I was just wondering what the MHRA assessment process looked like. It wouldn't tell me, you see, so I had to do something to fill the gap in my knowledge. I came up with this:
MHRA: Are your drugs the best in the world, ever?
Worshipful Company: Oh, yes!
MHRA: Are they really safe, and efficacious, such that none may doubt your great wisdom and excellence?
Worshipful Company: Oh, yes!
MHRA: Well, I think that's all I need to know: the Marketing Authorization will be in the post, tonight.
Anyway, yesterday's "Here's an interesting little snippet" reminded me that I wrote to the Head of the MHRA's ill-named Intelligence and Enforcement Unit back in September (see Sept, 2007 archives). I re-sent the query, copied to Brown, Johnson, Vara and blind copied to a whole bunch of people:
Dear Mr Deats,
You may remember that I contacted you, back in September, of last year. I don't appear to have had a response from you, on this point:
"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?"
Far be it from me to question the quality of the MHRA's response time to any but the most trivial of queries, but I think five months is probably enough thinking time. Would the scenario that I've drawn up for you qualify as a breach of Regulation 50? This is an example of one of those embarassing little questions that the MHRA is so piss poor at answering. However, the cumulative effect of all these unanswered questions is quite telling - they give me some idea of the areas where the MHRA does not wish to commit itself, and one may only speculate on why that would be...
Best regards
Matthew Holford
Thursday, 28 February 2008
Wednesday, 27 February 2008
Here's an interesting little snippet:
To the Ministry of Truth, at the MHRA, copied to Brown, Johnson and Vara, blind copied to lots of people:
Drug giants warned: Tell the truth on medicines
Towards the bottom of the piece, the D'oh is quoted as saying:
"The Government has consistently supported open access to information about research when the findings could affect decisions about treatment or health outcomes. We planned to support the principle of mandatory registration of clinical trials in the UK, but legal advice stated this would be illegal under EU law."
First, I don't think anybody should be positioned, such that they can make a decision upon whether findings "affect decisions about treatment..." The information should be made publicly available. End of. Second, it was my understanding, although the MHRA never explicitly confirmed that it was also its understanding, that the Medicines for Human Use (Clinical Trials) Regulations ("MHU") required that all trials be registered, and that regulators be notified when trials had ended (it didn't have to confirm it: it's Law). The MHU is itself an implementation of EU Law. So, the EU says that all trials must be registered and notified when they end, but there is no requirement to do other than submit the data to the regulator - the Worshipful Company is protected by EU Law from wider scrutiny?
The loophole (or should that be "black hole"?), here is the regulator. It has the power to demand data. It receives all data, we're told. And then it makes really fucking weird choices that other bodies making similar decisions (eg NICE), are altogether more circumspect about, given that they don't have access to the same data.
And all this, which as we know leads to abuse of trust (Vioxx, Avandia, Seroxat, Seroquel, etc, etc, ad nauseum), is permitted to continue, because the Worshipful Company is entitled to pretend that trials results are trade secrets. I think somebody's putting the wrong weighting on their decision-making. This is about public health and safety, not commerce, and if one approaches this problem from the former angle, this whole cluster fuck looks anomalous. It only looks proper and normal, when a minority interest is being protected.
Matt
Drug giants warned: Tell the truth on medicines
Towards the bottom of the piece, the D'oh is quoted as saying:
"The Government has consistently supported open access to information about research when the findings could affect decisions about treatment or health outcomes. We planned to support the principle of mandatory registration of clinical trials in the UK, but legal advice stated this would be illegal under EU law."
First, I don't think anybody should be positioned, such that they can make a decision upon whether findings "affect decisions about treatment..." The information should be made publicly available. End of. Second, it was my understanding, although the MHRA never explicitly confirmed that it was also its understanding, that the Medicines for Human Use (Clinical Trials) Regulations ("MHU") required that all trials be registered, and that regulators be notified when trials had ended (it didn't have to confirm it: it's Law). The MHU is itself an implementation of EU Law. So, the EU says that all trials must be registered and notified when they end, but there is no requirement to do other than submit the data to the regulator - the Worshipful Company is protected by EU Law from wider scrutiny?
The loophole (or should that be "black hole"?), here is the regulator. It has the power to demand data. It receives all data, we're told. And then it makes really fucking weird choices that other bodies making similar decisions (eg NICE), are altogether more circumspect about, given that they don't have access to the same data.
And all this, which as we know leads to abuse of trust (Vioxx, Avandia, Seroxat, Seroquel, etc, etc, ad nauseum), is permitted to continue, because the Worshipful Company is entitled to pretend that trials results are trade secrets. I think somebody's putting the wrong weighting on their decision-making. This is about public health and safety, not commerce, and if one approaches this problem from the former angle, this whole cluster fuck looks anomalous. It only looks proper and normal, when a minority interest is being protected.
Matt
Tuesday, 26 February 2008
Psych Drug Shocker: Antidepressant Drugs Work No Better than Placebo; Big Pharma Hoax Finally Exposed (Westender, Brisbane headline)
Well, the shit has well and truly hit the fan, hasn't it? Fidders has done a lovely little round up of some of the mainstream press coverage, if you hadn't seen it, yet:
Any comment from MHRA or DOH?
However, Seroxat Secrets' treatment of the matter reminded me of my discussion with Richard Goldfinch. I made this comment, which just about sums up my feelings on the way that I have been bullshitted and misled, as I have tried to understand this grotesque and unseemly mess:
Sorry to go over old ground, but do you remember all the fun and games that I had with Dick Goldfinch? He told me that there was no definition of efficacy. He told me that it was not known how much more beneficial than placebo Seroxat was. He told me that it just was, and then he told me to “fuck off” (actually he told me that I was vexatious and that no further correspondence was being entered into with me on the subject of Seroxat, but the effect is much the same).
Well, now, it seems that NICE has a definition of efficacy: 3 Hamilton points more effective than placebo (as such, SSRIs, at 1.8 points, are a big pile of kak). Also, it seems that NICE knew about this 1.8 points.
Am I fucking missing something here? Why does the body that passes drugs for use on the NHS know about this stuff, when the body that licences drugs for use by hoi polloi seems to know absolutely FUCK ALL? I must be missing something, because that looks like one mega-sized cluster fuck, to me.
Matt
Any comment from MHRA or DOH?
However, Seroxat Secrets' treatment of the matter reminded me of my discussion with Richard Goldfinch. I made this comment, which just about sums up my feelings on the way that I have been bullshitted and misled, as I have tried to understand this grotesque and unseemly mess:
Sorry to go over old ground, but do you remember all the fun and games that I had with Dick Goldfinch? He told me that there was no definition of efficacy. He told me that it was not known how much more beneficial than placebo Seroxat was. He told me that it just was, and then he told me to “fuck off” (actually he told me that I was vexatious and that no further correspondence was being entered into with me on the subject of Seroxat, but the effect is much the same).
Well, now, it seems that NICE has a definition of efficacy: 3 Hamilton points more effective than placebo (as such, SSRIs, at 1.8 points, are a big pile of kak). Also, it seems that NICE knew about this 1.8 points.
Am I fucking missing something here? Why does the body that passes drugs for use on the NHS know about this stuff, when the body that licences drugs for use by hoi polloi seems to know absolutely FUCK ALL? I must be missing something, because that looks like one mega-sized cluster fuck, to me.
