AUTH/3246/9/19 and AUTH/3247/9/19 - Complainant v Pfizer and Bristol-Myers Squibb

Promotion of Eliquis

  • Received
    27 September 2019
  • Case number
    AUTH/3246/9/19 and AUTH/3247/9/19
  • Applicable Code year
    2019
  • Completed
    13 May 2020
  • Breach Clause(s)
  • Sanctions applied
    Undertaking received
  • Additional sanctions
    Advertisement
  • Appeal
    Appeal by respondents
  • Review
    To be published

Case Summary

A complainant who described himself/herself as a concerned UK health professional, complained about the promotion of Eliquis (apixaban) by Pfizer Limited and Bristol-Myers Squibb Pharmaceuticals Limited. The material at issue appeared on the Pulse website (Pulsetoday.co.uk). Eliquis was indicated, inter alia, for the prevention of stroke and other vascular emergencies in adults such as deep vein thrombosis (DVT) and pulmonary embolism (PE).

The complainant explained that he/she had received a promotional email with the subject heading ‘Clot Busting – DVT/PE management at your fingertips [BMS/Pfizer Alliance funded content]’. There was nothing to indicate what medicine was at issue and there was no prescribing information in the email itself. There was nothing on the linked webpage to prevent those who were not health professionals from seeing it.

The complainant also noted the claim that ‘Eliquis can be used in a broad range of patients with VTE with no dose adjustments regardless of age, weight or renal function*’. The asterisk led to a statement which read ‘Eliquis should be used with caution in patients with severe renal impairment (CrCl 15-29ml/min) for both the treatment of DVT/PE and prevention of recurrent DVT/PE. Eliquis is not recommended in patients with CrCl<15ml/min, or in patients undergoing dialysis’. The complainant stated that thus, there clearly were dose adjustments.

The complainant recalled that a previous Eliquis advertisement failed to mention patients with lower eGFR. The complainant accepted that there was clarification in smaller text but given that most readers would not focus on the detail, the header of ‘no dose adjustments’ would be the main message. There were many contraindications listed in the summary of product characteristics (SPC) which were not mentioned in the ‘broad range of patients’. These were patient safety issues as the information was misleading.

The detailed response from Pfizer and Bristol-Myers Squibb, the Alliance, is given below.

The Panel noted that the email received by the complainant with the subject line ‘Clot Busting – DVT/PE management at your fingertips [BMS/Pfizer Alliance funded content]’ was, according to the Alliance, not the final certified version provided to Pulse. The Panel noted the Alliance’s submission that the email sent by Pulse differed from the final certified form with regard to the subject line and the date of preparation only; the content was the same as the certified version.

The Panel noted that the subject line of the email received by the complainant included the claim ‘Clot busting’ and the email referred to DVT/PE management, anticoagulation treatment and the BMS/Pfizer Alliance which marketed Eliquis, an anticoagulant used for, inter alia, the treatment of DVT/PE. Noting the broad definition of promotion in the Code, the Panel considered that the email was promotional. In that regard, the Panel noted that at the outset of the email, a prominent statement read ‘This email contains promotional content that has been developed and funded by the Bristol-Myers Squibb / Pfizer Alliance ….’. In the Panel’s view, given that readers might not click through to the Pulse website, the email should be capable of standing alone with regard to the requirements of the Code. The Panel ruled a breach in relation to the email and the failure to provide Eliquis prescribing information. Upon appeal, the Appeal Board considered that the email was promotional and in any event was inextricably linked to the promotional webpages. The Appeal Board consequently upheld the Panel’s ruling.

The Panel noted that in the screenshot provided by the complainant the claim ‘Eliquis can be used in a broad range of patients with VTE [venous thromboembolism] with no dose adjustments regardless of age, weight or renal function*’ appeared in the section of the website entitled ‘Eliquis in VTE’ below the emboldened heading in dark blue font ‘No dose adjustments’. The asterisk led the reader to a statement immediately beneath in smaller italic font which read ‘Eliquis should be used with caution in patients with severe renal impairment (CrCl 15-29ml/min) for both the treatment of DVT/PE and prevention of recurrent DVT/PE. Eliquis is not recommended in patients with CrCl<15ml/min, or in patients undergoing dialysis’. The Panel noted that following this was a table which summarised the dosing considerations of the four non-vitamin K antagonist oral anticoagulants (NOACs) by age, weight and renal function.

