Ask PAAB

Recently we've seen an APS that have been submitted where p-values were requested for safety data, otherwise it would not be admissible as data. The problem is, virtually no clinical trials power their adverse events to generate p-values. When did this become a requirement?

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  PAAB section 5.9 has required statistical analysis to support inclusion of comparative therapeutic data from clinical trials (whether active comparator or inactive comparator) for as long as I can remember. You might be thinking of comprehensive excerpts from the s/e tables of part 1 of the PM (which don’t require stats). PAAB can also consider claim neutral, non-comparative presentations of the incidences of sponsor drug’s side effects from an acceptable clinical trial provided those incidences are roughly aligned with the product monograph AND the product monograph’s most common adverse events (with incidences) are presented as copy specific balance copy.

Can I post a branded online banner on a website such as Canoe santé that already provides information on a prescription drug (i.e. there is information on the drug and the disease it treats).

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  No. I believe that Canoe Sante is non-gated. I therefore assume that the ‘information’ you are referring to exists completely independently from the manufacturer and it’s agents so as to be exempt from the advertising regulations. BUT, linking such content to advertising would render the combined entity subject to the advertising regulations. This would be problematic as this combined entity exceed the name/price/qty provisions that related to DTC Rx advertising. Even if the environment were to be gated, I’d advise against this as the independently generated content may exceed the limitations of the TMA and likely does not contain fair balance. Thus it would likely even contravene the HCP advertising regulations if it were rendered subject to them through paid placement of a banner ad in a gated environment.

Can a pharmaceutical company publish the results of a clinical study that was supported by a scientific grant. Would this have to be identified as advertorial?

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  Clinical trials which are published independently in medical journals do not fall under the PAAB code (even if the trial is supported by a grant). If the manufacturer purchases space within the publication to present findings of the study, that ad space would be reviewed by PAAB as advertising. For example we’d ensure that the study itself is on-label and meets the Code’s evidentiary standards. We’d also ensure that the messaging within the piece is accurate and also that it is balanced with respect to benefit vs risk. I hope I have correctly interpreted your question. If not, call me.

Hello! Would it be possible to know if there is a one year time limit for us to have an HCP education piece approved by PAAB after the launch of a new indication? Thank you!

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  Advertising pieces can be approved by PAAB at any time during their life cycle (provided the product is approved by Health Canada). However, claims of “new” are limited to 1 year after initial marketing per PAAB code s11.

Section 11 of the PAAB code states: Use of the word 'new' or statements implying "new" in advertising should be restricted to 1 year after initial marketing. Can you please clarify what is meant by "initial marketing"? Is this the NOC date or when "marketing" activity is initiated etc.?

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  One year from first distribution of any APS (Advertising/promotion Systems) into the marketplace.

Dear PAAB. The PAAB codes states that superlatives or special status cannot be used unless substantiation can be provided. What is the substantiation you are looking for? Is the monograph a source that would suffice?

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  PAAB code section 5.16 requires that claims of status be supported by authoritative sources. The terms of market authorization (e.g. product monograph) for the product in question would indeed be an acceptable source of support. As a courtesy, an alternative source of support could be authoritative consensus guidelines (provided the claim is consistent with the TMA). Note that the claim should be limited specifically to the meaning of the message in that reference. Also keep in mind that context is important to overall meaning.

Can I pharmaceutical company support the development of an independent third-party publication covering the highlights of a conference in a therapeutic area where it does not yet have an approved product? The report and a summary slide presentation with the same content is developed by an independent faculty of medical experts, who have full control of the content, and coordinated by a third-party communication agency. The content is completely unbiased (less than 10% of the content is about trials on the company's future potential product), and there is no involvement of the company in the distribution of the content. The content is housed on a third-party independent website that is distributed by this third-party and/or to medical associations only. Does the site have to be gated? Does the content have to be PAAB-reviewed or accredited? Thank you in advance for your answer.

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  All answers to your questions hinge on whether the document is subject to the advertising provisions or not. If it is subject to the advertising provisions, yes gating is required and yes the document should be submitted to PAAB for preclearance (assuming this would be intended for HCPs). You should note that discussion of the manufacturer’s unapproved product in drug advertising would not be permitted (per PAAB s3.1 and FDR C.08.002). If it is not subject to the advertising provisions, then gating and PAAB review is not required. The assessment of whether it is subject to the advertising provisions is made by applying the following 7 questions from the Health Canada policy document “The Distinction Between Advertising and Other Activities”:

   

  •       What is the context in which the message is disseminated?

  •       Who are the primary and secondary audiences?

  •       Who delivers the message? (the provider)

  •       Who sponsors the message and how?

  •       What influence does the drug manufacturer have on the message content?

  •       What is the content of the message?

  •       With what frequency is the message delivered?

