Dechra Veterinary Products found in breach of NOAH Code on promotion
At its meeting on 10 June 2011, the NOAH Code of Practice Committee, chaired by Mr Guy Tritton, heard one case.
Dechra Veterinary Products were found to be in breach of three items under complaint. This related to an advertisement and detailer promoting Felimazole® with the wording “Are you taking a heavy-handed approach to hyperthyroidism?” and “with Felimazole, you don’t have to!”. The Committee took the view that by implication this referred to Vidalta because Vidalta is the only other licensed oral treatment on the market for hyperthyroidism. Accordingly, the Committee found both promotions in breach of Clause 4.3 by their implication that Vidalta is less safe than Felimazole. The Committee did not consider the promotions disparaged the manufacturer as there is no evidence to show it is unsafe. The Committee also found that the table in the detailer (page 4) suggesting that one dosage of 5 mg per day of Felimazole has the same efficacy as two doses of 2.5 mg, (which is contrary to the dosing statement within the SPC: “If, for reasons of compliance, once daily dosing with a 5 mg tablet is preferable, then this is acceptable although reduced efficacy can be expected compared to a twice daily regime.”) was misleading, contrary to Clause 4.3 of the Code.
NOAH encourages those interested in finding out more to read the full details of the Committee’s rulings on the NOAH website at www.noah.co.uk/code. The full report of this particular case will be available shortly.
19 September 2011
Notes for Editors
The National Office of Animal Health represents the UK animal medicines industry. Its aim is to promote the benefits of safe, effective, quality medicines for the health and welfare of all animals.
Since 1974 the animal medicine industry has regulated the contents and quality of advertisements, leaflets and promotional activities under its Code of Practice for the Promotion of Animal Medicines which is obligatory for all NOAH members and companies participating in the NOAH Datasheet Compendium. The Code is administered by a committee of 15, including an independent chairman, veterinary and farming members as well as elected industry experts. This release summarises the Code of Practice Committee meeting on 10 June 2011.
10 . Case Number 281/05/11: complaint by Intervet /Schering-Plough Animal Health against Dechra Veterinary Products Limited regarding promotion of Felimazole®.
This case originally involved four items of complaint brought to the Committee’s attention by Intervet /Schering-Plough Animal Health involving promotion of Felimazole® by Dechra Veterinary Products Ltd in the 11 April 2011 edition of the Vet Times and also in their Felimazole detail aid/brochure. However one of the items was withdrawn by agreement of the parties prior to the meeting.
The original four items to which complaint was made are as follows: –
Item 1: As being that referred to in both paragraphs numbered (1), in connection with both the advertisement and the detailer, as being essentially the same, that is to say the words: “Are you taking a heavy-handed approach to hyperthyroidism?” combined with both the image of the hammer etc. and the supporting text “Felimazole offers you the smallest starting dose and dose adjustments of any licensed treatment for feline hyperthyroidism” together with the alleged vagueness of the brochure as a whole.
Item 2: As being the words from the advertisement: “Felimazole offers you the smallest starting dose and dose adjustments of any licensed treatment for feline hyperthyroidism’ comprising paragraph 2 of the complaint, but this has been withdrawn.
Item 3: Identified as being the words : “FELIMAZOLE, YOU DON’T HAVE TO!” combined with the words “ARE YOU TAKING A HEAVY-HANDED APPROACH TO HYPERTHYROIDISM?”, as contained in page 6 of the brochure and comprising paragraph two of the detailer.
Item 4: Identified as being the Felimazole dosing table on page 4 of the detailer comprising paragraph numbered 5 of the complaint.
The Chairman introduced to the meeting the various considerations behind the complaint sent by the Complainant and the response as supplied by the Respondent.
He drew attention to the two clauses of the Code whereby the Complainant maintained items one and three were in breach, that is to say clause 4.3, misleading, and clause 6.1, disparaging the Complainant’s product: Vidalta ™.
4.3 Information must be accurate, balanced and must not mislead, either directly or by implication, so that critical unbiased judgements and decisions can be made.
