Читать книгу Cobert's Manual Of Drug Safety And Pharmacovigilance (Third Edition) - William Gregory - Страница 111

As with the post-marketing requirements, the regulation of drug safety surveillance during clinical development has been updated over the last several years. The changes are not as dramatic as those put in place for post-marketing surveillance but are significant. EudraLex Volume 10 has been amended and new Regulations have been put in place (2019) (see w: Regulation (EU) No. 536/2014 — https://ec.europa.eu/health/human-use/clinical-trials/regulation_en). Contrary to Post-marketing Regulation for which specific PV documents (Directives, Practices, Q&A, etc.) are issued, the drug safety surveillance rules during clinical studies are part of the clinical study regulation.

Regarding clinical trial PV, the main changes represent a simplification of the rules on safety reporting as follows:

The protocol may provide that not all adverse events (AE) and suspected serious adverse events are recorded and reported as part of the safety assessment if they are used as efficacy endpoints, for example.

For a clinical trial involving more than one investigational medicinal product (IMP) it is now possible to submit a single safety report on all the IMPs used in the trial to the EudraVigilance database.

Suspected unexpected serious adverse reactions (SUSARs) are reported to the Clinical Trial Eudravigilance database:

Note 1: For multinational trials, all SUSARs, whether occurring within the EU or in a third country, are reported to the Agency.

Note 2: Fatal or life-threatening SUSARs are within 7 calendar days. Non-fatal or non-life-threatening SUSARs within 15 calendar Days.

The regulation requires Member States to collaborate in assessing the annual Development Safety Update Reports (DSURs) and SUSARs:

Note: Unexpected events which affect the benefit–risk balance of the clinical trial must be reported within15 calendar days.

The sponsor’s responsibilities are described in terms of collecting, recording, handling, and communicating. Additional requirements are explained regarding ethics committees, interactions with investigators, issues unique to trials (e.g., unblinding), expedited reporting, annual reporting, inspections’ outcomes disclosure, and other details.