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?
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.
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?
No.
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 company’s
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 CSM’s Expert Working Group on SSRIs. The MHRA/CHM additionally
reviewed the individual study reports from the paroxetine clinical trials. The report of
CSM’s 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 CSM’s 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
group’s 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.
Yours sincerely,
Sarah Wark
Direct line 020 7084 2763 |
