This statement has been issued following the BBC Panorama programme, ‘Secrets of The Drugs Trials’ which was aired on Monday 29th January.
GlaxoSmithKline (GSK) strongly denies the allegations made by Panorama in their programme that it has acted in any way improperly and wishes to make the following points:
· We are extremely concerned that as a result of the programme patients will be anxious about using their anti-depressant medication.
· Patients concerned by issues raised in the programme should seek advice from their doctor.
· Depression is a severe and disabling condition. A well-recognised, tragic outcome of the disease, particularly among young people, is suicide. Careful monitoring of all patients is essential, regardless of whether they are taking medication or not.
· In developing Seroxat , GSK has always been strongly conscious of the duty it owes to the millions of patients, including those under the age of 18, who suffer from depression and we refute any allegation that we have failed in this duty. GSK conducted nine studies, over eight years, to examine the use of Seroxat in treating patients under the age of 18 with depression and other psychiatric disorders, as treatment options for these vulnerable patients are extremely limited.
· GSK utterly rejects any suggestion that it has improperly withheld drug trial information. Results from its paediatrics studies were documented and submitted to regulators in accordance with regulatory requirements. Results were also presented publicly, published in scientific journals and are available on GSK’s website.
· No suicides were reported in any of the nine paediatric trials conducted by GSK. When reviewed individually, none of these trials were considered by GSK or independent investigators to show a clinically meaningful increase in the rate of suicidal thinking or attempted suicide. Only when all the data became available, at the end of the research programme, and were analysed together was an increased rate of suicidal thinking or attempted suicide revealed in those paediatric patients taking Seroxat . GSK brought this analysis to the attention of the regulatory authorities, including in the UK.
· GSK does not promote its medicines for indications for which they are not approved. The company strongly refutes any suggestion that Seroxat was promoted to UK doctors for use outside the terms of the UK marketing authorisation, whether through clinical experts (“Key Opinion Leaders”) or any other route.
· Seroxat has never been approved by EU or US regulators as a medicine for those under 18 years of age. GSK’s UK product labelling has been entirely consistent with that position, and at the time of the events in question, this label stated: “the use of Seroxat in children is not recommended, as safety and efficacy have not been established in this population.” Any decision to prescribe a medicine outside its authorised indications, in the EU or the US, is made by a doctor on the basis of his/her clinical judgement and the interests of their patient.
· The JAACAP (Keller) publication in July 2001 was authored by Dr. Keller and the other named authors. GSK acted appropriately in engaging a professional medical writer to provide assistance with the manuscript, under the direction of the authors, and the medical writer’s contribution was clearly disclosed on the front of the article. The authors had full responsibility and editorial control for the article. The article clearly presented, in full, the primary and secondary outcomes and adverse events reported in the study.
· GSK, in 2004, further demonstrated its commitment to data transparency by creating an unsurpassed on-line database, called the Clinical Trial Register (CTR). This is a record of detailed summaries of more than 2,800 clinical trials (published and unpublished) conducted in 50 countries to study 52 GSK prescription medicines and vaccines which is available to the public at http://ctr.gsk.co.uk.
Updated January 29, 2007
© 2001-2006 GlaxoSmithKline - All rights reserved
I accept that the press release was issued pursuant, I suspect, to a damage limitation exercize, following Secrets of the Drugs Trials. Similarly I accept that GSK would be very keen to deny the allegations made, and that it would be concerned that patients should stop taking their medication - although why it should be concerned escapes me, just for the moment. As such, the instruction to consult with doctors is unsurprising.
"Depression" to the extent that we have any understanding of the "disease" does not cause death. The suggestion that suicide victims would have killed themselves, anyway, and that the drug had no influence on the matter is the most repulsive piece of blame-shifting I've ever seen. GSK acknowledges that an increased suicide risk exists with the drug, and the argument that nobody killed themselves during clinical trials is grotesque, in my view: before somebody kills him/herself they have to have thought about it, first. And suicidal ideations (and, indeed, other forms of suicidality), most definitely did feature in the trials.
In any event, GSK acknowledges that once it had completed its trials programme, it was able to analyse all the data, at which point the incidence of increased suicidality became apparent. Now, excuse the shit out of me, but I rather thought that GSK had not "improperly withheld" trials data from the regulator. Now, let's just assume for the minute that that means that they submitted all trials data to the MHRA, in the UK (it doesn't, because the industry traditionally regards trials data as proprietary information, which companies may withhold, as they see fit). However, assuming that the MHRA received everything, then it would have been constantly monitoring the situation, because this is what it tells us it does, repeatedly. Did it not occur to anybody, before the results were in from the ninth trial, that there was a pattern emerging? What the fuck are you cunts doing? Not regulating, and that's for sure. So, eight years down the line, somebody does a meta analysis, and it suddenly dawns that there's an issue with respect to increased suicide, whereupon a marketing authorization for treatment of adolescent depression is applied for. Doesn't quite fucking scan, does it?
