Tuesday, October 10, 2006

Industry Influence: FDA "Critical Path"/ Biased Research: BMJ / NIH: still smoke & mirrors

ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP) Promoting Openness, Full
Disclosure, and Accountability http://www.ahrp.org


FYI

This Infomail deals with three interrelated issues:

1. A BMJ meta-analysis found pharmaceutical influence results in biased
research reports:
The US government publication, HealthDay News, reports (below) that an
independent authoritative analysis by the prestigious Cochrane Collaborative
Center (in Denmark) concludes: "drug reviews that are supported by the
pharmaceutical industry tend to be more biased and rate the drugs more
favorably than independent reviews."

The meta-analysis was published in the BMJ (British Medical Journal):
" Industry supported reviews of drugs should be read with caution as they
were less transparent, had few reservations about methodological limitations
of the included trials, and had more favourable conclusions than the
corresponding Cochrane reviews."
http://bmj.bmjjournals.com/cgi/content/abstract/bmj.38973.444699.0Bv1?hrss=1

The authors found--as did other similar comparison evaluations--that: All
seven of the industry-supported reviews recommended the drug in question
without hesitation, while none of the Cochrane reviews did. In both cases,
however, the estimated effect of the drug was similar. "This suggests that
the main problem with industry-supported reviews lies in how conclusions are
formulated."

2. A report in the Los Angeles Times (below), the latest in an ongoing saga
documenting ethics violations by high ranking government scientists at the
National Institutes of Health.
The LAT reports the responses given by Dr. Elias Zerhouni, Director of NIH,
to questions about his agency's staff failure to comply with his own
conflict of interest rules.

His responses reveal that after a two year battle, NIH researchers at
continue to refuse even to disclose their financial relationships to drug
and biotech companies.

"Question: How many government scientists at the NIH have taken consulting
fees or stock awards or options from drug companies?
Answer: After six congressional hearings spanning more than two years, we
still don't know because not all of the financial arrangements have been
revealed."

Their continued refusal to comply with Federal conflict of interest
regulations is a demonstration of unmitigated arrogance and disrespect for
both the integrity of science and their personal responsibility toward the
American taxpayer who pays these government scientists' salaries ranging
from $132,000 to $200,000. NIH scientists were shown to have published
biased scientific findings that promoted their corporate backers' products.
See Congressional transcripts and the ongoing series in The Los Angeles
Times.

These NIH rule breakers are operating under the delusion that they
are--"masters of the universe"-- and are therefore, entitled to privileges
above and beyond what other high ranking federal employees are. In point of
fact the conduct of these scientists--as they continue to dodge NIH
disclosure rules--is undermining our trust in the integrity of their
reported research findings.
In so doing they are undermining the credibility of the entire
Institute--and they should be ousted.

Contrary to their inflated self-image, they are replaceable. There are
plenty of honest scientists with untarnished expertise who would jump at the
opportunity to work toward medical breakthroughs that will benefit the
public--not their stock portfolios and those of their partners in industry.

We are reminded of Senator Domenici's verdict after witnessing the
spectacle at a Congressional hearing in March 2004, in which some of the
financial ties by NIH scientists were laid bare (e.g., copies of cancelled
checks). Sen. Domenici, who had for years been a staunch supporter of NIH
told The Hill:
"I hate to say it, but the NIH [have] turned into pigs. You know, pigs! They
can't keep their oinks closed. They send a senator down there [to] argue
[for increased budgets] as if they're broke."
http://www.ahrp.org/infomail/04/03/18.php

3. These latest reports underscore the need for vigorous open, public debate
such as took place at a two day conference that I attended at Hofstra
University School of Law.
The battle lines were drawn between those who recognize the corrosive effect
that the pharmaceutical industry is having on the safety and integrity of
medicine and medical research, and the powerful stakeholders--the
pharmaceutical-academic industrial complex--who profit from and wield
inordinate influence on every facet of the business of medical
research--including the very agency authorized to oversee and enforce safety
standards.

