I thought I might as well go through all the hoops and mail the Head of the absurdly-named Intelligence and Enforcement Unit, at the MHRA. This to Michael Deats, copied to Woods, Breckenridge, Vara, Johnson and the CPS:
Dear Mr Deats,
I am currently engaged in a discussion with Professors Woods and Breckenridge and the CPS (please see below) on a question over the application of Regulation 50 of the Medicines for Human Use (Clinical Trials) Regulations 2004 (as amended).
Would it be your position, as Head of the Intelligence and Enforcement Unit at the MHRA, that where trials have been carried out on a drug, and those trials have produced negative results, and that there are also trials of that same drug that have yielded results that are interpreted as positive, and it is subsequently only the positive results that are submitted in support of a marketing authorization application, that the presentation of only the positive data (owing to the suppression of the negative data) amounts to the provision of "false or misleading" information, under Regulation 50?
Best regards
Matthew Holford
Showing posts with label Criminal Investigation. Show all posts
Showing posts with label Criminal Investigation. Show all posts
Tuesday, 11 September 2007
Friday, 7 September 2007
More opaque than an opaque thing... Part III
I'm a bit disappointed with the feedback I'm getting from the MHRA, just now, so I thought I'd try a different angle. This was sent to Breckenridge and Woods, copied to Johnson, Vara and the CPS:
Dear Professors Breckenridge and Woods,
My apologies, I should have copied you in on this, earlier. There appears to be a consensus amongst the (disinterested) scientific community that the withholding of data on drugs is unscientific. I would argue that it is unlawful, although I am interested to understand whether that view is shared by the Establishment.
Either way, the practice of suppressing negative data has contributed significantly to the Seroxat farce, in all its ignominy. To date, the MHRA has done nothing to ensure that that does not happen again. I would hold that that is incompetence of the highest order, and I can only imagine that it is not doing anything, because it is not in the interests of the Worshipful Company to do anything. That is corruption, if it be true. Are you corrupt, gentlemen?
Best regards
Matthew Holford
*************************
Dear Sir or Madam,
I am currently engaged in a discussion with the MHRA, concerning the application of the Medicines for Human Use (Clinical Trials) Regulations 2004 (please see below). It appears that the MHRA is unable to provide an opinion, for whatever reason that it might have.
Is the CPS positioned such that it may provide definitive guidance as to the nature of conduct that would constitute a contravention of Regulation 50?
Best regards
Matthew Holford
********************************
Dear Professors Breckenridge and Woods,
My apologies, I should have copied you in on this, earlier. There appears to be a consensus amongst the (disinterested) scientific community that the withholding of data on drugs is unscientific. I would argue that it is unlawful, although I am interested to understand whether that view is shared by the Establishment.
Either way, the practice of suppressing negative data has contributed significantly to the Seroxat farce, in all its ignominy. To date, the MHRA has done nothing to ensure that that does not happen again. I would hold that that is incompetence of the highest order, and I can only imagine that it is not doing anything, because it is not in the interests of the Worshipful Company to do anything. That is corruption, if it be true. Are you corrupt, gentlemen?
Best regards
Matthew Holford
*************************
Dear Sir or Madam,
I am currently engaged in a discussion with the MHRA, concerning the application of the Medicines for Human Use (Clinical Trials) Regulations 2004 (please see below). It appears that the MHRA is unable to provide an opinion, for whatever reason that it might have.
Is the CPS positioned such that it may provide definitive guidance as to the nature of conduct that would constitute a contravention of Regulation 50?
Best regards
Matthew Holford
********************************
Wednesday, 5 September 2007
I see a sign... it is a good omen!
The MHRA was kind enough to follow up on a matter that I raised with it a little while back. I'm not sure that it says anything new, particularly, but it's always good to hear from somebody different. The MHRA's correspondence is emboldened, as usual:
Dear (redacted),
I have had an opportunity to read through your letter, for which, again, many thanks. I have the following comments/questions:
I believe the hypothetical scenario relates to a question that I put regarding the investigation into the GSK vaccine business, in Russia. As far as I know, there have been no decisions made as to GSK's culpability, as yet, and as such I understand that you would not wish to speculate on such a matter. In the event, one of the GSK shareholders in the House was kind enough to refer the matter to the then Secretary of State for Health, Patricia Hewitt. The DoH advised me, via the shareholder, that the MHRA does not concern itself with matters that relate to events in other jurisdictions. As such, I feel that I am as well informed on this matter as I care to be.
As to risk/benefit assessments, I believe that that very precise figure of 83 trials relates to a paper that I had read. If I remember aright, it was a piece by Peter Breggin. I regret that I do not have specific details of the trials to which (I presume) Dr Breggin was referring.