Matt
Saturday, 23 February 2008
Yellow Cards - Part II
To Phul, copied to Brown, Johnson and Vara:
Oh, and another thing, Mr Phul. How dare you tell me that the "benefits outweigh the risks," and that you are continually monitoring the safety profile of these drugs, when NICE, at least, already acknowledges (or should that be "recommends to doctors"?), that I could go for a run with some mates, or use psychotherapy, and experience the same level of improvement. That is the benefit of Seroxat, isn't it: 10 fucking Hamilton points, which may or may not be sustainable? You and your colleagues in the industry are pushing placebos with side effects, and that's the truth of the matter. I will not be made responsible for the fact that SSRIs are snake oil remedies, manufactured by charlatans, talked up by lackeys (KOLs), and prescribed by the medical equivalent of MacDonalds' counter staff.
The benefits did not outweigh the risks for me, Mr Phul. So kindly do not try to project your reality onto me. Is that clear? If you can be bothered, you will address my experience, and not try to reinforce the MHRA's beliefs (which appear to be skewed by its need to uphold the interests of the Worshipful Company), which run contrary to mine, on this point.
Best regards
Matthew Holford
Addendum:
The NICE reference is to the following document (see section 4.4): CG23 - Depression: Management of depression in primary and secondary care
Oh, and another thing, Mr Phul. How dare you tell me that the "benefits outweigh the risks," and that you are continually monitoring the safety profile of these drugs, when NICE, at least, already acknowledges (or should that be "recommends to doctors"?), that I could go for a run with some mates, or use psychotherapy, and experience the same level of improvement. That is the benefit of Seroxat, isn't it: 10 fucking Hamilton points, which may or may not be sustainable? You and your colleagues in the industry are pushing placebos with side effects, and that's the truth of the matter. I will not be made responsible for the fact that SSRIs are snake oil remedies, manufactured by charlatans, talked up by lackeys (KOLs), and prescribed by the medical equivalent of MacDonalds' counter staff.
The benefits did not outweigh the risks for me, Mr Phul. So kindly do not try to project your reality onto me. Is that clear? If you can be bothered, you will address my experience, and not try to reinforce the MHRA's beliefs (which appear to be skewed by its need to uphold the interests of the Worshipful Company), which run contrary to mine, on this point.
Best regards
Matthew Holford
Addendum:
The NICE reference is to the following document (see section 4.4): CG23 - Depression: Management of depression in primary and secondary care
Thursday, 21 February 2008
Yellow Cards
Too funny: this is a real bonus, because I wasn't expecting a reply to my original message. "The benefits outweigh the risks". Not for me, they fucking didn't, Mr Phul, and I would have appreciated being told that I could have had the benefits, without the risks, by exercizing for an hour, three times a week, or with psychotherapy. The MHRA's Great Words of Wisdom are in bold, as usual:
Dear Mr Phul,
Thank you for taking the time to respond, although it is something of a non-answer, from my perspective. SSRIs are a placebo substitute (given their level of efficacy), but have extreme side effects, which are acknowledged. It is regrettable that the Worshipful Company has chosen to profit from the fact that it is regarded as unethical to prescribe placebos.
Please do not express your regret at my experience. First, because you do not know what I have experienced (and thus you do not know what you are apologizing for), and second, because it is evident that you have no intention of seeking an understanding and making redress. What I experienced is not acceptable, irrespective of the pharmaceutical industry's lack of understanding of mental illness. The lack of concern that has been demonstrated subsequently, by all interested parties, merely suggests to me that not only are those parties determined to lock down their own position, but also to ensure that it is made clear to me that the only possible explanation for my experience is down to me. In other words, the MHRA, with others, is justifying what happened to me. I think you understand how I need to respond to that.
For the record, I do not accept that interpretation of events. Unpleasant as it is to conceive, the logical, alternative explanation for my experience is that the MHRA (and others), is incompetent. There are many factors that contribute to this being an reasonable alternative explanation, not least because it is apparently driven by the marketing concerns of the industry (which is itself marketing-led), that it purports to regulate. When an organization's culture is geared towards sales and marketing, compliance tends to go out of the window, in my experience.
When the MHRA speaks as freely to patients as it does to the companies it regulates, I will review my position. The problem is still Ms Raine's.
Best regards
Matthew Holford
********************************
Subject: Re: Yellow Cards
Date: Thu, 21 Feb 2008 13:43:13 +0000
From: [redacted]@mhra.gsi.gov.uk
To: [redacted]@hotmail.co.uk
Dear Mr Holford,
Thank you for your recent e-mail to Dr Raine regarding your concerns about fluoxetine and the side effects you experienced. I have attached a response to this message.
Kind regards
[redacted], BSc (Hons) Ph.D
Senior Pharmacovigilance Scientist
Vigilance and Risk Management of Medicines
Medicines and Healthcare products Regulatory Agency
Attachment:
Dear Mr Holford,
Thank you for your recent e-mail to Dr Raine regarding your concerns about fluoxetine and the side effects you experienced. I have been requested to reply on her behalf. I am sorry to hear of the problems you have had since taking this medicine.
I understand you have been in correspondence with other colleagues in the Agency and we have noted your concerns regarding the use of SSRIs and I would like to assure you that as with all medicines, the safety of fluoxetine is closely monitored by the Medicines and Healthcare products Regulatory Agency/Commission on Human Medicines to ensure that the benefits of this medicine outweigh any potential risks, and when evidence of a new safety issue comes to light, appropriate action is taken.
Thank you again for contacting us and taking the time to fill in a Yellow Card, your contribution to the scheme is important.
Yours sincerely
[redacted]
Senior Pharmacovigilance Scientist
Pharmacovigilance Information Unit
Vigilance and Risk Management of Medicines
Room 15-208
cc: [redacted], Pharmacovigilance Information Unit Manager
********************************
From: Matthew Holford
Sent: 18 February 2008 13:26
To: Raine, Dr June
Subject: Yellow Cards
Dear Ms Raine,
I understand that the following quotation is attributable to you:
"If you suspect that you have had a side-effect to your medicine, please tell us about it via the Yellow Card scheme."
I have filled out a Yellow Card report, as it happens, but I'll tell you about the side effect that I experienced consequent to using fluoxetine, too. It made me suicidal. I think it was the sense, as I paced in between my front room and kitchen, unable to settle, like a hunted animal (I believe this is known as akathasia), that it would never end. And that nobody cared, either. Do you care (servant) Raine? Really? How about you (servant) Texture? (servant) Johnson? (servant) Vara? Anybody? No, I didn't think so.
There: I've told you about it. Now, it's your problem.
Best regards
Matthew Holford
Dear Mr Phul,
Thank you for taking the time to respond, although it is something of a non-answer, from my perspective. SSRIs are a placebo substitute (given their level of efficacy), but have extreme side effects, which are acknowledged. It is regrettable that the Worshipful Company has chosen to profit from the fact that it is regarded as unethical to prescribe placebos.
