AUTH/1790/1/06 & AUTH/1791/1/06 - Merck Sharp & Dohme and Roche v GlaxoSmithKline

Promotion of Bonviva

  • Received
    25 January 2006
  • Case number
    AUTH/1790/1/06 & AUTH/1791/1/06
  • Applicable Code year
    2003
  • Completed
    10 May 2006
  • Breach Clause(s)
    7.2 and 7.3
  • Sanctions applied
    Undertaking received
  • Additional sanctions
  • Appeal
    Respondent appeal
  • Review
    Published in the August 2006 Review

Case Summary

Merck Sharp & Dohme complained about the promotion of Bonviva (ibandronic acid) by Roche and GlaxoSmithKline.

The material at issue, a pharmacy leavepiece, a mailer and a journal advertisement, inter alia compared patient preference for Bonviva vs alendronate, Merck Sharp & Dohme’s product Fosamax.

Merck Sharp & Dohme noted that in the leavepiece, the question ‘Faced with 52 or 12 tablets a year, what would [your] patients prefer?’ introduced the claims that ‘Patients prefer a monthly to a weekly bisphosphonate’ (stated twice) and ‘In a 6-month clinical study … [of those] patients expressing a preference’ … [71%] (from a graph) ‘preferred a once-monthly to a weekly bisphosphonate’. In the mailer and the advertisement, the question introduced the claim that ‘It’s no surprise that … 71% chose Bonviva once-monthly over alendronate once-weekly’. Merck Sharp & Dohme alleged that these claims referred to a comparison of Bonviva, prescribed one tablet monthly, and Fosamax Once Weekly, prescribed one tablet weekly, which was unfair, inaccurate and misleading.

The comparison implied that both medicines had the same clinical benefits which was not so. Fosamax Once Weekly had been shown to reduce the risk of vertebral and hip fractures in postmenopausal osteoporosis (PMO), whereas no efficacy in hip fractures had been demonstrated for Bonviva.

By omitting to mention this difference the material did not present the attributes of Bonviva objectively based on an uptodate evaluation of all the evidence and was thus incomplete and misleading. This failure to present the medicine objectively and without exaggerating its properties would amount to promotion not encouraging the rational use of a medicine and be in breach of the 2006 Code.

Merck Sharp & Dohme noted that the Bonviva summary of product characteristics (SPC) stated that the product was for ‘Treatment of osteoporosis in postmenopausal women in order to reduce the risk of vertebral fractures. Efficacy on femoral neck fractures has not been established’ whereas the Fosamax Once Weekly SPC stated: ‘Treatment of postmenopausal osteoporosis. ‘Fosamax’ reduces the risk of vertebral and hip fractures’.

Merck Sharp & Dohme understood that the patient preference study, BALTO (Bonviva Alendronate Trial in Osteoporosis, Emkey et al 2005), upon which the 71% claim was based, was performed by physicians (mainly GPs) who were satisfied that their patients would benefit equally from either treatment. Merck Sharp & Dohme questioned the basis of such a conclusion given the differences referred to above. Similarly there was no indication that patients were aware of the comparative efficacy of the two treatments (or of the fairness and accuracy of any information given), even though this would be expected to have a major influence on their choice of preferred treatment. On currently available information, the use of this clinical trial as the basis for promotion was highly questionable, as its results did not provide a platform for a fair, accurate and unambiguous comparison.

In conclusion, these three pieces of promotional material claimed that Bonviva and Fosamax Once Weekly had a comparable clinical profile and as a result of this it was reasonable to compare convenience of dosing in isolation from any other characteristics of the two products. Licensed indications and clinical data, however, showed that the two products did not have a comparable clinical profile, and that such a comparison was therefore unfair, inaccurate and misleading. Additionally, the patient preference study might have been methodologically flawed and so unsuitable for use in promotion.

