More opaque than an opaque thing... Part IV

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

The MHRA - taking patient reporting seriously - Part IV

Well, I feel properly satisfied with the outcome of this. Thank goodness my experience isn't a trivial matter for those who have an interest in the drugs I take:


Dear (redacted),

Many thanks for this. I believe it answers my questions satisfactorily, and I consider the complaint dealt with.

The issue, then, lies elsewhere: the manufacturers are not responsible, because the risk of suicidal ideation was noted on the PIL; my GP was not responsible, even though he was responsible for my care, because he brought the side effect to my attention, when he prescribed the drug (and then, when I experienced the side effect, told me that it wasn't the drug); the MHRA is not responsible, because it is not required to be responsible.

May I ask who is responsible - and this is not a rhetorical question, I would like an answer? Could you seek guidance from the Secretary of State on this one, please, because I am keen to understand whether it is believed that I should be responsible for my reaction to chemicals that, with the greatest of respect to the MHRA, are not controlled particularly effectively, judging by the less than scientific approach that is taken to licensing (both by manufacturers and regulators)?

I have to be honest, rarely have I experienced such a sorry catalogue of failure and incompetence as this. There are so many gaps in this system that it is a wonder to me that anybody survives it. More to the point, when a flaw is identified, the MHRA (and others) appear determined to argue that everything is just hunky dory, and that a complainant is somehow deranged to even suggest that anything is wrong. In short, full defensive mode is initiated. And yet, the MHRA is characterized as a world leader?

Best regards

(redacted)




********************************
From: "Pharmacovigilance,"
To: (redacted)
Subject: Yellow Card Complaint
Date: Mon, 10 Sep 2007 10:36:39 +0100


Dear (redacted)

You raised a formal complaint that your Yellow Card report was not subject to follow-up. This complaint has been investigated by the Signal Management Group and I will address your concerns below.

Further to your Freedom of Information (FOI) request FOI 07-246 on the 15th August 2007 concerning the Yellow Card Scheme, a response was sent to you on 30 August 2007 explaining what a ‘follow-up’ is and detailing the process by which it is determined whether it is necessary for a Yellow Card report to be followed-up. Please refer to this communication for further explanations of the process of ‘follow-up’. In summary I will reiterate that the term follow-up refers to the communication with the reporter to request further information regarding their Yellow Card report.

The following up of a report is at the discretion of our pharmacovigilance scientists and assessors at the MHRA and is in no way a compulsory part of the Yellow Card Scheme. As stated in the FOI 07-246 response the request for further information or ‘following up’ of a report does not necessarily signify these reports are of greater importance or interest.

With regards to your Yellow Card report, I can confirm it was determined a request for further information from yourself was not necessary at that time for two main reasons:

Firstly the report you completed was adequately filled in to provide enough information to be entered onto our database for rapid analysis and assessment by our physicians, pharmacists and scientists.

Secondly the suspected adverse reaction reported by yourself was suicidal ideation. As you are well aware, Suicidal ideation is listed as a potential side effect in the Patient Information Leaflet (PIL) for fluoxetine. Whilst we are not in any way dismissing the seriousness of this reaction, this in itself does not necessarily warrant a Yellow Card report being followed up.

The risk of suicidal ideation and suicide with SSRIs are continually monitored by the MHRA. In May 2003, in response to continuing public concerns about the safety of SSRIs, an Expert Working Group of the Committee on Safety of Medicines (CSM) was convened to investigate ongoing safety concerns with these medicines, in particular around suicidal behaviour and withdrawal reactions/dependence. I believe you are already aware of this ‘Report of the CSM Expert Working Group on the Safety of SSRI’s’ and your questions regarding its contents and conclusions have already been satisfactorily addressed.

With regards to provision of the manufacturer’s details of the generic fluoxetine you were prescribed, I am unable to provide you with this information. Currently there are approximately 32 marketing authorisation holders for generic brands of fluoxetine in the UK and therefore I am not able to inform you which of these MAHs provided the fluoxetine you were prescribed by your practitioner. However the MAHs name would clearly have been stated on the packaging and also on the Patient Information Leaflet provided with the pack as a legal requirement.

