As noted in the FDA Reviewer Guidance (2005) and ICH E3 (1995), a listing of deaths is expected and is recommended (Listing 11.1). As shown in the example listing, we recommend sorting by treatment. However, for multi-phase studies where patients are treated with different treatments across the phases, the listing can be modified to be sorted by patient ID, with treatments as a column (with all treatments provided in concatenated format, e.g., Placebo/TreatmentName/NoDrug). A summary table of deaths (Table 11.2) would also be recommended for indications in which death will be relatively frequent. Although the guidance documents do not specifically refer to a summary of SAEs, only a listing, we believe a summary table of all serious events during the treatment period is very helpful for data interpretation (Table 11.7). If the number of SAEs is expected to be extremely small, then a listing would be sufficient. The recommended summary table displays all Pts by decreasing frequency without sorting by SOC. The table could be sorted by SOC if deemed useful (e.g., a lot of SAEs across a number of SOCs). To understand further the severity of AEs, a summary of AEs leading to treatment discontinuation is recommended (Table 11.8). The guidance documents do not specifically refer to a summary table, only a listing, but it is commonly created across the industry and is considered very useful in understanding tolerability. The recommended summary table displays all preferred terms by decreasing frequency without sorting by SOC. The table could be sorted by SOC if deemed useful (e.g., a lot of events leading to discontinuations across a number of SOCs). Table 11.9a is recommended for AESI that comprise a list of pre-defined preferred terms. Table 11.9b is recommended when there is an AESI that can be defined by the use of a SMQ. Standardized MedDRA queries were created to define common medical concepts of interest by grouping relevant MedDRA PTs. See Section 10.4 for further discussion regarding SMQs.
As noted in the FDA Reviewer Guidance (2005) and ICH E3 (1995), a listing of deaths is expected and is recommended (Listing 11.1). As shown in the example listing, we recommend sorting by treatment. However, for multi-phase studies where patients are treated with different treatments across the phases, the listing can be modified to be sorted by patient ID, with treatments as a column (with all treatments provided in concatenated format, e.g., Placebo/TreatmentName/NoDrug). A summary table of deaths (Table 11.2) would also be recommended for indications in which death will be relatively frequent. Although the guidance documents do not specifically refer to a summary of SAEs, only a listing, we believe a summary table of all serious events during the treatment period is very helpful for data interpretation (Table 11.7). If the number of SAEs is expected to be extremely small, then a listing would be sufficient. The recommended summary table displays all Pts by decreasing frequency without sorting by SOC. The table could be sorted by SOC if deemed useful (e.g., a lot of SAEs across a number of SOCs). To understand further the severity of AEs, a summary of AEs leading to treatment discontinuation is recommended (Table 11.8). The guidance documents do not specifically refer to a summary table, only a listing, but it is commonly created across the industry and is considered very useful in understanding tolerability. The recommended summary table displays all preferred terms by decreasing frequency without sorting by SOC. The table could be sorted by SOC if deemed useful (e.g., a lot of events leading to discontinuations across a number of SOCs). Table 11.9a is recommended for AESI that comprise a list of pre-defined preferred terms. Table 11.9b is recommended when there is an AESI that can be defined by the use of a SMQ. Standardized MedDRA queries were created to define common medical concepts of interest by grouping relevant MedDRA PTs. See Section 10.4 for further discussion regarding SMQs.
Phuse_AE_August2016_ForPublicReview.docx