AUTH/3109/10/18 - Complainant v AstraZeneca

AstraZeneca website

  • Received
    29 October 2018
  • Case number
    AUTH/3109/10/18
  • Applicable Code year
    2016
  • Completed
    05 July 2019
  • Additional sanctions
  • Appeal
    No appeal
  • Review
    Published in the 2020 May Review

Case Summary

A complainant who described him/herself as a concerned UK health professional, complained about a number of companies’ websites including that of AstraZeneca UK.  The pages at issue concerned Forxiga (dapagliflozin), Onglyza (saxagliptin) and

Symbicort (budesonide/formoterol).  Forxiga and

Onglyza were used in certain patients with type 2 diabetes mellitus and Symbicort was used in certain patients with asthma or chronic obstructive pulmonary disease (COPD).

The detailed response from AstraZeneca appears below.

1 Forxiga

The complainant alleged that significant space was given to weight loss and reduction in blood pressure on a Forxiga promotional website, and these were both unlicensed indications. 

The Panel noted that Forxiga was used in certain adults with type 2 diabetes mellitus to improve glycaemic control.  The indication wording in section 4.1 of the SPC referred to, inter alia, Section 5.1 which featured clinical study results which referred to weight and blood pressure reductions.

In that regard, the Panel considered that reference to weight and/or blood pressure reduction was not necessarily unacceptable as part of the promotion of Forxiga, however, context was important.  In the Panel’s view, any references to weight and/or blood pressure reduction must be clearly set within the context of the primary reason to prescribe Forxiga ie to improve glycaemic control. 

The Panel noted that each section of the website where weight or blood pressure reductions with Forixga were referred to, stated in bold font that Forxiga was not indicated for weight loss or the management of high blood pressure. There were also references in these sections to weight change being a secondary endpoint in clinical trials.  It appeared  to the Panel that information with regard to weight and blood pressure was displayed directly after the HbA1c data in the relevant sections, with the exception of the ‘Pooled Data’ section where weight reduction was presented alongside HbA1c data. 

In relation to the website as a whole, given the context within which the information on weight and blood pressure reductions appeared, the Panel did not consider that the information was presented in such a way as to suggest that it was the primary reason to prescribe Forxiga.

On balance, the information on weight and blood pressure reduction for Forxiga in the context of the website in question did not amount to the promotion of unauthorized indications as alleged and the Panel ruled no breaches of the Code.

2            Onglyza

The complainant highlighted a claim and alleged that the difference in HbA1c reduction from baseline between Onglyza and sulphonylurea had been misrepresented.

The Panel noted that Goke et al stated that the mean changes from baseline HbA1c were -0.74% vs. -0.80% with Onglyza vs glipizide [sulphonylurea], respectively.  The Panel considered the layout of the graphic and the immediate impression to a health professional.  The Panel noted that -0.74% was in much larger font relative to the rest of the graphic and it appeared directly below the wording ‘Onglyza vs SU [sulphonylurea]’.  In addition, the information in the text box below compared the number of hypoglycaemic events over two years between Onglyza and an SU.

In the Panel’s view, the immediate impression was that -0.74% was the difference between Onglyza and sulphonylurea in change in HbA1c from baseline, which was not so, and in that regard, it was a misleading comparison of the two medicines.  The reference to the between-group difference, 0.06%, in very small font, was not sufficiently prominent and therefore did not negate the immediate misleading impression.  Breaches of the Code were ruled including that AstraZeneca had failed to maintain high standards.

3            Symbicort

  1. a) Use in COPD

The complainant alleged that exacerbations and symptom control had the relative rates of reduction displayed far more prominently than the absolute rate or indeed the co-primary endpoint that was not significantly different.  The complainant also alleged that by stating that symptom control improved by 83%, AstraZeneca appeared to have intentionally ignored the non-significant endpoint of the study.

With regard to the exacerbation reduction webpage, in the Panel’s view, the mention of the nonstatistically significant co-primary result (FEV1) was disproportionate to the prominent representation of the co-primary result that showed statistical significance (number of severe exacerbations).  The severe exacerbation rates with Symbicort Turbohaler vs formoterol (1.42 vs 1.84 per patient per year) were less prominently displayed than the relative risk reduction claim of 23%. 

In the Panel’s view, if relative risk reduction is stated, the absolute risk reduction should be presented together with the relative risk reduction in such a way as to allow the reader to make an immediate assessment of the clinical impact of an outcome.

In the Panel’s view, the 23% relative risk reduction in severe exacerbations for Symbicort Turbohaler vs formoterol was designed to be the primary take home message.  The webpage highlighted, and placed disproportionate emphasis on, the relative risk reduction for one of the co-primary endpoints that had favoured AstraZeneca’s product, without sufficient balance, and, in that regard, the immediate impression given by the webpage was a misleading comparison of Symbicort Turbohaler vs formoterol.  Breaches of the Code were ruled including that AstraZeneca had failed to maintain high standards.

With regard to the symptom control webpage, the

Panel noted that the primary endpoint of the study, PEF 5 minutes post-morning dose, was stated with a p-value of 0.603 which indicated that the difference observed between the two treatments was not statistically significant. The Panel noted that the main claim on the webpage related to a secondary endpoint, capacity of daily living (CDLM) score.  The Panel considered that it was not unacceptable to present secondary endpoint data, as long as it was presented in the context of the primary endpoint results and with proportionate emphasis. 

The Panel noted that the mean absolute change in CDLM score from baseline for both Symbicort Turbohaler and salmeterol/fluticasone (0.22 and 0.12, respectively) was mentioned on the webpage at issue, as was the difference between treatments of 0.10.  The Panel noted the study authors’ caution that, although statistically significant, the observed mean difference between treatments on this CDLM measure (0.10) was below the minimal important difference of 0.20. 

In the Panel’s view, the 83% relative improvement in total mean CDLM score for Symbicort Turbohaler vs salmeterol/fluticasone was designed to be the primary take home message.  The webpage highlighted, and placed disproportionate emphasis on, the relative improvement of a secondary endpoint which favoured Symbicort Turbohaler, without sufficient balance, and, in that regard, the immediate impression given by the webpage was a misleading comparison of Symbicort Turbohaler vs salmeterol/fluticasone.  Breaches of the Code were ruled including that AstraZeneca had failed to maintain high standards.

  1. b) Use in asthma

The complainant  alleged that the claim of a 39% reduction in exacerbations was not clear about what the absolute levels were; the seven times improvement in symptom control was again much more prominent than the absolute values and it was much harder to see that this was vs baseline and not vs alternate therapy.

With regard to exacerbation reduction, the Panel considered that there was no allegation with regard to the prominence of relative risk in relation to absolute risk.  The Panel noted AstraZeneca’s submission that the absolute figures for the claim in question were stated on the webpage. Based on the very narrow allegation the Panel ruled no breach of the Code.

With regard to symptom control, the Panel considered that it was sufficiently clear that the claim ‘7x more asthma control days vs baseline’ was versus baseline and not versus the comparator arm and ruled no breaches of the Code in that regard.

The Panel noted that the % of asthma control days at baseline and following treatment were stated for both Symbicort SMART and salmeterol/fluticasone + SABA, with a statement that the result was similar between the two groups.  The Panel noted that the claim of 7x more asthma control days was versus baseline and therefore it was not a claim of relative improvement vs a comparator medicine as alleged.  Based on the narrow allegation it considered that the claim at issue was not misleading and ruled no breaches of the Code.