Antidepressants, Advertising and writing on the wall
I do not know how long it is going to take to reveal the full extent of the 'official' mishandling of this whole antidepressant thing. The only thing that seems certain is that the regulatory and professional authorities are not suddenly going to come to their senses or see the light. The evidence seems overwhelming, in this case, that they are actively incapable of doing so.
Part of me believes that the end-game is nigh, but perhaps I am banking too much on the outcome of pending litigation and on the impact of a major TV programme, due soon. In the meantime, I shall proceed on the basis that the grand delusion will continue - probably until the industry comes up with new antidepressants, good enough to discredit the ones we use now.
Would these, by any chance, be those featured in The Lancet last week (11 March, 911-918) - "SNaRIs, NaSSAs and NaRIs: new agents for the treatment of depression? This unusually long report in the "New Drug Classes" section looked important - but it was nothing of the kind. The report was by Prof. Justine M Kent MD, a consultant to the manufacturers of nefazodone (Serzone/Dutonin, Bristol Myers Squibb).
Her report comes across as a grinding analysis intending to show up differences between the four "new" drugs, and between SSRIs and quasi-SSRIs. Remarkably, she managed not to mention withdrawal reactions in over one full page of text on "Adverse effects". Two of the four "new" treatments profiled in this article, were nefazodone and venlafaxine (Efexor/Effexor), both available in the UK since 1995. Mirtazepine and reboxetine came later - but none of them really offers much new hope for people with depression. For all the claims, their efficacy is comparable to all the rest.
And so to the question of dividing lines between honest science and product promotion - and thence to the impact of advertising on health. These questions are now very much in the air in Social Audit's continuing correspondence with the MCA, about standards of advertisements for SSRIs. (See below). And they seem all the more relevant when the threat is looming of global, wall-to-wall, direct-to-consumer advertising (DTCA) of prescription drugs.
Developments on DTCA One the key questions here is whether and to what extent this distinctively American phenomenon can usefully be transplanted into other countries - where regulatory capacity may be minimal and proper freedom of information laws unknown. Here I include the UK - our new "freedom of information" laws are truly a disgrace - though, obviously, we would better defended than many developing countries, with precious little health infrastructure and far more urgent health needs. The introduction of DTCA in poorer countries could a prove a real disaster. The last thing you need in a country struggling to provide essential (generic) drugs - and probably incapable even of enforcing prescription drug laws - is to stimulate demand for branded prescription products.
An interesting new review of the effects of DTC advertising has just been published by a team of academics in the USA (Wilkes et al, 2000). Along with many earlier studies, it reports that the educational quality of DTC adverts is "highly variable", describing also some of the "profound effects" that DTCA is having in the US - for better and for worse and, in many cases, simply unknown.
However, what is clear from the authors' list of "policy suggestions and future research needs", is how impossible many countries would find it to control this monster, lacking the kinds of control mechanisms available (at least in theory) in the USA. From a developing country perspective, if not in the European Union, some of these proposals amount to pure pie in the sky:
"To drug companies, we suggest that it is in the industry's long-term interest to communicate openly, honestly, and accurately with customers. Price comparisons, detailed explanations of benefits and risks, and discussions of cost are encouraged. We hope that the drug industry will realise that responsible self-regulation and self-policing are the best defences against unwanted government regulation ."
"The FDA (US Food & Drug Administration can increase the likelihood of effective self-regulation through strong, well-funded, and aggressive oversight. The FDA should also take the lead in providing accurate, unbiased information to consumers Congress should ensure that the FDA has the resources it requires to effectively monitor and regulate DTC advertising "
"The medical community needs to respond vigorously to DTC advertising. Individual physicians and medical associations should monitor the content of DTC advertisements for accuracy and balance. In addition, organised medicine needs to 'counter advertise' by suggesting the appropriate uses and limitations of medication. The public health community needs to create mechanisms for providing consumers with objective, independent information about available drug therapies, including their indications, risks, benefits and alternatives.
Meanwhile, what is the response in the UK and in Europe to the now intense pressure to permit direct-to-consumer advertising? Well, the most recent letter from the MCA suggests that little if any thought has been given to the possible impacts - while the European Commission (EC) has just set up a working group on information and advertising to start thinking about this issue. I think it highly likely that the Commission has already taken the view that DTCA should be allowed - but the group officially meets for the first time on 21 March.
Consumer interests are not at all well represented on this working group; nor is the meeting open to observers. Watch this space.
Advertising of SSRIs This brings us back to the question of how well professional advertising is now controlled - and to recent developments relating to advertisements for Efexor XL (venlafaxine, Wyeth) and Cipramil/Celexa (citalopram, Lundbeck) .
