The riddle of the drug regulators

[Guest guest]

> JustSayNo

> Thu, 29 Jul 2004 22:24:32 -0400

> [sSRI-Research] The riddle of the drug

> regulators

>

> The riddle of the drug regulators

>

> Critics press for review of licensing system

>

> Sarah Boseley, health editor

> Saturday March 13, 2004

> The Guardian

>

http://society.guardian.co.uk/mentalhealth/story/0,8150,1168505,00.html

>

> The resignation last night of Richard Brook, the

> chief executive of the mental health charity Mind,

> from an expert working group on antidepressants has

> prompted calls for a review of the system of

> regulating and licensing medical drugs.

> Mr Brook was appointed as a lay member of the group,

> set up by the Committee on the Safety of Medicines

> last year for a thorough look at all the allegations

> against the antidepressant Seroxat, after years of

> patients' and consumer groups' concern about the

> side-effects of modern antidepressants. Some people

> say they cannot stop taking them, because withdrawal

> makes them feel so bad, others say the drugs have

> made them violent or suicidal.

>

> On Thursday the CSM issued a warning to doctors

> about the appropriate dosage of Seroxat, a warning

> for which Mr Brook had been pressing in the light of

> trial data more than 14 years old which the CSM

> failed to consider in three successive reviews of

> the drug.

>

> Mr Brook's appointment was a departure from the

> CSM's normal practices of drawing on a pool of

> scientists and drug experts who, with few

> exceptions, have or in the past had links with the

> drug companies, from shareholdings to research

> grants to their universities. All members have to

> declare their interests and either withdraw from the

> room or not vote when conflicts arise. Even so,

> there have been allegations of " institutional bias " .

>

>

> The suggestion is that the regulating authorities

> and the drug companies are too closely interrelated.

> Key figures not only on the CSM but also in the

> Medicines and Healthcare Products Regulatory Agency

> - the drug licensing body which it advises - have a

> history of consultancy, research or even employment

> by pharmaceutical companies. Ian Hudson, for

> instance, the worldwide safety director of

> GlaxoSmithKline (GSK) until 2001, is now director of

> licensing at the MHRA.

>

> The MHRA and CSM say that they have to draw on the

> expertise of a relatively small pool of highly

> qualified individuals who inevitably have gained

> their experience in the industry, but critics say it

> would be possible to find academics who are

> completely independent.

>

> One of the fiercest critics, Charles Medawar of the

> consumer group Social Audit, will allege in a book

> to be published on Tuesday, Medicines Out of

> Control?, that the system is dangerously secretive,

> riddled with conflicts of interest, and indelibly

> flawed by chaotic and incompetent procedures for

> evaluating drug benefits and risks.

>

> " These revelations [of the Seroxat trials] provide

> compelling evidence of the need for transparency in

> drug regulation. Had the evidence from these

> dose-ranging studies been made publicly available

> the regulators' errors would have been apparent

> years ago, " he said.

>

> Mr Medawar believes that there may be problems with

> the dosage of many other drugs, not only

> antidepressants. Eli Lilly, he points out, conducted

> a study of its own SSRI (selective serotonin

> reuptake inhibitor) drug Prozac in both 20mg and 5mg

> formulations. About 53% of patients responded

> satisfactorily to the low dose and 64% to the higher

> dose. Yet the 20mg tablet was licensed for

> everybody. " That means 50% of people are being

> exposed to four times the dose they need. "

>

> Mr Medawar is one of those who are troubled by the

> revolving door between the drug regulators and the

> pharmaceutical industry. The MHRA chairman, Sir

> Alastair Breckenridge, resigned his position on

> Glaxo's scientific advisory committee to take up his

> previous position as chairman of the CSM, although

> he has usually left the room when Seroxat has been

> discussed.

>

> " For many years Breckenridge had close ties with the

> manufacturers of Seroxat, yet he played a key role

> in the regulation of that drug, " Mr Medawar said.

> While he was still on GSK's advisory board Professor

> Breckenridge took part in the Seroxat licensing

> discussions, although he did not vote.

>

> The data at the heart of the matter showed Seroxat

> to be ineffective and unsafe at high doses. An

> estimated 17,000 patients were put on doses higher

> than the recommended 20mg last year, according to

> the Department of Health. Seroxat is made by GSK in

> 20mg and 30mg tablets. But higher doses are no more

> effective than the 20mg pill, and carry the risk of

> increased side-effects.

>

> The data on the drug comes from one of the original

> trials carried out to establish the effect and

> safety of different doses before GSK applied for a

> licence to sell it in 1990. Patients in the trial,

> which was conducted in 1985-86, were started on 10,

> 20, 30 or 40mg doses. Many of those on the higher

> doses dropped out because of the side-effects.

>

> The MHRA and CSM were given this information by the

> company and they licensed it for depression, with

> 20mg as the recommended dose.

>

> The MHRA, it is understood, did not employ

> statisticians at the time of the 1990 licence

> approval and must therefore have relied on GSK (then

> SmithKline Beecham) for an explanation of the data.

>

> David Healy, director of the North Wales department

> of psychological medicine of the University of

> Wales, who claims that there is a suicide risk for a

> minority of patients on SSRIs, said: " This would

> look like a case of the MHRA taking what the company

> said. It's only when they get pushed beyond a

> certain point that they begin to systematically

> check things out. "

>

> Alastair Benbow, GSK's head of European clinical

> psychiatry, said yesterday that GSK did not agree

> with the MHRA's interpretation of the early study.

> He said the dosage study had been carried out in a

> way that would not be done today and that other

> studies, which had started patients on 20mg and then

> gradually increased the dose, should have been taken

> into account. Gradually increasing the dose was safe

> and some patients would benefit from taking doses of

> more than 20mg a day.

>

>

>

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