Fw: FW: Drug Safety Regulatory Agency Accused of Cover-Up_UK Guardian

[Guest guest]

>

>

> Drug Safety Regulatory Agency Accused of Cover-Up_UK

> Guardian

>

>

> >

> ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP)

> Promoting openness and full disclosure

> http://www.ahrp.org <http://www.ahrp.org/>

>

> FYI

>

> When push came to shove, the British Medicines and Healthcare Products

> Regulatory Agency (MHRA, equivalent to the FDA) put the interests of a

> drug

> company ahead of the public health interest. Following a

> behind-the-scenes-struggle, Mr. Brook, Executive Director of

> MIND,

> resigned from an expert workgroup of the Committee on Safety in

> Medicine

> reviewing SSRI antidepressant safety and efficacy data from clinical

> trials

> and reports by physicians and patients. Brook, the panel's only

> consumer

> advocate, charged the committee and the MHRA with a cover-up in its

> efforts

> to conceal the severity of the drug-related problems.

>

> The panel's review of the original Paxil / Seroxat data found that

> regulators have known since 1990 that higher than recommended doses

> (20mg)

> caused severe adverse side effects leading many patients testing the

> drug to

> drop out. Yet, neither physicians prescribing Paxil nor the public was

> informed about the potential hazards posed by higher doses. Regulators

> in

> Britain, Canada, and the US failed to protect the public health by

> requiring

> GlaxoKline to put prominent warnings on the drug's label. As a

> result,

> ill-informed doctors prescribe Paxil / Seroxat and other

> antidepressants

> at

> unsafe higher doses than recommended, leading to preventable harm and

> deaths.

>

> The evidence shows that regulators in the UK and the US have known

> about

> the

> risks for patients, but have tacitly aided and abetted manufacturers

> who

> concealed vital safety information from prescribing physicians and the

> public for over a decade.

>

> When it became apparent that the UK committee would cover-up the

> evidence of

> dose related harmful drug effects, Brook warned the CSM and MHRA that

> " he

> felt he had no choice but to go public [with the evidence] because of

> the

> risks to patients. " The Guardian reports that Brook " was warned in a

> letter

> last Monday from the MHRA that he could risk prosecution under the

> Medicines

> Act 1968, which protects the commercial confidentiality of information

> from

> drug trials. "

>

> The unraveling antidepressant saga both in the UK and the US provides

> a

> window into the secret world in which drug manufacturers and

> government

> regulators interact behind closed doors. This secret intermingling is

> undermining the safety of patients who take prescribed drugs because

> physicians who prescribe the drugs are kept uninformed about the known

> and

> potential dangers posed by these and probably other drugs. For some

> patients

> SSRIs can trigger violent and suicidal behavior.

>

> The Guardian reports: " 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 GlaxoKline (GSK) until 2001, is now

> director of licensing at the MHRA. "

>

> Cozy relationships between FDA officials and drug company officials

> are

> even

> more pervasive at the FDA because the financial stakes are so much

> greater.

> For example, the chief counsel for the FDA, Troy, filed an

> Amicus

> Curiae brief in 2003 with a US court siding with Pfizer, the

> manufacturer of

> the SSRI antidepressant, Zoloft. The issue was the company's failure

> to

> warn

> about suicidal risks of Zoloft. Troy argued that FDA would not permit

> Pfizer

> to put a warning on the Zoloft label about evidence suggesting a link

> between the drug and increased suicide risk, because that would be

> " misbranding the drug. "

>

> That Amicus Curiae brief is part of Congressional testimony submitted

> by

> the

> Alliance for Human Research Protection to the Senate Health,

> Education,

> Labor & Pension Committee hearing on Suicide Prevention and Youth:

> Saving

> Lives, March 2, 2004, and will be posted on the committee's website.

>

> The Guardian reports that failure to warn physicians about

> prescribing a

> higher than 20mg recommended dose of Paxil / Seroxat, has resulted in

> about

> 17,000 patients [in the UK]- out of an estimated 500,000 on the drug -

> to be

> started on higher doses than recommended last year. Experts informed

> AHRP

> that the equivalent estimates for the US would be between 250,000 and

> 500,000 (out of 3 million) Americans who would have been prescribed

> too

> high

> a dose. For estimates of US consumption of SSRI antidepressants, see a

> letter submitted by Dr. Healy, foremost expert on the effects of

> antidepressants to the FDA at the request of Dr. Temple, FDA

> Director

> of the Office of Drug Evaluation I at:

> http://www.ahrp.org/risks/healy/FDA0204.html

>

> On Thursday, March 11, a mildly phrased alert issued to UK physicians

> by

> the

> CSM appears to be a direct result of Mr. Brook's warning to the

> committee.

