The drug safety data generated by clinical trials demonstrates that the benefit-risk profile of the new drug (or approved drug with a proposed new purpose) is favourable for the condition being treated and is pivotal to support the application to market the drug. Whereas, the real world evidence (RWE) generated by non-interventional studies is used to confirm that the benefit-risk profile of the now approved drug continues to be favourable to the patient  when used in real life settings.

The safety reporting requirements for non-interventional studies are different to those for clinical trials as illustrated below in the context of Europe:

CLINICAL TRIAL SAFETY REPORTING

[as per Articles 42, 43 and Annex III of Regulation EU/536/2014]

1. Suspected Unexpected Serious Adverse Reactions (SUSARs) = 7 days (fatal or life threatening)
2. Suspected Unexpected Serious Adverse Reactions (SUSARs) = 15 days (other)
3. Serious Adverse Reactions (SARs) = Annual report
4. Adverse Reactions/ Adverse Events = Annual Report

NON-INTERVENTIONAL STUDY SAFETY REPORTING (PRIMARY DATA)

[as per Article 107.3 of Directive 2001/83/EC, § VI.C.1.2.1 of GVP Module VI, and § VIII.B.4.2. of GVP Module VIII]

1. Serious Suspected Adverse Reactions (SSARs) = 15 days
2. Non-Serious Suspected Adverse Reactions (SARs) = 90 days
3. Adverse Events = Interim Analysis and Final Study Report

NON-INTERVENTIONAL STUDY SAFETY REPORTING (SECONDARY DATA)

[as per § VI.C.1.2.1 of GVP Module VI, and § VIII.B.4.2. of GVP Module VIII]

1. Adverse Reactions/ Adverse Events = Interim Analysis and Final Study Report

Additionally, any new information that may affect the benefit-risk balance of the

medicinal product should be communicated immediately in writing as an emerging safety issue to competent authorities of the Member States in which the product is authorised and the EMA.

It’s worth noting (and being aware) that the terminology used is also different to those for clinical trials.  For example, in the context of clinical trials an SAR is a ‘serious adverse reaction’, whereas in the context of a non-interventional study, an SAR is a ‘suspected adverse reaction’, underlining the importance of context in understanding these terms.

In conclusion, understanding the differences in safety reporting requirements between clinical trials and non-interventional studies is crucial for accurate drug safety evaluation. Clinical trials focus on establishing the initial benefit-risk profile of a drug, requiring prompt reporting of adverse reactions, including Suspected Unexpected Serious Adverse Reactions (SUSARs) within 7 to 15 days and annual reports for other adverse events. In contrast, non-interventional studies, which examine approved drugs in real-world settings, have different timelines, such as 15 days for Serious Suspected Adverse Reactions (SSARs) and 90 days for non-serious reactions, with additional reporting in interim and final study reports. The terminology used in safety reporting also differs between clinical trials and non-interventional studies, underlining the importance of context in understanding these terms.