FDA shenanigans

[Guest guest]

Like many government agencies, FDA has had its problems and corruption.

Under Bush, as with all agencies, corruption has taken on a new

dementia...er...dimension of corporate sucking up--while at the same time

being infused with the great heaving stench of xtian fundamentalism.

A case in point of the former in terms of FDA's complete untrustworthiness.

It is not patients they give a damn about. Just stockholders.

M.

**

http://www.cancerdecisions.com/080606.html

FDA APPROVES GEMZAR FOR OVARIAN CANCER DESPITE ITS LACK OF EFFICACY - PART ONE

The Food and Drug Administration (FDA) has taken the rare step of

overruling one of its own advisory panels and has approved the drug Gemzar

(known generically as gemcitabine) for the treatment of recurrent ovarian

cancer. Earlier this year, the prestigious Oncologic Drugs Advisory

Committee (ODAC) strongly recommended against approval of the drug for this

indication. But the FDA - under the acting directorship of C. von

Eschenbach, MD - approved Gemzar in combination with carboplatin for women

whose disease had relapsed six months or more after their initial therapy.

In the past, FDA decision-makers have generally followed the advice of

their advisory panels, although they are not legally bound to do so. In

March, a spokesperson for Eli Lilly, the manufacturer of Gemzar, said that

the company was " really disappointed " with the panel's decision. So what

happened behind the scenes between March's disappointment and July's

triumphant announcement of approval? Lilly spokesman Dr. e

stated that the company had provided the regulatory agency with additional

information.

" This is a situation where we were able to provide the FDA with additional

analysis of the data that may have given a little more insight on the

benefits, " he said. Meanwhile, FDA officials have refused to comment on the

controversial decision. It seems decidedly odd that this " additional

analysis " was provided directly to FDA leaders and not to the expert panel

or the general public.

This is also the first time that the FDA has approved an ovarian cancer

drug based upon progression-free survival (PFS), rather than on the basis

of an improvement in overall survival (OS). The difference between these

two measures is not trivial. Although it sounds like a highly desirable

outcome, " progression-free survival " merely represents an interval of

variable length between the administration of treatment and the point at

which the cancer inexorably starts to advance again. Such delayed tumor

growth does not necessarily equate to an extension of the patient's

lifespan. Indeed, tumors that are arrested temporarily can then advance

more rapidly once they begin growing again, and patients may actually live

no longer than they would if they had not received the treatment.

The FDA panel found that the combination of Gemzar and carboplatin

increased median progression-free survival in patients by just 2.8 months

when compared with carboplatin alone. However, the key fact was that there

was no difference in the overall length of patients' survival. The

Gemzar-added group also experienced more adverse effects.

For those reasons, in March, this panel voted 9-2 against recommending

approval of the drug for ovarian cancer. The panel also commented on the

weakness of Lilly's trial data and criticized the way the company conducted

the 356-person clinical study (Pierson 2006). It was a landmark finding and

seemed to indicate a new determination on the part of advisors to draw the

line - to tell both the drug industry and regulators that they would have

to provide patients with real survival benefits if they expected to reap

the huge financial rewards that generally follow approval.

" The main issue is whether adding 2.8 months to median progression-free

survival at a cost of additional toxicity with no apparent effect on

survival is a sufficient basis for Gemzar approval for this use, " an FDA

spokesperson said at the time (Wall Street Journal 2006).

Eli Lilly countered, however, that the purpose of the drug was to prevent

the cancer from worsening, not necessarily to help patients live longer.

But, logically, if the Gemzar-treated patients die at the same time as

those denied this additional drug, how can that constitute an improvement

in their condition? Didn't their condition worsen significantly after the

drug stopped working, so that they then died at the same time as those who

weren't given the drug?

The company's other arguments in favor of Gemzar are convoluted in the

extreme. Dr. also asserted, in Gemzar's defense, that the drug

allowed patients to go longer without being treated again and therefore

could help spare them some side effects of chemotherapy. This is twisted

logic, since they would now have to face the side effects of both Gemzar

and carboplatin in combination - a regimen that carries a greater array of

side effects than either drug administered alone.

When he was asked why Lilly did not mention in its press release the drug's

failure to prolong life, Dr. Gaynor, head of cancer research at

Lilly, said: " I'm not sure that needed to be the focus. " Of course not, as

long as you're not the unlucky woman with ovarian cancer. Apparently, for

Lilly executives, the focus should be kept not on prolongation of life but

on the illusory benefit of " progression-free survival, " which will bring

concomitant benefits to their bottom line.

Dr. Gaynor also claimed that it is often difficult to determine if, and by

how much, a particular cancer drug helps prolong life because seriously ill

cancer patients often switch back and forth between different treatments.

But isn't that precisely why rigorous clinical trials were invented in the

first place, to tease apart and analyze the problems posed by the various

treatments that patients are offered?

The randomized clinical trial (RCT), gold standard of drug testing since

World War II, is now imperiled as never before in America. A glaring double

standard is in effect: clinical trials are deemed desirable when they

advance the financial interests of big pharmaceutical companies, but are

unceremoniously disposed of when they conflict with the pharmaceutical

industry's profit agenda. Regulatory agencies by their very nature are

supposed to put a restraint on the profit drive of private companies. That

is how the FDA's advisory board (ODAC) was trying to function. However,

sometimes those agencies become the tools of the powerful industries they

regulate, a phenomenon that Washington University law professor

Turley has dubbed " agency capture. " This is a situation that

should attract the attention of every legislator in the country as well as

every person who cares about the integrity of the drug evaluation process.

TO BE CONCLUDED, WITH REFERENCES, NEXT WEEK.