However, while I understand from your comments that the MHRA's risk/benefit analysis is perhaps more subjective than objective, I was rather more interested in the procedure involved? I see that 50 trials were held to demonstrate the efficacy of the drug - did any of these involve a review of the raw data, or were statistical summaries only provided?
Either way, I would be interested to understand how "efficacy" was demonstrated, given that Mr Goldfinch has advised me to the effect that it was not necessary for an applicant to demonstrate the level of efficacy, merely that there was efficacy. I must confess that I am struggling with this one, because if one doesn't have a frame of reference, then it will not be possible to judge whether a drug is efficacious, or not, I should have thought. Indeed, unless placebo and drug's performance are measured against the same scale, then any amount of numbers will be meaningless, irrespective of what the applicant says that the summary demonstrates. Furthermore, one may not say with confidence (nor with the conviction of truth) that a drug is better than placebo, if one does not know what the drug scored, relative to the placebo. Nor will it help if one is unaware as to what the placebo scored.
In summation, then, I am keen to understand the procedure followed in the assessment process, including the risk:benefit analysis, however mercurial the latter element may be?
Best regards
(redacted)
--------------------------------------------------------------------------------
From: (redacted)
To: (redacted)
CC: (redacted)
Subject: FOI 07/088 Seroxat
Date: Wed, 5 Sep 2007 15:56:57 +0100
Dear (redacted),
Please see attached response to your previous query, and please accept my apologies for the considerable delay in responding.
Kind regards
(redacted)
Licensing Division
MHRA
Tel 0207 084 2391
Fax 0207 084 2323
Attachment:
FOI 07/088
Dear (redacted),
Regarding you enquiry back in 9 March 2007, I regret that this was not addressed at the time, however I am able to address your queries which was as follows:
“I understand that the MHRA may have issues commenting on legal matters, particularly when such matters pertain to a jurisdiction outside its own. What would be its response, in the event that an (unnamed) pharmaceutical company were found to have breached a law in another jurisdiction, which also happened to be a law in the UK?”
The MHRA is unable to comment on a hypothetical scenario.
“I am interested to note your comment, concerning risk/benefit assessment. I understand that 83 trials were carried out on Seroxat, during the period 1980-91. What fraction of these did the MCA/MHRA view the results of? Indeed, I would be most interested to understand the technicalities of the MHRA's risk analysis. Perhaps you could advise me, on this point.”
Without a list of the 83 trials to which you refer it is not possible to say which of those trials the MHRA has viewed the results of. However, I have been able to ascertain the following information from the original assessment report:
Human Pharmacology: 59 studies were analysed and presented Pharmacokinetic data was obtained from over 60 studies; Drug interaction data was obtained from 30 studies; Efficacy data was supported by over 50 studies (11 Placebo controlled studies; 16 comparator studies; 4 double blind comparator studies, 5 long term efficacy studies; 19 open studies). Safety data will have been obtained from the above mentioned trials.
Regarding the technicalities of the MHRA’s risk analysis. There is no magic formula that can be used to weight the risk/benefit analysis, it is purely a case of considering the benefit(s) that the patients in the trials have experienced against the potential and demonstrated adverse reactions reported in the trials. Obviously the severity and the reversibility of reported adverse reactions need to be carefully balanced against the benefit to the patient of taking the product. The quality of life of the patient if untreated is also a factor that has to be taken into consideration. For some products it may be very easy to establish risk/benefit, however, there are those where the risk/benefit is less clear cut. This is one of the reasons why all new chemical entities (medicinal product) are considered by the Commission on Human Medicines (previously the Committee on the Safety of Medicine) and it subcommittees before a marketing authorisation is granted. It is also the reason why all new drugs have a black triangle for at least 3 years following the initial granting of a licence, to warn prescribers to be vigilant as this is a new product for which there is only limited experience.
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)
Licensing Division
MHRA
--------------------------------------------------------------------------------
From: (redacted)
Sent: 09 March 2007 17:21
To: MHRA Information Centre
Cc: The Four
Subject: RE:
Dear Sir or Madam,
Thank you for your kind reply.
I understand that the MHRA may have issues commenting on legal matters, particularly when such matters pertain to a jurisdiction outside its own. What would be its response, in the event that an (unnamed) pharmaceutical company were found to have breached a law in another jurisdiction, which also happened to be a law in the UK?
I am interested to note your comment, concerning risk/benefit assessment. I understand that 83 trials were carried out on Seroxat, during the period 1980-91. What fraction of these did the MCA/MHRA view the results of? Indeed, I would be most interested to understand the technicalities of the MHRA's risk analysis. Perhaps you could advise me, on this point.
