Summary of key PAAB rulings in agreement with the complainant:
The APS did not make explicit mention of a particular vaccine in a promotional claim. However, PAAB was of the view that the APS is subject to advertising regulations as it appears to promote the sale of the “advertisers” product for the following reasons:

• The APS content is about healthcare products (vaccines to be specific).
• The benefits of adjuvant flu vaccines are emphasized in the APS. The advertiser did not contest the complainant’s allegation that the advertiser is the sole distributor of adjuvant flu vaccines. The APS is therefore implicitly about the advertiser’s vaccines.
• The citation list in the advertisement includes the Fluad product monograph. This constitutes a more direct form of emphasis on Fluad specifically (one of the “advertiser’s” vaccines).
• Content generation and distribution was controlled by the Terms of Market Authorization Holder (i.e. the “advertiser”).

The claim “enhanced” was used in a broad and absolute manner. PAAB 2.3 & 2.6.

A poster abstract was utilized as a reference. Such references do not meet the evidentiary standards outlined in the PAAB code (e.g.: 3.1.1 & 3.1.2).

The advertisement selectively promoted the benefits of adjuvanted flu vaccine without discussing any risk. PAAB 2.1.2 & 2.4.

The APS also did not explicitly specify that adjuvant flu vaccines are only indicated in geriatric and pediatric populations. The omission of this information may promote off-label use of adjuvanted flu vaccine as this APS (which emphasizes the benefits of adjuvanted vaccines) discusses the herd immunity approach of vaccinating all those who interact with the elderly. PAAB 3.1.

In some instances, the level of evidence is not appropriate for the claim made. In other instances, the claims are broader or further reaching than permissible based on the evidence. The ultimate effect is an exaggeration of the benefits of the adjuvant-based vaccine and the drawbacks of other egg-based vaccines that are unadjuvanted. Additionally, the presentation positions addition of an adjuvant as the solution to the outlined egg-based issues. Neither the advertisement nor the “advertisers” response provides adequate support for this notion. The ad also implies comparisons that are not supported by head-to-head evidence presented in the piece. The comparisons therefore fail to meet the evidentiary standards in the PAAB code (s5.7). They also appear to fail to meet the standards outlined in Health Canada Directive “Therapeutic Comparisons”.

Requested Action:
The advertiser was requested to cease distribution of the APS and submit a revised version of the APS for preclearance.

Follow-up:
The advertiser complied with PAAB's request.

Summary of key PAAB rulings in agreement with the complainant:
The complaint mostly related to a conference booth. APS claim that advertiser’s product changes “the natural course” of the indicated condition was deemed to be insufficiently substantiated. Neither the APS nor the complaint correspondences included evidence that the demonstrated clinical outcomes are considered to represent a change in the natural course of the condition. This sort of status could be supported by Canadian Consensus Guidelines (PAAB s3.2).

The APS included a disease information statement about premature death. In a branded piece, issues cannot be raised for which there is no presented data quantifying the extent to which the product addresses the issue. There must therefore be no mention of premature death in the piece (PAAB s3.1 & 3.1.1). This is true regardless of the accuracy of the disease statement in and of itself.

The mechanism statement “ONPATTRO blocks the production of disease-causing proteins” was deemed to be an unsubstantiated absolute claim as it suggests a cessation in production of disease-causing proteins. The product monograph does not use the terminology “blocks”. PAAB s2.6.

The APS included a prominent claim featuring a study’s efficacy outcome for the ONPATTRO arm while the control arm data was presented in a footnote. This sort of separation between the sponsor’s product arm and the control arm is confusing and potentially misleading. In a controlled trial, the efficacy results for the sponsor’s product are only meaningful in the context of the control arm data. A controlled trial seeks to test (and hopefully reject) the hypothesis that there is no statistical difference between both arms for the measure of interest. The artificial nature of the controlled investigation environment does not necessarily provide a real-world expectation for either arm. This is part of the reason why the sponsor product’s data and the control arm data must not be separated into completely different presentations.

The medical booth was immediately next to the commercial booth which is subject to this complaint. Although the PAAB code does not speak to relative positioning between commercial and medical booths, it does speak to the principles of linkage. See section C of THIS LINK.
A key determinant of whether the proximity results in linkage between advertising and non-advertising is the nature of the separation between the two proximal booths. In this case, the complaint included pictured which showed a low partition separating the booths. The contents in the medical booth appeared to be visible from the commercial booth (and vice vera). Additionally, discussions in the medical booth could foreseeably be listened to from within the commercial booth (and vice versa). The resulting linkage between advertising and disease materials would render the disease materials in the medical booth subject to the advertising provisions. In this instance, this results in a contravention of PAAB code section 3.1 as some of the materials in the medical booth exceeded ONPATTRO’s Terms of Market Authorization. The advertiser was invited to take steps to improve separation between the commercial and medical booths in the future in order to avoid these sorts of linkage issues.

Requested Action:
The advertiser was requested to cease use of the APS. The PAAB strongly recommended that Alnylam begins submitting advertisng to PAAB for preclearance.