> The CSM alert informs physicians that higher doses of Paxil / Seroxat

> were

> no more effective than the recommended 20mg dose, but that higher

> doses

> cause more adverse effects. See:

> http://medicines.mhra.gov.uk/ourwork/monitorsafequalmed/safetymessages

> /p

> arox

> etine_11304.htm

>

> MIND, the largest nonprofit mental health agency in the UK, is calling

> for

> an independent review of the workings of drug regulation with patient

> representation at its heart. They were backed by Medawar of

> the

> consumer group Social Audit.

>

> The following links lead to additional Guardian reports Saturday March

> 13,

> 2004:

> Drug safety agency accused of cover-up Boseley, health editor

> http://politics.guardian.co.uk/publicservices/story/0,11032,1168613,00

> .h

> tml

>

> http://politics.guardian.co.uk/publicservices/story/0,11032,1168584,00

> .h

> tml

> A secretive system Editorial

>

>

> Contact: Vera Hassner Sharav

> Tel: 212-595-8974

> e-mail: veracare@a...

>

> ~~~~~~~~~~

>

> http://politics.guardian.co.uk/publicservices/story/0,11032,1168586,00

> .h

> tml

>

> The Riddle of the Drug Regulators

> Critics press for review of licensing system

>

> Boseley, health editor

> Saturday March 13, 2004

>

> The resignation last night of 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 GlaxoKline (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, 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

> Kline

> Beecham) for an explanation of the data.

>

> 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.

>

> FAIR USE NOTICE: This may contain copyrighted (C ) material the use of

> which

> has not always been specifically authorized by the copyright owner.

> Such

> material is made available for educational purposes, to advance

> understanding of human rights, democracy, scientific, moral, ethical,

> and

> social justice issues, etc. It is believed that this constitutes

> a 'fair

> use' of any such copyrighted material as provided for in Title 17

> U.S.C.

> section 107 of the US Copyright Law. This material is distributed

> without

> profit.

> --- End forwarded message ---

>

>

[Guest guest]

>

>

> Drug Safety Regulatory Agency Accused of Cover-Up_UK

> Guardian

>

>

> >

> ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP)

> Promoting openness and full disclosure

> http://www.ahrp.org <http://www.ahrp.org/>

>

> FYI

>

> When push came to shove, the British Medicines and Healthcare Products

> Regulatory Agency (MHRA, equivalent to the FDA) put the interests of a

> drug

> company ahead of the public health interest. Following a

> behind-the-scenes-struggle, Mr. Brook, Executive Director of

> MIND,

> resigned from an expert workgroup of the Committee on Safety in

> Medicine

> reviewing SSRI antidepressant safety and efficacy data from clinical

> trials

> and reports by physicians and patients. Brook, the panel's only

> consumer

> advocate, charged the committee and the MHRA with a cover-up in its

> efforts

> to conceal the severity of the drug-related problems.

>

> The panel's review of the original Paxil / Seroxat data found that

> regulators have known since 1990 that higher than recommended doses

> (20mg)

> caused severe adverse side effects leading many patients testing the

> drug to

> drop out. Yet, neither physicians prescribing Paxil nor the public was

> informed about the potential hazards posed by higher doses. Regulators

> in

> Britain, Canada, and the US failed to protect the public health by

> requiring

> GlaxoKline to put prominent warnings on the drug's label. As a

> result,

> ill-informed doctors prescribe Paxil / Seroxat and other

> antidepressants

> at

> unsafe higher doses than recommended, leading to preventable harm and

> deaths.

>

> The evidence shows that regulators in the UK and the US have known

> about

> the

> risks for patients, but have tacitly aided and abetted manufacturers

> who

> concealed vital safety information from prescribing physicians and the

> public for over a decade.

