Adverse events rates that are not included in the PM
-
Hello,
We wanted to clarify the requirements for including safety data (adverse events rates) that are not included in the PM. A PM can include an AE table for a particular study, but in some cases, certain AEs from the study may not be included in the P. .
We would like to present these additional "out-of-PM" AEs, and while there is no statistical analysis for these data (which is common for AE rates), we note that these AEs of interest were predefined, and that we are amenable to presenting the data in a claim-neutral manner, either with or without the comparator.
The rationale is as follows: When AE rates are particularly low, they may not appear in the PM. However, they may still come up in rep-to-HCP conversations if they are relevant in the therapeutic area. Therefore, it should be reasonable to include this information in an APS, especially if it is presented in a claim-neutral manner that does not impart a benefit from the drug.
-
Hello,
We wanted to clarify the requirements for including safety data (adverse events rates) that are not included in the PM. A PM can include an AE table for a particular study, but in some cases, certain AEs from the study may not be included in the P. .
We would like to present these additional "out-of-PM" AEs, and while there is no statistical analysis for these data (which is common for AE rates), we note that these AEs of interest were predefined, and that we are amenable to presenting the data in a claim-neutral manner, either with or without the comparator.
The rationale is as follows: When AE rates are particularly low, they may not appear in the PM. However, they may still come up in rep-to-HCP conversations if they are relevant in the therapeutic area. Therefore, it should be reasonable to include this information in an APS, especially if it is presented in a claim-neutral manner that does not impart a benefit from the drug.
Hey @dmauri
Please see PAAB Q&A 427.
In summary, as per PAAB code section 5.9 and 5.7, when a side-by-side comparative presentation of out-of-TMA safety profile data is desired, a head-to-head RCT with demonstrated statistical analyses between the adverse events that are being compared should be provided as substantiation. In cases where such substantiation is not available, a comparative presentation would not be acceptable. Note that PAAB can consider a neutral comparative side-by-side AE presentation without statistical analysis or conclusion, if it exists in the TMA.
-
Thank you! Based on the last sentence of Q&A you've mentioned, we can still present AE data from an acceptable clinical trial, even if the data do not exist in the TMA. However, special attention must be given to ensure that the presentation is neutral and noncomparative, and that the AE rates are "roughly" aligned with those of the TMA.
Does it make a difference if the comparator is included or excluded from the presentation?
-
Thank you! Based on the last sentence of Q&A you've mentioned, we can still present AE data from an acceptable clinical trial, even if the data do not exist in the TMA. However, special attention must be given to ensure that the presentation is neutral and noncomparative, and that the AE rates are "roughly" aligned with those of the TMA.
Does it make a difference if the comparator is included or excluded from the presentation?
Hi @dmauri
This would not apply to comparative data. As per the first sentence “statistical analysis to support inclusion of comparative therapeutic data” is required. The comment also states that the AEs have to be aligned. Your original question appears to suggest that you are looking to speak to AEs which are not presented in the TMA and therefore would be difficult to demonstrate alignment.
