X-WARK-PBO-SUICIDES

9 June 2006

Dear Mr Medawar, Ref: FOI 06-181

Seroxat/Placebo suicides

Thank you for your letter of 26 April asking for a formal review of my response of 7 April and for further information. I apologise for the delay in responding. Please find below answers to your questions. We will contact you with the outcome of the internal review shortly.

Please supply me with any minute or other documentation giving evidence that either of these bodies ever specifically considered this issue and/or made any decision not to request all available data on the three placebo suicides from GlaxoSmithKline.

My e-mail of 6 May 2005 provided you with the full set of minutes of the meetings of the Expert Working Group (EWG) on the Safety of SSRIs which relate to their consideration of paroxetine. At each stage of the evaluation the Expert Group considered what further data would be required from the MAH. The minutes record the further information to be requested from the MAH by the EWG in each case. The minutes of the meeting of 21 October 2003 include a request that the MAH ‘Provide the narratives of the case reports for the suicide that occurred during clinical trials and an expert report discussing these cases;’. This request was fed into discussions at the Committee on Medicinal Products for Human Use (CHMP) and the MAH responded to the question in their submission of January 2004 (please see answers to your questions below). The EWG’s discussion of this response is recorded in the minutes of the meeting of 27 February. There is no record in those minutes of a request from the EWG for additional information on individual cases of suicide.

Minutes of the CHMP are considered exempt from release under exemption 27 of the FOIA (International relations).

Please would you let me know how many GCP inspections have been carried out since 1997, indicating what proportion were conducted either [a] on a voluntary basis – i.e. effectively by invitation from the MAH; and [b] otherwise (i.e. in the course of routine law enforcement activity). Please would you also let me know – on the basis of all such investigations - if the MHRA is generally satisfied that companies’ summaries of clinical trial data can routinely be relied on to give a true and fair view of the raw data on which they are based. Please also refer me to any available documentation that might support the Agency’s view.

Between 1997 and the beginning of May 2004, 153 voluntary inspections were carried out MCA/MHRA. Roughly half of these were of sponsors/Contract Research Organisations (CROs), the other half were inspections of investigator sites.

The Statutory inspection programme began in May 2004. These inspections were initiated by MHRA, not by the inspected organizations. From that date, to April 2006, 85 inspections of Sponsors/CROs were carried out. On average, each of these inspections included at least one investigator site.

The inspections have, on a small number of occasions, identified issues which have affected the outcome of assessment of applications.

Was the MHRA aware on 7 April 2006, the date of your reply to my letter of 17 February: [a] that this patient had been withdrawn from the study on 1^st March 1999; [b] that the patient was treated for acute depression with clotiapine, oxazepam and fluoxetine prior to electro-convulsive therapy on 15 March 1999; before taking his own life on 18 March?

I can confirm that the case narratives for the three placebo suicides, which include the above information, were provided by the MAH to the CHMP and also to the Agency in January 2004 in the context of their response to the request to supply "the narrative of the case reports for the suicides that occurred during clinical trials and an expert report discussing these cases".

Please indicate: [a] whether or not all of the information contained in this attachment about each of these three ‘placebo suicide’ cases was held by the MHRA before 7 April 2006; [b] whether the summaries of data held by the MHRA before that date faithfully summarised all the evidence in the records attached; [c] if not, specifically what relevant data in the enclosed attachments were not previously known to the MHRA; and [d] whether or not the MHRA will be making representations to the MAH in relation to data they failed to supply.

I can confirm that the information attached to your letter was provided by the MAH to the CHMP and also to the Agency in January 2004.

In the course of the Expert Working Group enquiry, the MAH was asked to provide "the narrative of the case reports for the suicides that occurred during clinical trials and an expert report discussing these cases". Please supply copies of the narrative of these three case reports, plus the complete expert report.

The request from the Expert Working Group was fed through to the CHMP and formed one of a list of questions sent by European Medicines Agency (EMEA) to the MAH. The submission of January 2004 from the MAH provided a response to this question. I attach a copy of that response. This has been edited to remove any information which may potentially lead to the identification of a patient. We consider this information to be exempt under Section 40 (Personal Information) of the FOIA.

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.

Yours sincerely,

Sarah Wark