6.1 The products or services of other companies must not be disparaged either directly or by implication.
In relation to item 2, which had been withdrawn, the Chairman drew attention to the fact that the terms of agreement would make the promotion not make sense or would at least be ungrammatical, in that in the advertisement changing the word “smallest” in the phrase “Felimazole offers you the smallest starting dose and dose adjustments of any licensed treatment for feline hyperthyroidism” to “small” would not work.
In relation to item 3 the Chairman asked the Secretary to clarify the reasoning behind his determination as to the difference between this item and item one.
The Secretary explained that the basis whereby items were determined depended on the actual words used.
Thus in the case of item 1 the words to which complaint was being made were “are you taking a heavy-handed approach to hyperthyroidism?” as supported by other text and images. In the case of item three, the words to which complaint was being made were: “With Felimazole, you don’t have to!”, again, as supported by text; in particular the words: “are you taking a heavy-handed approach to hyperthyroidism?”.
As regards item four the Chairman referred to the table to which complaint was being made to which it was said that it was misleading (clause 4.3) and was inconsistent with the SPC of the product (clause 4.7).
4.7 Promotion must not be inconsistent with the SPC, except that a veterinary surgeon or other appropriately qualified person employed or engaged by a participating company may in appropriate circumstances give information about off-SPC use in response to a technical enquiry from another veterinary surgeon.
The Chairman asked the members, in particular the independent veterinary surgeon, to explain the meaning and the reasoning behind the complaint and its response, being referable to the difference between a daily dose of one 5 mg tablet compared with a twice daily dose of 2.5 mg.
The independent veterinary surgeon explained firstly that it was clearly stated in the product’s SPC, that the efficacy of 2×2.5 mg tablets daily was greater than 1×5 mg tablet daily.
He went on to explain that there were potentially compliance problems with asking pet owners to administer tablets orally to cats, which could be difficult. There was, therefore, a marketing advantage to have a single dose per day regime or try to imply that a daily dosage of a single 5 mg tablet application was as acceptable as twice daily 2.5 mg tablet application, when in fact this was not the case according to the SPC.
Other members drew attention to the asterisk which was on the previous page before the table, against the statement “2.5 mg twice a day” and its reference to the note on the last page of the detailer, which stated “for optimal efficacy, the starting dose for Felimazole should be 2.5 mg twice daily”, and suggested that the asterisk should have been against the 5 mg once a day entry, and moreover it should have been also put against the 5 mg reference on the table and that it would have been quite easy to have done so. Members pointed out, of course, that it was in the interest of the marketing thrust to avoid indicating any greater benefit which came from administering two tablets as opposed to one.
Reverting to discussing items one and three, which it was felt involved the same issues, it was explained by more than one member that it was correct that there was only one competitor licensed orally administered drug to treat hyperthyroidism in cats, and that was Vidalta, the Complainant’s product; that the latest science relied upon by the Respondent that starting with lower dosage was now perceived as being preferable was correct, but that the two drugs worked differently, in not having the same active ingredient. Vidalta’s active ingredient, carbimazole, works in vivo by being converted, in the body, to methimazole. The active ingredient in the Respondent’s product: thiamazole is effectively the same ingredient as methimazole. Accordingly Felimazole works directly once administered; Vidalta works indirectly, being converted first. Also it is produced in a manner whereby it is released over a period of time. The net effect of these features is that the dosage efficacy between the two are different: the Chairman drew attention to the article supplied by the Respondent with its formal response: “Canine and Feline Endocrinology and Reproduction (Feldman and Nelson) at page 201 where it states “a 5 mg dose of carbimazole is approximately equal to 3 mg of methimazole”. Likewise in the paper “Pharmacologic Management of Feline Hyperthyroidism” (Trepanier) it was stated at page 784 “a 5 mg dose of carbimazole yields approximately 50% lower methimazole in the plasma concentrations than does a 5 mg dose of methimazole. A number of members opined the view that, broadly speaking, a 5 mg dose of Felimazole (thiamazole) equates to 10 mg of Vidalta (carbimazole). They also stated that the 10 mg dose of Vidalta would be likely to be absorbed over a longer period of time than its equivalent 5 mg dose of Felimazole, which it could be assumed was the explanation for the contra indication in that product’s SPC, referred to above, which indicated that the greatest efficacy would come from a daily dose of two 2.5 mg tablets, rather than one 5 mg tablet.