I hope you feel this letter addresses your complaint in all respects. If you remain dissatisfied, you can make representations to the Central Complaints Officer:

(redacted)
MHRA
16-107 Market Towers
1 Nine Elms Lane
Vauxhall
SW8 5NQ

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

********************************

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)

Abuse of Trust IV - Russia charges 3 doctors over Glaxo vaccine tests

""Many of the children sent for trials had been diagnosed with diseases. They (GSK) had no right to put children with health problems through these clinical tests. It can lead to a deterioration in the child's condition, which has happened in the case of some of these children.”

...A company spokeswoman said its own internal audit showed informed consent had been given by all parents and doctors involved in the trial."

Read on: http://glaxosmithklinenews.blogspot.com/2007/03/uninformed-consent.html

This is a relatively old story (5 or 6 months, or so, and there doesn't appear to be anything new on it, judging by my Google search). This was the case that I contacted the DoH (and the MHRA) about, and it is the case that the One of the Four contacted me about ("Delighted to engage GSK shareholders" (below)). I was told that the MHRA knew no more about it than what was avaialable in the press.

What a bunch of jobsworths!

Matt

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.

Re: FOI 07/118

I had an afterthought, this morning, which I've just communicated to the Clinical Trials Unit:

Dear [redacted],

As an afterthought: if it is not a criminal offence to withhold trials data, nor, as I understand it from your letter, is it a criminal offence to fail to provide a summary of results/statistical analysis, may I ask how it is possible for the MHRA to investigate GSK for withholding trials data (an investigation that has gone on for over three years, now, I understand)?

Put another way, is there an offence on the statute book that amounts to "Withholding clinical trials data/statistical analysis/summary of results"?

Best regards

Matthew Holford

Re: FOI 07/118

I received a response from the MHRA to a query I put to it back in April, but which it overlooked, at the time. Much as it galls me, I've had to type it up, because I can't work out how to drop in the original Acrobat document, which was attached! My original 'mail is immediately below and my reply is beneath the MHRA's missive, which I've emboldened, for convenience. Make of it what you will, although I would like to draw your attention to the MHRA's "catchphrase," which is "Safeguarding Public Health."

Matt

From: Matthew Holford
Sent: 12 April 2007 15:51
To: MHRA Information Centre
Cc: [redacted]@gsk.com; [one of the Four]@parliament.uk; [one of the Four]@parliament.uk; [one of the Four]@cix.co.uk; [one of the Four]@parliament.uk; [my MP]@parliament.uk
Subject: FOI 07/118 - Medicines regulation and the pharmaceutical industry


Dear Sir or Madam,

I was interested to read the article, by your esteemed Chairman and CEO, respectively, Prof Breckenridge and Kent Woods:

http://www.bmj.com/cgi/content/full/331/7520/834

I must confess myself surprised and delighted to discover that the MHRA charges companies, for the purpose of licensing trials. As such, it is presumably aware of any trial, for which it has granted a licence, and for which it does not receive trials results, including details of elements of that trial conducted in other countries? Does the MHRA keep records of any such failure to notifiy, or is its interest limited to collection of the trial fee? If it does, may I ask from what date it began keeping this information? Also, may I ask what percentage of authorized trials do not have the results notified to the MHRA? May I ask what action it takes, in the event that a failure to notify has taken place? Indeed, may I ask what period of grace, after the end of the trial, does the MHRA permit companies, before commencing legal action, under the relevant legislation (The Medicines for Human Use (Clincial Trials) Regulations 2004 (http://www.opsi.gov.uk/si/si2004/20041031.htm#28))?

Finally, I note that the offences, identified under ss49-50, shall be subject to a fine or a maximum period of imprisonment not exceeding two years (ie, they are considered not to be a serious arrestable offences), upon conviction on indictment. The maximum fine, which is defined by statute, is currently £5,000, I believe. To what extent does the MHRA understand these penalties to be an adequate deterrant to non-compliance with the Law?

Best regards


Matthew Holford

***********************

22 August, 2007

Dear Mr Holford

It has been brought to my attention that you have not been provided with a response to your request for information under the Freedom of Information Act (FOIA) made on 12 April 2007. I apologise for this oversight and I provide a response below:

The Clinical Trials Directive 2001/20/EC and the UK implementing legislation (SI 2004/1031) refer to the sponsors' liability to notify the competent authorities of concerned Member States of the end of a trial within 90 days of its completion. There is no reference however to notification of trial results.