There are suggestions circulating that "off label" prescribing is promoted to quacks. I have nothing else to say on that.
THE NAMED AUTHORS DID NOT WRITE THAT ARTICLE. Keller co-wrote a letter to Dr Mina Dulcan, at JAACAP, with Dr Neal Ryan and "WHOEVER [sic] WANTS TO OR SHOULD CO-AUTHOR THIS." I suggest you scroll down and read "The Life and Times of Martin Keller, MD - Part V..." for fuller details of what actually happened. The article had already been submitted, published and criticized, by the time that draft was written. And people were still adding their names to it. You fucking charlatans.
Whoopee-doo to your online databases. The Yellow Card system is supposed to be a world leader, but it's apparently so poorly administered that healthcare professionals have no faith in it, and no longer submit reports, because they know that there's only an even money chance that they'll be followed up.
Matt
Tuesday, 31 July 2007
Friday, 27 July 2007
Forty-three Years of Yellow Cards, or Ethon's Retribution
The Yellow Card Scheme is a British initiative run by the Medicines and Healthcare products Regulatory Agency (MHRA) and the Commission on Human Medicines (CHM) to gather information on Adverse Drug Reactions (ADRs) to medicines. This includes all licensed medicines from medicines and vaccines issued on prescription to medicines bought over the counter from a pharmacist or supermarket. The Scheme also includes all herbal preparations and unlicensed medicines found in cosmetic treatments. ADRs can be reported by anyone; generally healthcare professionals including doctors, pharmacists and nurses, as well as patients and carers.
The sort of ADRs that should be reported are:
The sort of ADRs that should be reported are:
- ADR's that have caused death or a serious illness
- Any ADR, however minor, if associated with a new medicine or one that is under continued monitoring (highlighted in the British National Formulary (BNF) with a ▼ black triangle)
- Any ADR, however minor, if associated with a child (under 18 years of age)
Yellow Cards are available from pharmacies and a few are presented near the back of the BNF as tear-off pages.
Reports from the Yellow Card scheme are available from the MHRA website.
Source: Wikipedia
Well, that's clear enough, isn't it? Incidentally, to all intents and purposes, the above is the information provided on the MHRA website, where it accompanies links to online Yellow Card forms. So, if our doctor doesn't complete a Yellow Card on our behalf, when we complain to him/her of something subsequent to taking a drug, we can always go online and complete a form, which the MHRA will address. Incidentally, I should mention that the Yellow Card scheme was set up in 1964, following the Thalidomide tragedy (this is the language used by the NHS Wales website, by the way).
Mind you, this business of patients reporting their own experiences is a relatively new thing, seemingly prompted by a recommendation made by the Health Select Committee, following its report into the influence of the pharmaceutical industry, in 2005 - the only recommendation it made that was taken up, to my knowledge - which suggested that a country-wide system of patient reporting be put in place "as soon as possible". The NHS Wales website carries a nice little piece, complete with jolly quotes-you-like from your favourite healthcare bureaucrats, which is dated October, 2005, at the time of the UK pilot roll-out. I didn't realize it was as recent as that. Importantly, for Kent Woods, CEO of the MHRA, patient reporting would provide new insight and permit the public to become involved in medicines regulation. My own experience with the MHRA suggests that public involvement goes no further than filling out Yellow Cards.
Meanwhile, Dr Patricia Wilkie, Chairman of the CSM’s Working Group on Patient Reporting, was even more effusive about the role of direct patient reporting, declaring that it was essential for medicines safety monitoring. Moreover, it would be an important source of information for patients about their medicines. However, as ever, there is a counterproposition to this optimistic propoganda.
Back in August, 2003, Charles Medawar reported that he had conducted an analysis of anonymized Yellow Cards pursuant to a series of investigations undertaken by the BBC's Panorama, concerning the risks associated with Seroxat. He and his co-authors discovered significant failings in the way the system was being operated. "Chaotic and misconceived" was the upshot, if I remember correctly. The MHRA had seemingly systematically failed to follow up on reports of patient suicidality. Yellow cards submitted by drug companies used euphemistic language to conceal the true nature of the side effect experienced. Similarly, several different terminologies would be used to describe essentially the same complaint, thus making a side effect look less significant in terms of its occurrence than was the true case. And so on.
