A Summary of Clinical Safety (SCS) is a section of the Clinical Summary placed in Module 2.7.4 of the Common Technical Document. The purpose is to provide a summary of the data relevant to safety in the intended population, integrating the results of individual clinical study reports as well as other relevant reports, eg, the integrated analyses of safety that are routinely submitted in some regions.
The SCS summarizes the data on exposure to the drug; adverse events; clinical laboratory evaluations; vital signs, physical findings, and other observations related to safety; and safety in special groups and situations. If the drug has already been marketed, all available and relevant post-marketing data are also summarized.
The display of safety-related data can be considered at 3 levels. (1) The extent of exposure (dose, duration, number of patients, type of patients) should be examined to determine the degree to which safety can be assessed from the database. (2) The more common adverse events and changes in laboratory tests should be identified and classified, and their occurrence should be summarized. (3) Serious adverse events and other significant adverse events should be identified and their occurrence should be summarized. These events should be examined for frequency over time, particularly for drugs that may be used chronically.
The safety profile of the drug, described based on analysis of all clinical safety data, should be outlined in a detailed, clear, and objective manner, with use of tables and figures. The SCS will be developed based on the key messages, agreements on document content (eg, what to present first), and feedback from document review.
The Integrated Summary of Safety (ISS) is a critical component of the submission file in the US (placed in Module 188.8.131.52). Note that, despite the name, this is not a summary but rather an integrated analysis of all relevant safety data from clinical studies. The ISS text can be developed first and used to derive the SCS.
The role of the Medical Writer is to ensure that the data are well structured, the key messages are brought forward clearly, it is a high-level summary (avoiding duplication), and to ensure consistency with other CTD documents that are developed in parallel.