There was also discussion on the side-effects that could arise from the treatment by these drugs. The independent veterinarian said that in his experience vomiting was the most usual side effect, but unmasking of renal disease was an important consideration, well known by most small animal practitioners.
In response to the Chairman’s enquiry, it was confirmed by members that in general the oral administration of the two licensed products in question would be the preferred initial treatment to either surgery or radioactive iodine.
A member emphasised the importance of meeting “peaks” and “troughs” in treatment; arguably the controlled release of Vidalta was helpful in that regard, and it also emphasised one of the reasons for ideal efficacy arising through a daily dose 2 x 2.5 tablets, rather than a single 5 mg tablet of Felimazole.
The Chairman suggested that item 3 in its particular wording, specifically indicating that using Felimazole avoided a heavy handed approach, made it very clear that the promotion was directed against Vidalta, in a way which was arguably misleading. However, he counselled caution in suggesting that the promotion actually disparaged the competitor product.
A member suggested the key to understanding the purpose behind the promotion lay in considering starting doses. There was a sub-text innuendo.
Another member asked why the parties agreed on a change to “small” in the withdrawn item 2 where relating to the advertisement, when the obviously preferable alternative word was “lower”, as used in the detailer.
Another member suggested that the introduction to the market of the 2.5 mg Felimazole tablet is quite recent.
At this point the Chairman decided to ask the parties’ representatives to join the meeting
The Chairman then invited the Complainant’s representatives to make their presentation.
In summary the Complainant argued that the promotion involved a negative title and negative imagery, focusing on alleged negative safety aspects of the only other oral licensed treatment: Vidalta. Data was shown suggesting that the Complainant’s product Vidalta had increased market share over the years 2007 to date, at the expense of Felimazole, so that it was now the market leader, and it was suggested that this lay behind the marketing thrust of the promotion.
The use of the phrase “heavy-handed approach, combined with the picture of a hammer crushing a nut, could only be interpreted as suggesting using Vidalta was a heavy-handed approach.
The reference in the detailer to the words of Professor Gunn-Moore, raised issues of safety, suggesting serious harm may be caused by that heavy-handed approach. Again the Complainant’s view was that this could only be taken to relate to using Vidalta. In relation to item three, stating that with Felimazole, you don’t have to use a heavy-handed approach, the promotion inevitably implied that if the reader used Vidalta, it would be heavy-handed.
In commenting on the formal response of the Respondent, it was suggested that it did not seek to dispute that the promotion was directed against use of Vidalta, which as a result was disparaging that product; even if there was technical or medical support for the propositions relied upon, its form of presentation was inaccurate and as a result disparaging. The representatives drew attention to the Guidance Note no 2, relating to “safety”, which stated that attacking the safety of another licensed product, which given the existence of the licence must be deemed safe, would inevitably be a disparagement of that product, and that therefore items one and three were both misleading contrary to clause 4.3, but also disparaging, contrary to clause 6.1 (even if the Respondent did not intend to disparage the Complainant’s product).
Moving on to item four, the Complainant’s representatives suggested that the chart or table selectively omitted important SPC prescribing information on the difference between selecting 2.5 mg twice daily as opposed to 5 mg once daily, which should only be used where compliance is a problem, otherwise reduced efficacy will result.
Commenting on the Respondent’s response, it was suggested that this implied that the qualification of the “starting dose” section on the preceding page related to this table. However the table is in the “long-term medical management” section, and includes a dose which is not licensed for starting treatment. Accordingly the qualification referring to optimal efficacy for the starting dose for Felimazole being 2.5 mg twice daily does not in fact refer to long-term use. The Felimazole SPC indicates reduced efficacy will result from once daily use of 5 mg, regardless whether this is a starting or maintenance dose.
