Department of Health
Market Towers 1 Nine Elms Lane London SW8 5NQ
Telephone 020 7273 0642
Facsimile 020 7273 0286 .
28 July 2000

Dear Mr Medawar,

Thank you for your letters of 30 January, 14 February and 24 March (to Mr Alder) and of 25 July (to Mr Bagwell) concerning Detrusitol and the MCA's post marketing advertising surveillance activities . I repeat Mr Bagwell's earlier apologies that this reply has been delayed and is incomplete for the reasons outlined below. Perhaps I can take each of your points in turn:

"... a formal request for a copy of this [Detrusitol] assessment report.."

I hope you will by now have received Martin Bagwell's letter of 21 July (I enclose a copy). We are not yet able to let you have a copy of this report - edited or otherwise - but I hope to be able to do so by the end of September at the latest.

..whether and to what extent pressure from the manufacturers and/or the CSM prompted the behaviour of the CSM.. '

None. The CSM is an advisory body set up under the Medicines Act to give advice to the licensing authority with respect to the safety, quality and efficacy of medicinal products. The Committee's advice is based solely on a scientific assessment of the relevant evidence. It would be improper - and simply does not happen - for either manufacturers or the MCA to attempt pressurise the CSM to come to any particular conclusion when they finalise their advice.

"..please could you .. direct me to any source of information about the standards that are or are not acceptable in clinical studies relied on for licensing purposes.. "

The appropriate standards for clinical studies that are submitted for licensing purposes are described in regulatory guidelines. In the EU, regulatory guidelines are drawn up and issued by the CPW. They can be found on the EMEA website - and the ones relevant to the evaluation of clinical efficacy are listed under the heading "Efficacy Working Party". Also on this website (under the heading "ICH') can be found global ICH guidelines written to cover the USA, Europe and Japan and adopted by the CPW for use in Europe. These may be of more interest because they cover more general principles of clinical work. The current list of relevant ICH guidelines is as follows:

E1a: The Extent of Population Exposure to Assess Clinical Safety
E2a: Clinical Safety Data Management: Definitions and Standards for Expedited Reporting
E2b: Clinical Safety Data Management: Data Elements for Transmission of Individual Case Study Reports.
E2c: Clinical Safety Data Management: Periodic Safety Update Reports for Marketed Drugs
E3: Structure and Content of Clinical Study Reports
E4: Dose-Response Information to Support Drug Registration
E5: Ethnic Factors in the Acceptability of Foreign Clinical Data
E6: Good Clinical Practice: Consolidated Guideline
E7: Studies in Support of Special Populations: Geriatrics
E8: General Considerations for Clinical Trials
E9: Statistical Principles for Clinical Trials
EIO: Choice of Control Group in Clinical Trials (just finalised)
El 1: Clinical Investigation of Medicinal Products in the Pediatric Population (just finalised)

These guidelines are also available (as priced documents) from the EuroDirect Publications Service at the MCA (tel 0207 273 0352) or from the EMEA.

"what significant action [was taken and when] relating to Detrusitol advertising before our complaint was referred [October 1999].. "

The MCA monitored all advertising for this product while it had "black-triangle" status and as a result certain changes were made to the promotional material.

What does the MCA/CSM's post marketing surveillance of new medicines really amount to? I would be grateful for some idea of the resources devoted to routine scrutiny of advertising for new products.

The control of advertising of medicines is a small but important area of the Post Licensing Division's work in protecting public health. The Advertising Unit consists of four administrative staff and has access to professional assessors within PL Division and, when required, across the Agency to give their opinions on advertising material

The MCA carries out a number of activities relevant to controlling the advertising of medicines. The key functions are to protect public health, by promoting safe use of the medicines, and to ensure compliance with UK and EC law. To this end the MCA:

- monitors published material in a range of professional and lay journals and other media,
- checks advertising material prior to publication in certain circumstances,
- handles complaints about advertising of medicines

- offers advice to advertisers and industry, and

- takes enforcement action where advertising material does not comply with the Regulations.