Last week's letter from the MCA was a response to our complaint about that advertisement for Efexor XL (venlafaxine, Wyeth). For the most part, the MCA's letter suggested that I should brush up my law - fair enough. But all they said beyond that was that they were "satisfied" the advertisement complied with the law, because their "intensive surveillance" and "monitoring" schemes had been in action. That was all; it took three months to say it.
The question of what this "intensive surveillance" of advertising really involves is one we have raised with the MCA (30 January to Mr Alder). We await a reply. Still, if the MCA's response on Efexor XL is anything to go by, the regulators are barely scratching the surface of enforcement. In this case, it looks as if they will have to go a lot deeper to avoid another referral to the Ombudsman.
Still outstanding is the MCA's response to our complaint about Cipramil - but in the meantime there's been a fascinating twist to that story, on the side. By chance, and quite independently, the manufacturers of Prozac (fluoxetine, Lilly) made a complaint about the same advertisement. So, contrast what happened, in what was almost a double-blind trial.
While Social Audit complained to the Medicines Control Agency; Eli Lilly took its complaint to the Prescriptions Medicines Code of Practice Authority. This body was set up in 1993 by the Association of the British Pharmaceutical Industry, intended to operate "independently of the Association itself".
I do not know how independent the Code of Practice Authority (COPA) really is - and most of the complaints it handled last year involved one company complaining about another. Nevertheless, it reports its findings clearly and in some detail. At least COPA speaks its mind and defends its reasoning in public - something the Medicines Control Agency has never felt able to do.
So why was Eli Lilly complaining about the Cipramil ad? And should they or we feel the more embarrassed that the Social Audit complaint was more searching than theirs? Eli Lilly wasn't complaining about the claim that Cipramil was better than Prozac, or the scientific basis on which it was based. In fact, Lilly may have been prompted to complain in retaliation, because Lundbeck had complained about a Prozac advertisement, just a month before - a complaint that was later upheld.
Whatever the reason, the nub of the complaint was that Lundbeck had produced "knocking copy"; Eli Lilly felt that the CIPRAMIL advert had parodied one of theirs. Far from feeling embarrassed, I feel slightly proud to say that I'd never even noticed the features of the CIPRAMIL advert that that got so far up Lilly's nose. Here is the summary of the COPA report:
LILLY v LUNDBECK - Cipramil journal advertisement
"Lilly complained about a double spread journal advertisement for Cipramil (citalopram) issued by Lundbeck. The headline was 'Cipramil delivers' followed by text comparing Cipramil favourably with fluoxetine, Lilly's product Prozac. Lilly considered the advertisement to be knocking copy as it used the same wording as in Lilly's current campaign 'Prozac delivers' and similar imagery - a man with a bunch of flowers - to that of Lilly's - a man with red roses/red balloons/red wrapped parcels - seated in the background looking dejected. Lilly referred to an earlier case involving the use of parody (Case ALTTH/39812196). Lilly alleged that the text was also knocking, implying that citalopram delivered 'ahead of fluoxetine' and 'when fluoxetine doesn't'.
The Panel noted that in Case AUTH/398/2196 the Appeal Board had expressed some concerns about the use of parody in pharmaceutical advertising but had stated that each case would have to be judged on its merits. The Appeal Board had upheld the Panel's ruling of no breach of the Code in that case.
The Panel noted, in the case now before it, that the Cipramil advertisement was clearly based on the 'Prozac delivers' campaign. The advertisement featured the photograph of a man with a bouquet of cream flowers. In the background, sat on a bench and out of focus, was a dejected looking man holding a bunch of red roses and some red balloons with a red parcel at his side, these items had all been prominent in the Prozac campaign.
The Panel noted the claims 'Cipramil delivers ahead of fluoxetine' and 'Cipramil delivers when fluoxetine doesn't'. Adverse comments about competitor products were not in breach of the Code per se providing that such critical references were accurate, balanced, fair and could be substantiated. The Panel noted that there was no allegation that the claims were inaccurate, unbalanced, unfair or could not be substantiated. Lundbeck had produced evidence to support the claims. The Panel made no ruling in this regard.
Overall the Panel did not consider that the imagery and use of parody in the Cipramil advertisement in itself disparaged Prozac. No breach of the Code was ruled."
We shall see what the MCA has to say about the scientific basis of the Lundbeck claim. Meantime, what seems most significant is that Eli Lilly had no complaint about the science, assuming it to be "accurate, balanced and fair".
Or perhaps the point is that companies tend not to get at each others' scientific throats. They're all in this together, so why not passively collude in favour of softer science, when it allows them all to make bigger promises than they otherwise honestly might? What seems to matter most is that they don't step way out of line, or too hard on each other's toes.