In summary in relation to item four, the Respondent’s case was that the table omitted clinically important and commercially disadvantageous SPC information; its omission could be detrimental to the clinical treatment of hypothyroid cats and was therefore misleading (clause 4.3) and inconsistent with the SPC (clause 4.7).
During the course of the presentation the Chairman raised queries regarding to the withdrawn item 2, pointing out that the agreed alterations would not make grammatical sense to the current promotion in changing “small” for “smallest”. The response was that whilst the principle had now been agreed, obviously the actual wording of the promotion would have to be altered to make sense, within the terms of the agreed principle.
Again in response to queries the Respondent’s representatives confirmed their view that adopting treatment by surgery would be likely to be the last resort, and treatment by oral medication would generally be preferred. Inevitably that therefore meant that the adverse concerns expressed in the promotion in the view of the Representatives could only be said to apply to Vidalta.
The Chairman also drew attention to their presentation slide, which referred to questions coming back from vets, and queries as to the safety of using Vidalta. The Representatives were unable to provide supporting evidence for these statements but confirmed nevertheless that they had been received.
The Chairman raised concerns in the supporting material of the Respondent’s response governing the ratio between the two treatments and the extent to which it could be said that 10 mg of Vidalta would equate to 5 mg of Felimazole, which the Representatives confirmed was broadly an acceptable comparison. They would constitute very similar doses of pharmacologically active compound.
Another member raised the issue of the absorption of Felimazole and the sustained release feature of Vidalta. The Representatives agreed that the breaking down and conversion of Vidalta would operate over a longer time than would be the case with Felimazole. They also emphasised the distinction between a starting dose and incremental doses. There was very little difference in relation to incremental doses. The representatives confirmed in response to the Chairman’s comment that the fact that there are lower dosages available with Felimazole does not mean usage of 10 mg Vidalta tablets is unsafe. It was this aspect of the promotion which the Complainant felt was particularly disparaging. A discussion ensued about the relative benefits of the two products and in particular the manner in which there could be a residual retention of benefit in one product as against the other.
The Complainant’s representatives confirmed that the price of each product was similar.
The Respondent’s representatives were then invited to give their presentation.
They emphasised the importance of the evolution of treatment of feline hyperthyroidism and the importance of a low starting dose; the importance of small dose adjustments; and the need to manage the risks associated with renal disease and with hypothyroidism following treatment. It was suggested that historically there had been a heavy-handed approach with lower disease awareness and knowledge and unsophisticated treatment and monitoring, whereas recent developments in medical knowledge emphasised that with better knowledge of the disease a more measured approach with regular monitoring and optimum patient care was what was necessary. A table showing the development since 1988 of the medical approach to this disease was supplied. Reference was made to the various articles which had been supplied with the formal response and which the Committee had already discussed, (see above).
Having regard to that background the representatives of the Respondent then looked at the promotion firstly in the context of items one and three and thereafter item 4. In so far as items one and three were concerned it was stated that the objectives of the phrase “are you taking a heavy-handed approach to hyperthyroidism?” was to obtain and reflect current and developing key opinion leaders’ thinking in relation to treating feline hyperthyroidism. It was to promote the findings of the latest studies relating to feline hyperthyroidism. It was to translate the new information into best practice recommendations and point out the risks associated with non-adherence. It was designed to have the fullest impact and challenge vets’ current approach to all the treatments they currently employ and persuade them to adopt the emerging best practice recommendations and to promote Felimazole’s product features, namely a low starting dose, small dose adjustments and flexibility of dosing, in addressing the best practice recommendations.
It was stated that the promotional words to which complaint had been made had been comprehensively researched; accurately represented the attitudes of key opinion leaders; was based on sound documented scientific evidence; had a high level of resonance with vets, and was not misleading, exaggerated or disparaging to Vidalta and therefore was not in breach of clauses 4.3 in 6.1 of the Code of Practice.