Where that routine monitoring indicates that a breach of advertising regulations may have occurred, the company concerned is asked to forward all material relevant to that product advertising campaign to the Agency to enable the Advertising Unit to carry out a full assessment. That Unit also routinely monitors the advertising of products which are newly marketed in the UK and subject to the "black triangle" monitoring system. A range of professional journals and newspapers are scrutinised and all such advertising is assessed for compliance with the Regulations. Advertising copy selected in this way, together with any material accompanying complaints received by the MCA which are not referred to a self-regulatory body under the Monitoring Regulations, is assessed by the Advertising Unit before being referred to professional assessors within the MCA for an opinion. If appropriate the company is then notified of our concerns and maybe asked to withdraw the material. That letter to a company will refer to an advertisement as being 'potentially in breach' of Regulations. (I shall come back to your question about the definition of this term later in this letter.)

Would you also provide information 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 the complaint?

During the year 1998/99 the MCA dealt with 99 complaints and scrutinised 6638 published advertisements. In addition a total of 497 items of advertising material relating to 23 products were examined prior to publication. 135 potential breaches of legislation were identified, 74 through routine monitoring and 61 from complaints. Information about the type of breaches identified are not centralised within the MCA and can only be identified from individual paper files. I have not been able to discuss the scope of this work and the time it would take with the relevant staff within the MCA due to annual leave (and will not be able to do so until the end of August). I shall of course pursue that as soon as possible but I must flag up now that this work might incur a charge or - should the diversion of resources be considered to be too great - the MCA might decide that it cannot meet your request. As I say, I need to make further enquires within the MCA and, as outlined above for the assessment report, aim to have a final decision with you by the end of September at the latest.

What does the MCA mean by the terms 'potentially misleading' and 'potentially in breach' ?

The term 'potentially misleading' recognises that the response to an advertisement may differ from reader to reader and may depend on whether the advertisement is read carefully or not. In some cases the pictorial aspects may be misleading whilst the written material complies is satisfactory. It is the advertisement as a whole that is considered to be 'potentially misleading' rather than component parts. The MCA uses the term 'potentially in breach' when writing to companies about their advertising as a breach of the regulations is almost always a criminal offence, and it is for the Courts, and the Courts alone, to decide if a breach has occurred. In fact, the majority of 'potential breaches' are corrected in discussion with the company involved and do not reach the Courts.

Whether or not the MCA/CMS [a] had scrutinised the Pharmacia & Upjohn monograph for Detrusitol and [b] were aware of the FDA findings before October 1999?

The MCA was not aware of Pharmacia & Upjohn's monograph or the FDA concerns about the promotion of Detrusitol when the UK advertising was monitored. I can understand your concern that there may be differences of opinion on the advertising of this product between the FDA and the MCA. However, there are differences in culture and legislation between Europe and the USA and USA data sheets may not carry particulars identical to those listed in a European SPC.

Were any adverse findings relating to advertising for Detrusitol communicated to the company?

We are in contact with Pharmacia & Upjohn in relation to their advertising of Detrusitol and the company is aware of the nature of the complaints we have received. I am not prepared to disclose the nature of this correspondence under exemptions 4(a) and (c) of the Code.

"what, if anything, [is] the MCA proposing to do about the..claim for "selectivity" .."

Your letter has been sent to the MCA's Advertising Unit and they will reply to you direct. I have also sent them a copy of your latest letter of 25 July to Martin Bagwell.

Your letter of 14 February also sought information about "Direct to Consumer Advertising". That query was considered separately under MCA reference OGOO/05 and you have received in Alder's letter of 29 June.

Once again, I add my apologies to those of Martin Bagwell that this reply has been delayed. As you know, if you consider that your requests have not been properly handled under the Code or that any information has been unreasonably withheld, you may seek an internal review of my decisions. If you remain dissatisfied, you can ask a Member of Parliament to make a complaint on your behalf to the Parliamentary Commissioner for Administration who may decide to conduct his own investigation.

Yours sincerely
Mrs Anne Thyer
Executive Support


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