Department of Health
MEDICINES CONTROL AGENCY
Market Towers 1 Nine Elms Lane London SW8 5NQ
Telephone 0171-273 0600
Facsimile 0171- 273 0737	Our Ref: OG 98/18, 23, 24, 37 and 44
	11 September 1998

Dear Mr Medawar,

REQUESTS FOR INFORMATION RELATING TO THE COMMITTEE ON SAFETY OF MEDICINES

1. Thank you for your further letter of 3 August and the copy of your sample complaint which you hope will be referred to the Ombudsman.

2. I am now in a position to respond to the outstanding points from your correspondence with me and with Professor Rawlins which he referred to the MCA. I apologise once again for the time it has taken to complete this reply.

3. The criteria for deciding each of these requests are that, in relation to past proceedings of medicines advisory bodies, we maintain confidentiality, except where information is clearly available (e.g. in annual reports) and disclosure would not be prejudicial to past understandings of such confidentiality under which members have taken part at meetings.

Letter of 12 March to Professor. Rawlins

4. In this letter you asked for

i) formal votes in CSM meetings in 1991 and 1997 connected with the licensing of any particular drug;

ii) instances of members absenting themselves from meetings in 1991 and 1997 to avoid possible conflicts of interest; and

iii) copies of the full entries relating to personal specific interests declared in relation to (a) SSRI products discussed since 1987 and (b) to any "relevant product" at the last 5 CSM meetings.

5. I am able to provide the following anonymised, aggregated data from the records that we have researched. There were no formal votes in 1991, nor in 1997 at CSM meetings concerned with the licensing of a particular drug. In 1991, there were 71 declarations of interest at meetings of the CSM of members who either left the meeting or did not take part in discussions or decisions. In 1997, there were 86 such declarations. There were two occasions on which declarations of a personal specific interest were made in relation to fluoxetine, and none in relation to the other medicines you refer to between 1987 and 31 July 1998. There were no declarations of a personal specific interest at the five meetings of CSM held between 14 January and 11 March 1998. (It should be borne in mind that members, if they have a personal specific interest to declare in relation to a product under discussion, may simply not be present for that part of the meeting).

6. I am unable to provide further details of formal votes nor copies of the full entries from the minutes or elsewhere relating to personal specific interests for the reasons given in Exemptions 2 and 13 of Part II of the Code of Practice on Access to Government Information ('confidential communications between departments, public bodies and regulatory bodies" and "third party's commercial confidences"). It has not been our policy to make such information available nor would we be justified in so doing now under the criteria set out in paragraph. 3 above. The information you seek was either part of the deliberative process and we need to maintain the confidential nature of that process or is recorded in confidential papers and minutes of CSM. Release would risk damaging the working relationships between Ministers, the MCA and the CSM and undermining the integrity of past understandings concerning disclosure on which MCA and members of CSM have relied and proceeded. Disclosure of further information about specific votes would risk harming third party's commercial interests since it would reveal information about the fact of an application for, or further consideration of, a medicines licence. In reaching this decision, we have found no overriding public interest to justify disclosure.

Letter of 7 March to Mr Alder

7. You asked for copies of any discussions relating to commercial confidentiality recorded in (extracts of) CSM minutes over the last 5 years. I am unable to supply this information for the reasons I give in para. 6 above.

Letter of 20 March to Mr Whitbread

8. You asked for copies of all 1998 CSM and sub-committee minutes edited to remove confidential information and details of forthcoming CSM and subcommittee meetings. I am unable to supply copies of the edited minutes for the reasons I give in para. 6 above. I sent the details of CSM meetings to you on 23 July.

Letter of 14 May to Professor Rawlins

9. You asked for details of CSM's mandate in relation to Code requests. I believe I answered this point in my reply of 8 September to your letter of 8 August. As suggested in the Code Guidance (Section 2 of Part 11), advisory bodies such as the CSM are not usually within the remit of the Ombudsman and Code of Practice.

10. You asked for an extract of the relevant minute of CSMs meeting which discussed the request of 12 March. I am unable to provide this information for the reasons I give in para. 6 above.

11. You asked for:

i) details of any CSM/MCA consideration within the last 6 months (taken to mean since December 1997) of revisions to data sheet warnings about withdrawal reactions with SSRIs;

ii) if so, whether or not CSM is satisfied with them as they stand; and

iii)     if not, whether CSM has some substantial revision in mind

I am unable to provide the specific information for the reasons I give in para. 6 above. However, as you know, we have been reviewing all the available evidence about SSRIs and seeking a wide range of views. This review has included examination of the current advice given in data sheets about withdrawal reactions. We will advise you of revisions made in due course.

Letter of 10 June to Professor Rawlins

12. We have considered your letter very carefully and, on this occasion, are treating the following as requests for information under the Code of Practice.

i) at the time of licensing Seroxat and approving the data sheet, whether the CSM/MCA had significant evidence (other than the Montgomery and Dunbar paper) to support the view that "Long term treatment with Seroxat has shown that antidepressant efficacy is maintained for periods of at least one year".

We have not researched what information was generally available when Seroxat was first licensed for use in the UK on 11 December 1990 and I do not think it would be a reasonable use of our resources to do so, given the time that has elapsed and the time it would take to research this matter in depth. It was, however, licensed only after careful evaluation of all available evidence, including pre-licensing clinical trials data and safety information.

ii) why the recommendation for gradual withdrawal [appeared] 30 years after the introduction of antidepressants

We have not researched your claim and it would require an unreasonable diversion of our resources to investigate this further.

iii) on what basis the CSM/MCA accepts evidence of zero incidence withdrawal within the Montgomery and Dunbar study when other published studies suggest otherwise.

Professor Rawlins did not say that he accepted a zero incidence withdrawal. He pointed out that he did not accept your view that the study was invalid and provided reasons. Other available evidence as indicated in your letter has been taken into account.

iv) whether there is any evidence to suggest that prescribers have in the past or now clearly distinguished between symptoms of relapse and' those of withdrawal.

v) whether there is any evidence to suggest that a clear distinction between symptoms of relapse and those of withdrawal existed when the Montgomery and Dunbar study was undertaken in around 1991.

Reports of withdrawal reactions submitted on yellow cards since paroxetine was authorised in 1990 indicate that prescribers are distinguishing between relapse and withdrawal symptoms.

vi) whether the CSM/MCA were concerned that maintaining conditions for double-blind clinical trials is very hard and that this may have influenced the outcome.

We take into account the strengths and limitations of clinical trials in assessing applications for a marketing authorisation.

vii) the meaning of "efficacy" as used by Professor Rawlins in relation to the "efficacy of paroxetine in preventing relapse and recurrence of depression over the period of the study".

The meaning of the word efficacy here was literal. Withdrawal reactions and possible dependence are regarded as safety issues.

13. If you have any query about this letter, please contact me. If you are unhappy with my decision not to provide certain information, you should write to Dr Jones in the first instance and ask for a review. After that, if you remain unhappy, you may ask a Member of Parliament to make a complaint on your behalf to the Ombudsman (known officially as the Parliamentary commissioner for Administration) who will decide whether or not to conduct his own enquiry. His address is Millbank Tower, Millbank, London SWIP 4QP.

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