Molecular
Targeted Therapy
FDA
Accused of Silencing Internal Critics
Agency
Drug Expert Claims 'Intimidation'
By
DIEDTRA HENDERSON, AP
WASHINGTON (Oct. 7, 2004) - The Food and Drug Administration
silenced one of its drug experts, the chairman of the Senate Finance Committee
said Thursday.
Dr. David J. Graham, associate director for science in the FDA
Drug Center's Office of Drug Safety, told Senate investigators he faced stiff
resistance within the regulatory agency to his findings.
"Dr.
Graham described an environment where he was 'ostracized,' 'subjected to veiled
threats' and 'intimidation,''' Sen. Chuck Grassley, R-Iowa, said in a statement
after Finance Committee investigators interviewed the researcher Thursday.
Graham
told The Associated Press that Grassley's characterization was accurate. Raising
concerns within the agency is "extremely difficult,'' the 20-year employee
said, declining further comment.
In a
prepared statement, the FDA said it "values open discussion and frank
exchange about scientific and medical issues'' and subjects its scientists to
"more rigorous'' scrutiny than typical scientific peer reviews.
The
Government Accountability Office, an investigative arm of Congress, already has
been asked to look into whether the FDA muzzled another staffer.
Grassley's committee is one of three in Congress also scrutinizing the
FDA's actions.
A
"picture is emerging of an agency that can't see the forest for the
trees,'' Grassley said. "The Food and Drug Administration was busy
challenging its own expert and calling his work 'scientific rumor.'''
Graham,
scheduled to present research findings in late August during a conference in
France, said he ran into resistance when the FDA reviewed his abstract.
"I
think the recommendation unnecessary and particularly problematic since FDA
funded this study and David's travel to France to present it,'' Anne E. Trontell,
deputy director of the FDA's Office of Drug Safety, wrote in an Aug. 12 e-mail.
The
internal e-mail exchange was released by Grassley.
In the
e-mail, Trontell suggested that Graham defer his presentation in favor of a
journal article so dissenting scientists - including within the FDA - could
comment.
She also
said that the drug manufacturer involved should be alerted before the findings
became public "so they can be prepared for extensive media attention that
this will likely provoke.''
Others
within the agency suggested Graham's conclusion was too strongly worded, given
the FDA had not insisted on drug manufacturers adding warnings to labels.
"I've
gone about as far as I can without compromising my deeply held conclusions about
this question,'' Graham replied in an Aug. 13 e-mail.
The FDA
said such discussions are typical before scientific findings are published.
The
conclusion Graham presented in France was revised. The FDA said that it was Graham
who decided to revise his abstract conclusion. "He did so voluntarily,''
the agency said.
In
testimony before a congressional panel in mid-September, Andrew Mosholder, an
FDA epidemiologist, said his bosses asked him to soften recommendations about
antidepressants.
-----------------
New
Measures Aim to Improve Drug Safety
Drug
Safety Director to Be Appointed
By
DIEDTRA HENDERSON, AP
WASHINGTON
(Nov. 5, 2004) - Buffeted by criticism, the Food and Drug Administration said
Friday that it would appoint a director of drug safety and take other actions to
assure the safety of medications it approves.
As
sick and elderly Americans competed in lotteries for scarce flu vaccine, members
of Congress chided the FDA for relying on the word of Chiron Corp., the
vaccine's manufacturer, rather than investigating as aggressively as British
regulators.
Critics also have charged
the FDA ignored risks associated with antidepressants and the blockbuster drug
Vioxx, then intimidated its own reviewers when they pointed to safety problems
in both cases.
The Senate Finance
Committee, one of three Congressional panels investigating the FDA, sought from
the agency Friday a year's worth of correspondence between the agency and Merck
& Co. Inc., Vioxx's manufacturer. Investigators suspect the agency crumbled
under intense lobbying and placed cardiovascular risks less prominently on
Vioxx's label in 2002.
"The warning is in
there. It's a matter of whether it's effective or effectively buried," a
committee aide said.
FDA spokeswoman Kathleen
K. Quinn, provided by e-mail a copy of the letter from Sen. Chuck Grassley,
R-Iowa, the committee chairman, declined comment.
Dr. Steven Galson, acting
director of the FDA's Center for Drug Evaluation and Research, told reporters
the highly publicized disagreements on Vioxx and antidepressants were uncommon.