The Panel noted that Bonviva was indicated for the ‘Treatment of osteoporosis in postmenopausal women in order to reduce the risk of vertebral fractures. Efficacy on femoral neck [hip] fractures has not been established’. The Panel noted, however, that the material at issue went beyond solely promoting Bonviva for its licensed indication and compared it with Fosamax Once Weekly treatment. Fosamax Once Weekly was also indicated for the treatment of PMO but its SPC included the additional statement ‘Fosamax reduces the risk of vertebral and hip fracture’. The Panel noted Roche and GlaxoSmithKline’s submission about recent regulatory guidance and requirements regarding the licensing of medicines for PMO and the subsequent wording of an SPC but considered that most health professionals would not appreciate the arguments involved. What mattered was that information about medicines and their uses should be conveyed clearly in a way that did not mislead either directly or by implication. The Panel considered that by directly comparing the dosage frequency and patient preference of Bonviva and Fosamax Once Weekly most readers would assume, in the absence of a statement to the contrary, that they were otherwise identical. Prescribers might be persuaded to change patients from Fosamax Once Weekly to Bonviva in the belief that the proven benefits of therapy were the same for each. This was not so; the efficacy of Bonviva on hip fractures had not been established whilst Fosamax was specifically licensed to reduce the risk of hip fracture. The Panel considered that to directly compare Bonviva and Fosamax, and not point out this difference, was misleading. Breaches of the Code were ruled.

Upon appeal by Roche and GlaxoSmithKline, the Appeal Board noted that it had previously considered another complaint about the same Bonviva campaign (Cases AUTH/1779/11/05 and AUTH/1780/11/05).

The Appeal Board noted that Bonviva 150mg was indicated for the ‘Treatment of osteoporosis in postmenopausal women in order to reduce the risk of vertebral fractures. Efficacy on femoral neck fractures has not been established’. In Cases AUTH/1779/11/05 and AUTH/1780/11/05, in relation to the complaint about a claim ‘Bonviva once monthly for postmenopausal osteoporosis’, the Appeal Board had considered that the statement ‘Efficacy on femoral neck fractures has not been established’ in the indication section of the SPC provided the evidence base for Bonviva’s indication, which was the treatment of PMO. The Appeal

Board saw no reason to depart from that ruling in its consideration of the cases now before it.

Cases AUTH/1779/11/05 and AUTH/1780/11/05

included a complaint about the claim ‘Faced with 52 or 12 tablets a year, what would patients prefer?’ and the use of the BALTO study to claim greater patient preference for a monthly bisphosphonate compared with a weekly bisphosphonate (71% vs 29% respectively). The Appeal Board had noted that the BALTO study was started before the marketing authorization for Bonviva had been granted and thus before the evidence base for the product was fully assessed. Patients could not have known that, in contrast to alendronate, efficacy on hip fractures would not be established for Bonviva.

In that regard the patients did not have the full facts about Bonviva and thus, in the Appeal Board’s view, would not have been able to express a genuine, well informed preference between it and alendronate. In that regard the Appeal Board had considered that the comparison was unfair and was not based on an up-to-date evaluation of all the evidence and had upheld the Panel’s ruling of breaches of the Code. Roche and GlaxoSmithKline had provided the requisite undertaking and assurance in this regard.

Turning to the cases now for appeal, Cases AUTH/1790/1/06 and AUTH/1791/1/06, the Appeal Board considered that by directly comparing the dosage frequency and patient preference of Bonviva and Fosamax Once Weekly in the items at issue, most readers would assume, in the absence of a statement to the contrary, that they were otherwise identical. Prescribers might be persuaded to change patients from Fosamax Once Weekly to Bonviva in the belief that the evidence base for the indication was the same for each. This was not so; the efficacy of Bonviva on hip fractures had not been

established whilst Fosamax was specifically licensed to reduce the risk of hip fracture. The Appeal Board considered that to directly compare Bonviva and Fosamax in the materials at issue, and not point out this difference, was misleading. The Appeal Board upheld the Panel’s ruling of breaches of the Code.