>

> When it became apparent that the UK committee would cover-up the

> evidence of

> dose related harmful drug effects, Brook warned the CSM and MHRA that

> " he

> felt he had no choice but to go public [with the evidence] because of

> the

> risks to patients. " The Guardian reports that Brook " was warned in a

> letter

> last Monday from the MHRA that he could risk prosecution under the

> Medicines

> Act 1968, which protects the commercial confidentiality of information

> from

> drug trials. "

>

> The unraveling antidepressant saga both in the UK and the US provides

> a

> window into the secret world in which drug manufacturers and

> government

> regulators interact behind closed doors. This secret intermingling is

> undermining the safety of patients who take prescribed drugs because

> physicians who prescribe the drugs are kept uninformed about the known

> and

> potential dangers posed by these and probably other drugs. For some

> patients

> SSRIs can trigger violent and suicidal behavior.

>

> The Guardian reports: " 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 GlaxoKline (GSK) until 2001, is now

> director of licensing at the MHRA. "

>

> Cozy relationships between FDA officials and drug company officials

> are

> even

> more pervasive at the FDA because the financial stakes are so much

> greater.

> For example, the chief counsel for the FDA, Troy, filed an

> Amicus

> Curiae brief in 2003 with a US court siding with Pfizer, the

> manufacturer of

> the SSRI antidepressant, Zoloft. The issue was the company's failure

> to

> warn

> about suicidal risks of Zoloft. Troy argued that FDA would not permit

> Pfizer

> to put a warning on the Zoloft label about evidence suggesting a link

> between the drug and increased suicide risk, because that would be

> " misbranding the drug. "

>

> That Amicus Curiae brief is part of Congressional testimony submitted

> by

> the

> Alliance for Human Research Protection to the Senate Health,

> Education,

> Labor & Pension Committee hearing on Suicide Prevention and Youth:

> Saving

> Lives, March 2, 2004, and will be posted on the committee's website.

>

> The Guardian reports that failure to warn physicians about

> prescribing a

> higher than 20mg recommended dose of Paxil / Seroxat, has resulted in

> about

> 17,000 patients [in the UK]- out of an estimated 500,000 on the drug -

> to be

> started on higher doses than recommended last year. Experts informed

> AHRP

> that the equivalent estimates for the US would be between 250,000 and

> 500,000 (out of 3 million) Americans who would have been prescribed

> too

> high

> a dose. For estimates of US consumption of SSRI antidepressants, see a

> letter submitted by Dr. Healy, foremost expert on the effects of

> antidepressants to the FDA at the request of Dr. Temple, FDA

> Director

> of the Office of Drug Evaluation I at:

> http://www.ahrp.org/risks/healy/FDA0204.html

>

> On Thursday, March 11, a mildly phrased alert issued to UK physicians

> by

> the

> CSM appears to be a direct result of Mr. Brook's warning to the

> committee.

> The CSM alert informs physicians that higher doses of Paxil / Seroxat

> were

> no more effective than the recommended 20mg dose, but that higher

> doses

> cause more adverse effects. See:

> http://medicines.mhra.gov.uk/ourwork/monitorsafequalmed/safetymessages

> /p

> arox

> etine_11304.htm

>

> MIND, the largest nonprofit mental health agency in the UK, is calling

> for

> an independent review of the workings of drug regulation with patient

> representation at its heart. They were backed by Medawar of

> the

> consumer group Social Audit.

>

> The following links lead to additional Guardian reports Saturday March

> 13,

> 2004:

> Drug safety agency accused of cover-up Boseley, health editor

> http://politics.guardian.co.uk/publicservices/story/0,11032,1168613,00

> .h

> tml

>

> http://politics.guardian.co.uk/publicservices/story/0,11032,1168584,00

> .h

> tml

> A secretive system Editorial

>

>

> Contact: Vera Hassner Sharav

> Tel: 212-595-8974

> e-mail: veracare@a...

>

> ~~~~~~~~~~

>

> http://politics.guardian.co.uk/publicservices/story/0,11032,1168586,00

> .h

> tml

>

> The Riddle of the Drug Regulators

> Critics press for review of licensing system

>

> Boseley, health editor

> Saturday March 13, 2004

>

> The resignation last night of 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 GlaxoKline (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, 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

> Kline

> Beecham) for an explanation of the data.

>

> 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.

>

> FAIR USE NOTICE: This may contain copyrighted (C ) material the use of

> which

> has not always been specifically authorized by the copyright owner.

> Such

> material is made available for educational purposes, to advance

> understanding of human rights, democracy, scientific, moral, ethical,

> and

> social justice issues, etc. It is believed that this constitutes

> a 'fair

> use' of any such copyrighted material as provided for in Title 17

> U.S.C.

> section 107 of the US Copyright Law. This material is distributed

> without

> profit.