Best regards
(redacted)
Dear (redacted),
I have had an opportunity to read through your letter, for which, again, many thanks. I have the following comments/questions:
I believe the hypothetical scenario relates to a question that I put regarding the investigation into the GSK vaccine business, in Russia. As far as I know, there have been no decisions made as to GSK's culpability, as yet, and as such I understand that you would not wish to speculate on such a matter. In the event, one of the GSK shareholders in the House was kind enough to refer the matter to the then Secretary of State for Health, Patricia Hewitt. The DoH advised me, via the shareholder, that the MHRA does not concern itself with matters that relate to events in other jurisdictions. As such, I feel that I am as well informed on this matter as I care to be.
As to risk/benefit assessments, I believe that that very precise figure of 83 trials relates to a paper that I had read. If I remember aright, it was a piece by Peter Breggin. I regret that I do not have specific details of the trials to which (I presume) Dr Breggin was referring.
However, while I understand from your comments that the MHRA's risk/benefit analysis is perhaps more subjective than objective, I was rather more interested in the procedure involved? I see that 50 trials were held to demonstrate the efficacy of the drug - did any of these involve a review of the raw data, or were statistical summaries only provided?
Either way, I would be interested to understand how "efficacy" was demonstrated, given that Mr Goldfinch has advised me to the effect that it was not necessary for an applicant to demonstrate the level of efficacy, merely that there was efficacy. I must confess that I am struggling with this one, because if one doesn't have a frame of reference, then it will not be possible to judge whether a drug is efficacious, or not, I should have thought. Indeed, unless placebo and drug's performance are measured against the same scale, then any amount of numbers will be meaningless, irrespective of what the applicant says that the summary demonstrates. Furthermore, one may not say with confidence (nor with the conviction of truth) that a drug is better than placebo, if one does not know what the drug scored, relative to the placebo. Nor will it help if one is unaware as to what the placebo scored.
In summation, then, I am keen to understand the procedure followed in the assessment process, including the risk:benefit analysis, however mercurial the latter element may be?
Best regards
(redacted)
--------------------------------------------------------------------------------
From: (redacted)
To: (redacted)
CC: (redacted)
Subject: FOI 07/088 Seroxat
Date: Wed, 5 Sep 2007 15:56:57 +0100
Dear (redacted),
Please see attached response to your previous query, and please accept my apologies for the considerable delay in responding.
Kind regards
(redacted)
Licensing Division
MHRA
Tel 0207 084 2391
Fax 0207 084 2323
Attachment:
FOI 07/088
Dear (redacted),
Regarding you enquiry back in 9 March 2007, I regret that this was not addressed at the time, however I am able to address your queries which was as follows:
“I understand that the MHRA may have issues commenting on legal matters, particularly when such matters pertain to a jurisdiction outside its own. What would be its response, in the event that an (unnamed) pharmaceutical company were found to have breached a law in another jurisdiction, which also happened to be a law in the UK?”
The MHRA is unable to comment on a hypothetical scenario.
“I am interested to note your comment, concerning risk/benefit assessment. I understand that 83 trials were carried out on Seroxat, during the period 1980-91. What fraction of these did the MCA/MHRA view the results of? Indeed, I would be most interested to understand the technicalities of the MHRA's risk analysis. Perhaps you could advise me, on this point.”
Without a list of the 83 trials to which you refer it is not possible to say which of those trials the MHRA has viewed the results of. However, I have been able to ascertain the following information from the original assessment report:
Human Pharmacology: 59 studies were analysed and presented Pharmacokinetic data was obtained from over 60 studies; Drug interaction data was obtained from 30 studies; Efficacy data was supported by over 50 studies (11 Placebo controlled studies; 16 comparator studies; 4 double blind comparator studies, 5 long term efficacy studies; 19 open studies). Safety data will have been obtained from the above mentioned trials.
Regarding the technicalities of the MHRA’s risk analysis. There is no magic formula that can be used to weight the risk/benefit analysis, it is purely a case of considering the benefit(s) that the patients in the trials have experienced against the potential and demonstrated adverse reactions reported in the trials. Obviously the severity and the reversibility of reported adverse reactions need to be carefully balanced against the benefit to the patient of taking the product. The quality of life of the patient if untreated is also a factor that has to be taken into consideration. For some products it may be very easy to establish risk/benefit, however, there are those where the risk/benefit is less clear cut. This is one of the reasons why all new chemical entities (medicinal product) are considered by the Commission on Human Medicines (previously the Committee on the Safety of Medicine) and it subcommittees before a marketing authorisation is granted. It is also the reason why all new drugs have a black triangle for at least 3 years following the initial granting of a licence, to warn prescribers to be vigilant as this is a new product for which there is only limited experience.
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)
Licensing Division
MHRA
--------------------------------------------------------------------------------
From: (redacted)
Sent: 09 March 2007 17:21
To: MHRA Information Centre
Cc: The Four
Subject: RE:
Dear Sir or Madam,
Thank you for your kind reply.