In relation to the withdrawn item two, the representatives of the Respondent emphasised that in their view the original position was factually correct but they were prepared to concede the change to “lower starting dose” to “low starting dose as it related to their detail aid and to change “smallest dose adjustments” to “small dose adjustments” as it related to the detail aid and concede the change to “small starting dose and dose adjustment” as it related to the advertisement.
Again queries were raised as to how this would actually work grammatically and the representatives confirmed that it was a question of adopting a principle rather than specifically the exact wording.
The representatives of the Respondents then went on to discuss item 4 and presented slides of the table and the preceding page and rear page of the detailer, relying on the footnote to which on the previous page there had been made a reference as against the 5 mg position. It was suggested that the illustrated dose combinations are consistent with the current Felimazole’s SPC; the issue was already addressed by an asterisk on the previous page; and that whilst they were prepared to move the asterisk from “2.5 mg twice a day” to “5 mg once daily” and move the qualifying statement to the bottom of the same page, they did not see that the present detailer in relation to the table was in reality a breach of the Code of Practice clauses 4.3 and 4.7.
In answer to the Chief Executive and other members the Respondent’s representatives confirmed that they did not wish to rely on any question of there being a material difference in the treatments provided by the two medications; emphasising that the message they were trying to give in the promotions was to persuade vets not to overdose. They rejected that there was an implicit message that Vidalta was unsafe. They emphasised that there was no explicit or even implied reference to Vidalta. The intention was to emphasise the benefits of low dosage, not specifically to criticise or compare with Vidalta. In responding to a suggestion from a member that they were attempting to challenge the status quo and that Vidalta is a large part of that status quo, the representatives stated that they were challenging all earlier approaches to treatment, including the use of Vidalta but not specifically Vidalta. It was the purpose of the promotion to educate. In responding to another member’s query that the active ingredients of the two products in context of dosage was not in their final effect that different, the reference to 2:1 ratio and 10 mg to 6 mg comparison was accepted by the representatives. They accepted that in reality the appropriate comparable dose for the Vidalta was very similar to that of Felimazole. They conceded that the difference in ranges were not reflected by dosage. They were not in a position to deal with the issues of concentration in the blood and sustained release that one product might have as against the other and that in any event they were not seeking to challenge the sustained release or the clinical profile of Vidalta. In terms of sale comparisons they stated that they considered that Felimazole was now ahead of Vidalta. They suggested that the promotions had stimulated a lot of debate and they had had a number of congratulatory communications from readers. It was confirmed that a single 2.5 mg dose of Felimazole would be off label.
The Chairman congratulated both sets of representatives on their presentations and asked them to leave the room.
A lengthy discussion ensued. It became quickly clear that there was unanimity of agreement, largely on the basis of the discussion that had taken place prior to the presentations, that the promotion very definitely would be seen by readers to relate to Vidalta and did not seek simply to educate readers. In reality the starting dosage of each medicine, and incremental dosage for each medicine, were broadly similar, in their effect. To the extent, therefore, that there was a suggestion that Felimazole was preferable to Vidalta in that context was misleading. There was, however, much more difficulty in concluding that necessarily the promotions were disparaging of Vidalta. A number of members drew attention to Guidance Note 2 and the fact that suggesting a competitor product was unsafe was in the terms of that guidance note automatically likely to be taken to disparage that product. However, assisted by the Chairman’s comments that drew a distinction between stating a product was unsafe, as opposed to being less safe, there was eventual unanimity that whilst items one and three were misleading, they did not disparage Vidalta, because there was no suggestion, even implicitly, from the promotions that Vidalta was unsafe. They could, however, reasonably be taken by a reader to infer that using Vidalta was less safe than using Felimazole, which was misleading.
In relation to item four, there was general agreement that the failure to place the asterisk against the 5 mg entry in the table was misleading. A number of members emphasised their concern that the present failure to draw attention to the different efficacy between a daily dosage of two tablets of 2.5 mg of Felimazole, as opposed to a single 5 mg tablet, would lead to veterinary surgeons to prescribe the latter single tablet, because of the difficulties of compliance in getting cats to accept orally the tablets. Apart from the obvious difficulties that can arise with the owner being bitten, cats could quite often hold the tablet in their mouths and subsequently reject it.
