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AUTH/1951/2/07 and AUTH/1952/2/07 and AUTH/1953/2/07 and AUTH/1954/2/07 and AUTH/1955/2/07 - Pharmacists v AstraZeneca

Case number:AUTH/1951/2/07 and AUTH/1952/2/07 and AUTH/1953/2/07 and AUTH/1954/2/07 and AUTH/1955/2/07
Case ref:Pharmacists v AstraZeneca
Description:Insert on statins in the Pharmaceutical Journal document
Breach:AUTH/1951/2/07 and AUTH/1952/2/07 – Breaches Clauses 2, 7.2, 7.4, 9.1 and 10.1 AUTH/1953/2/07 - Breaches Clauses 2, 4.1, 7.2, 7
Appeal:Respondent appeal
Status:Report Published
Review:Published in the August 2007 Review
Received:05/02/2007
Completed:03/07/2007
Case Summary:
Five letters published in The Pharmaceutical Journal on 3 February criticised a twelve page supplement entitled ‘The new NICE [National Institute for Health and Clinical Excellence] guidance on the use of statins in practice - Considerations for implementation’ which had been distributed with the journal two weeks previously. The supplement, financially supported by AstraZeneca, had been written by a general practitioner and a pharmacist and it detailed the NICE guidance on the use of statins and charted the evolving guidance on statin use from 2000 until 2005. Optimization of statin treatment strategies was discussed as was the cost of implementing the NICE guidance across a primary care trust population. A cost effectiveness model was presented wherein either atorvastatin or rosuvastatin (AstraZeneca’s product Crestor) was used when patients had failed to reach cholesterol targets on simvastatin (the medicine with the lowest acquisition cost). Finally the role of the pharmacist in helping to tackle cardiovascular disease was discussed.
In accordance with established procedure, the letters were taken up by the Director as complaints under the Code.
In Case AUTH/1951/2/07 the complainant stated that she found the inclusion of the AstraZeneca document masquerading as NICE guidance within The Pharmaceutical Journal profoundly depressing. When pharmacists and others were striving to improve the cost-effectiveness and evidence base of statin prescribing here was the pharmacists’ own professional journal distributing a document which advocated JBS (Joint British Societies: British Cardiac Society; British Hypertension Society; Diabetes UK; HEART UK; Primary Care Cardiovascular Society; the Stroke Association) targets which were not national policy and were usually unachievable for the average patient, and the use of a statin [Crestor] for which there was no evidence to demonstrate that it saved lives or reduced cardiovascular events, and which was not even licensed as such.
The NHS statin of first choice for most patients was simvastatin based on a wealth of evidence, as detailed in the NICE guidance, and the targets to reach were those of the National Service Framework for coronary heart disease, affirmed by the cardiovascular disease ‘tsar’ in December 2006.
In Case AUTH/1952/2/07 the complainant stated that rather than being a useful publication covering the evidence base for the use of statins and practical issues on cost-effective implementation of national guidance, the supplement appeared to be a promotional brochure for Crestor.
The brochure appeared to support the JBS-2 lipid targets of 4 and 2mmol/L although these were not evidence based as recognised by the JBS itself in the statement ‘There are no clinical trials which have evaluated the relative and absolute benefits of cholesterol lowering to different total and LDLcholesterol targets in relation to clinical events’ (JBS 2005).
The complainant stated that the Heart Protection Study had provided strong evidence that treating high-risk individuals with simvastatin 40mg/day for five years significantly reduced their chance of having a serious vascular event, irrespective of their lipid level (MRC/BHF Heart Protection Study 2002). The complainant noted that Crestor did not have this sort of patient-oriented evidence to support its use.
The complainant noted that the NICE guidance referred to in the supplement deemed it cost effective to extend access to statins on the NHS. Its costeffectiveness analysis assumed that half of the prescriptions for statins would be simvastatin 20mg/day and half simvastatin 40mg/day. Arguably, more expensive statins would not be cost-effective and would waste scarce resources.
The complainant submitted that a policy of simvastatin 40mg/day for all those at high risk, irrespective of lipid level, was simple to implement, evidence based and cost effective.
The complainant stated that the bottom line was find the high risk patients, offer them simvastatin 40mg/ day, strongly encourage them to take it, and do not worry too much about non-evidence based targets.