I understand that the MHRA may have issues commenting on legal matters, particularly when such matters pertain to a jurisdiction outside its own. What would be its response, in the event that an (unnamed) pharmaceutical company were found to have breached a law in another jurisdiction, which also happened to be a law in the UK?
I am interested to note your comment, concerning risk/benefit assessment. I understand that 83 trials were carried out on Seroxat, during the period 1980-91. What fraction of these did the MCA/MHRA view the results of? Indeed, I would be most interested to understand the technicalities of the MHRA's risk analysis. Perhaps you could advise me, on this point.
Best regards
(redacted)
Friday, 24 August 2007
Re: FOIA 07/040
I just thought I'd put the previous two posts into context:
Sent: 01 February 2007 01:53
To: MHRA Information Centre
Subject: Panorama: Secrets of the Drugs Trials
Dear Sir or Madam,
I note from the BBC's reportage that the MHRA initiated criminal proceedings against GSK, presumably with respect to its (GSK's) claims and misrepresentations about its anti-depression drug, Seroxat (Paxil, in the US):
http://news.bbc.co.uk/1/hi/health/6308871.stm
I note that this case is some three years old, and wondered what, if any, progress had been made? For what it's worth, the allegations have caused consternation, anger and resentment amongst the "depressed community", if commentary on the internet forums that I post on are anything to go by. If you were able to disclose the status of the investigation, I imagine it would be a benefit to a lot of people to know that this matter is being taken very seriously indeed by those in a position to regulate the drugs industry, and to punish those who take advantage of the desperation of people, who have little choice but to take drugs owing to the paucity of alternatives offered, generally-speaking.
Please note, for your information, that I have discussed this matter (in the context of corporate manslaughter/gross negligence manslaughter) with my local police force, and it is currently logged as an incident.
MHRA Reply
Sent: 21 February 2007 15:19
To: @hotmail.co.uk
Cc: MHRA Information Centre
Subject: RE: FOI 07/040 - FW: Panorama: Secrets of the Drugs Trials
Dear
Thank you for your e-mail of 1st February concerning reports of an MHRA investigation into GSK with respect to claims and misrepresentations concerning its anti-depression drug, Seroxat.
MHRA has considered your request under the provisions of the Freedom of Information Act 2005 and I am pleased to be able to provide the following response. The MHRA has a duty to protect public health and takes seriously any report of a suspected breaches of medicines regulations.
The MHRA investigation into GlaxoSmithKline and its alleged failure to supply pharmacovigilance information to the MHRA relating to the paediatric use of Seroxat (paroxetine) commenced on 1st October 2003. The investigation is still in progress and will continue until the relevant lines of enquiries have been concluded. No decision has yet been made on whether or not to prosecute GSK.
I hope this clarifies the position.
Sent: 01 February 2007 01:53
To: MHRA Information Centre
Subject: Panorama: Secrets of the Drugs Trials
Dear Sir or Madam,
I note from the BBC's reportage that the MHRA initiated criminal proceedings against GSK, presumably with respect to its (GSK's) claims and misrepresentations about its anti-depression drug, Seroxat (Paxil, in the US):
http://news.bbc.co.uk/1/hi/health/6308871.stm
I note that this case is some three years old, and wondered what, if any, progress had been made? For what it's worth, the allegations have caused consternation, anger and resentment amongst the "depressed community", if commentary on the internet forums that I post on are anything to go by. If you were able to disclose the status of the investigation, I imagine it would be a benefit to a lot of people to know that this matter is being taken very seriously indeed by those in a position to regulate the drugs industry, and to punish those who take advantage of the desperation of people, who have little choice but to take drugs owing to the paucity of alternatives offered, generally-speaking.
Please note, for your information, that I have discussed this matter (in the context of corporate manslaughter/gross negligence manslaughter) with my local police force, and it is currently logged as an incident.
MHRA Reply
Sent: 21 February 2007 15:19
To: @hotmail.co.uk
Cc: MHRA Information Centre
Subject: RE: FOI 07/040 - FW: Panorama: Secrets of the Drugs Trials
Dear
Thank you for your e-mail of 1st February concerning reports of an MHRA investigation into GSK with respect to claims and misrepresentations concerning its anti-depression drug, Seroxat.
MHRA has considered your request under the provisions of the Freedom of Information Act 2005 and I am pleased to be able to provide the following response. The MHRA has a duty to protect public health and takes seriously any report of a suspected breaches of medicines regulations.
The MHRA investigation into GlaxoSmithKline and its alleged failure to supply pharmacovigilance information to the MHRA relating to the paediatric use of Seroxat (paroxetine) commenced on 1st October 2003. The investigation is still in progress and will continue until the relevant lines of enquiries have been concluded. No decision has yet been made on whether or not to prosecute GSK.
I hope this clarifies the position.
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