The implementing European Commission guidance ENTR/F2/BL/D 2003 Revision 2:

Detailed guidance for the request for authorisation of a clinical trial on a medicinal product for human use to the competent authorities, notification of substantial amendments and declaration of the end of the trial. [MHRA's emphasis]

refers in section 4.3.2.4: Clinical Trial Report: "The sponsor should provide a summary of the clinical trial report within one year of the end of the trial to the competent authorities of the concerned member states..."

The above legislation and guidance came into effect on 01 May, 2004. In the UK prior to that date the clinical trial legislation placed no obligation on trial sponsors to notify the competent authority of the results from clinical trials, at the end of the trial.

The MHRA has therefore to date, not kept records of where trials results have not been notified to it, following completion of clinical trials in the UK.

I hope this is helpful and once again I apologise for the delay in replying.

Yours sincerely

[redacted]
Clinical Trials Unit

*************************

Dear [redacted]

As you may appreciate, I'm not fully conversant with the way in which the various pieces of legislation "mesh". If I understand correctly, then, a clinical trial must be licensed in order to proceed. Upon completion (or presumably early termination) this must be communicated to the MHRA (in the UK), within a certain specified period of time, with failure to do so being a criminal offence. It is also my understanding that the Medicines for Human Use (Clinical Trials) Regulations 2004 (as amended) provide that information must not be provided that is false or misleading. Regulation 50 provides, if I remember aright.

From your comments, it is apparent that a sponsor may, if it so wishes, not provide the results of trials that have been completed and such completion presumably properly reported. If received wisdom is to be believed, this will be because a trial has "failed". In any event, results data is regarded as proprietary within the industry, and a company may not be compelled to give it up. Indeed, if I understand correctly, trials data is not generally given up, even where a trial is deemed "successful" and used in the marketing authorization application portfolio to demonstrate the "efficacy" of a drug, even where, as is apparently the case with Seroxat, the level of efficacy has not been demonstrated. Instead, a statistical analysis is usually provided. None of this sounds terribly scientific to me, but then I'm a compliance professional, not a drugs regulator.

I would be interested to understand how the MHRA views this withholding of data? We know that certain Seroxat trials "failed", and the results were not made public. Others were held to demonstrate efficacy, and a statistical report based on the successful trials was presumably made available to the MCA/MHRA with the licensing portfolio. This presumably purported to demonstrate efficacy (although not very precisely, as I understand it), safety and quality, or else the product would not have been licensed.

If something similar were to happen today, would this withholding of data be deemed to amount to an offence under Regulation 50 by the MHRA? That is, if a company provides less than all the information about a drug, and the information withheld is negative, then the information that is provided is presumably false, or misleading. Also, does the MHRA endeavour to ensure that it has, at least, a statistical report from all trials conducted on a particular drug, in the event that a marketing authorization is sought for that drug?

I would be interested to read of your views.

Best regards

Matthew Holford

The MHRA: taking patient reporting seriously

Dear All,

I've just spent a short break down in the West Country. And very nice it was, too. Now, fully rejuvenated, I felt inclined to escalate my complaints up the MHRA foodchain. To which end, I've just had this little exchange with our esteemed drugs regulator. I've emboldened the MHRA's reply, for convenience:

Dear Sean,

It's remarkable how one's memory can play tricks on one, is it not? Perhaps it was the DoH that I had that conversation with. Or the ABPI. Or my doctor. Or the NHS. Or the Samaritans. Or my colleagues. Or my blog. In any event, my primary concern is not that the MHRA overlooked an issue that I believe I raised with it, but rather that it appears to have failed to do what it purports to do; that which it appears to exist to perform; and, moroever, that which it asserted to be valuable. Perhaps we should focus on that?

In any case, thank you for your kind attention. Given the background to this particular request, perhaps I can rely on the MHRA not to brand it vexatious, on this occasion?

Best regards

Matthew Holford

From: [redacted]
To: Matthew Holford, "MHRA Information Centre" info@mhra.gsi.gov.uk
CC: [Alan Johnson], [Shailesh Vara], [Alasdair Breckenridge], [Kent Woods]
Subject: RE: Yellow Card scheme
Date: Wed, 15 Aug 2007 10:38:31 +0100

Dear Mr Holford,

I refer to your email below.

Having read through your earlier FOI requests which form the subject of my review, I have not encountered any questions which relate to the Yellow Card Scheme. You are, therefore, correct in stating that this is not under consideration in my review.