However, you will be pleased to know that the MHRA's excellent Chairman, Prof Sir Alasdair (that's D-A-I-R) Breckenridge, regarded the Yellow Card scheme as "an important way that the MHRA monitors drug safety." Back in January, 2005, when Prof Breckenridge gave this thunderous endorsement of the reporting scheme, the Health Minister, Lord Warner, was announcing the publication of anonymized data, taken from Yellow Cards, on the MHRA's website, thus permitting public scrutiny, and access to data for the purposes of further research.
But I think it's worth taking another look at the view of Prof Alasdair (that's D-A-I-R) Breckenridge. We've already established that the Yellow Card scheme is important in providing fresh data on side effects, post-licensing. The MHRA, which has as its primary goal the protection of the public from shite medical products, lest we forget, has told us that this is true, in the person of its Chairman. I just thought I'd reiterate that.
In fact, the MHRA regarded the Seroxat Yellow Cards as so important that Prof Breckenridge claimed that
"...in the appropriate... in the appropriate cases, this is... these patients are followed up. The follow up rate for Yellow Card reports is some 48% - 49%."
That quotation is taken from the transcript of the Panorama programme Taken on Trust, a precursor to Secrets of the Drugs Trials. And, yes, he really did struggle as much as those ellipses suggest (no, they don't indicate that I have edited his words!). I should say that I'm not quite clear as to whether Breckenridge is referring to Yellow Cards in general, or Seroxat suicide reports, when he advises Shelley Jofre that 49% are followed up.
So, we have euphemisms. We have semantics. We have poor follow up - certainly in the case of Seroxat suicidality reports, and, I suspect, more generally. Indeed, I filed a Yellow Card myself, consequent to suicidal ideations experienced when I took fluoxetine. I received a hard copy of the report, and I've heard nothing since. This patient regards that as unforgiveable.
The MHRA is four years old.
Matt
Thursday, 26 July 2007
The Life and Times of Martin B Keller, MD - Part V: Ghost in the Machine
The first four parts of my little homage to the great genius that is Dr Keller are to be found on Bob Fiddaman's Seroxat Sufferers, under "Matthew Holford rant". However, this one's my personal favourite, and I couldn't help but reproduce it, here.
Ghost in the Machine
It is from Gilbert Ryles' critique of Descartes' view of dualism that I have taken the title of Part V. It is a play on words, though, because this little offering is about ghostwriters within the medical establishment. One particular ghostwriter, in fact, and one particular ghostwriting incident. Having said that, whilst conducting the research on this piece, my colleagues and I have, perhaps, clarified something that is potentially more valuable.
However, as an opening gambit, I would like to observe that mind/body dualism is not an original theory, by any means, and I would like to do this, because I can't conceive that I can make the subject matter of this piece any more bizarre than it already is by doing so. Once again, Classical Antiquity appears to witness the first recorded instance of this idea being discussed. Consider Plato's Concept of Forms, whereby universal concepts (ideas) permit us to understand the world. The intellect, then, may not be attributed to any particular organ of the body. Presumably this holds true of corporate persons, as well as natural persons. More recently, Descartes believed that the immaterial mind causally interacted with the material body, and vice versa.
Presumably, this means that body language is capable of being read: the mind will cause the body to behave in a particular way (I'm a fan of the practical benefits of theoretical discourse, as you may have gathered). If the understanding of a person was sufficiently subtle, this might even be done with precision, given that the eye takes in more information than any other organ of the senses, I'm told. This is fine, as long as mind, body and verbal communication are fully congruent. That doesn't happen very often, though, in my experience: people tend to modify their verbal language, in accordance with what is socially acceptable, for example, or to gain an advantage (lie, in other words).
This issue becomes significant, when the "incongruent person" insists that the verbal communication represents a truth. Consider the stiff body language of politicians, for example, when judging the value of this suggestion. Are people subconsciously aware that their body language communicates more than they would like it to, and attempt to suppress it?