Please do not express your regret at my experience. First, because you do not know what I have experienced (and thus you do not know what you are apologizing for), and second, because it is evident that you have no intention of seeking an understanding and making redress. What I experienced is not acceptable, irrespective of the pharmaceutical industry's lack of understanding of mental illness. The lack of concern that has been demonstrated subsequently, by all interested parties, merely suggests to me that not only are those parties determined to lock down their own position, but also to ensure that it is made clear to me that the only possible explanation for my experience is down to me. In other words, the MHRA, with others, is justifying what happened to me. I think you understand how I need to respond to that.
For the record, I do not accept that interpretation of events. Unpleasant as it is to conceive, the logical, alternative explanation for my experience is that the MHRA (and others), is incompetent. There are many factors that contribute to this being an reasonable alternative explanation, not least because it is apparently driven by the marketing concerns of the industry (which is itself marketing-led), that it purports to regulate. When an organization's culture is geared towards sales and marketing, compliance tends to go out of the window, in my experience.
When the MHRA speaks as freely to patients as it does to the companies it regulates, I will review my position. The problem is still Ms Raine's.
Best regards
Matthew Holford
********************************
Subject: Re: Yellow Cards
Date: Thu, 21 Feb 2008 13:43:13 +0000
From: [redacted]@mhra.gsi.gov.uk
To: [redacted]@hotmail.co.uk
Dear Mr Holford,
Thank you for your recent e-mail to Dr Raine regarding your concerns about fluoxetine and the side effects you experienced. I have attached a response to this message.
Kind regards
[redacted], BSc (Hons) Ph.D
Senior Pharmacovigilance Scientist
Vigilance and Risk Management of Medicines
Medicines and Healthcare products Regulatory Agency
Attachment:
Dear Mr Holford,
Thank you for your recent e-mail to Dr Raine regarding your concerns about fluoxetine and the side effects you experienced. I have been requested to reply on her behalf. I am sorry to hear of the problems you have had since taking this medicine.
I understand you have been in correspondence with other colleagues in the Agency and we have noted your concerns regarding the use of SSRIs and I would like to assure you that as with all medicines, the safety of fluoxetine is closely monitored by the Medicines and Healthcare products Regulatory Agency/Commission on Human Medicines to ensure that the benefits of this medicine outweigh any potential risks, and when evidence of a new safety issue comes to light, appropriate action is taken.
Thank you again for contacting us and taking the time to fill in a Yellow Card, your contribution to the scheme is important.
Yours sincerely
[redacted]
Senior Pharmacovigilance Scientist
Pharmacovigilance Information Unit
Vigilance and Risk Management of Medicines
Room 15-208
cc: [redacted], Pharmacovigilance Information Unit Manager
********************************
From: Matthew Holford
Sent: 18 February 2008 13:26
To: Raine, Dr June
Subject: Yellow Cards
Dear Ms Raine,
I understand that the following quotation is attributable to you:
"If you suspect that you have had a side-effect to your medicine, please tell us about it via the Yellow Card scheme."
I have filled out a Yellow Card report, as it happens, but I'll tell you about the side effect that I experienced consequent to using fluoxetine, too. It made me suicidal. I think it was the sense, as I paced in between my front room and kitchen, unable to settle, like a hunted animal (I believe this is known as akathasia), that it would never end. And that nobody cared, either. Do you care (servant) Raine? Really? How about you (servant) Texture? (servant) Johnson? (servant) Vara? Anybody? No, I didn't think so.
There: I've told you about it. Now, it's your problem.
Best regards
Matthew Holford
Monday, 18 February 2008
Fluoxetine
To the Ministry of Truth, at the MHRA, copied to Brown, Johnson and Vara:
Dear Sir or Madam,
It is my undertstanding, given previous correspondence with the MHRA, that there are three statutory criteria involved in the assessment of a drug for a marketing authorization. Those three criteria are efficacy, safety and quality.
A drug must, then, do the thing that is claimed, and that thing must be a benefit to the patient (efficacy). This benefit is then assessed against the safety of the drug. During this process, the nature of the condition is taken into consideration, and the less serious the condition is, the less tolerant the regulator will be of serious side effects. As such, a drug designed to treat a condition that is not life-threatening is unlikely to be licensed, if the side effects are life-threatening. This comparison between benefit and safety, I understand, is known as a risk:benefit analysis and the benefits must outweigh the risks, in order for the drug to be licensed. Finally, it has to be demonstrated that the drug can be produced to a consistently high standard (quality).
I would like to conduct my own risk:benefit analysis on fluoxetine, and I would like to use the MHRA's methodology, if it has one. Could you explain to me what the benefit of the drug is, please?
Best regards
Matthew Holford
Dear Sir or Madam,
It is my undertstanding, given previous correspondence with the MHRA, that there are three statutory criteria involved in the assessment of a drug for a marketing authorization. Those three criteria are efficacy, safety and quality.
A drug must, then, do the thing that is claimed, and that thing must be a benefit to the patient (efficacy). This benefit is then assessed against the safety of the drug. During this process, the nature of the condition is taken into consideration, and the less serious the condition is, the less tolerant the regulator will be of serious side effects. As such, a drug designed to treat a condition that is not life-threatening is unlikely to be licensed, if the side effects are life-threatening. This comparison between benefit and safety, I understand, is known as a risk:benefit analysis and the benefits must outweigh the risks, in order for the drug to be licensed. Finally, it has to be demonstrated that the drug can be produced to a consistently high standard (quality).
I would like to conduct my own risk:benefit analysis on fluoxetine, and I would like to use the MHRA's methodology, if it has one. Could you explain to me what the benefit of the drug is, please?
Best regards
Matthew Holford
Sunday, 17 February 2008
What I know about SSRIs...
...is fuck all. And it's fuck all, because the people who ought to be able to explain these things to me can't. Or won't. I've tried to believe that the system isn't as crooked as fuck, truly I have, but the numbers don't stack up. The argument that I am continually faced with is "these drugs work and are reasonably safe, because somebody else has said that that's true," and, usually, that other person is unavailable for comment (eg, Keller, Ryan, Dunner, Breckenridge, Woods, Benbow, etc, etc). I regret to say that when you've been where I've been, that argument doesn't fucking wash. I could have limited my reading to the fucking PIL, and been just as informed as I am now, well over a year into my research, and having tried to speak to every official source of information that I could (most of which decided that they had no obligation to speak to me, apparently).
I posted the following as a comment on a Pharmalot thread, about the Northern Illinois University shooter, Stephen Kazmierczak.
I’ll tell you what I know about SSRIs, and I would like to acknowledge that my own experience of them is negative (fluoxetine). Most of my comments will be about Paxil/Seroxat, though, seeing as I have seen one report that suggests the shooter was on that drug.
There are significant side effects with these drugs. We may regard this as a fact, not speculation based on a correlation between changes in behaviour, as against the taking of these drugs by those experiencing said behaviour. And we may regard it as fact, because the people who make them, and the people who regulate the manufacturers agree that it is so by producing a PIL. So let’s put that to bed: SSRIs DO cause suicidality, and homicidality (and withdrawal, and akathasia, and…).
Next, there is no evidence that the drugs work any better than placebo. Bald statement though that is, it appears to be a fact. The MHRA (the current UK regulator) was unable to explain to me what the benefit of Seroxat (Paxil) is. Neither was GSK, nor the Department of Health, nor the UK industry lobbying body, the ABPI. The fact that the drug is on the market does not appear to be evidence of its efficacy, then, given that the UK regulator at the time, the MCA, appears not to have chosen to scrutinize the original trials data that Glenmullen recently reported on.
