More opaque than an opaque thing... Part II

I've still got no idea what this is about:

Dear (redacted),

Many thanks for this. I'm not quite sure of the context of the enquiry, given the passage of time, but if I may just clarify:

At the time of the two protocols mentioned, and, indeed, the original trials on the drug, presumably carried out at some point in the late 80s, then, there was no requirement to track any side effects manifesting themselves after treatment stopped (I take it that the Note for Guidance is binding on those trialling drugs?). However, if I understand you correctly, GSK picked up on the discomfort felt by those ceasing to use the drug, anyway, and monitored it? Prior to the EWG's report, it was presumably held (by whom, or what?) that the side effect being monitored was not a matter of "addiction," but was "withdrawal".

As such, repeated denials that Seroxat was addictive were entirely justified. The EWG's findings/conclusions then validated that holding. At what point did GSK/the MHRA come to the conclusion that the discomfort being experienced was withdrawal, and was this communicated to patients/doctors prior to the publication of the EWG's Report?

On the subject of trials 329/377, I have a couple of outstanding queries, in process. As it stands, I am struggling to understand how it is that the MHRA is investigating the withholding of trials data, when there is no specific criminal offence of that nature, to my knowledge? In any event, the pertinent legislation (the Medicines for Human Use (Clinical Trials) Regulations 2004 (as amended)), succeeds any action that GSK may have taken - given the bar on retrospective legislation, generally, there is nothing to investigate, I should have thought?

As such, even if one chose to investigate an offence under Regulation 50 (provision of false or misleading information), the legislation would have come into force after any suspected "providing" took place, and would not apply. Are you able to clarify that point, for me?

Best regards

(redacted)

****************************
From: (redacted)
To: (redacted)
CC: (redacted)
Subject: FOI 07/066 Seroxat
Date: Thu, 6 Sep 2007 11:17:46 +0100


Dear (redacted),

Thank you for your e-mail that has only recently been forwarded to me to deal with. I have been requested to address your first query in paragraph 1 below and my response is attached. I regret that your question in the second paragraph of your e-mail is outside the MHRA’s jurisdiction, therefore, the MHRA will not be able to respond to this query.

Kind regards

(redacted)
Licensing Division
MHRA
Tel 0207 084 2391
Fax 0207 084 2323

Attachment:
FOI 07/066

Dear (redacted),

Regarding you enquiry back in 26 February 2007, I regret that this was not addressed at the time, however I am able to address the second part of your query which was as follows:

“Was GSK required to assess side effects outside the treatment period? I understand that some patients, I think GSK finally accepted 25% as the figure, were impacted by withdrawal symptoms, which GSK initially denied to be a factor. I have seen analysis and GSK internal documentation, concerning Trials 329 and 377, which were conducted when GSK was attempting to get a label change, at the end of the 90s. Would you be able to point me in the direction of the original trials' analysis, which secured Seroxat's licence, for adults, c. 1990?”

GSK would only be required to assess effects outside of a treatment period if that was a requirement of the trial protocol. You may be interested to know that the Note for Guidance on Clinical Investigation of Medicinal Products in the Treatment of Depression was only finalised in April 2002, see link to this guideline: (HYPERLINK http://www.emea.europa.eu/pdfs/human/ewp/051897en.pdf
http://www.emea.europa.eu/pdfs/human/ewp/051897en.pdf)

This guidance clearly recommends the investigation of the effect on stopping medication. Therefore, this guideline was developed some time after the marketing authorisation for Seroxat was granted. However, it is evident from the assessment report that the effect of abrupt withdrawal of paroxetine was followed in a number of patients and described in the original application.

With regard to trials 329 and 377, these clinical trials (and others) are part of an ongoing MHRA investigation and are exempt under section 30 of the FOIA. I understand that you can find a great deal of information about these trials on GSK's website.

You ask to be pointed in the ‘direction of the original trials' analysis, which secured Seroxat's licence, for adults, c. 1990. As already mentioned above, GSK have published a full list of trials conducted on seroxat on its website ( HYPERLINK "http://ctr.gsk.co.uk/Summary/paroxetine/studylist.asp" \o "http://ctr.gsk.co.uk/Summary/paroxetine/studylist.asp" http://ctr.gsk.co.uk/Summary/paroxetine/studylist.asp), summaries of each trial are also provided.

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 the above 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 in withholding information from you.

Yours sincerely



(redacted)
MHRA
Licensing Division
MHRA
****************************
From: (redacted)
Sent: 23 February 2007 10:17
To: (redacted)
Subject: RE: FOI 07/066

Dear (redacted),

Thank you, that clarifies considerably.

Was GSK required to assess side effects outside the treatment period? I understand that some patients, I think GSK finally accepted 25% as the figure, were impacted by withdrawal symptoms, which GSK initially denied to be a factor. I have seen analysis and GSK internal documentation, concerning Trials 329 and 377, which were conducted when GSK was attempting to get a label change, at the end of the 90s. Would you be able to point me in the direction of the original trials' analysis, which secured Seroxat's licence, for adults, c. 1990?

Incidentally, while I understand that the MHRA's investigation concerns the possibility of fraudulently withheld information (have I got the gyst of it?), is there likely to be a separate investigation into its activities, in attempting to undermine the democratic process of the House of Commons? Indeed, if it is shown that GSK withheld knowledge of suicidal behaviour, is it likely to be investigated for gross negligence manslaughter?

Best regards

(redacted)