Medicines and Healthcare products
1 Nine Elms Lane, London SW8 5NQ
Mr Charles Medawar
Social Audit Ltd
P.O. Box 111
London NW1 8XG
Telephone 020 7084 20000
Fax 020 7084 2353
Ref: FOI 06038
7 April 2006
Dear Mr Medawar,
Subject : Seroxat/Placebo suicides Thank you for your letter of 17 February. I apologise for the delay in responding. I have answered your questions in turn.
1a) What is the current status of investigations for possible criminal prosecution of GSK?The conduct of the investigation required the Enforcement Division of the MHRA to consider over a million pages of scientific and other documentation which comprised the factual background to the case. A team of medics and scientists from across the MHRA assisted with this. The process of considering documents is now completed and documents are only reviewed now if they come to light as new evidence. Potential witnesses from inside the MHRA have been interviewed and notes have been taken from them, from which statements will be drafted. These statements seek to convert the findings of the review of the scientific and regulatory documentation in to evidence suitable for the conduct of a criminal trial, if appropriate. 1b) Has any decision been made not to prosecute GSK?
There is only one criminal investigation currently being conducted in to offences allegedly committed by GSK. It is concerned with alleged failure to supply pharmacovigilance information to the MHRA in respect of the paediatric use of Seroxat.
1c) When was that decision made and by which organisation?
Once the criminal investigation has been concluded a file will be forwarded to prosecuting lawyers within the legal department of the Department of Health. They will apply the Code for Crown Prosecutors to decide whether or not there will be a prosecution.
1d) What was the estimated cost of the investigation?
It is not possible to provide a figure for this as the investigation has not concluded.
1e) Was any other disciplinary or cautionary action taken in relation to any matter that was the subject of investigation for possible criminal prosecution?
There has not been a decision not to prosecute, and the investigation has not concluded. Therefore consideration has not been given to other forms of action as an alternative to prosecution.
2a) Please will you explain the basis on which MHRA et al considered, that this question had been adequately addressed and no further information was requested on these cases of suicide?
The judgment was taken by the Expert Working Group of the Committee on Safety of Medicines and by the Committee for Medicinal Products for Human Use (CHMP) in the context of a detailed review of data from a number of different sources.
2b) Has the MHRA (or the MCA) conducted any systematic audit(s) within the last decade, designed to establish the completeness and veracity of any companys summaries of clinical trial data, in relation to the raw data on which they were based?
The MCA/MHRA GCP Inspectorate has performed a significant number of GCP inspections of clinical trial sponsors and investigators since 1997, during which clinical trial source ("raw") data have been examined. In addition, during the criminal investigation referred to above, case report form data (some of which are "raw data") and a wide range of other trial documents for the paroxetine paediatric clinical trials have been examined by the investigation team and compared with the trial summaries.
3) What is the basis for considering that the MHRA investigation into suicidal behaviour with paroxetine was adequate?
When any review is undertaken decisions are made on the scope of the review and the analyses to be conducted. The decision on the scope of the review of the risks and benefits of paroxetine was made by the CHMP. The UK position on this committee was informed by the CSMs Expert Working Group on SSRIs. The MHRA/CHM additionally reviewed the individual study reports from the paroxetine clinical trials. The report of CSMs Expert Working Group on SSRIs aims to set out what data were considered and how conclusions were reached allowing individuals to draw their own conclusions on the adequacy of the review. The consideration of the balance of risks and benefits of paroxetine has not ended we continue to monitor its safety and consider the implications of any new data for the regulatory position.
4a) Does the MHRA stand by the inclusion of the event which occurred 33 days after last study medication as a placebo suicide.?
All the assessments considered by the CSMs Expert Working on the Safety of SSRIs and the European Scientific Advisory committee have clearly stated that in the paroxetine placebo-controlled trials there were 4 completed suicides one in the paroxetine group (on therapy) and three in the placebo group (all in the post-treatment period). The analyses considered by the Expert Group during its review include one which examined the incidence of suicidal behaviour during the on- therapy period (including taper phase) and another analysis which examined the incidence of suicidal behaviour during the on therapy period (including taper phase) plus 30 days post-therapy.
4b) 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?
Please see response to question 4a this information was not included in the analyses considered by the Expert Group.
5a) You wrote that the second placebo suicide had received ECT treatment three days before he/she committed suicide. Do you not agree 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?
I am not in a position to comment on what would or would not be usual care in this situation.
5b) Will the MHRA now request from the MAH details of all drugs prescribed for this alleged placebo suicide case?
The case narrative has already been provided to the MHRA. It is considered that further details in relation to a single case would not alter the findings of the Expert groups review and therefore we do not propose to seek further information in relation to this particular case.
6) Please supply any information relating to the follow up of the 3rd placebo suicide.
We do not have any additional information on this other than that provided in your letter.
7) Please provide the Protocol Title and patient number of each of the three placebo suicides plus one paroxetine suicide?
The protocol numbers of the trials in which the three placebo suicides and the paroxetine suicide were reported are 29060/057, 29060/627, 29060785 and 29060/502. We have made the decision not to release the patient numbers requested. This information is being withheld under Section 40 of the FOIA (Personal information) as we consider its release could potentially lead to the identification of individual patients.
If you have a query about this letter, please contact me. If you are unhappy with our decision, you may ask for it to be reviewed. That review will be undertaken by a senior member of the Agency who has not previously been involved in your request. If you wish to pursue that option please write to the Communications Directorate, 10th Floor, Medicines and Healthcare products Regulatory Agency, at the above address quoting reference. After that, if you remain dissatisfied, you may ask the Information Commissioner at The Information Commissioner's Office, Wycliffe House, Water Lane, Wilmslow, Cheshire SK9 5AF to make a decision on whether or not we have interpreted the FOIA correctly.
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