If the drug has no efficacy, then no risk:benefit analysis can ever have been carried out, because there is no benefit against which to offset risks. I’m still waiting for somebody to explain how my logic is incorrect. The MHRA justified the continued presence of Seroxat on the pharmacists’ shelves by declaring that the drug was good, because the manufacturer had said so (what it actually said was that it’s decision to license the drug was based on a positive statistical analysis (provided by the manufacturer), backed up by peer-reviewed articles (the less said about those, the better)).
Now, we can get into a discussion about dodgy marketing, suppression of side effects, routine withholding of negative data, “information laundering” (due deference to Pharmalot, for coining this phrase) via KOLs and clinicians, bribery and corruption, if you like. However, the fact remains: the manufacturers and the regulators cannot explain how the drugs work (nor even how they were assessed), and they DO cause severe side effects - that’s a given. It’s on the PIL.
That some people are more severely impacted than others appears to be the case. That not every patient on these drugs goes out to a mall/high school/university campus and starts blasting away does not prove that the drugs are not to blame.
Matt
Addendum:
The term "information laundering" was coined by Clinical Psych, and not Pharmalot (please see post, below).
I posted the following as a comment on a Pharmalot thread, about the Northern Illinois University shooter, Stephen Kazmierczak.
I’ll tell you what I know about SSRIs, and I would like to acknowledge that my own experience of them is negative (fluoxetine). Most of my comments will be about Paxil/Seroxat, though, seeing as I have seen one report that suggests the shooter was on that drug.
There are significant side effects with these drugs. We may regard this as a fact, not speculation based on a correlation between changes in behaviour, as against the taking of these drugs by those experiencing said behaviour. And we may regard it as fact, because the people who make them, and the people who regulate the manufacturers agree that it is so by producing a PIL. So let’s put that to bed: SSRIs DO cause suicidality, and homicidality (and withdrawal, and akathasia, and…).
Next, there is no evidence that the drugs work any better than placebo. Bald statement though that is, it appears to be a fact. The MHRA (the current UK regulator) was unable to explain to me what the benefit of Seroxat (Paxil) is. Neither was GSK, nor the Department of Health, nor the UK industry lobbying body, the ABPI. The fact that the drug is on the market does not appear to be evidence of its efficacy, then, given that the UK regulator at the time, the MCA, appears not to have chosen to scrutinize the original trials data that Glenmullen recently reported on.
If the drug has no efficacy, then no risk:benefit analysis can ever have been carried out, because there is no benefit against which to offset risks. I’m still waiting for somebody to explain how my logic is incorrect. The MHRA justified the continued presence of Seroxat on the pharmacists’ shelves by declaring that the drug was good, because the manufacturer had said so (what it actually said was that it’s decision to license the drug was based on a positive statistical analysis (provided by the manufacturer), backed up by peer-reviewed articles (the less said about those, the better)).
Now, we can get into a discussion about dodgy marketing, suppression of side effects, routine withholding of negative data, “information laundering” (due deference to Pharmalot, for coining this phrase) via KOLs and clinicians, bribery and corruption, if you like. However, the fact remains: the manufacturers and the regulators cannot explain how the drugs work (nor even how they were assessed), and they DO cause severe side effects - that’s a given. It’s on the PIL.
That some people are more severely impacted than others appears to be the case. That not every patient on these drugs goes out to a mall/high school/university campus and starts blasting away does not prove that the drugs are not to blame.
Matt
Addendum:
The term "information laundering" was coined by Clinical Psych, and not Pharmalot (please see post, below).
Friday, 15 February 2008
Information Laundering
This is a "hot topic," which is being discussed quite widely, just now. Take some bullshit, give it a positive spin, sell it to a KOL, who disseminates it to frontline clinicians via seminars and papers, and the clinicians disseminate the information, completely free of nasty, negative stuff, to the patient.
Anyway, Clinical Psych has a post on it, just now. And Fidders touches upon it, in a broadside on a GSK spin document.
I'll leave you with a quote from the Joint Money Laundering Steering Group's "Prevention of Money Laundering - Guidance Notes for the UK Financial Sector - 2003 Edn". It's not a catchy title, but it's an important document:
Money Laundering is the process by which criminals attempt to hide and disguise the true origin and ownership of the proceeds of their criminal activities, thereby avoiding prosecution, conviction and confiscation of the criminal funds
Section 5., entitled "Recognizing and Reporting Suspicious Activity" is especially interesting, and there are several parallels in the process of "information laundering".
Matt
Anyway, Clinical Psych has a post on it, just now. And Fidders touches upon it, in a broadside on a GSK spin document.
I'll leave you with a quote from the Joint Money Laundering Steering Group's "Prevention of Money Laundering - Guidance Notes for the UK Financial Sector - 2003 Edn". It's not a catchy title, but it's an important document:
Money Laundering is the process by which criminals attempt to hide and disguise the true origin and ownership of the proceeds of their criminal activities, thereby avoiding prosecution, conviction and confiscation of the criminal funds
Section 5., entitled "Recognizing and Reporting Suspicious Activity" is especially interesting, and there are several parallels in the process of "information laundering".
Matt
Wednesday, 13 February 2008
Lying through your teeth
Fidders has put together a video, which is very nicely done - lots of very useful information, with a musical accompaniment:
Tuesday, 12 February 2008
Re: Glaxo chief curses media and issues profit warning
I was sent the link, below, which was delightfully convenient, because I'd been sharpening my quill, in anticipation of Garnier saying something fucking stupid. This to the Guardian's Business Section, copied to Johnson and Vara.
Dear Sirs,
I saw this piece, today:
Glaxo chief curses media and issues profit warning
It's hilarious, isn't it? Garnier appears to think that, given time, the Avandia thing will blow over, and it will be back to business, as usual. Staggering.
Well, who knows, perhaps he knows his audience better than we do? Anyway, he's got a fucking nerve to demand that "scientists" (all scientists, or just the ones that agree with GSK (I'm thinking of the way that we're told Garnier orchestrated the slating of John Buse)?), are the only ones who are able to proclaim the truth, and the media should report on what the scientists say, provided that that casts GSK in a good light. I'm sorry: I've only to read the correspondence between McCafferty, Oakes, Keller and Laden (who were responsible for the travesty of science that was the write-up of Paxil Protocol 329), to know that, in the context of the sordid world of pharmaceuticals, the view of the experts is worth precisely dick. Besides, if scientists are the only ones who get to say what is true, then patients have no right to speak, and are merely the glad recipients of the great wisdom of the scientists - whereupon we may be fed any old shite, which I imagine would suit Garnier, just fine.
However, it's perhaps worth pointing out that it is not scientists that report on the efficacy of a drug, it is the patients ("I'm feeling better, doctor"). When this happens, the pharmaceutical industry is only too delighted to report patient views. It's only when patient feedback is negative that we don't have the right to speak, according to Garnier, whereupon the shutters come down and a sign with "sue me" written on it is affixed. All very scientific. Garnier is a charlatan, and a bully, as far as I'm concerned.
Best regards
Matthew Holford
Dear Sirs,
I saw this piece, today:
Glaxo chief curses media and issues profit warning
It's hilarious, isn't it? Garnier appears to think that, given time, the Avandia thing will blow over, and it will be back to business, as usual. Staggering.