The episodes don't merit tweaking the agency's culture to ensure dissenting
views are heard.
"It's
a rarity. It doesn't represent the culture, so we don't really think there is a
need for an overwhelming cultural change," Galson said.
However, Dr. Eric Topol,
the Cleveland Clinic cardiologist who pointed to increased cardiovascular risks
with Vioxx in 2001, said he's spoken to at least three other FDA researchers who
complained the agency minimized their concerns about the drug.
"There has been a
climate there ... of suppression of ideas and concerns," Topol said.
Lester M. Crawford,
acting FDA commissioner, said the agency's stamp of approval means American
drugs are the world's safest. "The measures we are taking are designed to
strengthen this quality as well as our consumers' confidence that FDA's
processes ensure the highest protection of the public health," he said in a
statement.
Galson said the FDA will
name a director of the Office of Drug Safety, vacant since October 2003, to
oversee the safety of drugs after their approval.
In addition, the agency
is asking the Institute of Medicine to study whether improvements are needed to
tease out more about a drug's side effects as it comes into more widespread use.
The study also will examine whether the agency is too close to the drug industry
to regulate it effectively.
The institute is an arm
of the National Academy of Science, which advises the government on scientific
matters.
"We think most of
the charges that have been leveled are just not accurate," Galson said.
Still, Dr. Wayne A. Ray,
a Vanderbilt professor of preventive medicine, said the agency faces an internal
conflict. One arm approves drugs, while the drug safety office tests the rigor
of those decisions.
"Once the people in
the reviewing decision approve a drug, there is a natural human tendency to not
confront information that shows that decision might be faulty," Ray said,
renewing a call for an independent drug safety board.
To bridge differences
among its scientific reviewers, the agency said it would convene an independent
panel to review documents and make recommendations.
Acting commissioner
Crawford said the FDA'S clinical reviewers and epidemiologists "evaluate
and respond to identified concerns. This is what occurred recently with
antidepressants and Vioxx."
Yet, in both cases
reviewers told members of Congress they faced resistance within the agency after
raising alarms.
Consumer advocate Sidney
Wolfe said he was cynical that Crawford would make meaningful changes, such as
correcting the power imbalance that hobbles the drug safety office and making
public dissenting reviewers' comments. "This is an attempt to put up a
cosmetic fix to a serious problem."
This week, the FDA
released a Sept. 30 memo from David Graham, the associate director for science,
that said Vioxx safety concerns continued to mount after 2000. Besides
heightened cardiovascular risks, the drug was linked to "significantly
increased" risk of hospitalization for gastrointestinal bleeding.
Also, the editor of the journal The Lancet this week pointed to "lethal weaknesses" in FDA's regulatory oversight.
----------------------------
NOTE: It would be wrong to conclude, however, that the FDA must be even more cautious before releasing new drugs. What the current investigations stand to reveal is that in the cases of drugs already approved (and after considerable testing and caution), the FDA failed to respond to subsequent data that the drugs may not be safe after all --- and failed to pull the already released drugs ... for political reasons; like protecting their own jobs, and protecting the revenues of the drug manufacturers.
In
all likelihood, the wrong lesson will be learned from this, and now the FDA will
probably become even more conservative about releasing potentially
lifesaving drugs. (With non-fatal diseases this may indeed be in the public
interest).
A
very different way of thinking is critical if cures for diseases requiring a
“cocktail” approach are to be effectively found. “Cocktail” components
cannot be subjected to the same long-term criteria as single drug regimens for
illness --- for the reasons explained in POSITION
PAPER --- even though such “cocktail” components would continue with
further long-term testing even after interim approval.
Essentially,
there are two totally different mentalities required for the two types of
approaches to treating illness: (a) a very cautious and conservative approach
for “one illness
>>> one drug”;
versus (b) “fatal
illness >>> drug cocktail”.
Today, both types of drug approval being controlled by a single agency is akin to having a single agency to (a) protect the environment; and (b) to seek new oil exploration. It makes no sense, and will not result in either goal being properly handled.
A NEW AGENCY must be formed immediately to handle the testing and approval of drug "COCKTAILS" for diseases such as HIV and incurable cancers. see POSITION PAPER.
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AP:
FDA Silences Internal Critics
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