> --- End forwarded message ---

>

>

[Guest guest]

>

>

> Drug Safety Regulatory Agency Accused of Cover-Up_UK

> Guardian

>

>

> >

> ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP)

> Promoting openness and full disclosure

> http://www.ahrp.org <http://www.ahrp.org/>

>

> FYI

>

> When push came to shove, the British Medicines and Healthcare Products

> Regulatory Agency (MHRA, equivalent to the FDA) put the interests of a

> drug

> company ahead of the public health interest. Following a

> behind-the-scenes-struggle, Mr. Brook, Executive Director of

> MIND,

> resigned from an expert workgroup of the Committee on Safety in

> Medicine

> reviewing SSRI antidepressant safety and efficacy data from clinical

> trials

> and reports by physicians and patients. Brook, the panel's only

> consumer

> advocate, charged the committee and the MHRA with a cover-up in its

> efforts

> to conceal the severity of the drug-related problems.

>

> The panel's review of the original Paxil / Seroxat data found that

> regulators have known since 1990 that higher than recommended doses

> (20mg)

> caused severe adverse side effects leading many patients testing the

> drug to

> drop out. Yet, neither physicians prescribing Paxil nor the public was

> informed about the potential hazards posed by higher doses. Regulators

> in

> Britain, Canada, and the US failed to protect the public health by

> requiring

> GlaxoKline to put prominent warnings on the drug's label. As a

> result,

> ill-informed doctors prescribe Paxil / Seroxat and other

> antidepressants

> at

> unsafe higher doses than recommended, leading to preventable harm and

> deaths.

>

> The evidence shows that regulators in the UK and the US have known

> about

> the

> risks for patients, but have tacitly aided and abetted manufacturers

> who

> concealed vital safety information from prescribing physicians and the

> public for over a decade.

>

> When it became apparent that the UK committee would cover-up the

> evidence of

> dose related harmful drug effects, Brook warned the CSM and MHRA that

> " he

> felt he had no choice but to go public [with the evidence] because of

> the

> risks to patients. " The Guardian reports that Brook " was warned in a

> letter

> last Monday from the MHRA that he could risk prosecution under the

> Medicines

> Act 1968, which protects the commercial confidentiality of information

> from

> drug trials. "

>

> The unraveling antidepressant saga both in the UK and the US provides

> a

> window into the secret world in which drug manufacturers and

> government

> regulators interact behind closed doors. This secret intermingling is

> undermining the safety of patients who take prescribed drugs because

> physicians who prescribe the drugs are kept uninformed about the known

> and

> potential dangers posed by these and probably other drugs. For some

> patients

> SSRIs can trigger violent and suicidal behavior.

>

> The Guardian reports: " 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 GlaxoKline (GSK) until 2001, is now

> director of licensing at the MHRA. "

>

> Cozy relationships between FDA officials and drug company officials

> are

> even

> more pervasive at the FDA because the financial stakes are so much

> greater.

> For example, the chief counsel for the FDA, Troy, filed an

> Amicus

> Curiae brief in 2003 with a US court siding with Pfizer, the

> manufacturer of

> the SSRI antidepressant, Zoloft. The issue was the company's failure

> to

> warn

> about suicidal risks of Zoloft. Troy argued that FDA would not permit

> Pfizer

> to put a warning on the Zoloft label about evidence suggesting a link

> between the drug and increased suicide risk, because that would be

> " misbranding the drug. "

>

> That Amicus Curiae brief is part of Congressional testimony submitted

> by

> the

> Alliance for Human Research Protection to the Senate Health,

> Education,

> Labor & Pension Committee hearing on Suicide Prevention and Youth:

> Saving

> Lives, March 2, 2004, and will be posted on the committee's website.

>

> The Guardian reports that failure to warn physicians about

> prescribing a

> higher than 20mg recommended dose of Paxil / Seroxat, has resulted in

> about

> 17,000 patients [in the UK]- out of an estimated 500,000 on the drug -

> to be

> started on higher doses than recommended last year. Experts informed

> AHRP

> that the equivalent estimates for the US would be between 250,000 and

> 500,000 (out of 3 million) Americans who would have been prescribed

> too

> high

> a dose. For estimates of US consumption of SSRI antidepressants, see a

> letter submitted by Dr. Healy, foremost expert on the effects of

> antidepressants to the FDA at the request of Dr. Temple, FDA

> Director

> of the Office of Drug Evaluation I at:

> http://www.ahrp.org/risks/healy/FDA0204.html

>

> On Thursday, March 11, a mildly phrased alert issued to UK physicians

> by

> the

> CSM appears to be a direct result of Mr. Brook's warning to the

> committee.