Well, who knows, perhaps he knows his audience better than we do? Anyway, he's got a fucking nerve to demand that "scientists" (all scientists, or just the ones that agree with GSK (I'm thinking of the way that we're told Garnier orchestrated the slating of John Buse)?), are the only ones who are able to proclaim the truth, and the media should report on what the scientists say, provided that that casts GSK in a good light. I'm sorry: I've only to read the correspondence between McCafferty, Oakes, Keller and Laden (who were responsible for the travesty of science that was the write-up of Paxil Protocol 329), to know that, in the context of the sordid world of pharmaceuticals, the view of the experts is worth precisely dick. Besides, if scientists are the only ones who get to say what is true, then patients have no right to speak, and are merely the glad recipients of the great wisdom of the scientists - whereupon we may be fed any old shite, which I imagine would suit Garnier, just fine.
However, it's perhaps worth pointing out that it is not scientists that report on the efficacy of a drug, it is the patients ("I'm feeling better, doctor"). When this happens, the pharmaceutical industry is only too delighted to report patient views. It's only when patient feedback is negative that we don't have the right to speak, according to Garnier, whereupon the shutters come down and a sign with "sue me" written on it is affixed. All very scientific. Garnier is a charlatan, and a bully, as far as I'm concerned.
Best regards
Matthew Holford
Thursday, 7 February 2008
Did GSK trial data mask Paxil suicide risk?
My interest was caught by this New Scientist piece, which Furious Seasons and Pharmalot have already looked at. This to Woods, copied to Johnson and Vara:
Dear Mr Woods,
I read with interest, recently, of the MHRA's decision to place a warning on SSRIs, concerning the risk of increased adult suicidality, but only with respect to adults between the ages of 18-25. I was also interested to read this piece, today:
Did GSK trial data mask Paxil suicide risk?
Regrettably, the NS piece doesn't mention the ages of the trial participants, but what's the betting that some of those who were made suicidal by paroxetine were over the age of 25? If you want to open a book, I'll have a score on it. OK? Now, remind me, how long have you been investigating the Bedford Massive, concerning allegations of suppressing negative data? It doesn't look good, Mr Woods, truly it doesn't. Did you even bother to look?
Now, as you may know, I have a very particular interest in this story. You see, I don't think that there's a whole lot of difference between the way that the SSRIs (don't) work, and in what they do to the human brain to cause the side effects that they do.
Quack, quack, quack.
Best regards
Matthew Holford
Addendum: Be sure to read Sen Grassley's letter to Chris Viebacher, at GSK, on the Pharmalot page.
Dear Mr Woods,
I read with interest, recently, of the MHRA's decision to place a warning on SSRIs, concerning the risk of increased adult suicidality, but only with respect to adults between the ages of 18-25. I was also interested to read this piece, today:
Did GSK trial data mask Paxil suicide risk?
Regrettably, the NS piece doesn't mention the ages of the trial participants, but what's the betting that some of those who were made suicidal by paroxetine were over the age of 25? If you want to open a book, I'll have a score on it. OK? Now, remind me, how long have you been investigating the Bedford Massive, concerning allegations of suppressing negative data? It doesn't look good, Mr Woods, truly it doesn't. Did you even bother to look?
Now, as you may know, I have a very particular interest in this story. You see, I don't think that there's a whole lot of difference between the way that the SSRIs (don't) work, and in what they do to the human brain to cause the side effects that they do.
Quack, quack, quack.
Best regards
Matthew Holford
Addendum: Be sure to read Sen Grassley's letter to Chris Viebacher, at GSK, on the Pharmalot page.
Wednesday, 6 February 2008
Withdraw Seroxat petition - Part II
Mr Goldfinch then sought to rely on peer-reviewed journals. Laugh. My. Fucking. Arse. Off. Incidentally, this post (and the previous one) is so-named, because that was the title that I posted the correspondence under, on Uncommon Knowledge.
Uncommon Knowledge
Dear Mr Goldfinch,
Well, I'm inclined to refer you to the 1998 US PIL, again, where Seroxat is "significantly more affective [sic] than placebo..." The Company, then, if only in the US, regarded the drug, not as negligbly better than placebo, which I understand is the case, but significantly better. On what ground? If, alternatively, the drug is not any better, or negligibly better, than placebo, shouldn't people be taking placebos, instead, given that sugar pills presumably don't give rise to suicidality, and so on?
I don't understand your line of argument, to be honest. There has to be a benefit to Seroxat, and if that benefit is a mere 2 Hamilton points(1), which is the case, I understand, then suicidality is not an acceptable side effect, and the drug should not be on the market, I would contest. So, what is the benefit of the drug? As to peer-reviewed journals, and published trials, I have two words for you: "Marty Keller".
I am delighted that you regard my requests as vexatious, but contest that they are, other than subjectively, from your perspective. You are aware that I have complained, and you know why, because I have explained that to you. I have nothing else to say on that matter.
Best regards
Matthew Holford
*******************************
From: "MHRA Information Centre"
To: "Matthew Holford"
Subject: Reply
Date: Fri, 8 Jun 2007 15:24:25 +0100
Dear Mr Holford
Thank you for your email of 8th May. Please note that an applicant only has to demonstrate that the drug is more effective than a placebo and there is no requirement to demonstrate any scale of impact nor is there any requirement to show comparative benefits over any other type of treatment or other drug. It is the responsibility of NICE to advise prescribers on the comparative efficacy of treatments for a particular condition. The benefit of a particular drug is assessed by carrying out placebo controlled clinical trials in large numbers of patients. As I have pointed out to you before, summaries of these are published in the scientific literature in peer-reviewed academic journals and you can ask a library to conduct a literature search for these.
Thank you for copying the MHRA in on your correspondence with Mr Chapman of the ICO. It is apposite as we are refusing to reply to your emails of 22 May to Stephen Fawbert or your emails to the MHRA of 29th May, 31st May and 3rd June (and any other emails you may have sent or may send in the future on the same or substantially similar subjects), on the grounds that the requests have now become vexatious. Clearly, you feel that you have not had the answers you wanted to receive, but this is not the same as not being answered, and we have given such information as we are able, from what we actually hold. Consequently, there is nothing further we can add in this regard.
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 requests. 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.
After that, if you remain dissatisfied, you may write to the Information Commissioner at;
The Information Commissioner's Office
Wycliffe House
Water Lane
Wilmslow
Cheshire
SK9 5AF
They will make a decision on whether or not we have interpreted the FOIA correctly in withholding information from you.
Yours sincerely
R Goldfinch
Information Centre
Notes:
(1) The reference to the benefit being 2 points, as opposed to 10 points (see my previoius post), is explained thus: I have read that Seroxat was adjudged to have moved trialists 10 Hamilton points (this based on a meta analysis of the "positive" trials, ie, the ones that were published). Placebo, meanwhile, moved the patients 8 Hamilton points. The difference between drug and placebo (and thus the real benefit of taking the drug, over placebo), is, then, 2 Hamilton points, which is regarded as "clinically negligible," I understand.
