing the use of alternate laboratory or imaging centers, video conferencing and postmarketing studies.
Serious adverse events
The updated guidance includes two new questions and answers on serious adverse event reporting requirements in different circumstances.
The first question addresses situations where a company studying an already approved drug to treat COVID-19 under an investigational new drug application (IND) receives a spontaneous report of a serious adverse event stemming from the product’s off-label use in clinical practice to treat Covid-19.
FDA explains that serious adverse events that occur in clinical practice “must be reported in accordance with the applicable post-marketing reporting requirements,” whether or not the adverse event is included in labeling to the appropriate FDA database, the Vaccine Adverse Event Reporting System (VAERS) for vaccines and the FDA Adverse Event Reporting System (FAERS) for drugs and biologics.
When the serious adverse event occurs during a clinical trial, FDA says the event “must be reported as an IND safety report … if they are unexpected and the sponsor determines that there is a reasonable possibility that the drug caused the SAE.”
“Regardless of whether an SAE occurs in the course of clinical practice or during a clinical trial, and regardless of where it is first reported, [a new drug application or biologics license application] holder who is also the sponsor of an IND investigating the same drug for COVID-19 is responsible for monitoring the safety of its drug and evaluating all accumulating safety data,” FDA writes, adding that if that data indicated there may be a new serious risk associated with the drug that an IND safety report must be filed.
In the second question, FDA explains how sponsors studying drugs for non-Covid-19 indications should handle reporting serious adverse events associated with Covid-19 during the trial.
FDA again explains that sponsors are required to report any serious adverse events that are unexpected and could reasonably have been caused by the drug.
As such, FDA says that sponsors must determine whether the investigational drug “might be causally related to a SAE associated with COVID-19,” though the agency acknowledges that doing so “likely requires more than single or even a few cases.”
For randomized controlled trials, FDA says sponsors should compare the rate of observed serious adverse events in participants with Covid-19 in the investigational to those in the control arm of the study. Because such assessments would involve unblinded data, FDA says they should only be done by a data monitoring committee or a “firewalled” and independent specially constituted safety committee.
For nonrandomized studies, FDA says sponsors should compare the rate of serious adverse events and mortality for trial participants diagnosed with Covid-19 to a similar external population.
“If the difference in SAEs across treatment arms or compared to an external population suggests a causal relationship between the investigational product and the SAEs in subjects diagnosed with COVID-19, this finding must be submitted to FDA as an IND safety report,” FDA writes.
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RAPS: First published in Regulatory Focus™ by the Regulatory Affairs Professionals Society, the largest global organization of and for those involved with the regulation of healthcare products. Click here for more information.