Summary of key PAAB rulings in agreement with the complainant:
The advertisement did not include a reference list. While only one reference was used as the evidentiary basis for the advertisement, and that reference was the product monograph, the reference is nonetheless required to be identified in healthcare professional targeted advertisements for clarity and to enable adherence to PAAB Code section 3.3.

Required Action:
No immediate action was required. However, the ruling indicated that the PAAB will require insertion of the reference citation upon resubmission of the advertisement for preclearance.

Summary of key PAAB rulings in agreement with the complainant:
The complaint pertained to communication materials that were part of a healthcare professional targeted virtual presentation that was organized by the advertiser. The communication materials included an invitation to the virtual event and screen captures of twenty-one of the presentation slides. Based on interpretation of the Health Canada policy document "The Distinction Between Advertising and Other Activities, the PAAB considers the healthcare professional targeted presentation in question to be subject to advertising regulations and, consequently, subject to the standards outlined in the Code of Advertising Acceptance. While the advertiser stated that the slides were generated by a healthcare professional who had full editorial control over the content and that the advertiser had no review privileges over the content, BOTH the event invitation (distributed by the advertiser) and the provided slides were singularly about the sponsor's product. In PAAB's view, the presentation had the net effect of promoting the sale of the product for which the sponsor had a vested interest. While the entire slide deck was not made available to the Commissioner, this did not impair the PAAB's ability to make a ruling. The invitation and stated objectives alone were sufficient to have rendered the entire program to be deemed subject to advertising regulations.

The fact that healthcare professionals (HCPs) must have editorial control over content they present, as HCPs to HCPs, does not absolve the sponsor of responsibility to ensure that such sponsored presentations are not subject to advertising regulations. Manufacturers often deliver on this responsibility, without implementing manufacturer review privileges, through appropriate speaker selection AND by outlining clear expectations with the speaker in the contract (particularly with regards to the need for balance across the therapeutic area). Nothing prevents providing full editorial control to the HCP with the understanding that the content is expected to be created and presented such that it does not directly or indirectly promote the sale of a product. The following litmus test is particularly effective, succinct, and clear:

• a standard HCP should be unable to guess which manufacturer sponsored the activity without consuming the sponsorship disclosure statement.
• competitors should, theoretically, be just as willing to sponsor this activity.

Sharing this litmus test with the HCP is a best practice. It is PAAB's view that a standard HCP consuming the invitation or any segment of the presentation could likely readily identify the sponsor without consuming the sponsorship disclosure statement. Additionally, it is unlikely that competitors would wish to sponsor this presentation. The latter point is further supported by the fact that the presentation triggered this complaint.

After determining that the standards in the PAAB code were applicable to the slides, numerous contraventions of the PAAB code were identified. For examples, the slides attributed clinical significance to the emulsion vehicle without substantiation (PAAB s2.6.2, 3.1.4, and 5.10.2). The presentation also included switching instructions based on a selected individual HCP's practice as opposed to the Product Monograph or authoritative consensus guidelines (PAAB s2.1, 3.1, 3.2). There were additional code infractions, some of which related to inclusion of elements which were rejected during preclearance reviews of unrelated Duobrii APS.

Required Action:
The advertiser was to confirm that the invitation and slides would not be used in the future. Additionally, in the spirit of promoting self-regulation, the Commissioner was to be provided an outline of the steps to be undertaken to avoid recurrence of similar instances in the future.

Summary of key PAAB rulings in agreement with the complainant:
The complaint pertained to a journal ad which was not PAAB approved.

The PAAB agreed with the complainant's allegation that the claim "Helps patients get to sleep and stay asleep longer" was not accompanied by supportive clinical trial data. The magnitude of benefit (along with the corresponding inferential statistics) from an acceptable RCT would be required to support this sort of claim so as to enable HCPs to weigh the benefits against the risks (PAAB s2.1, 4.2, 4.2.1). The claim is also noted to be a hanging comparison as a comparator is not identified (PAAB s5.6.i).

The PAAB also ruled in favour of the complainant with respect to the claim "...was generally well tolerated..." as neither the safety nor tolerability profile was quantified. The claim included the segment "even when used up to 1 year", however, long term tolerability data was not presented. PAAB s2.1, 4.2, 4.2.1).