I will leave the gentle reader to ponder that particular question as I return to the issue at hand. Now, we should, perhaps, recall that Study 329 was a cluster fuck, as far as SmithKline Beecham ("SKB") was concerned (my succinct appraisal of its position). The data suggested that the drug was dangerous and inefficacious in the target demographic (minors), by the Company's own admission. We should recall that the Company engaged a PR company, Scientific Therapeutics Information, Inc. ("STI"), to prepare a piece for publication in a peer-reviewed journal, JAACAP, and that Dr Martin Keller seemingly was chosen to endorse this piece, because he was perceived to be a key opinion leader, whatever that might be. Although, in the words of Drs Keller and Ryan, it seems that anybody who wanted to put their name to it, should feel free to do so, according to their draft letter to the Editor of JAACAP, Dr Mina Dulcan. I suppose that's one way to bulk out one's CV. Next, the piece, written by one Sally Laden, I am reliably informed, who no longer works for STI, received some stiff criticism from reviewers, if I may understate it like that, before having marketing authorizations refused in both the UK and US, although, as far as I am aware, none of the criticism was ever acted upon. Amusingly, in the draft letter to Dulcan, Keller and Ryan argue that if a trial fails to demonstrate efficacy, then the regulator will refuse to license. I was similarly amused by the additional detail that Keller and Ryan read into Drs Jureidini and Tonkin's critique. By extension, anybody who agrees with Drs Keller and Ryan will be as intellectually and morally superior, as they are, in their view.
Anyway, I don't like to dish dirt, so you can Google Laden's name, for yourself. Actually, no. Here's one perspective on the Cyberonics business, in the Write Stuff. And here's another, from the Alliance for Human Research. Make of that what you will, although I would note that Cyberonics is not directly concerned with ghostwriting, and so doesn't fit my theme as well as I would have liked, because, per Laden's own words, as quoted by Bloomberg News, she was just a facilitator (ie, she made things easier, presumably). A ghostwriter, as in the 329 case, will always be anonymous.
Now, I've tried to restrict myself to the bare facts, without engaging in histrionics, supposition or hyperbole, but I have to say, in my opinion as a compliance professional, the whole 329/JAACAP thing doesn't look good. And yet, because I have access to some very talented people, aside from my own skills and experience, I understand that this is by no means a complete picture of the process that was followed in order to transform Seroxat/Paxil from a dubious-looking piece of chemistry into a product that was "generally well tolerated and effective for major depression in adolescents."
So, who is the ghost in the machine, today? Is it Sally Laden? Was she given SKB's "disappointing" data, and then took to spinning it for the benefit of Dr Keller and his co-authors? Well, one of my good friends and colleagues (a pathologist) has rejected that possibility, and I'm inclined to agree with him. It seems that the likely scenario was that a SKB statistician was given the data, and, how shall I put this most delicately, was led or led him/herself to understand what was required? This re-jigged data would then have been presented, most likely in the form of a statistical report, to Sally Laden, who would have proceeded to base her view on that, possibly in complete ignorance of the true position. So taken were we by this theory that we decided to test it, and the upshot is that somebody else, aside from the statistician, is the ghost, so we're still looking, but it's only a matter of time.
Now, at the time that 329's numbers were being crunched, Rosemary Oakes was a senior statistician at SKB, or is that "Senior Statistician"? The person who managed and directed the US-based phase four (whatever that means) Paxil clinical trials was a chap by the name of James McCafferty, per his deposition made pursuant to several actions brought against SKB in various states, in 2006. This deposition is concerned with a discussion of primary endpoints and covariant analyses, which a dumbass like me isn't going to pretend to understand, although I found it quite amusing, because McCafferty doesn't appear to understand it, either. Now, Oakes and McCafferty were concerned with the generation of data from 329, as evidenced by this exchange, taken from Oakes' deposition, and, presumably, with the generation of the statistical report that most likely would have been presented to Laden.
"So, what?", I hear you ask, and quite rightly. Well, we know that in October, 1998, SKB believed that it had a turkey on its hands. And quite rightly. And yet, in March, 1999, we have Oakes and McCafferty's 'mail to Laden, which is appended, here, which is of greater interest to me, just now. McCafferty, then, was apparently Laden's primary contact at SKB. Given the juxtaposition between these various communications, one might also lead oneself to understand that the document that Oakes and McCafferty are working on is an early draft of Laden's finest work. It is also in this exchange that we see the first appearance of Dr Marty Keller (remember him?), and it is clear that McCafferty is in direct contact with both him and Ryan, which may or may not be an issue.
Moving on to July, 1999, and McCafferty is now in contact with Laden, here. He has noticed the incongruence between the claims made as to the drug's safety in Laden's latest draft, as against the admission in the same draft of significant reports of adverse events. He also expresses his concern that the editors (of JAACAP, or just generally?) will rumble this inconsistency, which I find quite amusing, given that Dulcan's failure to do so was, by exension, what Drs Jureidini and Tonkin were complaining of, so Keller tells us. In the words of Michael Stipe the "shit's so thick, you could stir it with a stick." Even SKB had noticed the stench. Two days later, McCafferty again contacts Laden, apparently this time to suggest a solution to the issue raised in his mail of 19 July, here.
