EMA Offers Draft Guideline on Serious Breaches of Clinical Trial Regulations

Regulatory NewsRegulatory News | 23 May 2017 |  By 

The European Medicines Agency (EMA) on Tuesday opened for public consultation a draft guideline on serious breaches of clinical trial regulations or clinical trial protocols.

The agency says the guideline is intended to "outline the practical arrangements for notification of serious breaches … provide advice on what should and what should not be classified as a serious breach and what must be reported … [and] To outline possible actions that may be taken by the EU/EEA Member States concerned (MSC) in response to notifications of serious breaches."


The draft says that within seven calendar days, the sponsor or anyone that has a contractual agreement with the sponsor (including contract research organizations, co-development partners, etc.) and is aware of the breach must report it.

And though the majority of deviations from clinical trial protocols and good clinical practice (GCP) "are technical deviations that do not result in harm to the trial subjects or significantly affect the scientific value of the reported results," EMA says the judgment on the significance of the breach "depends on a variety of factors, for example: the design of the trial, the type and extent of the data affected by the breach, the overall contribution of the affected data to key analysis parameters, the impact of excluding the data from the analysis etc."

EMA adds: "It is the responsibility of the sponsor to thoroughly perform a root cause analysis to identify the cause of the serious breach and to assess the impact of the breach on the scientific value of the trial as well as the impact on the subject’s safety and rights."

The agency also offers the example of a breach that leads to the removal of data from the overall analysis, which it says does not negate the fact that a breach has occurred and "should be treated according to the legal requirements. In the same way, if one or more overdose(s) occurred due to a miscalculation, this would still meet the criteria for a serious breach regardless of whether or not the subject(s) suffered adverse reactions as a result of that overdose."

An appendix in the draft guideline also features other examples of serious breaches.

Draft guideline for the notification of serious breaches of Regulation (EU) No 536/2014 or the clinical trial protocol


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