Follow-up:
The advertiser confirmed that the APS would no longer be used and that future APS would address all points highlighted above. The advertiser also confirmed that medical affair booths and commercial booths would be adequately seperated in the future.

Summary of key PAAB rulings in agreement with the complainant:
Several issues were raised in the initial complaint. All but one did not require a ruling as they had been addressed through inter-company dialogue in stage 1. For the only remaining issue registered in stage 2, the PAAB agreed with the advertiser.

Requested Action:
No action was requested.

Follow-up:
Not applicable.

Summary of key PAAB rulings in agreement with the complainant:

The complainant alleged that the APS presentation containing the claim “Demonstrated 26-28% reduction in the combined endpoints of MI, stroke and vascular deaths with ASPIRIN alone in patients with vascular disease (at doses of 75 to 325 mg daily)” did not also include the corresponding reduction in absolute terms.

The PAAB had approved the APS presentation as it was consistent with the product monograph. The monograph contained the same relative reduction without making reference to the reduction in absolute terms.

Ultimately, the complaint ruling would necessitate the weighing of two competing factors. The ad is potentially misleading while simultaneously being consistent with the product monograph. In recognition of the fact that both the ad and the product monograph may require revision in the interest of Canadian patients, the PAAB consulted Health Canada. The omission of absolute risk values or event rates may confuse the reader as to whether the ad claim is an absolute or relative risk reduction. Additionally, omission of data expressed in absolute terms (e.g. the actual event rates) may mislead by creating an erroneous/exaggerated impression as to the product’s efficacy. The applicable PAAB code sections are 2.1 and 4.2.3.

The PAAB therefore reached out to Health Canada for consultation. Health Canada confirmed the position that all ads must be consistent with the product monograph and, when referring to reduction data in advertising, market authorization holders should do so in absolute terms. Health Canada will take steps to reach out to the advertiser to request a revision to the product monograph. In the meanwhile, based on consultation with Health Canada regarding the interim period, PAAB requested that data expressed in absolute terms (e.g. the actual event rates) be prominently inserted into the APS.

Requested Action:
The advertiser was requested to resubmit a revised version of the APS for approval.

Follow-up:
The advertiser complied with PAAB's request.

Summary of key PAAB rulings in agreement with the complainant:

The code infractions fit into the following key themes:

• Accredited CME videos were placed on a promotional website. This rendered them subject to advertising regulations. This is problematic as CME videos are understandably not created with consideration of the regulations that are pertinent to advertising a particular healthcare product.
• The APS contained claims that are unsubstantiated superlatives in contravention of PAAB code section 5.16.
• The APS contained comparative bioavailability, efficacy, and tolerability claims that were unsubstantiated. Some of these were direct quotes from a reference. As the quote appeared in advertising, they are subject to the standards in the PAAB code. This contravenes several PAAB code sections including 3.1 and 5.7.

Other issues raised in the initial complaint did not require a ruling as the advertised had already agreed to address those issues in stage 1 of the complaint process.

Requested Action:
The advertiser was requested to immediately take down the HCP section of the website and to perform the necessary revisions.

Follow-up:
The advertiser took down the HCP section of the website.

Summary of key PAAB rulings in agreement with the complainant:

The piece featured a treatment algorithm adapted from consensus guidelines. Callouts were associated with this APS presentation in a manner which could cause the reader to incorrectly presume that those callouts originated from the guideline’s algorithm. Additionally, the callouts would not have been accepted in advertising even if they were lifted from the guideline’s algorithm as they implied an efficacy comparison. Consensus guidelines alone do not meet the standard for evidentiary support for efficacy comparisons in drug advertising. Acceptable head-to-head studies are required for such messages in APS per PAAB code section 5.7.

The piece had an insufficient level of risk disclosure. Specifically, it had middle level fair balance while requiring highest level fair balance (due to the presence of efficacy and place in therapy messages). This contravened PAAB code section 2.4.

The guideline position statement for each of the advertiser’s products were both introduced as guideline recommendations in the APS. This has the potential to mislead as the cited guideline labels the statement pertaining to one of those products as a “suggestion”. This particular guideline provides definitions outlining a different intended meaning for “suggest” and “recommend”. This therefore contravened PAAB Code sections 2.1 & 3.2.

Requested Action:
The advertiser was requested cease use of any affected APS and to submit revised versions to PAAB for review.

Follow-up:
The advertiser complied with PAAB's request.

Summary of key PAAB rulings in agreement with the complainant:

The APS was deemed have the potential to mislead because of:

• emphasis on benefits without prominent disclosure of risks (PAAB s 2.4).
• a presentation that inflated the market experience of the advertiser’s currently manufactured product by piggybacking it onto the market experience from the previously compounded product. The potential to mislead was accentuated by structuring the message in a manner attributing therapeutic significance to the experience claim (PAAB s2.1).
• superlative claims in which the implied status was not supported (PAAB s5.16).
• unclear claims (PAAB s2.1).
• hanging comparisons (PAAB s5.6.i).
• Absolute claims which were not substantiated (s2.6).