Now, being the nitpicker that I am, I am not satisfied that this demonstrates that Laden had seen the original 329 trial data, particularly given that Oakes was still crunching 329 data eight months after the trial ended, according to that deposition. I am not even sure that this crunching of data means that Oakes was arranging for a "biased" statistical report to be made available to Laden. However, given McCafferty's comments with respect to suggested amendments to Laden's draft, she might have come to the conclusion that a rigorous appraisal of the data that was made available to her was not what was required, although I say this as a compliance professional, and not a medical writer. As to Dr Keller, being an honourable man, I don't doubt that he would be appalled to have a piece of work such as this on his CV.
Matthew Holford (c) 2007
Related Links:
Bad Day Lyrics (REM)
BBC Panorama
Brown University
Glaxo SmithKline
Ghost in the Machine
It is from Gilbert Ryles' critique of Descartes' view of dualism that I have taken the title of Part V. It is a play on words, though, because this little offering is about ghostwriters within the medical establishment. One particular ghostwriter, in fact, and one particular ghostwriting incident. Having said that, whilst conducting the research on this piece, my colleagues and I have, perhaps, clarified something that is potentially more valuable.
However, as an opening gambit, I would like to observe that mind/body dualism is not an original theory, by any means, and I would like to do this, because I can't conceive that I can make the subject matter of this piece any more bizarre than it already is by doing so. Once again, Classical Antiquity appears to witness the first recorded instance of this idea being discussed. Consider Plato's Concept of Forms, whereby universal concepts (ideas) permit us to understand the world. The intellect, then, may not be attributed to any particular organ of the body. Presumably this holds true of corporate persons, as well as natural persons. More recently, Descartes believed that the immaterial mind causally interacted with the material body, and vice versa.
Presumably, this means that body language is capable of being read: the mind will cause the body to behave in a particular way (I'm a fan of the practical benefits of theoretical discourse, as you may have gathered). If the understanding of a person was sufficiently subtle, this might even be done with precision, given that the eye takes in more information than any other organ of the senses, I'm told. This is fine, as long as mind, body and verbal communication are fully congruent. That doesn't happen very often, though, in my experience: people tend to modify their verbal language, in accordance with what is socially acceptable, for example, or to gain an advantage (lie, in other words).
This issue becomes significant, when the "incongruent person" insists that the verbal communication represents a truth. Consider the stiff body language of politicians, for example, when judging the value of this suggestion. Are people subconsciously aware that their body language communicates more than they would like it to, and attempt to suppress it?
I will leave the gentle reader to ponder that particular question as I return to the issue at hand. Now, we should, perhaps, recall that Study 329 was a cluster fuck, as far as SmithKline Beecham ("SKB") was concerned (my succinct appraisal of its position). The data suggested that the drug was dangerous and inefficacious in the target demographic (minors), by the Company's own admission. We should recall that the Company engaged a PR company, Scientific Therapeutics Information, Inc. ("STI"), to prepare a piece for publication in a peer-reviewed journal, JAACAP, and that Dr Martin Keller seemingly was chosen to endorse this piece, because he was perceived to be a key opinion leader, whatever that might be. Although, in the words of Drs Keller and Ryan, it seems that anybody who wanted to put their name to it, should feel free to do so, according to their draft letter to the Editor of JAACAP, Dr Mina Dulcan. I suppose that's one way to bulk out one's CV. Next, the piece, written by one Sally Laden, I am reliably informed, who no longer works for STI, received some stiff criticism from reviewers, if I may understate it like that, before having marketing authorizations refused in both the UK and US, although, as far as I am aware, none of the criticism was ever acted upon. Amusingly, in the draft letter to Dulcan, Keller and Ryan argue that if a trial fails to demonstrate efficacy, then the regulator will refuse to license. I was similarly amused by the additional detail that Keller and Ryan read into Drs Jureidini and Tonkin's critique. By extension, anybody who agrees with Drs Keller and Ryan will be as intellectually and morally superior, as they are, in their view.
Anyway, I don't like to dish dirt, so you can Google Laden's name, for yourself. Actually, no. Here's one perspective on the Cyberonics business, in the Write Stuff. And here's another, from the Alliance for Human Research. Make of that what you will, although I would note that Cyberonics is not directly concerned with ghostwriting, and so doesn't fit my theme as well as I would have liked, because, per Laden's own words, as quoted by Bloomberg News, she was just a facilitator (ie, she made things easier, presumably). A ghostwriter, as in the 329 case, will always be anonymous.
