Social Audit Ltd
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Mr Roy Alder, Head of Executive Support
Medicines Control Agency
Market Towers, 1 Nine Elms Lane
London SW8 5NQ

30 January 2000

Dear Mr Alder,

Thank you for your letter of 24 January about the advertising of Detrusitol (tolterodine, Pharmacia & Upjohn). I shall need a few weeks to study the documents you sent us. In the meantime, perhaps I can share with you some general impressions and observations about your letter and enclosures, and also make some further information requests.

1. You sent me a small bundle of papers attached to your letter. It pained me to see so many deletions of text, but not only because of the secrecy. What really got me was that someone at the MCA - I do hope it was not you - had handwritten on these papers essentially the same message, over 20 times. To simplify matters, last week I ordered a self-inking rubber stamp (red ink) for you to use in handling future requests - maybe starting with item 2 below. I hope to be able to forward it to you within the next few days. It says:

Withheld under Exemption 13
of the Code of Practice on
Access to Government Information

2. Your letter mentions the Assessment Report on Detrusitol, prepared by the MCA, which was considered by the CSM. I should like now to make a formal Code request to see a copy of this Assessment report - with amendments and deletions if you must. Your letter gives, I think, strong prima facie evidence of unacceptable bias, if not impropriety, by the regulators (see below) and naturally I want to check what's what.

3. Against the recommendation of the Swedish regulatory authority, the CSM "objected" to the inclusion of certain information in the product SPC which would have been as helpful to consumers and prescribers as it would have been unhelpful to the manufacturers. The data clearly indicated that relatively few patients felt the drug had helped them much. I am very concerned that the CSM (and MCA?) wanted to see these data deleted from the SPC.

Inexplicably, the CSM argued for deletion on the grounds that these data were not self-explanatory and were not the main thing measured in the studies. In fact, it is quite clear what they mean, and patients' opinions of response is clearly a very important measure of the effectiveness of treatment for incontinence - or in this case, of the relative ineffectiveness of the test drug in relation to placebo and non-drug alternatives. You indicate that the CSM was determined to have this information suppressed - in spite of its value to users - when you wrote that they withdrew their objection, instead of going to arbitration, because "the inclusion of these data was not regarded as a potential risk to human health". Blimey. Naturally I want to know whether and to what extent pressure from the manufacturers and/or the MCA prompted such extraordinary behaviour by the CSM.

4. Your letter indicates that the CSM was, in effect, prepared to overlook the evidence from controlled trials that indicated tolterodine had very limited efficacy for most patients, after 12 weeks - on the grounds that the Company had provided data from uncontrolled trials showing that "the benefit of Detrusitol was maintained …over time". I suppose it is arguable that the "open" continuation studies on which the CSM relied do provide "at least some evidence of a relationship with the therapeutic effect" - but I cannot accept that is proper that such evidence should be allowed to override the "statistically compelling" evidence of lack of efficacy on which the licensing approval would have been based. All the published evidence of long-term effectiveness from Phase III trials that I've been able to find seems very thin.

Independently of our request for the Assessment Report, please could you also direct me to any source of information about the standards that are or are not acceptable in clinical studies relied on for licensing purposes - apart from those mentioned in the Table you included as Annex 1. Underlying this request are some further specific concerns in this case: e.g.

[a] the trials involved relatively high doses of the comparator drug in a fairly elderly population - inevitably exaggerating the problem of side-effects with oxybutynin, thereby making Detrusitol look better than it otherwise might;

[b] the fact that the reductions in the scores for the main study measures, recorded after prolonged treatment with Detrusitol, are numerically so modest as to permit in general a formal (ICS) diagnosis of incontinence, after treatment as well as before; and

[c] Minimal reference is made to the relatively impressive results obtained from behavioral and other non-drug treatments for incontinence.

5. You studiedly wrote that the MCA had considered the advertising for Detrusitol, not because any complaint had been referred to it, but "as part of our post marketing surveillance for this newly marketed medicine". Are you saying that scrutiny of advertisements for new products is a routine part of post marketing surveillance? And would you want website visitors to understand that the MCA had taken any significant action relating to Detrusitol advertising before our complaint was referred to it, three months ago? If so, perhaps you could explain what was done, and when.

In any case, I'd be grateful if you could give me some idea of the resources (person hours/week) devoted to routine scrutiny of advertising for new products, as part of the MCA's post licensing surveillance programmes. Since all this activity is paid for by fees from the manufacturers, I had always imagined this to be a modest part of licensing work. Please would you also provide information (or direct me to the appropriate published source, say, for the period 1998/99) about the number of occasions on which the MCA has made representations about advertising to licence holders, also the identity of manufacturer/product in each case, and the nature of complaint?

6. I am not at all sure what you meant by "potentially misleading" - the description of the MCA's finding in this case? This term seems to me essentially meaningless in relation to drug advertising - surely the MCA's post-marketing surveillance has established that most advertising is potentially misleading, if only by omission and/or because prescribers are not (and could never be expected to be) fully informed? Please correct me if I'm wrong, but I'm inclined to believe that "potentially misleading" is yet another nonsense term the MCA relies on - in this case, to allow it to look as if it's busy with enforcement, but without actually tangling with any company, in the courts. Anyway, I'd be grateful if you could point me to any formal definition of this term - something to indicate the difference between being "in breach" or "potentially in breach" of the regulations. I find it hard to see how - as you say was the case here - a company could exaggerate the properties of a product without misleading as to its safety or efficacy.

Thank you for your attention; I look forward to hearing from you.

Yours sincerely,
Charles Medawar



Contents page
List of correspondence with MCA/CSM