The Panel noted the layout of the relevant webpages which were, in its, designed to be viewed digitally. The Panel queried how the information would be viewed on different devices and if the text within the table would be legible across different platforms/devices particularly a mobile phone. It appeared to the Panel that the site made use of infinite scrolling which was a web-design technique that loaded content continuously as the user scrolled down the page, eliminating the need for pagination. In the Panel’s view, some readers might have read the claim at issue without scrolling down further to see the footnote or table, or scroll directly past the footnote and table particularly noting that it appeared from the headline and claim that Eliquis could be used in a broad range of patients with VTE and there were no dosage adjustments or concerns with regards to patients with impaired renal function.

The Panel noted that Section 4.2 of the Eliquis SPC stated that for VTEt no dose adjustment was required for body weight, gender or the elderly. The Panel noted that Section 4.2 stated under the heading ‘Renal impairment’ that for the treatment of DVT, treatment of PE and prevention of recurrent DVT and PE (VTEt): in patients with mild or moderate renal impairment no dose adjustment was necessary; in patients with severe renal impairment (creatinine clearance 15-29ml/min) apixaban was to be used with caution; and in patients with creatinine clearance <15 ml/min, or in patients undergoing dialysis, there was no clinical experience therefore apixaban was not recommended.

The Panel noted the Alliance’s submission that as there were no contraindications related to the age and weight of VTE patients, Eliquis could be prescribed in a broad range of patients. The Panel disagreed with the Alliance’s submission that the recommendations for patients with severe renal impairment (creatinine clearance 15-29ml/min) and in patients with creatinine clearance <15 ml/min, or in patients undergoing dialysis did not equate to dose adjustments and therefore the claim at issue was not misleading. The Panel noted that these recommendations were included in Section 4.2 of the SPC which dealt with posology and method of administration and were included in the table referred to above which summarised the dosing considerations of the four NOACs by age, weight and renal function. In the Panel’s view, the recommendations therefore would be considered within the context of dose adjustments and the fact that a medicine should only be used with caution or not at all in patients with VTE and certain levels of renal impairment was relevant and important information; it might mean that no dose at all might be appropriate as opposed to an adjusted dose.

In the Panel’s view, the claim implied that Eliquis could be used in all patients with VTE and without dose adjustment regardless of their renal function which was not so. This implication was compounded by the heading, prominent by virtue of its emboldened blue font. In the Panel’s view, the claim ‘Eliquis can be used in a broad range of patients with VTE with no dose adjustments regardless of age, weight or renal function*’, in conjunction with the heading ‘No dose adjustment’ was misleading. Material had to be capable of standing alone and could not rely on qualification in a footnote etc to ensure Code compliance. Noting its comments above about how the claim might be seen by the reader, in the Panel’s view, it was not sufficient to rely on the footnote below to qualify the strong and unequivocal claim. On balance, a breach was ruled. The Panel noted that the misleading claim in conjunction with the heading was incapable of substantiation and a further breach was ruled. Upon appeal, the Appeal Board did not consider that it was acceptable to rely on the qualifying text/footnote below to qualify the strong and unequivocal claim. The material was not sufficiently clear. The Appeal Board further considered that the misleading claim in conjunction with the heading was incapable of substantiation. The Panel’s rulings were upheld.

In the Panel’s view, the misleading claim did not encourage the rational use of the medicine and it considered that the Alliance had failed to maintain high standards and a breach was ruled. This ruling was upheld on appeal.

The Panel noted the unequivocal nature of the heading and claim and that information critical to patient safety had been relegated to a footnote. In the Panel’s view, it was wholly inappropriate, in the particular circumstances of this case to place such critical information as a footnote to a more prominent claim and heading; some readers might not have seen the footnote or table of dosing considerations and as a result would not have considered subsequent relevant safety information. The Panel considered that patient safety was of the utmost importance and the Alliance’s failures in this regard brought discredit upon, and reduced confidence in, the pharmaceutical industry. A breach of Clause 2 was ruled which was upheld on appeal