Hi @Danielle Section 1.1.4 Endpoints/ Outcomes of the Guidance on Real-World Evidence states “Endpoints/Outcomes must be “consistent with” (though not necessarily “the same as”) those in the TMA. Regardless of whether the evidentiary basis for the presentation is RWE/RWD or an RCT, endpoints are not generally limited to those explicitly included within the TMA. Though the approach for RWE/RWD mirrors that for RCTs in this respect, the following examples are intended to clarify questions received during the consultation process.” You can review the examples in the linked document. Assessment of “consistent with” is made in the context of the combination of the endpoint, TMA and the therapeutic area. The submitter should provide authoritative support within the submission, to support that the endpoint is consistent or similar to those in the TMA and that it is a recognized endpoint within the therapeutic area.

Hey @mef Thank you for flagging this. We've discussed the matter with the review team to ensure alignment and are updating both internal and external guidance documents for clarity. In most cases, study design footnotes may appear outside the box.

Good Morning @dmauri This is a specific review question. Please submit the guidelines and proposed product claims. This can be done in a full submission or an opinion if you’d like further clarification prior to building out tools.

Good morning, @Username Comparative data remains subject to the guidance for evidentiary basis to support comparative claims. As noted above, consideration may apply when the study can be demonstrated to be the basis for approval of the biosimilar. A study that is NOT part of the basis for approval and completed post approval, should meet the standards for high quality evidence (i.e. pre-defined statistically significance endpoints).

Hey @JDilly11 Hard to provide comments without seeing the updated TMA copy. This question is likely better submitted as an opinion so that we can look at the update and the nature of the claims being made in current or proposed future pieces. As a general guiding principle, the assessment is made by looking at the update in combination with the APS copy to ensure it reflects the same context as the TMA. If there is something that would trigger the inclusion, then it will likely have to be added. Whether both data presentations are required will also depend on the APS copy and the finalized TMA copy.

Hey @mimi77 While we don’t provide reviews of the Forum, in general terms the claim should reflect the nature of the update. From our understanding of the description, this would be authorization in a new population (pediatrics) and not a net new indication. As such, claims should reflect “Now authorized for use in pediatric patients for x” or something similar.

Hey @HollyMed Yes, per the copy "In the scenario described above where guidelines lower in the aforementioned hierarchy are being used over the available US guidelines, evidence must be provided to support that these guidelines are a true reflection of Canadian practice". Note that there may be instances where we ask for more information about US guidelines. This is extremely rare and the rationale is disclosed during the review process. If you find yourself in this rare instance, please reach out to the reviewer for clarification.

@Jennifer_CM Example 3 appears to be about the product monograph web link destination. The original question above is about linking middle level fair balance to highest level fair balance. Linking middle level fair balance to highest requires that it’s within the same tool or directly attached. A print journal ad is not the same medium as a URL link (web based) and therefore would not be acceptable.

Hello @dmauri PAAB will generally consider alternate cut offs from the TMA if it does not appear to be minimizing the risks of the product. The alternate cut-offs should not remove pertinent ADRs/safety information that would otherwise be important to the product and within the therapeutic landscape. The TMA should also not have other safety considerations that would preclude the higher percentage cutoff.

Good Morning @Constance PAAB would need additional information to make the assessment of the claim proposed above. There are many considerations outside of just the source such as, does it suggest equivalence between products on a per unit basis and what is the intent of the per unit comparison. Given these unknowns, it is difficult to provide a definitive answer in a general space. We suggest submitting the copy for review.

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.

Hey @mimi77 This sounds like a file specific question which should be addressed with the review through the eFiles ticket system. If the question is with respect to “attestation letters” in general term, there are many different reasons an attestation letter might be required in a file. The person signing the attestation letter can vary depending on the copy. Most commonly attestation letters are signed by a representative of the manufacturer’s medical or regulatory team. It may be possible for it to be a representative from the global team. There are a number of Q&As which address attestations which may also support your understanding.

Hi @hollymed Please see this PAAB Forum Q&A

Hi @chagali-toney-0 Per the Guidance on Advertising for Drugs with Notice of Compliance with Conditions NOCc “3. For NOC/c product advertising, studies and/or data which are not presented in the Terms of Market Authorization will not be accepted.” Please note that this does not state “verbatim”. However, it should be interpreted to mean that no data from outside of the PM can be presented.

Hello @gmc Hard to say whether this is even acceptable without looking at the study, but as a general question, we can state that this would require highest level fair balance. It is an implied claim of efficacy which would likely require quantification from the study (i.e., presentation of data). If it was stopped due to safety concerns, that would also prompt inclusion of that information and render it subject to highest level fair balance. With respect to “what other data is required for it’s inclusion?”, this is a review specific question. Please submit for an opinion as there are a number of factors that would need to be considered.

Good Morning @jennifer_cm The letter should be from the national body to support that it is widely used by Canadian health professionals. If you would like confirmation prior to building out a piece, the PAAB opinion service can be used to assess the guidelines.

Good morning @jdilly11 Apologies for missing this question earlier. It is possible. There are a number of things to consider, and the following should not be considered an exhaustive list. The mechanism of disease (MoD) must be supported by an authoritative source. There should be no inference that a particular part of the mechanism is a more impactful target than another. There should be no explicit or implicit outcomes of targeting the MoD. There should be complete separation from the drug MOA and nothing that is inconsistent with or contradicts the TMA would be considered. These are high-level guiding principles. All aspects of the Code should be considered when presenting MoD.

@jennifer-thomson Please see PAAB Code section 3.4, and 4.2.2 as well as PAAB resource PAAB Guidance Documents for Market Share Claims in Advertising and Retention and Market Share Claims. The reference to "data" within these resources is to the data itself. An attestation letter alone is insufficient. If a claim of #1 within a province can be supported by high quality data from a recognized source with acceptable methodological practices to reach such a conclusion, we can consider the claim. The piece would be required to have restricted distribution to the province mentioned.

Hello @alee Provision 8 of the Guidance Document for Claims Based on Kaplan Meier Analysis does not apply to retrospective studies. The Guidance on Real-World Evidence/Data is intended for RWE/D and does not apply to (Kaplan-Meier analyses in) randomized, controlled trials. The use of multivariate analyses to identify prognostic factors associated with overall survival pertaining to a drug product may provide insights for future investigation but it also creates implications for subgroups with specific patient/disease characteristics that would not be acceptable in the absence of pre-planned evaluation of these subgroups (s. 1.4 of the Guidance on Real-World Evidence/Data for RWE/D and s. 3.1.1 of the PAAB Code for randomized, controlled trials).