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Mr Charles Medawar
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MHRA Reference: FOI 06/007

13 February 2006

Dear Mr Medawar

Thank you for your email of 16 January 2006 requesting information under the Freedom of Information (FOI) Act. Please find below our responses to the questions that you asked relating to paroxetine (Seroxat): 

1. Did the MHRA request from the GlaxoSmithKline, the License Holder for paroxetine (Seroxat) access to the detailed case reports of the four suicides ('the data') reported in all paroxetine and placebo trials? What was the date at which those data were first requested by MHRA?

Because of concerns about the balance of risks and benefits of paroxetine, particularly in relation to its use in children and adolescents, on 12 June 2003 the UK made a formal request to the European scientific committee, the then Committee for Proprietary Medicinal Products (CPMP), for its opinion under Article 31 of Directive 2001/83 EC on whether the marketing authorisations (MAs) for medicinal products containing paroxetine should be maintained, withdrawn or varied.

An initial review of the available data was considered by the CSM Expert Working Group on the safety of SSRIs and also by the CPMP at its November 2003 meeting. These Committees recommended that the MA holders should provide responses to a list of additional questions. This list, which included a request for the case narratives of all suicides that occurred during the paroxetine clinical trials, was sent to the MA holders by the European Medicines Evaluation Agency in December 2003.

2. If so, did the MHRA obtain all the data requested? Was the MHRA refused any of the data requested? Was the MHRA fully satisfied with the quality of the data supplied? And if those data were supplied to the MHRA by the License Holder, please explain why they were not seen by members of the Expert Working Group?

In January 2004 the Marketing Authorisation Holder for Seroxat provided a full response to the list of questions issued by the EMEA in December 2003. The request for the case narratives was only one of a list of questions and the Netherlands and the UK as the lead Member States for the European review prepared assessment reports on the MA holder's response to these questions. In these assessment reports which were considered by both the CSM Expert Working Group on the Safety of SSRIs and the then Committee for Proprietary Medicinal Products (CPMP), the information contained in the case narratives for all suicides that occurred in relation to the paroxetine clinical trials was summarised but the full case narratives were not provided at that time. The Expert Working Group and the CPMP considered that this question had been adequately addressed and no further information was requested on these cases of suicide.

3. Can the MHRA confirm that all three `placebo suicides' involved patients involved in clinical trials for patients with depression? If not, please identify the treatment groups (diagnosis) in which each of these placebo suicides occurred.

Two of the three placebo suicides' occurred in individuals enrolled in depression clinical trials. The third case was a patient with a past medical history of major depressive disorder who was enrolled in post-traumatic stress disorder trial.

4. Please identify, in the case of each of the three placebo suicides, how many days had elapsed after the end of the treatment phase when each suicide occurred.

In the first case the patient had made a suicide attempt during the study and a further attempt 14 days after last dose of medication. They committed suicide 33 days after the last dose of study medication.

In the second case the patient committed suicide 17 days after their study medication was stopped. They had received ECT therapy 3 days earlier.

In the third case the patient committed suicide 19 days after their study medication was stopped.

5. Can the MHRA confirm that none of the three people on placebo who committed suicide during cite host-treatment phase had been taking an antidepressant drug at or around the time they died? If not, please identify which drugs were being taken by each of the three patients identified as 'placebo suicides', and how many days had elapsed between commencement of that drug treatment and the date of suicide.

From the case narratives reviewed it does not appear that any of the individuals in these three placebo suicides were receiving an antidepressant drug around the time they died. In one of the cases the individual had received a course of ECT 3 days prior to the date that they committed suicide.

6. Is the MHRA entirely satisfied that the sponsoring company (MAH) fully and properly investigated tile circumstances of each of the three `placebo suicides'? If not, please identify, in each case, what data were missing and why.

The level of detail provided in these cases is similar to that which would be expected in clinical trial adverse events. The MHRA has had no reason to question the investigation of these cases by the MA holder.

7. Will the MHRA now publish all (appropriately anonymised) information in its possession at the time of publication of the Expert Working Group report (December 2004) relating to each of the three `placebo suicides' and if not, why not.

Detailed information on the data considered by the CSM Expert Working Group on the safety of SSRIs in reaching its conclusions has been provided in the Group's full report that was published in December 2004. We do not consider that publication of these three 'placebo suicides' adds significantly to this information and therefore do not propose to release anonymised information on these cases. Also the MHRA will not release data on individual cases that could potentially lead to the identification of an individual.

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

Dr Julie Williams
Therapeutic Team Leader
Pharmacovigilance Risk Assessment Unit
Post Licensing Division

Cc Ms Sarah Wark MHRA/PL