Ref Mr. Brook, .......from (AHRP)ALLIANCE FOR HUMAN RESEARCH PROTECTION

[Guest guest]

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/safetymessage

s/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/0,11032,1168613,0

0.h

tml

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

0.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/0,11032,1168586,0

0.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.

Ref Mr. Brook, .......from (AHRP)ALLIANCE FOR HUMAN RESEARCH

PROTECTION

[Guest guest]

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/safetymessage

s/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/0,11032,1168613,0

0.h

tml

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

0.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/0,11032,1168586,0

0.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.

Ref Mr. Brook, .......from (AHRP)ALLIANCE FOR HUMAN RESEARCH

PROTECTION

[Guest guest]

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/safetymessage

s/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/0,11032,1168613,0

0.h

tml

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

0.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/0,11032,1168586,0

0.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.

Ref Mr. Brook, .......from (AHRP)ALLIANCE FOR HUMAN RESEARCH

PROTECTION

[Guest guest]

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/safetymessage

s/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/0,11032,1168613,0

0.h

tml

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

0.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/0,11032,1168586,0

0.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.

Ref Mr. Brook, .......from (AHRP)ALLIANCE FOR HUMAN RESEARCH

PROTECTION