In Case AUTH/1953/2/07 the complainant stated that two points were of particular concern. The first was that the supplement, although purporting to be a summary of the NICE guidance, was in fact a marketing case for Crestor and argued heavily for lipid goals of 4 and 2mmol/L. Yet nowhere in the supplement was it stated that confirmed national health policy was for targets of 5 and 3mmol/L. The second was that AstraZeneca’s own health economic data showed that if lipid goals of 4 and 2mmol/L were aimed for, nearly 40% of patients would require Crestor 40mg/day, a dose which, due to safety concerns, was restricted to specialist use only (Medicines and Healthcare products Regulatory Agency (MHRA) 2004).
The complainant queried if the requirements for specialist care had been factored into the economic analysis, never mind whether patients would actually want to use this therapy option if presented with the balanced data.
The complainant was concerned that distribution of the supplement via The Pharmaceutical Journal, might have lent it an air of credibility it did not deserve.
This complainant subsequently wrote separately to the Authority and noted that despite the title of the supplement ‘The new NICE guidance on the use of statins in practice’ the NICE technology appraisal it related to barely featured. Instead the supplement presented a health economic argument for using rosuvastatin (Crestor) in preference to atorvastatin (Lipitor) as it would be more cost effective. The case for lipid goals of 4 and 2mmol/L (as opposed to 5 and 3mmol/L) was heavily featured despite this not being discussed at all in the NICE appraisal. No mention was made that confirmed national health policy was for targets of 5 and 3mmol/L, which had been made absolutely clear by the Department of Health just weeks previously.
The complainant stated that in his view the supplement was essentially an advertisement for rosuvastatin, yet it did not contain appropriate prescribing information. Further despite the fact that the health economic case being strongly argued would end up with nearly 40% of the eligible population (or approximately 5% of the entire population) being treated with the 40mg dose, no mention was made of the MHRA warnings about this dose. Indeed, the supplement stated ‘… whether all currently marketed statins have a very similar low risk of serious adverse events. Based on the data thus far available, the answer is yes’. The complainant found this hard to reconcile with the MHRA advice and was concerned about the implications it could have for safe prescribing practice.
In Case AUTH/1954/2/07 the complainant was, inter alia, disappointed to see that the supplement was included with The Pharmaceutical Journal. Whilst industry supported documents were distributed with journals which relied heavily on advertising revenue, they were promotional and should be declared as such.
This complainant subsequently wrote separately to the Authority. The complainant stated that in his view the supplement was promotional and breached the Code in at least two areas:
• It took the form of a discussion paper but made claims for the superior cost-effectiveness of rosuvastatin/simvastatin combinations compared to atrovastatin/simvastatin combinations. The evidence to support the claim was referenced as ‘Data on File’. The insert was clearly promotional material but was not declared as such.
 • Prescribing information on rosuvastatin was absent.
In Case AUTH/1955/2/07 the complainant considered that the supplement was disguised promotion for Crestor, but no prescribing information was included.
The Panel noted that it was acceptable for companies to sponsor material. It had previously been decided, in relation to material aimed at health professionals, that the content would be subject to the Code if it was promotional in nature or if the company had used the material for a promotional purpose. Even if neither of these applied, the company would be liable if it had been able to influence the content of the material in a manner favourable to its own interests. It was possible for a company to sponsor material which mentioned its own products and not be liable under the Code for its contents, but only if it had been a strictly arm’s length arrangement with no input by the company and no use by the company of the material for promotional purposes.
The supplement in question, sponsored/financially supported by AstraZeneca, had been initiated by the company and its communications agency had contacted the two authors. AstraZeneca was aware of the outline of the supplement and had, on request of one of the authors, provided cost-effectiveness tables for rosuvastatin vs simvastatin as well as data on file. The supplement was reviewed by AstraZeneca to ensure that it was factually correct. The two authors had full editorial control.
The Panel considered that AstraZeneca was inextricably linked to the production of the supplement. There was no arm’s length arrangement between the provision of the sponsorship and the generation of the supplement. Given the company’s involvement and content, the Panel considered that the supplement was, in effect, promotional material for Crestor. The supplement should have included Crestor prescribing information. Given that allegations were made in that regard in Cases AUTH/1953/2/07 to AUTH/1955/2/07, breaches of the Code were ruled in those cases. The Panel considered that the supplement was disguised promotion; it appeared to be independently written which was not so, the authors had, in effect, been chosen by AstraZeneca. The statement on the front cover ‘Supported by AstraZeneca’ added to the impression of independence. A breach of the Code was ruled in all five cases. The Code required that material relating to medicines and their uses, whether promotional in nature or not, which is sponsored by a pharmaceutical company must clearly indicate that it has been sponsored by that company. The Panel concluded that although the phrase ‘supported by AstraZeneca’ did not give details about the company’s role, AstraZeneca’s support was clearly stated on the front cover of the supplement. No breach of the Code was ruled in all five cases.