As there does not appear to be a record of you having asked a question on the Yellow Card Scheme before, I have requested the Information Centre to treat this as a new FOI request. They will acknowledge your request and refer your questions to the appropriate unit who will respond to you directly.

Kind regards,

[redacted]

From: Matthew Holford [mailto:m.holford@hotmail.co.uk]
Sent: 15 August 2007 02:46
To: MHRA Information Centre
Cc: Alan Johnson; [Shailesh Vara]; [redacted]; [Alasdair Breckenridge]; [Kent Woods]
Subject: Yellow Card scheme

Dear Sean,

It occurred to me recently that I have asked about the Yellow Card scheme, during the course of my enquiries. However, this does not appear to be under consideration, in your review.

I was keen to understand how the scheme operated, or didn't operate, as the case may be. At the time of its roll-out, back in October, 2005, Dr Patricia Wilkie, Chairman of the CSM’s Working Group on Patient Reporting, declared that direct patient reporting was essential for medicines safety monitoring. Moreover, it would be an important source of information for patients about their medicines. Meanwhile, the MHRA's CEO, Kent Woods, declared that it would provide new insight - he was right about that, at least - and that it would permit patient involvement in regulation. I would be interested to understand how those objectives are achieved? In detail, please.

Also, you may be aware that just less than half of Yellow Card reports are followed up (according to your esteemed Chairman, Professor Sir Alasdair (that's D-A-I-R) Breckenrdige). Perhaps the MHRA could explain to me how it is that this fact contributes to either Dr Wilkie's or Mr Wood's objectives?

Finally, having submitted a Yellow Card myself, following suicidal ideations experienced whilst taking fluoxetine, I regret to report that I have been one of the unlucky 51% who has received a perfunctory hard copy, but no follow up. Having no experience of the process, I would be grateful if the MHRA could explain what "follow up" means? Does it have any familial relationship with NICE's "careful and frequent monitoring," by any chance?

I find it difficult to believe that my experience is untypical. However, I don't imagine that I'm your typical dissatisfied customer, either. The MHRA's response has been slipshod at best. At worst I daren't think what it is. Either way, I'm going to find out.

Best regards


Matthew Holford

PS to Mr Johnson: is it true that the Police and Criminal Justice Act 2001 had several key provisions introduced at the behest of the Worshipful Company of Apothecaries (ie, Big Pharma)? If so, could I request just one inclusion, the next time an amendment is made to the CJA - not to be treated like a twat by government bodies? I know that this is a personal request, but I'm sure others could benefit. Thanks everso.

"FOI Review - Seroxat"

My latest jolly exchange with the MHRA, copied to Alan Johnson (the incumbent Secretary of State for Health, though for how much longer is debateable), Shailesh Vara (my MP), and the Information Commissioner's Office:

Dear ,

I have received your letter and attachments of 10 July, and I would respond as below. However, please be clear that while you have identified this series of communications to concern Seroxat, they at least equally concern the MHRA's conduct, with Seroxat being used as a case study:

FOI 07/040 - my request of 1 February and the MHRA's response of 21 February

I understand that there is a limit to the information that the MHRA is able to provide, in the context of an ongoing investigation. Having looked at this question in conjunction with the Medicines for Human Use (Clinical Trials) Regulations 2004 (as amended), I have come to the conclusion that the information made available to the public is scant - it is difficult to establish a reasoned view of the conduct of the Company, even where one assumes that the 2004 Regulations apply in terms of the bar on retrospective application. The extent to which the MHRA wishes to publicize its belief that the Company has complied with the relevant legislation in certain respects, whilst continuing to investigate other areas, would be a matter for the MHRA.

FOI 07/104 - my requests of 27 March and the MHRA's response of 23 April

I raised several questions in my emails, most of which have been dealt with, although I do have a couple of outstanding queries. Thus, I am still unclear as to what the Company considered "significantly more affective" to constitute. Mr Fawbert suggested that I contact the Company for this information, which I have done, on several occasions. However, the Company appears unwilling to communicate with me, though I can't imagine why. As such, I would be keen for the MHRA to approach the Company, because I would be keen to understand what the Company thought the benefit of the drug was, if only in the US. Presumably the MHRA has the authority to compel a response - if it doesn't, I would be grateful if you could clarify that, because I would be keen to have a more complete understanding of the limits of the MHRA's authority.

Also, given the lack of information in the public domain, mentioned above, I am disappointed to note that where a member of the public wishes to conduct his/her own investigation into the conduct of a company or its regulator, (s)he will be precluded from doing so, with the FOIA being cited as authority.

