Dr Julie Williams, Post-Licensing Division
Medicines and Healthcare products Regulatory Agency
Market Towers, 1 Nine Elms Lane
London SW8 5NQ	17 February 2006

 

Dear Dr Williams,

Your Reference FOI 06007 Mine: Seroxat/Placebo suicides

Thank you for your letter of 13 February, responding to our FOI request of 16 January relating to Seroxat/placebo suicides. I have a number of observations and further questions relating to the information you sent me.

Your letter explained that neither the MHRA, nor the EU regulators, nor two leading experts who were members of the SSRI Working Group saw any need to verify the raw data on these four cases of suicide. In spite of their critical relevance to the enquiry, and the deeply anomalous results reported in those trials, the MHRA et al decided not to investigate, but to rely instead on the company’s summary of events. You wrote: "the MHRA had had no reason to question the investigation of these cases by the MAH" (GlaxoSmithKline) – which seemed an extraordinary admission when the MHRA also claimed to be leading a criminal investigation of the company.

What is the current status of those investigations for possible criminal prosecution? Has any decision been made not to prosecute GSK? When was that decision made, by which organisation(s), and on what date was it publicly announced and how? What was the estimated cost of the investigation? Was any other disciplinary or cautionary action taken in relation to any matter that was the subject of investigation for possible criminal prosecution? If so, please disclose available details of all formal communications between the MHRA and the MAH (GlaxoSmithKline) relating to insufficiency of standards of adverse drug reaction investigation and/or reporting.

Please will you explain the basis on which the MHRA et al considered, "that this question had been adequately addressed and no further information was requested on these cases of suicides". There is no reason to think this judgement was informed, since none of the parties had ever verified that the raw evidence was honestly summarised. Moreover, SmithKline had publicly acknowledged previous mistakes in attributing events that happened in the washout phase of these trials as suicidal behaviour on placebo.

Has the MHRA (or the MCA) conducted any systematic audit(s), within the last decade, designed to establish the completeness and veracity of any company’s (or companies’) summaries of clinical trial data, in relation to the raw data on which they were based? If so, please give the date(s), relevant references, and outline conclusions of any such audit(s).

I note that that the MHRA et al - in the course of an allegedly assiduous and ‘independent’ investigation - were satisfied to receive evidence where "the level of detail is similar to that which would be expected in clinical trial adverse events." Your language is perhaps deliberately meaningless, in that adverse reaction reports from clinical trials vary hugely in quality. Even so, this seems an extraordinary admission after years of concealment of suicidal behaviour as ‘non-accidental overdose’ and/or ‘emotional lability’. On what basis might the man or woman on the Clapham Omnibus conclude that such investigations were adequate, when this is an industry in which data suppression, ghost-writing, bribery (however ‘civilised’) and layers of gloss seem to be the norm?

The MHRA stands by its analysis – that one patient on paroxetine committed suicide, compared with three on placebo – when the first of the ‘placebo suicides’ occurred beyond the trial cut-off point at 30 days. That seems exactly like adding a goal to the score line when it was shot after the final whistle. What on earth is going on? Can you imagine reporting a suicide on paroxetine after 33 days? You’d have GSK lawyers crawling all over the MHRA and no doubt they would win. Please confirm that this alleged case of ‘placebo suicide’ was excluded from the analysis prepared by GSK on 2^nd April 2002, and that its inclusion by the MHRA and CSM Expert Working Group was improper.

How many cases of non-fatal suicidal behaviour attributed to placebo in these trials in fact occurred more than 30 days after study medication was ceased?

You wrote that the second placebo suicide had received ECT treatment three days before he/she committed suicide? Do you not agree that it would be very unusual to subject a patient to ECT before some drug treatment had been tried – especially when the patient was under supervision in a controlled clinical drug trial?

Will the MHRA now request from the MAH details of all drugs prescribed for this alleged ‘placebo suicide’ case? Having examined those data, does the MHRA stand by its affirmation that the patient was prescribed [a] no antidepressant drug (notwithstanding an impending ECT)? [b] no benzodiazepine? and [c] no antipsychotic medication?

In relation to the third ‘placebo suicide’ case, I am especially concerned to know if the MHRA is satisfied that the MAH undertook any searching independent investigation. My understanding is that the evidence on this suicide examined by the MHRA et al was based on no more than two telephoned reports from a relative of the deceased. Please supply any evidence that indicates otherwise.

I fully appreciate the need to withhold data that might lead to the identification of any patient. However, please identify the Protocol Title and Patient Number of each of the three placebo suicides plus the one paroxetine suicide. (e.g. the first placebo suicide case was from Study 057 and involved patient number 057.012.1217).

I am sending a copy of this letter to Mr Goldfinch, requesting that it be treated as a new Freedom of Information Act request. I look forward to hearing from you, within the 20-day response time. I would appreciate an electronic version of your reply (email attachment) as well as a hard copy.

Sincerely,
Charles Medawar

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