 The Panel considered that although the supplement was about the NICE guidance on the use of statins for the prevention of cardiovascular events, the document did not masquerade as NICE guidance as alleged in Case AUTH/1951/3/06. It was clear from the title on the front cover that the supplement discussed the implementation of the guidance. The Panel considered that the supplement was not misleading in that regard and no breach of the Code was ruled. In its consideration of Cases AUTH/1951/2/07 and AUTH/1952/2/07 the Panel noted that the NICE guidance on statins recognised the body of evidence for reduction in cardiovascular morbidity and overall mortality associated with statin use across a broad spectrum of the population. It did not give targets for cholesterol levels, stating this was outside its remit. With respect to the choice of statin NICE recommended that therapy should usually be initiated with a medicine with a low acquisition cost (taking into account required daily dose and product price per dose). For many patients, the least expensive statin would be simvastatin. The supplement recognised this but put forward arguments for the use of rosuvastatin which was more expensive. By implication, therefore, the supplement advocated the use of rosuvastatin to reduce cardiovascular morbidity. Crestor, however, was not so licensed. Whereas simvastatin (Merck Sharp & Dohme’s product, Zocor) was licensed for reduction of cardiovascular mortality and morbidity in certain patients, Crestor was only licensed for primary hypercholesterolaemia or homozygous familial hypercholesterolaemia. There would of course be benefits in lowering cholesterol but there was a difference between promoting a product for a licensed indication and promoting the benefits of treating a condition. The differences between the licensed indications was not made clear. Thus the Panel considered that by implication the supplement was misleading as to the licensed indication of Crestor. A breach of the Code was ruled in Cases AUTH/1951/2/07 and AUTH/1952/2/07.
The Panel noted in Case AUTH/1951/2/07 that it was stated on the supplement that the date of preparation was December 2006. In November 2006, the national director for heart disease and stroke had issued guidance confirming the current national policy on statin prescribing. This stated that national policy currently accepted 5mmol/L for total cholesterol and 3mmol/L for LDL cholesterol as targets for therapy as per the NSF for CHD and that the JBS-2 guidance was not national policy. This guidance had not been included in the supplement. The Panel noted AstraZeneca’s submission that the supplement had been developed before the guidance was written. Nonetheless, the date of preparation of the supplement was a month after the November guidance was issued and the supplement was not distributed until 20 January 2007. Given the time frame involved the Panel considered that it was misleading to distribute the supplement which did not refer to important national guidance and was thus not up-to-date. A breach of the Code was ruled in Case AUTH/1951/2/07. A breach of the Code was similarly ruled in Case AUTH/1953/2/07. With regard to the allegation in Cases
The Appeal Board further noted that the costeffectiveness data presented in Tables 3 and 4 only accounted for the acquisition costs of the medicine. This was not entirely clear from the headings, ‘Budget impact’ and ‘Treatment Strategy’ and associated text which referred to ‘cost-effectiveness’, ‘financial implications’ and the need to look at other ‘costs’ associated with treatment, which implied more than simply acquisition costs. There was no account taken of the cost of specialist supervision and routine patient follow-up associated with the use of rosuvastatin 40mg which would have an impact on budget. The Appeal Board considered that the data was thus misleading. The Appeal Board upheld the Panel’s ruling of a breach of the Code in this regard in Case AUTH/1953/2/07.
 
 
The Appeal Board further noted that the costeffectiveness data presented in Tables 3 and 4 only accounted for the acquisition costs of the medicine. This was not entirely clear from the headings, ‘Budget impact’ and ‘Treatment Strategy’ and associated text which referred to ‘cost-effectiveness’, ‘financial implications’ and the need to look at other ‘costs’ associated with treatment, which implied more than simply acquisition costs. There was no account taken of the cost of specialist supervision and routine patient follow-up associated with the use of rosuvastatin 40mg which would have an impact on budget. The Appeal Board considered that the data was thus misleading. The Appeal Board upheld the Panel’s ruling of a breach of the Code in this regard in Case AUTH/1953/2/07.