Social Audit Ltd
P O Box 111 London NW1 8XG
Telephone/Fax 44 (0)171 586 7771


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

28 December 2000

Dear Mr Alder,

On 24 March, I wrote to complain about the advertising of tolterodine (Detrusitol/Detrol, Pharmacia and Upjohn). In particular, I drew attention to the prominent claim made for the 'selectivity' of this drug. I informed you that the FDA had previously asked the company to withdraw this claim, because it was based on a study of the drug in cats (their emphasis): "It has not been demonstrated in adequate and well controlled clinical trials that Detrol is more selective for the bladder in humans. Therefore these claims and related representations are misleading because they suggest clinical significance when, in fact, no such clinical significance has been demonstrated" (FDA, 13 April 1999).

I wrote again (to Mr Bagwell) on 25 July. The offending advertisements were still appearing and it seemed they did not even comply with the industry's Code. Beyond the general requirement that claims be "accurate, fair, objective and unambiguous", this Code says that "care must be taken (in using data from in vitro and animal studies) so as not to mislead as to its significance." In particular, "the extrapolation of such data to the clinical situation should only be made where there is data to show that it is of direct relevance and significance."

I am writing to you again because:

I have only just been able to look at the censored Assessment Report for Detrusitol sent on 20 September. As I picked my way through the remnants of text you sent, I did wonder more than once why on earth I sent you that rubber stamp. It has been used with such abandon; it is hard to believe that the public interest was anywhere near uppermost in the censor's mind. It is alarming to see deletions even in the sections on 'Efficacy - Statistical Assessment' and 'Clinical Assessor's Conclusions'.

However, I was interested to see (for the first time) roughly what an Expert Report and Pharmaceutical Assessment Report look like. Are all Expert Reports like this? Do they routinely tow the company line? This particular Expert's enthusiasm for such a mediocre therapy is remarkable, as are his/her views on selectivity. What is one to make of the fact that the European Expert view is, by FDA standards, unwarranted and misleading? Do you not think that the relevant Expert should be questioned about the basis of such views?

"Tolteridone … exhibits a selectivity for the urinary bladder over salivary glands, which has been demonstrated in non-clinical pharmacological in vivo studies and confirmed in clinical trials".

It may be that you have deleted text in the Assessor's Report which questioned this claim, and I note the Assessor concluded that any greater selectivity was relative to another drug, oxybutynin - which is not saying much at all. What happened to this assessment is anyone's guess. Mine would be that no-one on the CSM, and none of the battalions of European Assessors and Committees, ever really challenged the clinical significance of the claim - the consensus being just to tone it down a bit instead. But the text that survives in the SPC is still strong enough to support prominent claims that the FDA would find misleading:

Pharmaceutical Assessment Report: "The active ingredient (tolterodine) … shows better selectivity for action on the bladder compared to salivary glands than oxybutynin. It is equipotent to oxybutynin on bladder muscarinic receptors."

Summary of Produce Characteristics (1997): "Tolterodine … exhibits a selectivity for the urinary bladder over salivary glands"

Summary of Produce Characteristics (2000): "… with a selectivity for the urinary bladder rather than salivary glands in-vivo."

US Label (2000): " … in the anesthetized cat, tolterodine shows a selectivity for the urinary bladder over salivary glands: however, the clinical relevance of this finding has not been established."

This will explain why I am anxious to get a response to the complaint I made nine months ago. It seems that the MCA is failing to uphold section 3A(2) of the Advertising Regulations (S.I. 267, 1999): "No person shall issue an advertisement relating to a relevant medicinal product unless that advertisement encourages the rational use of that product by presenting it objectively and without exaggerating its properties". Unless the FDA is very much mistaken, the MCA/CSM has to decide between abetting misleading advertising and stopping it. I should like to know which.

I am sending a copy of this letter to Mr Richard Walker at the Office of the Parliamentary Ombudsman, also to Mr Mike Stone at the Patients' Association.

I look forward to hearing from you and wish you a Happy New Year too.

Yours sincerely,
Charles Medawar


Contents page
List of correspondence with MCA/CSM