Uncommon Knowledge
Dear Mr Goldfinch,
Well, I'm inclined to refer you to the 1998 US PIL, again, where Seroxat is "significantly more affective [sic] than placebo..." The Company, then, if only in the US, regarded the drug, not as negligbly better than placebo, which I understand is the case, but significantly better. On what ground? If, alternatively, the drug is not any better, or negligibly better, than placebo, shouldn't people be taking placebos, instead, given that sugar pills presumably don't give rise to suicidality, and so on?
I don't understand your line of argument, to be honest. There has to be a benefit to Seroxat, and if that benefit is a mere 2 Hamilton points(1), which is the case, I understand, then suicidality is not an acceptable side effect, and the drug should not be on the market, I would contest. So, what is the benefit of the drug? As to peer-reviewed journals, and published trials, I have two words for you: "Marty Keller".
I am delighted that you regard my requests as vexatious, but contest that they are, other than subjectively, from your perspective. You are aware that I have complained, and you know why, because I have explained that to you. I have nothing else to say on that matter.
Best regards
Matthew Holford
*******************************
From: "MHRA Information Centre"
To: "Matthew Holford"
Subject: Reply
Date: Fri, 8 Jun 2007 15:24:25 +0100
Dear Mr Holford
Thank you for your email of 8th May. Please note that an applicant only has to demonstrate that the drug is more effective than a placebo and there is no requirement to demonstrate any scale of impact nor is there any requirement to show comparative benefits over any other type of treatment or other drug. It is the responsibility of NICE to advise prescribers on the comparative efficacy of treatments for a particular condition. The benefit of a particular drug is assessed by carrying out placebo controlled clinical trials in large numbers of patients. As I have pointed out to you before, summaries of these are published in the scientific literature in peer-reviewed academic journals and you can ask a library to conduct a literature search for these.
Thank you for copying the MHRA in on your correspondence with Mr Chapman of the ICO. It is apposite as we are refusing to reply to your emails of 22 May to Stephen Fawbert or your emails to the MHRA of 29th May, 31st May and 3rd June (and any other emails you may have sent or may send in the future on the same or substantially similar subjects), on the grounds that the requests have now become vexatious. Clearly, you feel that you have not had the answers you wanted to receive, but this is not the same as not being answered, and we have given such information as we are able, from what we actually hold. Consequently, there is nothing further we can add in this regard.
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 requests. 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.
After that, if you remain dissatisfied, you may write to the Information Commissioner at;
The Information Commissioner's Office
Wycliffe House
Water Lane
Wilmslow
Cheshire
SK9 5AF
They will make a decision on whether or not we have interpreted the FOIA correctly in withholding information from you.
Yours sincerely
R Goldfinch
Information Centre
Notes:
(1) The reference to the benefit being 2 points, as opposed to 10 points (see my previoius post), is explained thus: I have read that Seroxat was adjudged to have moved trialists 10 Hamilton points (this based on a meta analysis of the "positive" trials, ie, the ones that were published). Placebo, meanwhile, moved the patients 8 Hamilton points. The difference between drug and placebo (and thus the real benefit of taking the drug, over placebo), is, then, 2 Hamilton points, which is regarded as "clinically negligible," I understand.
Withdraw Seroxat petition
I've just been reminded by Bob Fiddaman of an exchange I had with Richard Goldfinch, of the Nine Elms Massive. It was on the subject of "efficacy," or the absence, thereof.
I'll precis it for you: a drug is efficacious, because the manufacturer says so. The MHRA's commentary is in bold, as usual.
Dear Richard,
Thank you for this additional clarification, although I am aware what GSK, as the responsible party, believes that Seroxat should be used to treat; a view with which the MHRA concurs apparently, as evidenced by the PIL - it being a collaboration between manufacturer and regulator, I am told. With respect, this was not the question that I asked, though.
What I am interested in divining is the extent to which it is believed that the drug treats these various syndromes. I understand that there is no global definition of "efficacy", and I have no objection to that, but then I am not asking about any other drug: I only wish to know about Seroxat, for the time being. What does the manufacturer (and the regulator) anticipate in terms of improved wellbeing? Put another way, how much better will a patient feel, by any criterion or scale that it chooses, when that patient is being treated for, say, depression? Is the patient to expect, as an average, a 10-point improvement on Hamilton, for example? And over what time period? Put another way, how does the patient know when the drug is, or is not, working?
Finally, assuming that a risk:benefit analysis has been carried out, as you suggest, then it must be true that the benefit of the drug has been assessed accurately, and not taken for granted? How has this been achieved? At present, I am assuming the benefit assessed to be beyond my comprehension, because otherwise the risk of suicide/homicide/self harm, etc, etc, would not be tolerated, under the MHRA's risk:benefit principles (ie, where the condition to be treated is not life-threatening, tolerance of serious adverse reactions will be low). So, how has the benefit been demonstrated, and what is the benefit believed to be?
Best regards
Matthew Holford
--------------------------------------------------------------------------------
From: "MHRA Information Centre"
To: "Matthew Holford"
Subject: RE: Enquiry
Date: Tue, 8 May 2007 09:01:33 +0100
Dear Mr Holford
I thought I should clarify for you that the licence (marketing authorisation) for medicines approved in the UK specifies what the medicine is licensed to treat and these are the 'licensed indications' approved by the MHRA and are published in the Summary of product Characteristics (SmPC) which is in the public domain. (see the electronic medicines compendium at http://emc.medicines.org.uk/ ).
For example the current licensed indications for Seroxat are:
Treatment of
- Major Depressive Episode
- Obsessive Compulsive Disorder
- Panic Disorder with and without agoraphobia
- Social Anxiety Disorders/Social phobia
- Generalised Anxiety Disorder
- Post-traumatic Stress Disorder
A positive benefit:risk ratio will have been demonstrated and approved for each of these conditions.
Regards
Richard Goldfinch
Information Centre
MHRA
********************************
Dear Richard,
I understand the concept of risk:benefit, and the flexible meaning of the word "efficacy", as it applies to the pharmaceutical industry. I was discussing this issue with one of your colleagues, not long ago, and he made the same argument that you have done, of course. That is, that a drug's benefits must be considered in conjunction with its side effects.
I would make the same response to you as I did him: before one may consider side effects, one must understand that a drug does what is claimed, and that what is claimed is a benefit to the patient. In the case of Seroxat, I do not know what is claimed, other than some vague reference on the 1991 PIL, which says that the drug "alleviates depressed mood and related symptoms," which still leaves a great deal unsaid. Are you able to clarify this for me, because if you're not, we will find ourselves in a debate about side effects, which seems to be where people who are inclined to defend SSRIs feel that they are on safe ground.
I will say that again, in brief terms: the discussion about side effects is, by your own criteria, irrelevant, until we know what the drug is supposed to do: it is quite beside the point to argue that the drug is "reasonably safe" or somesuch, if it doesn't work any better than placebo. Should one accept suicidal behaviour, and the rest, as a side effect, when one is being moved 10 points on Hamilton? Besides which, when a condition is not life threatening, then again, by your own criteria, having a side effect like suicidal behaviour (and suicidal ideations will lead to suicide eventually, whatever Dr Benbow says) attached to a drug should disqualify it from being used as a treatment for that condition. In short, you are arguing that the argument is complex, without having even defined your terms. That's rather lazy, if you don't mind my saying so. And patronizing.
