model is applicable would be very helpful in this context. E.g., which aspects need to be considered? Which conditions must be met and what defeats an application of these models? 172-173 Comment: The so-called Extrapolation concept and Extrapolation plan are formal documents that need to be developed prospectively by the applicant and be approved by the Agency to initiation of the programme. It follows that any prospective data-driven modelling activity that is not included in the plan cannot be performed unless the plan is amended. Such a regulatory strategy amounts to a duplication of the PIP efforts and to a further leap in the administrative burden, a loss of agility and potential additional delays in the overall clinical development programme. Also, in all circumstances, the agency consider that the applicant should bring forward the evidence supporting the extrapolation concept for any disease and target population, instead of the agency determining beforehand whether such extrapolation is generally endorsed. The burden of evidence gathering is thus transferred to all applicants individually and this is not an efficient process. The agency may wish to suggest an overall strategy of extrapolation concept, extrapolation plan, mitigation plan etc, but should not impose mandatory review and approval at each step of the procedure which is of doubtful/questionable added value while tremendously increasing the delays and administrative costs. The obvious exception is when the extrapolation concepts are included in a PIP (which is to be approved and amended according to existing processes, which are already formal and 174-176 Comment: is important to seek regulatory agreement on an “It extrapolation concept and proposed extrapolation plan before studies are conducted, and again for important
model is applicable would be very helpful in this context. E.g., which aspects need to be considered? Which conditions must be met and what defeats an application of these models? 172-173 Comment: The so-called Extrapolation concept and Extrapolation plan are formal documents that need to be developed prospectively by the applicant and be approved by the Agency to initiation of the programme. It follows that any prospective data-driven modelling activity that is not included in the plan cannot be performed unless the plan is amended. Such a regulatory strategy amounts to a duplication of the PIP efforts and to a further leap in the administrative burden, a loss of agility and potential additional delays in the overall clinical development programme. Also, in all circumstances, the agency consider that the applicant should bring forward the evidence supporting the extrapolation concept for any disease and target population, instead of the agency determining beforehand whether such extrapolation is generally endorsed. The burden of evidence gathering is thus transferred to all applicants individually and this is not an efficient process. The agency may wish to suggest an overall strategy of extrapolation concept, extrapolation plan, mitigation plan etc, but should not impose mandatory review and approval at each step of the procedure which is of doubtful/questionable added value while tremendously increasing the delays and administrative costs. The obvious exception is when the extrapolation concepts are included in a PIP (which is to be approved and amended according to existing processes, which are already formal and 174-176 Comment: “It is important to seek regulatory agreement on an extrapolation concept and proposed extrapolation plan before studies are conducted, and again for important
efpia-comments_extrapolation-rp_final-22jan2018.docx