FOI 07/105 - my request of 30 March and the MHRA's undated reply

It is reasonably clear from the MHRA's reply that it felt the Government had taken the appropriate course. However, with respect, I asked what the MHRA's response was to the allegations made by the HSC, and not the Government's. Also, while the legislation is no doubt rigourously drafted, at all times, I don't imagine that any regulator is precluded from introducing additional procedures where it perceives a need.

I believe I am correct in stating that the MHRA has no written internal procedures, nor does the MHRA publish and enforce an industry Rulebook, for the benefit of its members? For what it's worth, if I am correct in this understanding, then I consider this to be an appalling state of affairs. I believe I am also correct in stating that I asked for detailed information concerning the way that assessments were carried out (in a separate request, which it does not appear that you are considering in your review). As to the first point, I am keen to understand why? As to the second point, I believe this to be critical in my understanding of the MHRA's commitment to safeguarding public health.

In short, I believe it appropriate that I should be permitted to understand the rules that the MHRA purports to operate by. I fail to understand the secrecy.

FOI 07/130 - my request of 24 April and the MHRA's response of 22 May

I accept the explanations put forward by Mr Fawbert, concerning the changes to the PIL. However, you will note, perhaps, that this ties in with the question concerning the withholding of trials data, touched upon in FOI 07/040. Dr Benbow's comments are at odds with the 1998-2000 UK exercize, which Mr Fawbert mentions in his response to FOI 07/104, and with the Company's internal dialogue, dated October, 1998. I was interested to undersand whether the MHRA, as regulator, concerned itself with this incongruence, a point also covered under FOI 07/140?

FOI 07/131 - my request of 23 April and the MHRA's response of 22 May

I believe I sent a follow-up mail to Mr Fawbert's reply (indeed, I imagine I tend to regard these things as a dialogue, rather than simple, one-off requests for information, as you will probably have noted), in which I suggested that, owing to the risk of suicide, it would be appropriate for the largescale study mentioned to be carried out. As I recall, I also took issue with Mr Fawbert's claim that suicide was symptomatic of depression, or that depression causes suicide.

Perhaps the MHRA regards this as a semantic argument, but depression does not cause death in the same way that cancer does, as such I am still struggling to understand the acceptance of the increased suicide risk acknowledged to be created by Seroxat, given the apparent absence of an identified benefit.

Incidentally, the link that Mr Fawbert provided, for further information on the Licensing process (http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&nodeId=102), does not appear to work.

FOI 07/140 and 142 - my request of 29 and 30 April and the MHRA's responses of 3 May

My queries concern Dr Benbow's claims, my wish to understand why these are so clearly at odds with official perception of the risks and with my ongoing concern regarding the absence of any clear definition of "efficacy" or "benefit", as those words pertain to Seroxat. I am concerned that such key questions were stonewalled.

I believe that is everything, aside from the issue of "vexatious" requests. Mr Goldfinch may not have understood where I was going with my enquiries, but then he should have asked, shouldn't he? He is a public servant, much as Mr Johnson is. "Another to go to Mr Holford"? Perhaps Mr Goldfinch would not be so flippant, if he understood better what I had experienced, coincidental to SSRI useage?

Best regards



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From:
To:
CC:
Subject: FOI Review - Seroxat Date: Mon, 9 Jul 2007 12:22:06 +0100
Dear ,

I have now managed to locate your earlier FOI requests on our database. There are 12 requests, 10 of which relate to Seroxat. Of these 10, 7 have been replied to and it appears that you have not received a reply to 3 of the requests.

Your email of 22 June 2007 raises a number of complaints about the MHRA's failure to provide you with some of the requested information. As you may appreciate, it would be very difficult to conduct an effective review of the MHRA's responses to your requests based on general complaints, nor would I want to run the risk of linking your complaints to the incorrect FOI requests. I propose, therefore, to send you hard copies of your requests and the responses sent to you from the MHRA. I will not send you papers relating to the 3 requests for which you have not received a reply, however, I will address these in my review.

I would be grateful if you could consider your requests and the replies received and then identify the specific areas that you would like reviewed. Grounds for review may include the failure to answer a question, or disagreement with the application of a FOI exemption applied etc.

Could you please provide me with your postal address so that I can send you the hard copies.

Many thanks,