Various other issues raised in the initial complaint did not require a ruling as the advertiser had already agreed to address those issues in stage 1 of the complaint process.

Requested Action:
The advertiser was requested to cease use of the APS and submit a revised version of the APS for approval.

Follow-up:
The advertiser complied with PAAB's request. The review was ongoing at the time of creation of this ruling summary.

Summary of key PAAB rulings in agreement with the complainant:

The complaint pertained to an email sent to healthcare professionals by employees of the advertiser. Although the email did not explicitly name the advertiser’s product (Inflectra), it was alleged to:

• be advertising which is in the scope of the PAAB Code
• promote Inflectra in manner which is broader to than its indication

The advertiser advertiser’s position was that the email was informational in nature and not promotional. The advertiser argued that the email was not subject to advertising regulations and therefore could not be in violation of the PAAB Code of Advertising Acceptance.

The email outlined a province’s biosimilar initiative which involved switching well-controlled patients from biologics to biosimilars. The email specified that this would include “switching patients from Janssen’s REMICADE infliximab to Pfizer and Merk’s biosimilar infliximab products”. Although only 3 of the 54 email recipients where physicians practicing in the affected province, the news that a Canadian province will be requiring switching well-controlled patients to “Pfizer and Merck’s biosimilar infliximab products” may beneficially impact attitudes that Canadian prescribers have toward these products (even in jurisdictions outside of the affected province). Impacting attitudes toward a sponsor’s products is one of the key purposes of advertising.

PAAB found the email in question to be advertising which is in the scope of the PAAB code. This finding was based on the following combination of factors:

• Content (part I): The email alluded to the advertiser’s product (i.e. “Pfizer and Merck’s biosimilar infliximab products”) even though the product was not specifically mentioned.
• Content (part II): The email presented the manufacturer’s product in a favorable light (i.e. a province has chosen to require well-controlled patients to switch either to it or the other biosimilar).
• Sponsorship: The email was sponsored by the advertiser.
• Influence: The email was controlled / created by the manufacturer.
• Delivery: The email was distributed proactively by the manufacturer.

Importantly, the email did not fit any of the exemption criteria in the PAAB code. Consequently, it should have been reviewed by PAAB. This would be true even if it were largely comprised of content extracted from the province’s announcement. This is analogous to the PAAB code requirement that APS which restate a formulary coverage decision be submitted for preclearance if they exceed a simple message of “now on formulary”.

Although the advertiser maintained that this email was sent to HCPs who had participated on advisory panels, PAAB was not provided any evidence that this information was provided to support ongoing advisory work. Furthermore, the email did not refer to this purpose. It also did not appear that the email itself was the subject of advisory work as there was no request for input on the email content. The email simply informed HCPs about a matter that favoured two products (including the advertiser’s product). It is important to note that the concepts of “informing” and “advertising” are not mutually exclusive. It is equally important to note that the fact that an HCP has previously worked on an advisory panel, and may potentially do so again at some point in the future, should not compel a manufacturer to send unsolicited communications without consideration of the applicable advertising regulations. When content is disseminated because it is relevant to a specific scope of ongoing advisory work, it would appear logical to send that content in the context of that specific activity.

In addition to ruling that the provisions of the PAAB code were applicable to the email, the PAAB also deemed that the email contravened PAAB code sections 2.1, 2.4, 2.10, 3.1, and 7.3. The email was considered to be potentially misleading as it spoke broadly to “rheumatology” and “dermatology” indications without including the actual indications. The indications are narrower than “rheumatology” and “dermatology”. Additionally, the email contained no reference to risks associated with these products.

Requested Action:
The advertiser had already clarified that the email is no longer in use. Therefore, no immediate action was requested. However, the advertiser was informed that similar future emails should be submitted for preclearance.

Follow-up:
Not applicable.

Summary of key PAAB rulings in agreement with the complainant:
The APS contained a side-by-side presentation of the number of pills and the number of product packages in a treatment course for Epclusa versus Maviret. This presentation was found to contravene sections 2.1 and 5.10.2.iii of the PAAB Code by artificially inflating the difference in volume of space taken up by the number of pills and the number of product packages in a treatment course for each of these products. Particularly as:

• The actual relative dimensions of the Epclusa and Maviret tablets were not accurately reflected
• The monthly pill bottle was used for the depiction of Epclusa’s packaging while the inside weekly cartons were used for the depiction of Maviret packaging (as opposed to fewer exterior monthly cartons which would have made for a fairer comparison).
• The Epclusa bottles were recessed while the Maviret boxes were not.

The exaggerated difference in volume of space occupied by the tablets & product packaging was particularly noteworthy in the context of a campaign featuring messages relating to simplicity of some aspects of Epclusa's dosing.

Submitters should note that the PAAB relies on the manufacturer to ensure the technical accuracy of comparative representations of characteristics such as tablet dimensions and packaging. For these and similar non-therapeutic comparisons, the PAAB generally focuses on the appropriateness of presenting the content in the selected context.

Requested Action:
The advertiser was requested to cease use of the APS and resubmit a revised version of the APS for approval.

Follow-up:
The advertiser complied with PAAB's request.