Members also noted two issues not included in the actual complaint of the Complainant. Firstly the failure to draw attention to the contra indication in the SPC of Felimazole, which required a minimum dosage of 2×2.5 mg per day, meant that the promotion could be read as suggesting an off label use. Secondly there was an omission of the information required by clause 7.2 of the Code of Practice, specifically 7.2 (iv).
In terms of what had actually been stated in the complaint, however, it was in due course agreed by the members that item 4 of the promotion was not inconsistent with the SPC of Felimazole.
Accordingly the unanimous decisions of the Committee were: –
1. In relation to items one and three referable to the words in the advertisement and detailer “Are you taking a heavy-handed approach to hyperthyroidism”? (as supported by text and image); and to the words in the detailer “with Felimazole, you don’t have to!” relating to the strapline “Are you taking a heavy-handed approach to hyperthyroidism?”, the Committee took the view that this advertisement and detailer by implication referred to Vidalta, in particular because Vidalta is the only other licensed oral treatment on the market for hyperthyroidism. Both the advertisement and the detailer implied that Vidalta is less safe in treating hyperthyroidism than Felimazole because Vidalta’s smallest dose is 10 mg/day. The Committee, whilst acknowledging that the scientific reports emphasized the importance of using low doses to avoid causing hypothyroidism in cats, was of the view that it was significant that the active ingredient in Vidalta (carbimazole) was different to that for Felimazole (methimazole) and studies presented to the Committee suggested that carbimazole needed to be taken in larger quantities to achieve the same pharmacokinetic effect as methimazole, Accordingly, the Committee was of the view that such an implication that Vidalta is less safe is in fact not correct, and therefore constitutes misleading promotions. The Committee, however, did not consider that the implication of these promotional items was that Vidalta is unsafe, which would have been a more serious finding, especially as there is no evidence to show that it is unsafe, nor, it should be recorded, did the Respondent, whether in its formal response or its submissions, suggest that such an implication was being made by the Respondent’s promotional words or image.
Accordingly the Committee found that both the advertisement and the detailer by reason of these two items misleads contrary to Clause 4.3 of the Code of Practice, by reasons of their implication that Vidalta is less safe than Felimazole. The Committee, however, did not agree that the promotional items disparaged the Complainant by being the manufacturer of Vidalta, which might have been the case if the implication had been that Vidalta was unsafe. Accordingly, it did not find any breach of Clause 6.1 of the Code of Practice.
2. In relation to item four, the Committee found that the table in question, on page four of the detailer, suggests that one dosage of 5 mg per day of Felimazole has the same efficacy as two doses of 2.5 mg, without any reference to the actual contrary indication (that 2 x 2.5 mg per day has greater efficacy than 1 x 5 mg per day) is thus misleading, contrary to Clause 4.3 of the Code of Practice.
The Committee would add that it considered that a contributory background fact to its finding of breach was because prescribers and users generally prefer to administer 1 rather than 2 doses because of difficulties in administering tablets to cats, which raises compliance concerns.
Nevertheless, the Committee did not consider that the table constituted a breach of Clause 4.7 of the Code of Practice, in that it was considered not inconsistent with the product’s SPC.
Although not part of the complaint, and therefore not discussed with the parties’ Representatives, the Committee also recommend that future promotional material for Felimazole should not:-
a. Imply a single 2.5 mg dose per day is a permitted starting dose, because that is contrary to the product’s SPC; (in this regard, the Committee considered that an asterisk appropriately placed referencing a footnote to this effect would be an effective way of avoiding such an implication) and
b. Omit the inclusion of the information required by Code of Practice Clause 7.2, in particular 7.2(iv) that “at a minimum, side effects, precautions, contra-indications and withdrawal periods of the product in the recommended dosage, and any other warnings relevant to the advertised indication(s) and the species of animal to which reference is made, consistent with the SPC”.