Article 52 requires reporting of serious breaches of the regulation or of the protocol. A serious breach is defined in much the same way that it was in the UK legislation: a breach likely to affect to a significant degree the safety and rights of a subject or the reliability and robustness of the data generated in the clinical trial. Serious breaches are to be reported through the EU portal “without undue delay” but within 7 days of becoming aware of the breach. The CTR is silent on whether breaches that occur outside the EU require reporting, but, it is likely (as in the existing UK legislation) that a serious breach that occurs at any site anywhere in the world in a trial being conducted in the EU must be reported. Sponsor companies and other organizations involved in clinical trials (such as CROs, IP manufacturing and packaging sites, and central laboratories) will need to consider how they may be affected by this requirement and update their SOPs accordingly. This consideration is particularly crucial for organizations working outside the EU but on trials being conducted in the EU, for example, an American CRO monitoring US sites of a trial also being conducted in the EU or a central laboratory in Switzerland analyzing clinical samples from trial subjects in the EU.
Article 53 significantly broadens the requirements for safety reporting by requiring the sponsor the sponsor to report all unexpected events that might materially affect the benefit-risk balance of the clinical trial but are not suspected unexpected serious adverse reactions. Such events must be reported again “without undue delay” but within 15 days from the date the sponsor became aware of the event. Examples provided are an increase in the rate of occurrence of expected serious adverse reactions that may be clinically important, a significant hazard to the patient population such as lack of efficacy of a medicinal product, or a major safety finding from a newly completed animal study (such as carcinogenicity). This requirement brings EU safety reporting into closer alignment with US requirements, but sponsors need to take a close look at their SOPs to confirm that company safety review and reporting procedures promote compliance with the CTR.
Article 53 also requires a sponsor to submit all inspection reports from countries outside the EU through the EU portal.
Taking another leaf out of the UK book, Article 54 requires notification when urgent safety measures are taken to protect subjects in the case of occurrence of an unexpected event likely to seriously affect the benefit-risk balance of the trial. Such events and the measures taken must be reported again “without undue delay” but within 7 days of the measure(s) taken. Sponsors need to ensure that their SOPs effectively prompt reporting in these situations, in which the study medical and operational team are intensely focussed on subject safety.
A post on the reporting requirements at the end of the study follows soon.