> The CSM alert informs physicians that higher doses of Paxil / Seroxat

> were

> no more effective than the recommended 20mg dose, but that higher

> doses

> cause more adverse effects. See:

> http://medicines.mhra.gov.uk/ourwork/monitorsafequalmed/safetymessages

> /p

> arox

> etine_11304.htm

>

> MIND, the largest nonprofit mental health agency in the UK, is calling

> for

> an independent review of the workings of drug regulation with patient

> representation at its heart. They were backed by Medawar of

> the

> consumer group Social Audit.

>

> The following links lead to additional Guardian reports Saturday March

> 13,

> 2004:

> Drug safety agency accused of cover-up Boseley, health editor

> http://politics.guardian.co.uk/publicservices/story/0,11032,1168613,00

> .h

> tml

>

> http://politics.guardian.co.uk/publicservices/story/0,11032,1168584,00

> .h

> tml

> A secretive system Editorial

>

>

> Contact: Vera Hassner Sharav

> Tel: 212-595-8974

> e-mail: veracare@a...

>

> ~~~~~~~~~~

>

> http://politics.guardian.co.uk/publicservices/story/0,11032,1168586,00

> .h

> tml

>

> The Riddle of the Drug Regulators

> Critics press for review of licensing system

>

> Boseley, health editor

> Saturday March 13, 2004

>

> The resignation last night of 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 GlaxoKline (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, 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

> Kline

> Beecham) for an explanation of the data.

>

> 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.

>

> FAIR USE NOTICE: This may contain copyrighted (C ) material the use of

> which

> has not always been specifically authorized by the copyright owner.

> Such

> material is made available for educational purposes, to advance

> understanding of human rights, democracy, scientific, moral, ethical,

> and

> social justice issues, etc. It is believed that this constitutes

> a 'fair

> use' of any such copyrighted material as provided for in Title 17

> U.S.C.

> section 107 of the US Copyright Law. This material is distributed

> without

> profit.

> --- End forwarded message ---

>

>

[Guest guest]

>

>

> Drug Safety Regulatory Agency Accused of Cover-Up_UK

> Guardian

>

>

> >

> ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP)

> Promoting openness and full disclosure

> http://www.ahrp.org <http://www.ahrp.org/>

>

> FYI

>

> When push came to shove, the British Medicines and Healthcare Products

> Regulatory Agency (MHRA, equivalent to the FDA) put the interests of a

> drug

> company ahead of the public health interest. Following a

> behind-the-scenes-struggle, Mr. Brook, Executive Director of

> MIND,

> resigned from an expert workgroup of the Committee on Safety in

> Medicine

> reviewing SSRI antidepressant safety and efficacy data from clinical

> trials

> and reports by physicians and patients. Brook, the panel's only

> consumer

> advocate, charged the committee and the MHRA with a cover-up in its

> efforts

> to conceal the severity of the drug-related problems.

>

> The panel's review of the original Paxil / Seroxat data found that

> regulators have known since 1990 that higher than recommended doses

> (20mg)

> caused severe adverse side effects leading many patients testing the

> drug to

> drop out. Yet, neither physicians prescribing Paxil nor the public was

> informed about the potential hazards posed by higher doses. Regulators

> in

> Britain, Canada, and the US failed to protect the public health by

> requiring

> GlaxoKline to put prominent warnings on the drug's label. As a

> result,

> ill-informed doctors prescribe Paxil / Seroxat and other

> antidepressants

> at

> unsafe higher doses than recommended, leading to preventable harm and

> deaths.

>

> The evidence shows that regulators in the UK and the US have known

> about

> the

> risks for patients, but have tacitly aided and abetted manufacturers

> who

> concealed vital safety information from prescribing physicians and the

> public for over a decade.

>

> When it became apparent that the UK committee would cover-up the

> evidence of

> dose related harmful drug effects, Brook warned the CSM and MHRA that

> " he

> felt he had no choice but to go public [with the evidence] because of

> the

> risks to patients. " The Guardian reports that Brook " was warned in a

> letter

> last Monday from the MHRA that he could risk prosecution under the

> Medicines

> Act 1968, which protects the commercial confidentiality of information

> from

> drug trials. "

>

> The unraveling antidepressant saga both in the UK and the US provides

> a

> window into the secret world in which drug manufacturers and

> government

> regulators interact behind closed doors. This secret intermingling is

> undermining the safety of patients who take prescribed drugs because

> physicians who prescribe the drugs are kept uninformed about the known

> and

> potential dangers posed by these and probably other drugs. For some

> patients

> SSRIs can trigger violent and suicidal behavior.

