Information Department
Medicines and Healthcare products Regulatory Agency
Market Towers, 1 Nine Elms Lane
London SW8 5NQ	12 March 2007

 

          Dear Sirs,

Please treat the following as a request under the FOI Act. I am seeking to establish whether and in what way the MHRA defines and requires appropriate standards of behaviour, and levels of personal responsibility, when Agency representatives [a] offer "information and advice to improve public and professional awareness", when expected to reflect "robust and fact-based judgements"; and [b] are found to have made false, misleading and potentially damaging representations, albeit in good faith.

In this FOI request, I refer specifically to statements made by the MHRA Chairman, Professor Sir Alasdair Breckenridge, in the interview recorded for the BBC-1 Panorama programme, ‘Taken on Trust’, broadcast on 3 October 2004. A transcript of his broadcast remarks is available on the Panorama website, but in framing this FOI request I have also taken account of context, given the reservations expressed by Sir Alasdair in his evidence to the House of Commons Health Select Committee (20 January 2005, at Q815): "The bits of my robust defence of the position of the Agency were not shown and I cringed from behind the sofa when I saw the bits they did show of what I had said. It was very embarrassing"

In the broadcast programme, Breckenridge stated: "There is very good clinical trial evidence that these drugs do not cause suicide, they do not cause suicidal thoughts in adults". This claim appears fully consistent with other statements Breckenridge made when interviewed. He was asked: "Why should the public now trust you when you say the benefits outweigh the risks in adults?" He replied: "Because of overwhelming evidence that it does … we have looked at over 300 studies of Seroxat in adults". Later in the same interview, he emphasised the same point: "There are in over 300 studies which have been analysed and studies using epidemiological databases the drugs do not cause suicide, they do not cause suicidal thoughts."

The following FOI requests arise in the light of evidence to the contrary that was available at the time this interview took place, notably from data provided to the CSM/MHRA Expert Working Group on SSRI antidepressants. However, the relevance of these FOI requests is underlined by information made available since then - notably in May 2006 by GlaxoSmithKline (GSK), following the independent re-examination of essentially the same data, and in the December 2006 hearings by the US Food & Drugs Administration Psychopharmacologic Drugs Advisory Committee.

1. Does the Agency consider that the categorical assurances given by the Chairman, and his references to "overwhelming evidence" in support of his views, were justified in the light of the conclusion of the Expert Working Group on SSRI antidepressants: "From the available clinical trial data, both published and unpublished, a modest increase in the risk of suicidal thoughts and self-harm for SSRIs compared with placebo cannot be ruled out"?

2. In the broadcast interview, the MHRA Chairman sought to explain the linkage between onset of treatment and emergence of suicidal behaviour solely in terms of the delayed onset of drug effect, again wholly discounting the possibility of drug induced suicidal behaviour:

BRECKENRIDGE: There is a period of time when the drug does not act, it takes a period of 3 or 4 weeks before effect.

JOFRE: But it's in your bloodstream immediately. Are you suggesting it has no effect on you?

BRECKENRIDGE: It has no beneficial effect for some 3 or 4 weeks.

JOFRE: But it might have a detrimental effect.

BRECKENRIDGE: And during that period of time there is a risk of suicide which remains from the period as before, and that is the period when the practitioner must monitor the patient very carefully.

Does the Agency consider that this assumption by Breckenridge was justified in the light of the conclusion of the CSM/MHRA Expert Working Group on SSRI antidepressants? (e.g. "It is very difficult to assess whether these reactions are due to the drug, would have occurred if the person was treated with any antidepressant, or are part of the underlying course of the disease." And: "This may be suggestive of a causal association but also may be due to the fact that an event occurring shortly after treatment initiation is far more likely to be linked to the treatment by the patient and the prescriber than an event occurring after some time on the drug.")

3 In the course of the Panorama interview, the MHRA Chairman stated: "In fact, what you can say is, that the prescribing of SSRIs has increased dramatically since the 1980s, end of the 1980s (and) the risk of suicide has fallen dramatically in that period of time." Does the Agency consider this to be "a reliable and fact-based judgement", taking into account the conclusion of the Expert Working Group, that: "Studies generally indicate that increases in the prescribing of SSRIs have not been associated with an increase in population suicide rates, although interpretation of these findings is difficult …"

4. In the broadcast interview, Breckenridge stated: "In the adult population the drugs are effective. There are many, many studies to show that." Does the MHRA accept [i] that of the order of two-thirds of all SSRI prescriptions for depression are written for "mild depression"? [ii] that the EWG was correct in concluding that, "The effectiveness of SSRIs in mild depression has not been clearly demonstrated in RCTs"? And [iii] that the MHRA Chairman therefore failed to comply with the MHRA’s mission, to give "robust and fact-based judgements to ensure that benefits to patients and the public justify the risks"?

In relation to each and all of the above:

5. Does the MHRA now accept that Breckenridge’s assessment of the risk of paroxetine-induced suicidal behaviour in adults was inappropriate and/or unreliable, and therefore did not reflect the "robust and fact-based judgements" that the Agency claims underpins its work?

6. Has either the Agency, or its Chairman, ever withdrawn or apologised for these broadcast remarks? Has any consideration ever been given to doing so? If so, please provide relevant documentary evidence?

7. Did the Chairman undertake any media training, rehearsal and/or formal preparation for this Panorama interview – and please give details if so. Whether or not he did, [i] please identify by date and title any memoranda, briefing notes or advice prepared by or for the Chairman in advance of this interview; and [ii] please disclose the contents of all such documentation.

8. Did the Agency make any assessment either of that Panorama programme and/or of the Chairman’s performance in his broadcast interview? If so, please provide a copy of any appraisal(s) made.

9. Did the Agency, or the Chairman, make any representations to the BBC, following the broadcast interview, to complain of unfair or unjustified treatment of either the subject matter or the Chairman (e.g. relating to his complaint to the Health Committee, referred to above)? If so, please provide a copy of any representation(s) made.

10. Please provide any documentary evidence to show what lessons the Agency learned, following the independent re-analysis of paroxetine clinical trial data, leading to the May 2006 statement by GSK? Specifically, did the Agency consider [i] that the Expert Working Group had been unwise to rely on company analyses of those trial data; and [ii] that Agency representatives should be restrained from making bullish presentations, in the absence of fully reliable analyses and data?

I look forward to receiving the Agency’s response to these questions. In framing them, I have been mindful of the requirements put on pharmaceutical sales representatives under the ABPI Code of Practice for the Pharmaceutical Industry, and specifically clauses 7.2 and 20.2:

7.2 Information, claims and comparison, must be accurate, balanced, fair, objective and unambiguous and must be based on an up to date evaluation of all the evidence and reflect that evidence clearly. They must not mislead, either directly or by implication, by distortion, exaggeration or undue emphasis"

20.2 Information about prescription only medicines which is made available to the public either directly or indirectly must be factual and presented in a balanced way

I would need some persuading that the MHRA Chairman would have passed such tests. On the other hand, it would be encouraging to find evidence that lessons had been learned. Failing that, I shall seriously consider passing this and further evidence to the Fitness to Practice Directorate of the General Medical Council.

Yours faithfully,

Charles Medawar
Director

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