Extension Study switching from blinded IRC assessment to unmasked investigator assessment
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We are exploring the use of an extension study in branded APS that is not included in the sponsor’s TMA. This is an extension of the original study included in the sponsor’s TMA. If the only methodological discrepancy from the initial pivotal trial is that the primary endpoint of PFS in the extended duration analysis was evaluated by unmasked Investigator Assessment, whereas the PFS presented in the original pivotal was determined by blinded, independent, central review (BICR), would the extended duration data be viable in a branded APS?
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We are exploring the use of an extension study in branded APS that is not included in the sponsor’s TMA. This is an extension of the original study included in the sponsor’s TMA. If the only methodological discrepancy from the initial pivotal trial is that the primary endpoint of PFS in the extended duration analysis was evaluated by unmasked Investigator Assessment, whereas the PFS presented in the original pivotal was determined by blinded, independent, central review (BICR), would the extended duration data be viable in a branded APS?
Good morning @dmauri
In order for an extension trial to be considered acceptable, it must meet all the criteria outlined in Guidance Regarding Duration of Clinical Trials Used as Reference Support in Advertising. If there is no comparator, and all the criteria outlined in the guidance are met, the unmasked assessment of PFS may be acceptable for inclusion in APS in a neutral fashion following and separate from the presentation results from the original study.
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Good morning @dmauri
In order for an extension trial to be considered acceptable, it must meet all the criteria outlined in Guidance Regarding Duration of Clinical Trials Used as Reference Support in Advertising. If there is no comparator, and all the criteria outlined in the guidance are met, the unmasked assessment of PFS may be acceptable for inclusion in APS in a neutral fashion following and separate from the presentation results from the original study.
@jennifer-carroll Thank you for your quick reply! We note that the cited guidance does not mention any caveats with regards to the presence or absence of a comparator in the extension study. Based on your response here, it seems that an out-of-label extension study would be acceptable if the comparator arm is dropped (and if the criteria from the guidance are met). Is this understanding correct? If so, why would PAAB be more open to extension studies that do not have comparators?
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@jennifer-carroll Thank you for your quick reply! We note that the cited guidance does not mention any caveats with regards to the presence or absence of a comparator in the extension study. Based on your response here, it seems that an out-of-label extension study would be acceptable if the comparator arm is dropped (and if the criteria from the guidance are met). Is this understanding correct? If so, why would PAAB be more open to extension studies that do not have comparators?
Hey @dmauri
We were providing a general answer to a general question. If the study is comparative with no blinding, there is a higher likelihood that it will not be acceptable. Unfortunately, there is no “one size fits all” answer to this question as studies (both the original RCT and the extension) and TMAs have many variables and they all need to be considered in a determination of acceptability. If you have a specific study in mind, we suggest submitting for an opinion. -
Hey @dmauri
We were providing a general answer to a general question. If the study is comparative with no blinding, there is a higher likelihood that it will not be acceptable. Unfortunately, there is no “one size fits all” answer to this question as studies (both the original RCT and the extension) and TMAs have many variables and they all need to be considered in a determination of acceptability. If you have a specific study in mind, we suggest submitting for an opinion.@jennifer-carroll Thank you for your input, Jennifer! We'll take this all into consideration.
