OFF TOPIC - FDA & Drug Safety
Posted: Sat Feb 26, 2005 5:58 pm
Safety concerns at the FDA
The Lancet
Available online 25 February 2005.
The US Food and Drug Administration is in crisis. Under fire for its record
on drug safety, brought to a head when Merck voluntarily withdrew rofecoxib
in September, 2004, and suffering from prolonged lack of leadership, the
FDA is in a sorry state.
Three decisions in the past few weeks were heralded as cause for optimism.
On Feb 14, President Bush nominated Lester Crawford, the acting
commissioner of the FDA, to become its permanent commissioner. An advisory
panel spent 3 days last week hearing evidence on the efficacy and safety of
the COX-2 inhibitors rofecoxib (Vioxx), valdecoxib (Bextra), and celecoxib
(Celebrex). And on Feb 15, the FDA announced that it was creating a Drug
Safety Oversight Board.
Lester Crawford has been acting commissioner or deputy commissioner to the
FDA for almost 3 years under the Bush administration. The permanent post
has been vacant since March, 2004, when the previous chief, Mark McClellan,
left after only 17 months. Crawford is a veterinarian with a PhD in
pharmacology. It is during his reign as acting commissioner that concern
over drug safety has reached a head. Sidney Wolfe, a long-time critic of
the FDA and a director at Public Citizen, a consumer advocacy group, told
The Lancet that Crawford had done a "terrible job", with a poor record on
drug safety issues, failing to warn adequately about the cardiovascular
risks of rofecoxib. "Crawford won, so the American public loses", said
Wolfe on Crawford's nomination as FDA chief. Crawford has shown repeatedly
that he lacks the determination to strengthen the weak regulatory culture
within the FDA. He has failed to protect agency scientists who try to speak
openly about drug safety concerns. And he has refused to recognise that his
primary duty is to protect the public, not to facilitate the entry of
inadequately tested medicines onto the market.
The FDA took the unusual step of holding a joint public meeting of its
Arthritis Advisory Committee and its Drug Safety Risk Management Advisory
Committee between Feb 16 and 18. The aim was to discuss the overall benefit
to risk considerations for the three COX-2 selective non-steroidal
anti-inflammatory drugs currently approved in the USA. The conclusion of
the panel was that the potential benefits outweighed the risks. Support for
marketing was stronger for celecoxib (with 31 panellists in favour, and one
against) than for valdecoxib (17 in favour, 13 against) or rofecoxib (17
for, 15 against). All three drugs should, said the panel, be marketed as
painkillers accompanied by strong warnings of the risks, including the
cardiovascular risks, which the panel concluded were likely to be a class
effect and not unique to rofecoxib. The FDA usually follows its committees'
advice. When the FDA does issue its conclusions, which may not be for a few
weeks, clear guidance on which patients are most likely to benefit, and
least likely to be harmed, and on dose and duration is needed, assuming the
data are available.
Announcing the creation of the Drug Safety Oversight Board, Crawford and
Health and Human Services Secretary Mike Leavitt said that the board would
consist of scientists drawn from throughout the federal government. The
board will advise on the management of drug safety issues within the Center
for Drug Evaluation and Research. It will not have the independent power to
force the withdrawal or relabelling of drugs, but can only advise the FDA.
The board will make its conclusions public via a new Drug Watch internet
site, which will allow discussion of emerging or potential safety issues
before the FDA has reached conclusions that would prompt regulatory action.
In addition, changes at the FDA will allow information about adverse
effects of drugs to be collated from databases, including those at Medicaid
and other government or private health plans, and will increase the number
of FDA-approved fact sheets that patients receive with their prescriptions.
However, analyzing adverse event data held on large databases will cost
millions of dollars each year, yet no additional funding has been provided.
Until now, it has been the remit of the Office of Drug Safety at the FDA to
monitor adverse events. But with a staff of around 100 to analyze the
miscellaneous reports sent in by doctors and drug companies, and a
reporting structure submerged within the FDA's drug review division, the
Office of Drug Safety has neither the power nor the independence needed to
reliably detect drug side-effects and to take action to protect patients.
This solution to the problem of monitoring drug safety is flawed. The new
Drug Safety Oversight Board is a hurriedly put together substitute to
fundamental change in the structure and power of the Office of Drug Safety.
What is needed is an Office of Drug Safety with increased staff, and the
same power and political clout as the Office for New Drugs. Monitoring drug
safety can be done within the FDA if there are no ties with the division
that is responsible for approving new drugs, and if enough money is given
to fund database analyses. In addition, the Bush administration must grant
the FDA greater legal authority to demand that manufacturers conduct
postmarketing surveillance or give the FDA the resources to fund its own
drug-surveillance studies. Creating a board with only advisory powers on an
issue as important as drug safety is unacceptable.
"The FDA is an icon of trust, a certifier of safety, an enabler of
innovation and a repository of information", said Leavitt when announcing
the new Drug Safety Oversight Board. If only all that were the case. He
continued, "We will keep the promise of the FDA brand by putting in place
more rigorous oversight and collecting and sharing important and emerging
information about drug safety and effectiveness". What is in place or being
created so far is, unfortunately for the US public, inadequate to monitor
drug safety. What is needed is an FDA chief with the foresight and ability
to change a lumbering organisation, armed with the legal framework to
achieve an effective drug safety monitoring system, and the power to then
act promptly when safety concerns arise.