>

> The Guardian reports: " 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 GlaxoKline (GSK) until 2001, is now

> director of licensing at the MHRA. "

>

> Cozy relationships between FDA officials and drug company officials

> are

> even

> more pervasive at the FDA because the financial stakes are so much

> greater.

> For example, the chief counsel for the FDA, Troy, filed an

> Amicus

> Curiae brief in 2003 with a US court siding with Pfizer, the

> manufacturer of

> the SSRI antidepressant, Zoloft. The issue was the company's failure

> to

> warn

> about suicidal risks of Zoloft. Troy argued that FDA would not permit

> Pfizer

> to put a warning on the Zoloft label about evidence suggesting a link

> between the drug and increased suicide risk, because that would be

> " misbranding the drug. "

>

> That Amicus Curiae brief is part of Congressional testimony submitted

> by

> the

> Alliance for Human Research Protection to the Senate Health,

> Education,

> Labor & Pension Committee hearing on Suicide Prevention and Youth:

> Saving

> Lives, March 2, 2004, and will be posted on the committee's website.

>

> The Guardian reports that failure to warn physicians about

> prescribing a

> higher than 20mg recommended dose of Paxil / Seroxat, has resulted in

> about

> 17,000 patients [in the UK]- out of an estimated 500,000 on the drug -

> to be

> started on higher doses than recommended last year. Experts informed

> AHRP

> that the equivalent estimates for the US would be between 250,000 and

> 500,000 (out of 3 million) Americans who would have been prescribed

> too

> high

> a dose. For estimates of US consumption of SSRI antidepressants, see a

> letter submitted by Dr. Healy, foremost expert on the effects of

> antidepressants to the FDA at the request of Dr. Temple, FDA

> Director

> of the Office of Drug Evaluation I at:

> http://www.ahrp.org/risks/healy/FDA0204.html

>

> On Thursday, March 11, a mildly phrased alert issued to UK physicians

> by

> the

> CSM appears to be a direct result of Mr. Brook's warning to the

> committee.

> The CSM alert informs physicians that higher doses of Paxil / Seroxat

> were

> no more effective than the recommended 20mg dose, but that higher

> doses

> cause more adverse effects. See:

> http://medicines.mhra.gov.uk/ourwork/monitorsafequalmed/safetymessages

> /p

> arox

> etine_11304.htm

>

> MIND, the largest nonprofit mental health agency in the UK, is calling

> for

> an independent review of the workings of drug regulation with patient

> representation at its heart. They were backed by Medawar of

> the

> consumer group Social Audit.

>

> The following links lead to additional Guardian reports Saturday March

> 13,

> 2004:

> Drug safety agency accused of cover-up Boseley, health editor

> http://politics.guardian.co.uk/publicservices/story/0,11032,1168613,00

> .h

> tml

>

> http://politics.guardian.co.uk/publicservices/story/0,11032,1168584,00

> .h

> tml

> A secretive system Editorial

>

>

> Contact: Vera Hassner Sharav

> Tel: 212-595-8974

> e-mail: veracare@a...

>

> ~~~~~~~~~~

>

> http://politics.guardian.co.uk/publicservices/story/0,11032,1168586,00

> .h

> tml

>

> The Riddle of the Drug Regulators

> Critics press for review of licensing system

>

> Boseley, health editor

> Saturday March 13, 2004

>

> The resignation last night of 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 GlaxoKline (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, 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

> Kline

> Beecham) for an explanation of the data.

>

> 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.

>

> FAIR USE NOTICE: This may contain copyrighted (C ) material the use of

> which

> has not always been specifically authorized by the copyright owner.

> Such

> material is made available for educational purposes, to advance

> understanding of human rights, democracy, scientific, moral, ethical,

> and

> social justice issues, etc. It is believed that this constitutes

> a 'fair

> use' of any such copyrighted material as provided for in Title 17

> U.S.C.

> section 107 of the US Copyright Law. This material is distributed

> without

> profit.

> --- End forwarded message ---

>

>