Now, I've tried to restrict myself to the bare facts, without engaging in histrionics, supposition or hyperbole, but I have to say, in my opinion as a compliance professional, the whole 329/JAACAP thing doesn't look good. And yet, because I have access to some very talented people, aside from my own skills and experience, I understand that this is by no means a complete picture of the process that was followed in order to transform Seroxat/Paxil from a dubious-looking piece of chemistry into a product that was "generally well tolerated and effective for major depression in adolescents."
So, who is the ghost in the machine, today? Is it Sally Laden? Was she given SKB's "disappointing" data, and then took to spinning it for the benefit of Dr Keller and his co-authors? Well, one of my good friends and colleagues (a pathologist) has rejected that possibility, and I'm inclined to agree with him. It seems that the likely scenario was that a SKB statistician was given the data, and, how shall I put this most delicately, was led or led him/herself to understand what was required? This re-jigged data would then have been presented, most likely in the form of a statistical report, to Sally Laden, who would have proceeded to base her view on that, possibly in complete ignorance of the true position. So taken were we by this theory that we decided to test it, and the upshot is that somebody else, aside from the statistician, is the ghost, so we're still looking, but it's only a matter of time.
Now, at the time that 329's numbers were being crunched, Rosemary Oakes was a senior statistician at SKB, or is that "Senior Statistician"? The person who managed and directed the US-based phase four (whatever that means) Paxil clinical trials was a chap by the name of James McCafferty, per his deposition made pursuant to several actions brought against SKB in various states, in 2006. This deposition is concerned with a discussion of primary endpoints and covariant analyses, which a dumbass like me isn't going to pretend to understand, although I found it quite amusing, because McCafferty doesn't appear to understand it, either. Now, Oakes and McCafferty were concerned with the generation of data from 329, as evidenced by this exchange, taken from Oakes' deposition, and, presumably, with the generation of the statistical report that most likely would have been presented to Laden.
"So, what?", I hear you ask, and quite rightly. Well, we know that in October, 1998, SKB believed that it had a turkey on its hands. And quite rightly. And yet, in March, 1999, we have Oakes and McCafferty's 'mail to Laden, which is appended, here, which is of greater interest to me, just now. McCafferty, then, was apparently Laden's primary contact at SKB. Given the juxtaposition between these various communications, one might also lead oneself to understand that the document that Oakes and McCafferty are working on is an early draft of Laden's finest work. It is also in this exchange that we see the first appearance of Dr Marty Keller (remember him?), and it is clear that McCafferty is in direct contact with both him and Ryan, which may or may not be an issue.
Moving on to July, 1999, and McCafferty is now in contact with Laden, here. He has noticed the incongruence between the claims made as to the drug's safety in Laden's latest draft, as against the admission in the same draft of significant reports of adverse events. He also expresses his concern that the editors (of JAACAP, or just generally?) will rumble this inconsistency, which I find quite amusing, given that Dulcan's failure to do so was, by exension, what Drs Jureidini and Tonkin were complaining of, so Keller tells us. In the words of Michael Stipe the "shit's so thick, you could stir it with a stick." Even SKB had noticed the stench. Two days later, McCafferty again contacts Laden, apparently this time to suggest a solution to the issue raised in his mail of 19 July, here.
Now, being the nitpicker that I am, I am not satisfied that this demonstrates that Laden had seen the original 329 trial data, particularly given that Oakes was still crunching 329 data eight months after the trial ended, according to that deposition. I am not even sure that this crunching of data means that Oakes was arranging for a "biased" statistical report to be made available to Laden. However, given McCafferty's comments with respect to suggested amendments to Laden's draft, she might have come to the conclusion that a rigorous appraisal of the data that was made available to her was not what was required, although I say this as a compliance professional, and not a medical writer. As to Dr Keller, being an honourable man, I don't doubt that he would be appalled to have a piece of work such as this on his CV.
Matthew Holford (c) 2007
Related Links:
Bad Day Lyrics (REM)
BBC Panorama
Brown University
Glaxo SmithKline
Withdraw-Seroxat petitition
I suppose it would be remiss of me if I were not to tout the petition I had authorized on the Downing Street website. I regret that after the initial burst of enthusiasm, I have been, erm, "relaxed" about promoting it. This, perhaps combined with a lack of support for the objective, explains the fact that it's managed to clock just one signature every three days since it was authorized!