I understand that drug companies are regarded as powerful, although quite what relevance this has to an unbiased assessment of the products they market, I have no idea. It may be that Seroxat is propping up GSK's balance sheet: that is not my concern, frankly, nor are the jobs of the 100,000 people they employ in this country. As to the question of FOIA requests: you should feel free to implement whatever exemptions you deem appropriate. Had the MHRA been willing and able to answer my questions, we could have saved it £575.
Best regards
Matthew Holford
--------------------------------------------------------------------------------
From: "MHRA Information Centre"
To: "Matthew Holford"
Subject: RE: Enquiry
Date: Wed, 2 May 2007 09:32:23 +0100
Dear Mr Holford
In reply to your email of 20th April (our references ICE 07/297 and FOI 07/105), I can confirm that the MHRA does not have a formal definition of the term 'efficacy'.
Applicants for marketing authorisations must demonstrate that their product works and this is 'efficacy'. Applicants achieve this by submitting to us the summary results of clinical trials and an expert report as descibed in the European Guidance documents in 'Notice to Applicants'. The results of the clinical trials must support the claims the applicant wants to include on their licence. As no medicine is 100% safe, you should note that the effectiveness of a medicine is always assessed in conjunction with its safety and not in isolation. For this reason it is not possible to have a 'catch all' explanation of how efficacy is determined. Every product will have a unique 'risk:benefit' ratio. For example a cancer treatment may be very toxic and have serious side effects, but it also has life saving benefits. Providing the benefits outweigh the risks, then the product may be considered to have an acceptable benefit:risk ratio. New medicines are also referred to the independent committee, the Commission on Human Medicines (formerly the CSM) for their expert opinion. Every class of medicine will require different clinical trial design and the clinical 'end-point' will be different for different diseases and conditions. Again the European guidance documents you have previously been referred to contain specific guidance for designing clinical trials for different diseases and classes of medicine. I hope this has clarified things for you.
I would also like to point out that according to our records we have received 7 FOI requests from you in the last 3 months as well as numerous other miscellaneous emails to various MHRA staff. Section 12 (4) (a) of the Freedom of Information Act (FOIA) allows public authorities to aggregate - for costing purposes - where two or more requests for information have been made by the same person (or from different persons who appear to be acting in concert) for the same or similar information, within a space of 60 consecutive working days. The Act provides for public authorities to refuse requests for information where the cost of dealing with them would exceed the appropriate limit which is £600 for central government. We have estimated that your requests for information since February have required us to spend at least £600 (calculated at £25 per hour). You should be aware that any further requests for information may be refused under section 12 (1) of the FOIA. I would therefore like to recommend that all future correspondence with the MHRA is sent only to our Central Enquiry Point (info@mhra.gsi.gov.uk). In addition it would help us if you could telephone the Information Centre with straightforward requests for advice. Please phone 020 7084 2000. Please ask to speak to me if you wish and I will try my best to help you and advise if your request would be considered as 'FOI' or not.
Yours sincerely
Richard Goldfinch
Information Centre
MHRA
Market Towers
London SW8 5NQ
I'll precis it for you: a drug is efficacious, because the manufacturer says so. The MHRA's commentary is in bold, as usual.
Dear Richard,
Thank you for this additional clarification, although I am aware what GSK, as the responsible party, believes that Seroxat should be used to treat; a view with which the MHRA concurs apparently, as evidenced by the PIL - it being a collaboration between manufacturer and regulator, I am told. With respect, this was not the question that I asked, though.
What I am interested in divining is the extent to which it is believed that the drug treats these various syndromes. I understand that there is no global definition of "efficacy", and I have no objection to that, but then I am not asking about any other drug: I only wish to know about Seroxat, for the time being. What does the manufacturer (and the regulator) anticipate in terms of improved wellbeing? Put another way, how much better will a patient feel, by any criterion or scale that it chooses, when that patient is being treated for, say, depression? Is the patient to expect, as an average, a 10-point improvement on Hamilton, for example? And over what time period? Put another way, how does the patient know when the drug is, or is not, working?
Finally, assuming that a risk:benefit analysis has been carried out, as you suggest, then it must be true that the benefit of the drug has been assessed accurately, and not taken for granted? How has this been achieved? At present, I am assuming the benefit assessed to be beyond my comprehension, because otherwise the risk of suicide/homicide/self harm, etc, etc, would not be tolerated, under the MHRA's risk:benefit principles (ie, where the condition to be treated is not life-threatening, tolerance of serious adverse reactions will be low). So, how has the benefit been demonstrated, and what is the benefit believed to be?
Best regards
Matthew Holford
--------------------------------------------------------------------------------
From: "MHRA Information Centre"
To: "Matthew Holford"
Subject: RE: Enquiry
Date: Tue, 8 May 2007 09:01:33 +0100
Dear Mr Holford
I thought I should clarify for you that the licence (marketing authorisation) for medicines approved in the UK specifies what the medicine is licensed to treat and these are the 'licensed indications' approved by the MHRA and are published in the Summary of product Characteristics (SmPC) which is in the public domain. (see the electronic medicines compendium at http://emc.medicines.org.uk/ ).
For example the current licensed indications for Seroxat are:
Treatment of
- Major Depressive Episode
- Obsessive Compulsive Disorder
- Panic Disorder with and without agoraphobia
- Social Anxiety Disorders/Social phobia
- Generalised Anxiety Disorder
- Post-traumatic Stress Disorder
A positive benefit:risk ratio will have been demonstrated and approved for each of these conditions.
Regards
Richard Goldfinch
Information Centre
MHRA
********************************
Dear Richard,
I understand the concept of risk:benefit, and the flexible meaning of the word "efficacy", as it applies to the pharmaceutical industry. I was discussing this issue with one of your colleagues, not long ago, and he made the same argument that you have done, of course. That is, that a drug's benefits must be considered in conjunction with its side effects.
I would make the same response to you as I did him: before one may consider side effects, one must understand that a drug does what is claimed, and that what is claimed is a benefit to the patient. In the case of Seroxat, I do not know what is claimed, other than some vague reference on the 1991 PIL, which says that the drug "alleviates depressed mood and related symptoms," which still leaves a great deal unsaid. Are you able to clarify this for me, because if you're not, we will find ourselves in a debate about side effects, which seems to be where people who are inclined to defend SSRIs feel that they are on safe ground.
I will say that again, in brief terms: the discussion about side effects is, by your own criteria, irrelevant, until we know what the drug is supposed to do: it is quite beside the point to argue that the drug is "reasonably safe" or somesuch, if it doesn't work any better than placebo. Should one accept suicidal behaviour, and the rest, as a side effect, when one is being moved 10 points on Hamilton? Besides which, when a condition is not life threatening, then again, by your own criteria, having a side effect like suicidal behaviour (and suicidal ideations will lead to suicide eventually, whatever Dr Benbow says) attached to a drug should disqualify it from being used as a treatment for that condition. In short, you are arguing that the argument is complex, without having even defined your terms. That's rather lazy, if you don't mind my saying so. And patronizing.
I understand that drug companies are regarded as powerful, although quite what relevance this has to an unbiased assessment of the products they market, I have no idea. It may be that Seroxat is propping up GSK's balance sheet: that is not my concern, frankly, nor are the jobs of the 100,000 people they employ in this country. As to the question of FOIA requests: you should feel free to implement whatever exemptions you deem appropriate. Had the MHRA been willing and able to answer my questions, we could have saved it £575.
