FDA Clarifies Adverse Event Reports for Clinical Trials

FDA adverse event reporting

FDA Final Rule Clarifies
AE Reporting for
Clinical Trials

On 28 September 2010 FDA announced that it was issuing a final rule that clarifies safety reporting for adverse events during clinical trials. The final rule impacts drug and biologic regulations for clinical trials conducted under an investigational new drug (IND) application (21 CFR 312) and bioequivalence studies (21 CFR 320). The draft rule was published in 2003 and received numerous comments. These comments, combined with increased concern over drug safety, led to significant changes by FDA. The new rule defines the separation of clinical trial safety adverse event reports and post-market safety reporting. The agency is working on new regulations for post-market safety reports. FDA stated that the separation was necessary to improve the quality of safety reporting, monitor the safety of drugs and biologics, and harmonize adverse event reports internationally. There are some significant differences between the draft rule of 2003 and the final rule published on 28 September 2010 including:

Replace the defined phrase ‘‘associated with the use of the drug’’with the term ‘‘suspected adverse drug reaction (SADR),’’
• Require submission of expedited reports of ‘‘information sufficient to consider product administration
• Make it clear that safety reports of overall findings or data in the aggregate must be submitted in a narrative format,
• Permit the determination that an SADR is life-threatening to be based on the opinion of either the investigator orsponsor (as opposed to only the investigator),
• Require that the sponsor notify FDA and all participating investigators of each SADR that is both serious and unexpected, based on the opinion ofeither the investigator or sponsor (asopposed to only the sponsor),
• Require a ‘‘minimum data set’’ for each report of an SADR submitted toFDA, and
• Clarify the sources of information that sponsors must review for safety surveillance and reporting purposes.

FDA clarifies adverse events clinical trials

FDA Adopts ICH E2A Definitions

Perhaps the most significant change in the final rule is that FDA is adopting the terms and definitions in the ICH guidance document E2A that are used throughout the world. Prior to issuing the final rule FDA regulations did not specifically define the term “adverse event” although the term was referred to repeatedly in the regulations and there was a definition for “serious adverse event.” Using the ICH definitions will make it easier for clinical trial professionals to “speak the same language” when conducting research. As FDA clarifies definitions, communications between sponsors and investigators should become easier. Hopefully, researchers will now understand that it isn’t necessary to “report all SAEs immediately.” FDA is stating clearly that:

“… the revisions to the IND safetyreporting requirements will improve theoverall quality of safety reporting andthe agency’s ability to review critical safety information by ensuring that theinformation that FDA receives in an INDsafety report is relevant and useful.

Under former regulations, there may have been over-reporting of serious adverse events for which there was little reason to believe that the drug had caused the event, complicating or delaying FDA’s ability to detect a safety signal.

In this final rule, FDA clarifies definitions, provides examples of the types of evidence that suggest a causal relationship for purposes of reporting asuspected adverse reaction to the IND and participating investigators, and revises the requirements for expedited reporting of serious and unexpected suspected adverse reactions to the IND.”

The ambiguity over reporting adverse events has caused friction between many study coordinators and CRAs. Hopefully, FDA clarifying AE reporting will help researchers focus on issues of significance.

FDA Announcement of Final Rule

At the same time FDA issued a draft guidance on Safety Reporting Requirements which will be the topic of a future post. The comment period is OPEN!

Safety Reporting Requirements for INDs and BA/BE Studies

++++In news from GxP Perspectives++++

clinical trials adverse event FDA

TMF Webinar on Thursday, 14 October 2010

Special Announcement: TMF Webinar 14 October

Read the updated article on the Form FDA 1572 in:

Applied Clinical Trials “Closing Thought” on FDA 1572

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