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
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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
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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