[Non-text portions of this message have been removed]
The Lancet
Available online 25 February 2005.
The US Food and Drug Administration is in crisis. Under fire for its record
on drug safety, brought to a head when Merck voluntarily withdrew rofecoxib
in September, 2004, and suffering from prolonged lack of leadership, the
FDA is in a sorry state.
Three decisions in the past few weeks were heralded as cause for optimism.
On Feb 14, President Bush nominated Lester Crawford, the acting
commissioner of the FDA, to become its permanent commissioner. An advisory
panel spent 3 days last week hearing evidence on the efficacy and safety of
the COX-2 inhibitors rofecoxib (Vioxx), valdecoxib (Bextra), and celecoxib
(Celebrex). And on Feb 15, the FDA announced that it was creating a Drug
Safety Oversight Board.
Lester Crawford has been acting commissioner or deputy commissioner to the
FDA for almost 3 years under the Bush administration. The permanent post
has been vacant since March, 2004, when the previous chief, Mark McClellan,
left after only 17 months. Crawford is a veterinarian with a PhD in
pharmacology. It is during his reign as acting commissioner that concern
over drug safety has reached a head. Sidney Wolfe, a long-time critic of
the FDA and a director at Public Citizen, a consumer advocacy group, told
The Lancet that Crawford had done a "terrible job", with a poor record on
drug safety issues, failing to warn adequately about the cardiovascular
risks of rofecoxib. "Crawford won, so the American public loses", said
Wolfe on Crawford's nomination as FDA chief. Crawford has shown repeatedly
that he lacks the determination to strengthen the weak regulatory culture
within the FDA. He has failed to protect agency scientists who try to speak
openly about drug safety concerns. And he has refused to recognise that his
primary duty is to protect the public, not to facilitate the entry of
inadequately tested medicines onto the market.
The FDA took the unusual step of holding a joint public meeting of its
Arthritis Advisory Committee and its Drug Safety Risk Management Advisory
Committee between Feb 16 and 18. The aim was to discuss the overall benefit
to risk considerations for the three COX-2 selective non-steroidal
anti-inflammatory drugs currently approved in the USA. The conclusion of
the panel was that the potential benefits outweighed the risks. Support for
marketing was stronger for celecoxib (with 31 panellists in favour, and one
against) than for valdecoxib (17 in favour, 13 against) or rofecoxib (17
for, 15 against). All three drugs should, said the panel, be marketed as
painkillers accompanied by strong warnings of the risks, including the
cardiovascular risks, which the panel concluded were likely to be a class
effect and not unique to rofecoxib. The FDA usually follows its committees'
advice. When the FDA does issue its conclusions, which may not be for a few
weeks, clear guidance on which patients are most likely to benefit, and
least likely to be harmed, and on dose and duration is needed, assuming the
data are available.
Announcing the creation of the Drug Safety Oversight Board, Crawford and
Health and Human Services Secretary Mike Leavitt said that the board would
consist of scientists drawn from throughout the federal government. The
board will advise on the management of drug safety issues within the Center
for Drug Evaluation and Research. It will not have the independent power to
force the withdrawal or relabelling of drugs, but can only advise the FDA.
The board will make its conclusions public via a new Drug Watch internet
site, which will allow discussion of emerging or potential safety issues
before the FDA has reached conclusions that would prompt regulatory action.
In addition, changes at the FDA will allow information about adverse
effects of drugs to be collated from databases, including those at Medicaid
and other government or private health plans, and will increase the number
of FDA-approved fact sheets that patients receive with their prescriptions.
However, analyzing adverse event data held on large databases will cost
millions of dollars each year, yet no additional funding has been provided.
Until now, it has been the remit of the Office of Drug Safety at the FDA to
monitor adverse events. But with a staff of around 100 to analyze the
miscellaneous reports sent in by doctors and drug companies, and a
reporting structure submerged within the FDA's drug review division, the
Office of Drug Safety has neither the power nor the independence needed to
reliably detect drug side-effects and to take action to protect patients.
This solution to the problem of monitoring drug safety is flawed. The new
Drug Safety Oversight Board is a hurriedly put together substitute to
fundamental change in the structure and power of the Office of Drug Safety.
What is needed is an Office of Drug Safety with increased staff, and the
same power and political clout as the Office for New Drugs. Monitoring drug
safety can be done within the FDA if there are no ties with the division
that is responsible for approving new drugs, and if enough money is given
to fund database analyses. In addition, the Bush administration must grant
the FDA greater legal authority to demand that manufacturers conduct
postmarketing surveillance or give the FDA the resources to fund its own
drug-surveillance studies. Creating a board with only advisory powers on an
issue as important as drug safety is unacceptable.
"The FDA is an icon of trust, a certifier of safety, an enabler of
innovation and a repository of information", said Leavitt when announcing
the new Drug Safety Oversight Board. If only all that were the case. He
continued, "We will keep the promise of the FDA brand by putting in place
more rigorous oversight and collecting and sharing important and emerging
information about drug safety and effectiveness". What is in place or being
created so far is, unfortunately for the US public, inadequate to monitor
drug safety. What is needed is an FDA chief with the foresight and ability
to change a lumbering organisation, armed with the legal framework to
achieve an effective drug safety monitoring system, and the power to then
act promptly when safety concerns arise.
[Non-text portions of this message have been removed]