Conference attendees learned about a range of problems besetting medical
research under the influence of Big Pharma--in particular the multi-faceted
Vioxx debacle. Thoughtful participants having different perspectives
discussed and debated both the economic, public policy, and philosophical
issues involved. http://www.ahrp.org/cms/content/view/354/55/

However, attendees also witnessed a display of arrogance, misrepresentation
(of FDA's performance over the last decade and a half), and denial of drug
safety failures. Those who defend Big Pharma and its financial "support" of
academia and the FDA (since 1992) deny there is a problem. Absent entirely
from their perspective is a recognition that preventable human casualties
are evidence of a failed system that needs to be fixed. The defenders of
PhRMA and the FDA are focused only on the number of new drugs brought to
market--whether these drugs are helpful or harmful; and on sales statistics.
They disregard the tens of thousands--no, hundreds of thousands--of
preventable drug-related human casualties--as if these have no value.

One presentation verged on buffoonery. Peter Barton Hutt, a former FDA
chief Counsel, 1971-1975, began with blistering attacks on those who
criticized Big Pharma and the performance of FDA. He vented his spleen by
invecting against effective critics such as Dr. Marcia Angell (former editor
of The New England Journal of Medicine) who was not present. He then
proceeded to make unilateral absurd assertions as if he were Moses
presenting the 10 Commandments.

Mr. Hutt asserted that: the FDA is the most powerful government agency in
existence; FDA has supreme legal authority which has never been challenged
by anyone successfully; industry shakes in terror of incurring FDA's power
to harm their marketing; industry meekly accepts FDA directives so as not
bring the wrath of FDA. And he asserted that no one can challenge or
overrule the FDA. Although scheduled to participate in a round table debate
between the defenders and critics, he took aim, fired, and fled.

A presentation by Dr. Rachel Behrman, FDA deputy director, Office of Medical
Policy, Center for Drug Evaluation and Research (CDER), failed to
acknowledge with a single word that FDA has repeatedly received failing
grades for its drug safety monitoring. Numerous independent investigations
of FDA's performance-most recently by the Government Accountability Office
(GAO) and the Institute of Medicine-have concluded that FDA's poor
performance in drug safety shows this crucial function of the agency to be
dysfunctional.

Had knowledgable critics who were familiar with the IOM report content,
conference attendees would have thought the agency's performance was
distinguished, worthy of pride.

Dr. Behrman's presentation and affect lent validity to the devastating
evaluation the IOM report gave the CDER staff, noting its culture of
arrogance and disregard for safety issues. Even as the agency has been
severely criticized for its failure to protect the public from lethal drugs,
the FDA has embarked on a radical new venture-Critical Path-to speed up the
process of testing and bringing to market new classes of genetically
engineered drugs and biologics. No mention whatsoever was made about any
safeguards. Critical Path was designed by Dr. Janet Woodcock, CDER's former
director who now is in the Commissioner's office. It was designed to help
industry out of its developmental slump.
http://www.fda.gov/oc/initiatives/criticalpath/

If this radical departure from current drug testing methods is implemented
without meaningful enforceable safeguards or specified meaningful penalties
to deter cost-cutting short cuts that endanger lives-as happened in the
catastrophic, monoclonal antibody experiment, TGN1412, we fear the worst.
The near fatal TGN1412 experiment in which all 6 healthy volunteers were
exposed (within the span of 12 minutes) to a drug-induced "cytokine storm"
led to multi-organ failure that nearly killed all of them.
http://www.ahrp.org/cms/index.php?searchword=tgn1412&option=com_search&Itemi
d=5

Without specified mandatory safeguards and the agency's commitment to
enforce those safeguards, as well as its willingness to impose severe
penalties for violators, TGN1412 foreshadows the likelihood that similar
safety infractions will result in preventable human casualties.


References:
1. Anders W Jørgensen , Jørgen Hilden , Peter C Gøtzsche. Cochrane reviews
compared with industry supported meta-analyses and other meta-analyses of
the same drugs: systematic review, BMJ, 6 October 2006

2. Earle G. Domenici slams Specter and NIH 'pigs', THE HILL. March 17, 2004
www.hillnews.com/news/031704/domenici.aspx


Contact: Vera Hassner Sharav
212-595-8974
Veracare (at) ahrp.org

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