Anyway, the petition will be "live" for another six months, or so, and I would like to get the requisite 200 (I think) signatures to have the thing considered by Brown and his mates, so if you feel strongly about this issue, I would urge you to sign:
http://petitions.pm.gov.uk/Withdraw-Seroxat/
Matt
Anyway, the petition will be "live" for another six months, or so, and I would like to get the requisite 200 (I think) signatures to have the thing considered by Brown and his mates, so if you feel strongly about this issue, I would urge you to sign:
http://petitions.pm.gov.uk/Withdraw-Seroxat/
Matt
Delighted to engage GSK shareholders...
Welcome back, gentle reader (I'm in Aesop mode). People often ask me where I get the ideas for my stories. I always answer as truthfully as I am able: that my inspiration tends to be the people whom I meet and the events that I witness. It was only the other day... (that's enough Aesop. Ed.)
It was way back in February, this year, when the most recent Panorama expose, Secrets of the Drugs Trials, aired that GSK took to contacting MPs of constituencies in which GSK had premises (as I understand it) and asked them to not sign the Motions for Early Day ("EDMs") of a certain MP, Paul Flynn, who has been known to be critical of Big Pharma. I have to say, I took a dim view of GSK, which does not vote as a member of the electorate, influencing the democratic process, in this way. So, I took to copying The Four, as they're probably not known, on my correspondence with the MHRA, by way of reprise - a state of affairs that I was sure to communicate to them. The Four are the four MPs who identify themselves in the Register of Interests as being shareholders of GSK.
Some time ago, I had cause to write to the MHRA concerning an incident in Russia, whereby GSK were being investigated over some alleged research transgressions involving vaccinations of children. I was delighted to have one of The Four seek clarification of the MHRA's powers from the then Secretary of State for Health, Patricia Hewitt. The upshot was that the MHRA is under no obligation to take any interest in any allegations of wrongdoing made in other jurisdictions.
I wrote back to the one of the Four expressing my disappointment. I pointed out that in Compliance circles, it is well known that those who are up to no good will target territories with weak controls. This was not to say that I was pre-judging GSK's conduct. God forbid that I should be so precipitous. No, I was merely pointing out that as a matter of due diligence, it was my opinion that a good regulator would regard an incident such as that in Russia as a flag, and would undertake an investigation.
Today, I received another letter from the One, where he expressed the belief that legislation would be required to permit that kind of multi-jurisdictional authority. I fear I was a little scathing in response, as I pointed out that one does not need legislation to pick up the phone and ask one's Russian counterpart what the story is. Nor does one need legislation to call the UK HQ of one's member company and cordially invite it to have a discussion about the incident at one's offices.
I was quite blunt in owning up that I regard the MHRA as a non-regulator. I have no idea what it's doing, to be honest, but I'm quite convinced that it's not regulating. I wonder what it thinks it's doing?
I have to say, it's a bit worrying that the MHRA is regarded as a world leader in this regulatory field. What are everybody else's regulators like, I wonder? Of course, while those of a generous nature might point out that people are flocking to the UK to do their research and get their drugs licensed, which validates the claim of the MHRA's excellence, I think I might be inclined to reiterate my observation to the One and suggest that the UK has actually got the weakest controls, which would also explain it's popularity.
Matt
It was way back in February, this year, when the most recent Panorama expose, Secrets of the Drugs Trials, aired that GSK took to contacting MPs of constituencies in which GSK had premises (as I understand it) and asked them to not sign the Motions for Early Day ("EDMs") of a certain MP, Paul Flynn, who has been known to be critical of Big Pharma. I have to say, I took a dim view of GSK, which does not vote as a member of the electorate, influencing the democratic process, in this way. So, I took to copying The Four, as they're probably not known, on my correspondence with the MHRA, by way of reprise - a state of affairs that I was sure to communicate to them. The Four are the four MPs who identify themselves in the Register of Interests as being shareholders of GSK.
Some time ago, I had cause to write to the MHRA concerning an incident in Russia, whereby GSK were being investigated over some alleged research transgressions involving vaccinations of children. I was delighted to have one of The Four seek clarification of the MHRA's powers from the then Secretary of State for Health, Patricia Hewitt. The upshot was that the MHRA is under no obligation to take any interest in any allegations of wrongdoing made in other jurisdictions.
I wrote back to the one of the Four expressing my disappointment. I pointed out that in Compliance circles, it is well known that those who are up to no good will target territories with weak controls. This was not to say that I was pre-judging GSK's conduct. God forbid that I should be so precipitous. No, I was merely pointing out that as a matter of due diligence, it was my opinion that a good regulator would regard an incident such as that in Russia as a flag, and would undertake an investigation.