The PAAB also rules in favour of the complainant with respect to the claim "Next-morning driving and cognitive performance were statistically similar to placebo". The claim is an inaccurate interpretation of the statement in the Action and Clinical Pharmacology section of the product monograph. This presentation also omits key safety disclosures that are required to accompany this claim (e.g., the fact that Dayvigo can impair wakefulness even when used as prescribed and that this impairment can be exacerbated when the drug is taken with less than 7 hours of sleep remaining). PAAB s3.1, 2.4, 3.5.

Nine additional code infractions which were not identified by the complainant were also noted in the complaint ruling. In the interest of protecting Canadians, PAAB notified Health Canada of the advertisement and the complaint ruling. However, PAAB also informed Health Canada that the manufacturer was cooperating with PAAB to address the issues expediently.

Required Action:
To pull the ad immediately. Distribution did not resume until the ad was precleared by PAAB.

Summary of key PAAB rulings in agreement with the complainant:
The complainant alleged that the claims "... a citrate-free formulation for your patient's comfort" and "Citrate-free formulations help to reduce injection-site pain" were misleading. While the advertiser provided sufficient evidence to support that the product was indeed citrate-free, the PAAB considers both claims to be misleading for several reasons identified in the complaint ruling. This summary only includes a subset of the rationales provided in the ruling.

"Reduced" is a hanging comparison as no comparator is explicity identified (PAAB s5.6.i). Presumably, the intended comparator is Humira (the reference product for this biosimilar). However, neither the references cited in the advertisement, nor the references provided in response to the complaint meet the evidentiary threshold to adequately support a claim that Hulio demonstrated a reduction in injection site pain versus Humira (PAAB s3.1 & 3.1.1). Additionally, the magnitude of the difference is not quantified in the APS to enable the healthcare professional to assess the clinical meaningfulness of the difference (PAAB s4.2 & 2.1). The claims also do not read as past-study findings (PAAB s2.3) and study parameters are not disclosed (PAAB s5.11). Even if the notion of reduced injection pain were to be acceptable, the claim of "comfort" extends beyond injection site pain and would require additional data focused on an endpoint whose operational definition somehow captured a rating of patient comfort. As per above, that data would be required to be included in the APS in a manner that reflected past-study findings and included relevant study parameters.

It is also note worthy that Health Canada considered the adverse drug reaction profile of Hulio to be comparable to its reference product (page 24 of 159 of the product monograph). In fact, in specific reference to the results of the studies cited in the advertiser's response (FKB327-001, FKB327-002, FKB327-003), the monograph states that “The types, frequency and severity of adverse events were comparable between the biosimilar and the reference biologic drug” (page 73 of 159). The Hulio product monograph contains several mentions of the risk / incidence of injection site reactions (including, but not limited to, injection site pain). These mentions occur throughout the monograph. In fact, for some indicated conditions, injection site reactions were the most common adverse reaction. Although the adverse reactions content is based on the reference product, this product monograph still acts as the Terms of Market Authorization for Hulio. The Hulio product monograph would lead the reader to conclude that injection site pain is an ongoing concern for this product. Note that we accessed the Product Monograph from Health Canada's Drug Product Database on July 14, 2021 (Control # 229124 with a Nov 24, 2020 date of approval).

Required Action:
To pull the ad immediately.

Summary of key PAAB rulings in agreement with the complainant:
The main issue in the complaint pertained to the claim "...with a unique dual action of antihistamine and antiplatelet activating factor". The complainant provided information demonstrating that the claim was potentially misleading. The claim therefore needed to be revised so as to render the conveyed superlative status substantiated (PAAB s5.15). Contrary to the complainants position, a claim containing the element "unique" was possible with revision. The remaining issues pertained to minor clarity issues and technical errors in data presentation, some of which were not made in the approved version of the copydeck.

Required Action:
Cease distribution of the ad (distribution may have already ceased given the expired approval period). PAAB notified the advertiser that the corrections would need to be made through the preclearance process prior to resumption of distribution/dissemination of the ad.