   

  It is important to consider each question as no single factor can determine whether the advertising provisions apply. This assessment can be done internally through the manufacturer’s own regulatory department. If you would like, PAAB can provide an objective opinion on any particular tool/material based on the aforementioned Health Canada policy document (see the fee schedule on our website www.paab.ca). 

   

  As a side-note, the fact that up to 10% of the document would be on the sponsor’s potential future product is actually somewhat of a red flag.  Amongst other considerations, you might want to consider whether the document includes equal emphasis on all the other potential products from other manufacturers? If a different potential product would have been covered had the sponsor of this third party tool had been a different manufacturer, you are likely dealing with advertising.

What are the requirements for display signs at a conference? The display sign contains pictures of drug products and contains general information about the product. Would fair balance need to be applied to this display? Are we required to include the indications on the display? This sign would only be used at conferences along with brochures which contain the indications and fair balance information.

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  Whether high, middle, or low level of fair balance (FB) is required will depend on the type of product content conveyed (i.e. whether explicit or implicit [e.g. visuals]). Please refer to the PAAB document “Guidance on Base Fair Balance Level and Selection (HCP Advertising)” available on our website for considerations in this assessment. In cases where FB is required, the indication must also be included in the APS (s2.10). An example where FB and indication would not be required is an ad containing drug name only plus dosage form (NOT dosing instructions) which is exempt from PAAB review (s6.6iv). Regarding the comment about using the sign only at conferences along with brochures containing the indication and fair balance, please note the display sign and brochures would be reviewed as distinct APS and each APS must satisfy the PAAB Code requirements for indication and FB.  Similarly, any content related to the booth should also conform to the regulations for product branded advertising.

Can a reprint be distributed by the Sales force where the use is within the approved indication, yet the reprint discusses endpoints that are not discussed within the Approved Product Monograph?

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  Let’s first discuss why the question matters. A sales call is an advertising activity. What you distribute during sales calls should therefore be aligned with the provisions of the Food and Drugs Act (e.g. not off-label).

  Although rep activities do not fall under the PAAB code, advertising/promotional systems (APS) are indeed covered by this code. This means that although a published and peer reviewed clinical trial which has NOT been modified in any way wouldn’t  require preclearance, using the study as a rep detailing tool would render it subject to the provisions in the PAAB code.

  Now, on to the answer to your specific question (which I’ll assume relates only to distribution, NOT detailing/discussing). It is not unusual for references to include an endpoint which is not presented in the TMA. This alone might not render the reference to be overtly off-label. Some important considerations you might find helpful include (not an exhaustive list):

  ·       The nature of the endpoint which does not appear in the PM. For example, say Drug X is an antidepressant. It currently only has an indication for Major Depressive Disorder. An endpoint showcasing the drug’s beneficial effect on an anxiety score would be overtly off-label. This is quite different from a situation where the endpoint in the study (which isn’t in the PM) is the drug’s effect on quality of life (presumably secondary to improvements in depression).

  ·       the number of endpoints which do not appear in the PM and the extent to which these endpoints are discussed or emphasized (hint: more emphasis = bigger deal)

  ·       whether the endpoint was primary or secondary (hint: primary is a bigger deal)

  ·       whether statistical significance was attained (hint: if the product did not show a beneficial effect on the endpoint, the issue might be moot)

  Feel free to make use of our optional opinion service if there is any doubt as to whether the paper is overtly off-label (see the fee schedule on our website). It is advisable to train your reps not to modify the publication in any way.  

  If you’d like to use the reference in a manner which it would not be subject to the advertising provisions (e.g. not linked to advertising activities), then refer to the section “Reference texts, Peer-reviewed Journal Articles” in the Health Canada guidance document “The Distinction Between Advertising and Other Activities”.

Explanatory note 4.4.3 states the following: "Where mandated by the consumer advertising regulations [s6.5.6], the web link destination must either be gated or de-indexed from search engines. If the site is gated, the URL or electronic link promoted in the APS must bypass the gate such that password entry is not required to access these disclosure documents. The URL and electronic link must therefore be promoted only to HCPs." Could you please explain the criteria a website must meet to be considered "de-indexed"?

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  In cases where the website doesn't have a rigorous mechanism preventing members of the general public from consuming advertising content which the regulations only permit for HCPs, then the manufacturer must take steps to ensure that the general public won't arrive onto the site in the first place. Pages on a website are de-indexed so as not to appear as an organic search result. In the absence of a password gating mechanism, to the extent which is within the manufacturer's control, you need to ensure that the only way for someone to arrive to this site is by:

  o   entering the URL which was obtained through a means only accessible to HCPs

  o   clicking a link from an HCP gated environment

  This can be done quite effectively by using a "No Index" command meta tag on EVERY page of the website.

  The general principle is always that the general public should not have access to a site when its content exceed the consumer regulations.