Today, I received another letter from the One, where he expressed the belief that legislation would be required to permit that kind of multi-jurisdictional authority. I fear I was a little scathing in response, as I pointed out that one does not need legislation to pick up the phone and ask one's Russian counterpart what the story is. Nor does one need legislation to call the UK HQ of one's member company and cordially invite it to have a discussion about the incident at one's offices.
I was quite blunt in owning up that I regard the MHRA as a non-regulator. I have no idea what it's doing, to be honest, but I'm quite convinced that it's not regulating. I wonder what it thinks it's doing?
I have to say, it's a bit worrying that the MHRA is regarded as a world leader in this regulatory field. What are everybody else's regulators like, I wonder? Of course, while those of a generous nature might point out that people are flocking to the UK to do their research and get their drugs licensed, which validates the claim of the MHRA's excellence, I think I might be inclined to reiterate my observation to the One and suggest that the UK has actually got the weakest controls, which would also explain it's popularity.
Matt
Wednesday, 25 July 2007
"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
--------------------------------------------------------------------------------
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,
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
--------------------------------------------------------------------------------
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,
Overdue update...
Well, quite a lot has happened, since I started this blog. I was having difficulty logging on, for some reason, and I lost interest, which explains the lengthy gap in between the first post and this one.
Anyway, I've been writing a couple of things for Bob Fiddaman's Seroxat Sufferers, which you may be interested in taking a read of: http://fiddaman.blogspot.com/search/label/Matthew%20Holford%20Rant, and which will probably give you a fair understanding of what I've been up to. I quite enjoyed writing the Marty Keller series, even though it's old ground. I should mention that those mentioned in the various pieces were given advance warning of publication, and were invited to comment. Nobody did, not surprisingly.
I've also engaged in quite a lengthy exchange with the MHRA. I'll include my most recent exchange under a separate post, but the upshot is that my correspondence with them was truncated by some jobsworth by the name of Richard Goldfinch, who branded my queries as "vexatious". In reprise, I raised several complaints, which are supposedly being investigated by the MHRA, even as I write this.
Also, I've been spending a bit of time on the Uncommon Knowledge fora. I still haven't worked out why people perceive the need to take drugs for their problems, but there you go. Oh, this'll make you laugh, my ex-employer sent the police round to my house, alleging that I was harassing it (I'd copied it in on some emails to various MPs, including mine, where the subject matter touched upon its behaviour). I told the PC who attended that, amongst other things, Albourne Partners Limited, for such it is, had the most dubious attitude towards anti-money laundering legislation, and a peculiar approach towards employee relations, generally. We agreed that I would only pursue my allegations, if Albourne felt inclined to pursue its allegations against me. I await further intelligence with great eagerness!
Anyway, I'll post the latest from the MHRA, and I promise to keep things up-to-date, from now on.
Matt
Anyway, I've been writing a couple of things for Bob Fiddaman's Seroxat Sufferers, which you may be interested in taking a read of: http://fiddaman.blogspot.com/search/label/Matthew%20Holford%20Rant, and which will probably give you a fair understanding of what I've been up to. I quite enjoyed writing the Marty Keller series, even though it's old ground. I should mention that those mentioned in the various pieces were given advance warning of publication, and were invited to comment. Nobody did, not surprisingly.
I've also engaged in quite a lengthy exchange with the MHRA. I'll include my most recent exchange under a separate post, but the upshot is that my correspondence with them was truncated by some jobsworth by the name of Richard Goldfinch, who branded my queries as "vexatious". In reprise, I raised several complaints, which are supposedly being investigated by the MHRA, even as I write this.
Also, I've been spending a bit of time on the Uncommon Knowledge fora. I still haven't worked out why people perceive the need to take drugs for their problems, but there you go. Oh, this'll make you laugh, my ex-employer sent the police round to my house, alleging that I was harassing it (I'd copied it in on some emails to various MPs, including mine, where the subject matter touched upon its behaviour). I told the PC who attended that, amongst other things, Albourne Partners Limited, for such it is, had the most dubious attitude towards anti-money laundering legislation, and a peculiar approach towards employee relations, generally. We agreed that I would only pursue my allegations, if Albourne felt inclined to pursue its allegations against me. I await further intelligence with great eagerness!
Anyway, I'll post the latest from the MHRA, and I promise to keep things up-to-date, from now on.
Matt
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