Guidance Regarding Duration of Clinical Trials Used as Reference Support in Advertising
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@Agency and @Manufacturer
The PAAB has posted a new guidance on study durations as a results of our global benchmarking initiative and based on industry consultation. Please see the Guidance Regarding Duration of Clinical Trials Used as Reference Support in Advertising and post any questions you have regarding this document, below.
Please note that this guidance will go into effect April 18th. PAAB will not be accepting submissions with updated data prior to this date to ensure all companies have sufficient time to assess the changes.
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@Agency and @Manufacturer
The PAAB has posted a new guidance on study durations as a results of our global benchmarking initiative and based on industry consultation. Please see the Guidance Regarding Duration of Clinical Trials Used as Reference Support in Advertising and post any questions you have regarding this document, below.
Please note that this guidance will go into effect April 18th. PAAB will not be accepting submissions with updated data prior to this date to ensure all companies have sufficient time to assess the changes.
@admin
Hi, we would like to get some clarity on the type of studies that this guidance document encompasses, specifically for:
• Extension study of pivotal trials that have a longer duration of follow-up than the one mentioned in the product monograph. In this case, the duration of use (# of cycles or # of years) of the drug is as per the recommended duration in the product monograph but the median follow-up is longer than the median follow-up mentioned in the product monograph, which include information on the primary and secondary outcomes data.
• Further, the extension study is published in a peer-review journal and was a pre-planned extension or subsequent interim/final analyses of randomized, controlled trials (RCTs).With the appropriate balance and disclosures, would the above study be considered as reference support for advertising messages ?
Thank you in advance for your response.
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@admin
Hi, we would like to get some clarity on the type of studies that this guidance document encompasses, specifically for:
• Extension study of pivotal trials that have a longer duration of follow-up than the one mentioned in the product monograph. In this case, the duration of use (# of cycles or # of years) of the drug is as per the recommended duration in the product monograph but the median follow-up is longer than the median follow-up mentioned in the product monograph, which include information on the primary and secondary outcomes data.
• Further, the extension study is published in a peer-review journal and was a pre-planned extension or subsequent interim/final analyses of randomized, controlled trials (RCTs).With the appropriate balance and disclosures, would the above study be considered as reference support for advertising messages ?
Thank you in advance for your response.
Hey @demerssy
Based on the information provided, the study may be acceptable. However, we will need to review the specifics of the claims and the study prior to final comment. The PAAB offers an opinion review if you would like to obtain a detailed assessment of the study and proposed claims prior to developing APSs based on the study.
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@admin Can PAAB please clarify if it is one or both of these criteria for extension trials that need to be met in order for a reference to be accepted:
Out-of-label studies evaluating a duration of use that is longer than the product’s pivotal trials for the corresponding condition
Published, pre-planned extensions and subsequent interim and final analyses of randomized, controlled trials (RCTs)
Additionally, should it be disclosed in the extension publication that:“These post-hoc analyses evaluated several endpoints related to response, complete response, and clinically relevant response. Of note, in these post-hoc analyses, statistical tests applied to these endpoints were not prespecified in the original study and may be considered hypothesis-generating in nature.”
would the PAAB accept this publication as a reference to support advertising messages?
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@admin Can PAAB please clarify if it is one or both of these criteria for extension trials that need to be met in order for a reference to be accepted:
Out-of-label studies evaluating a duration of use that is longer than the product’s pivotal trials for the corresponding condition
Published, pre-planned extensions and subsequent interim and final analyses of randomized, controlled trials (RCTs)
Additionally, should it be disclosed in the extension publication that:“These post-hoc analyses evaluated several endpoints related to response, complete response, and clinically relevant response. Of note, in these post-hoc analyses, statistical tests applied to these endpoints were not prespecified in the original study and may be considered hypothesis-generating in nature.”
would the PAAB accept this publication as a reference to support advertising messages?
Hello @theadpharm
The answer is “AND” as claims still need to be supported by high-quality evidence (i.e. RCT with pre-defined study endpoints).
Based on the second bullet point “Published, pre-planned extensions and subsequent interim and final analyses of randomized, controlled trials (RCTs)”, this publication would not be considered an acceptable reference to support advertising messages. Section 2 provides additional guidance.
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If a published, pre-planned extension study meets the requirements in the advisory, can the extension study's safety data appear following a presentation of safety data from the product monograph in an APS? Or is content related to the safety profile in an APS still limited to what appears in the product monograph? I was not clear on this aspect after reviewing the guidance that was released this past March.
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If a published, pre-planned extension study meets the requirements in the advisory, can the extension study's safety data appear following a presentation of safety data from the product monograph in an APS? Or is content related to the safety profile in an APS still limited to what appears in the product monograph? I was not clear on this aspect after reviewing the guidance that was released this past March.
Hello @keoca
If all other aspects of the requirements are met, then the safety profile can be presented in a claim neutral manner (e.g. “Demonstrated safety profile” NOT “Excellent safety profile”)
"All other aspects" include:
- It must be considered consistent with the TMA
- No comparisons unless predefined and statistically validated, EVEN if data from the original study is presented comparatively in the PM
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Thank you so much. And safety data from the extension study must be preceded by data from the Product Monograph correct?
@keoca Correct.
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Hi Jennifer - as a follow-up to the March 2022 Q&A above, would data from a preplanned published extension study of a PM pivotal study be acceptable in the following circumstance: The Sponsor's product, drug A, has no restrictions on duration of use, it is used in combination with drug B, which is restricted to 1 year. The PM contains data at the end of year 1. The median follow-up of the extension study was 2 years. There were no amendments to the study design and it aligns with the PM in terms of the dosing, outcomes and patient population assessed. Understanding that the sponsor of drug B would not be able to leverage this data, would the sponsor of drug A be in a position to use the extension?
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Hi Jennifer - as a follow-up to the March 2022 Q&A above, would data from a preplanned published extension study of a PM pivotal study be acceptable in the following circumstance: The Sponsor's product, drug A, has no restrictions on duration of use, it is used in combination with drug B, which is restricted to 1 year. The PM contains data at the end of year 1. The median follow-up of the extension study was 2 years. There were no amendments to the study design and it aligns with the PM in terms of the dosing, outcomes and patient population assessed. Understanding that the sponsor of drug B would not be able to leverage this data, would the sponsor of drug A be in a position to use the extension?
Hi @alee
The full TMA of both Drugs A and B along with original study would be required to assess the extension study. As an example, PAAB would need to assess the TMA of drug B to determine the parameters for the 1 year restriction—Does the 1 year restriction also relate to safety or is it only that the clinical trials were one year in length? Etc. The consideration for acceptability of the extension is dependent on the pertinent information. Given the nature of the required assessment, it would be advisable to consider the PAAB’s written opinion service (refer to the fee schedule on the PAAB website).
