helpful if methods for validation could be expanded. The pathway for a extrapolation concept needs to be “failed” further detailed. 438-440 Comment: The title of 5.2.2 includes "validation" but this first sentence implies updating the model with the new paediatric data. Lines 442 and Comment: 443 The phrase "the extrapolation concept needs to be updated (see section 5.2)" does not make sense in context. Section 5.2 is the extrapolation plan, not the extrapolation concept. Furthermore, section 5.2)” is inconsistent with how “(see sections have been referred to earlier in the document (see comments above regarding lines 295, 300, and 304). Consider correcting the cross references. Proposed change (if any): "the extrapolation concept plan needs to be updated (see section 5.2, Extrapolation plan)". Section 5.3 448-450 Comment: We suggest the term risks instead of “minimize” “mitigate” Proposed change (if any): A formal, structured plan to mitigate minimize risks and address key uncertainties during development and in the post-authorisation setting should be proposed as part of the extrapolation plan and updated in response to the results of the studies conducted. 452 Comment: We suspect that the word is missing and the “population” end of the first sentence Proposed change (if any): being generated in the target population.” “… 454-455 Comment:
helpful if methods for validation could be expanded. The pathway for a “failed” extrapolation concept needs to be further detailed. 438-440 Comment: The title of 5.2.2 includes "validation" but this first sentence implies updating the model with the new paediatric data. Lines 442 and 443 Comment: The phrase "the extrapolation concept needs to be updated (see section 5.2)" does not make sense in context. Section 5.2 is the extrapolation plan, not the extrapolation concept. Furthermore, “(see section 5.2)” is inconsistent with how sections have been referred to earlier in the document (see comments above regarding lines 295, 300, and 304). Consider correcting the cross references. Proposed change (if any): "the extrapolation concept plan needs to be updated (see section 5.2, Extrapolation plan)". Section 5.3 448-450 Comment: We suggest the term “minimize” risks instead of “mitigate” Proposed change (if any): A formal, structured plan to mitigate minimize risks and address key uncertainties during development and in the post-authorisation setting should be proposed as part of the extrapolation plan and updated in response to the results of the studies conducted. 452 Comment: We suspect that the word “population” is missing and the end of the first sentence Proposed change (if any): “… being generated in the target population.” 454-455 Comment:
efpia-comments_extrapolation-rp_final-22jan2018.docx