Best regards
Matthew Holford
--------------------------------------------------------------------------------
From: "MHRA Information Centre"
To: "Matthew Holford"
Subject: RE: Enquiry
Date: Wed, 2 May 2007 09:32:23 +0100
Dear Mr Holford
In reply to your email of 20th April (our references ICE 07/297 and FOI 07/105), I can confirm that the MHRA does not have a formal definition of the term 'efficacy'.
Applicants for marketing authorisations must demonstrate that their product works and this is 'efficacy'. Applicants achieve this by submitting to us the summary results of clinical trials and an expert report as descibed in the European Guidance documents in 'Notice to Applicants'. The results of the clinical trials must support the claims the applicant wants to include on their licence. As no medicine is 100% safe, you should note that the effectiveness of a medicine is always assessed in conjunction with its safety and not in isolation. For this reason it is not possible to have a 'catch all' explanation of how efficacy is determined. Every product will have a unique 'risk:benefit' ratio. For example a cancer treatment may be very toxic and have serious side effects, but it also has life saving benefits. Providing the benefits outweigh the risks, then the product may be considered to have an acceptable benefit:risk ratio. New medicines are also referred to the independent committee, the Commission on Human Medicines (formerly the CSM) for their expert opinion. Every class of medicine will require different clinical trial design and the clinical 'end-point' will be different for different diseases and conditions. Again the European guidance documents you have previously been referred to contain specific guidance for designing clinical trials for different diseases and classes of medicine. I hope this has clarified things for you.
I would also like to point out that according to our records we have received 7 FOI requests from you in the last 3 months as well as numerous other miscellaneous emails to various MHRA staff. Section 12 (4) (a) of the Freedom of Information Act (FOIA) allows public authorities to aggregate - for costing purposes - where two or more requests for information have been made by the same person (or from different persons who appear to be acting in concert) for the same or similar information, within a space of 60 consecutive working days. The Act provides for public authorities to refuse requests for information where the cost of dealing with them would exceed the appropriate limit which is £600 for central government. We have estimated that your requests for information since February have required us to spend at least £600 (calculated at £25 per hour). You should be aware that any further requests for information may be refused under section 12 (1) of the FOIA. I would therefore like to recommend that all future correspondence with the MHRA is sent only to our Central Enquiry Point (info@mhra.gsi.gov.uk). In addition it would help us if you could telephone the Information Centre with straightforward requests for advice. Please phone 020 7084 2000. Please ask to speak to me if you wish and I will try my best to help you and advise if your request would be considered as 'FOI' or not.
Yours sincerely
Richard Goldfinch
Information Centre
MHRA
Market Towers
London SW8 5NQ
Monday, 4 February 2008
Dear Doctor...
This to my previous doctor, copied to Vara and Johnson.
Re: Depression, Anxiety attacks, prescription of fluoxetine and consequent suicidal ideations
I am a former patient of yours, and it was during the last year that I lived in Chadwell Heath that I experienced what I take to be quite severe anxiety and depression, owing to certain work-related issues. At the time, you took my word that I was suffering from depression (that is, you did not have me complete any kind of depression rating questionnaire), and prescribed me with fluoxetine, the generic name for Prozac.
As bad as I was feeling, at the time, there is no question in my mind that my state worsened, as a consequence, and I began to experience the sense that “I couldn’t go on,” which I reported to you. You gave me a prescription for a different drug, which I don’t remember the name of - I filled the prescription, and then binned the drugs without starting it, which I believe to be the best decision that I ever made. You told me that the suicidality that I was experiencing was consequent to my condition. At one point, I phoned the Samaritans, who directed me to the NHS Emergency line. In turn, I was directed to some response centre at Barking Hospital, I think it was. The “expert” who saw me reiterated what you had said.
You are both liars. The side effect that I experienced is noted on the PIL. Why did you seek to deflect responsibility for the side effect that I experienced back on to me, Dr Patel?
I have spent the past year or two piecing together the sordid story of the way that SSRIs have been marketed as miracle drugs. Perhaps you would like to refer yourself to the recent paper in the New England Journal of Medicine, which would appear to indicate that manufacturers routinely suppress the negative data on their drugs, thus making them appear less dangerous than they are. And more efficacious. It might also interest you to know that the MHRA is unable to explain to me how it assesses drugs for licence. Apparently because it doesn’t bother - it appears to take the word of the manufacturer.
I have also come to understand that there is a whole industry devoted to creating a false picture of the benefits and safety attributed to drugs, in general, and not just SSRIs, from the bribing of doctors, through promotion of off-label indications, via “interested” academics putting their names to ghostwritten papers, to the provision of free CPD. It is a massive fraud, Dr Patel. And the ones paying are the patients, of which I was one. I am very angry, Dr Patel. I would like an apology, Dr Patel. If I do not get one, then I will extract one.
Incidentally, I note that NICE recommends that patients on SSRIs are given “close and continual monitoring”. Could you explain what arrangements you made for my close and continual monitoring, Dr Patel?
Best regards
Matthew Holford
Re: Depression, Anxiety attacks, prescription of fluoxetine and consequent suicidal ideations
I am a former patient of yours, and it was during the last year that I lived in Chadwell Heath that I experienced what I take to be quite severe anxiety and depression, owing to certain work-related issues. At the time, you took my word that I was suffering from depression (that is, you did not have me complete any kind of depression rating questionnaire), and prescribed me with fluoxetine, the generic name for Prozac.
As bad as I was feeling, at the time, there is no question in my mind that my state worsened, as a consequence, and I began to experience the sense that “I couldn’t go on,” which I reported to you. You gave me a prescription for a different drug, which I don’t remember the name of - I filled the prescription, and then binned the drugs without starting it, which I believe to be the best decision that I ever made. You told me that the suicidality that I was experiencing was consequent to my condition. At one point, I phoned the Samaritans, who directed me to the NHS Emergency line. In turn, I was directed to some response centre at Barking Hospital, I think it was. The “expert” who saw me reiterated what you had said.
You are both liars. The side effect that I experienced is noted on the PIL. Why did you seek to deflect responsibility for the side effect that I experienced back on to me, Dr Patel?
I have spent the past year or two piecing together the sordid story of the way that SSRIs have been marketed as miracle drugs. Perhaps you would like to refer yourself to the recent paper in the New England Journal of Medicine, which would appear to indicate that manufacturers routinely suppress the negative data on their drugs, thus making them appear less dangerous than they are. And more efficacious. It might also interest you to know that the MHRA is unable to explain to me how it assesses drugs for licence. Apparently because it doesn’t bother - it appears to take the word of the manufacturer.
I have also come to understand that there is a whole industry devoted to creating a false picture of the benefits and safety attributed to drugs, in general, and not just SSRIs, from the bribing of doctors, through promotion of off-label indications, via “interested” academics putting their names to ghostwritten papers, to the provision of free CPD. It is a massive fraud, Dr Patel. And the ones paying are the patients, of which I was one. I am very angry, Dr Patel. I would like an apology, Dr Patel. If I do not get one, then I will extract one.
Incidentally, I note that NICE recommends that patients on SSRIs are given “close and continual monitoring”. Could you explain what arrangements you made for my close and continual monitoring, Dr Patel?
Best regards
Matthew Holford
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