Fw: Lancet: FDA Far Too Cozy with Drug Industry

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Sent: Wednesday, May 23, 2001 3:26 AM

Subject: Lancet: FDA Far Too Cozy with Drug Industry

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Lancet: FDA far too cozy with drug industry

By Woodman

May 18, 2001 ã LONDON (Reuters Health) - Patients taking a controversial

new drug for irritable bowel syndrome may have died because the US Food

and Drug Administration (FDA) has become a " servant of [the drug]

industry, " the editor of The Lancet medical journal claimed in the May

19th issue.

In a devastating editorial, Horton said that although

GlaxoKline (GSK) voluntarily withdrew Lotronex (alosetron) from the

US market last November after the deaths of five patients, senior FDA

officials were now seeking to reintroduce it.

" This story reveals not only dangerous failings in a single drug's

approval and review process but also the extent to which the FDA, its

Center for Drug Evaluation and Research (CDER) in particular, has become

the servant of industry, " he said.

The two-page editorial, entitled " Lotronex and the FDA: a fatal erosion of

integrity, " accuses the FDA of receiving hundreds of millions of dollars

funding from industry.

It claims the views of FDA scientists who raised safety questions about

the drug were dismissed by FDA officials and that the scientists were

excluded from further discussion about the drug's future.

And it alleges that negotiations between the FDA and GSK on the drug's

future involved a " two-track process, one official and transparent, one

unofficial and covert. "

Lotronex was licensed by the FDA in February 2000 but was never approved

by the European Medicines Evaluation Agency.

The company withdrew the product in the US on November 28 after 49 cases

of ischaemic colitis and 21 of severe constipation, including instances of

obstructed and ruptured bowel. In addition to five deaths, 34 patients had

required admission to hospital and 10 needed surgery.

The Lancet says that as early as July, it was known that seven patients

had developed serious complications. The clinical data confirmed

" substantial and potentially life-threatening risks " but instead of

withdrawing Lotronex the FDA issued a medication guide. " This decision was

to prove fatal. "

The editorial says FDA scientists knew that the medication guide advising

patients to stop taking Lotronex if they felt " increasing abdominal

discomfort " was impractical since abdominal pain is also a cardinal

symptom of an irritable bowel.

FDA scientists argued that it was unreasonable to expect either patients

or their physicians to judge pain as an early warning of possibly fatal

ischaemic colitis. This view was dismissed by FDA officials.

" The scientists who raised these issues felt intimidated by senior

colleagues and were excluded from further discussions about Lotronex's

future. "

The journal says that in a memorandum dated November 16, FDA scientists

said, " Early warning of the dire side effects of this drug is clearly not

feasible " and added a " risk management plan cannot be successful. "

However, this conclusion was blurred by the time of the key November 28th

meeting between GSK and FDA officials. Rather than reject the company's

risk management proposal and withdraw Lotronex, the FDA offered several

conciliatory options including voluntarily withdrawal pending further

discussion.

The editorial claims " many within the FDA's leadership now want to bring

Lotronex back. An advisory committee meeting set up to do so is being

planned for June or July. "

In April, GSK chief executive Jean-Pierre Garnier said he believed the

odds were low that Lotronex would be relaunched because of the difficulty

of predicting which patients might be at risk of severe side effects. But

industry analysts who have met R & D head Tachi Yamada more recently told

Reuters the company now appeared to be more optimistic about a Lotronex

relaunch.

GSK spokesman Sutton told Reuters, " We regard the editorial as

misleading. There have been discussions between FDA and GlaxoKline

officials. These meetings have all been conducted according to usual

regulatory and industry practices. Both the FDA and ourselves are trying

to find a resolution that will benefit and protect patients. "

He added that the timing of any advisory committee meetings was a matter

for the FDA.

An FDA spokesperson said the agency is still formulating its response to

the editorial.

Horton told Reuters Health he became interested in Lotronex because The

Lancet published some of the trial data that led to the FDA approving the

drug. " As the year went on, we noticed that there were increasing reports

of adverse events.

" Then as I got more intrigued about what was happening, it opened up into

an issue of how science is dealt with by the FDA and how, because of

industry funding, it has fatally compromised its independence.

" The scientists within the FDA who analyze and interpret adverse drug

reactions have been largely ignored after the drug was approved and

marketed. That is where there has been a terrible failure in evaluating

the safety of this drug.

" The FDA is not only compromised because it receives so much funding from

industry but because it comes under incredible Congressional pressure to

be favourable to industry. That has led to deaths. "

Horton pointed out that irritable bowel syndrome may be extremely

unpleasant but is not life-threatening. To approve a drug that can lead to

ruptured bowel and death was at odds with the normal balance between risk

and benefit, he said.

" This is a drug whose application was approved for full unrestricted

marketing within 7 months. That is insufficient to gather safety data.

Pushing through an application so quickly is irresponsible. "

Horton said that GlaxoKline " has failed to gather sufficient evidence

to justify the safety of this product. " He added that the company had

applied pressure through private communication to senior FDA officials.

" Instead of an accountable review process, one has a covert, unofficial

process. "

This is not Horton's first attack on the drug industry. In recent

editorials he has criticised the " tightening grip of big pharma " over what

researchers can publish in medical journals.

His latest editorial demands that:

* Lotronex should be reclassified as an investigational new drug, thus

limiting its use to experimental settings only.

* Covert private communications between FDA officials and industry must

stop.

* Drug approvals and safety reviews should take place through accountable

procedures.

* Greater weight should be given to the epidemiologic advice provided to

advisory committees.

* There should be an independent congressional audit of the FDA's drug

approval processes.

* Oversight of the pharmaceutical industry should be removed from CDER's

control because safety cannot be overseen by a centre that received

industry funding.

* FDA should welcome, not censure, differences of opinion within the

organisation.

* The FDA's new commissioner should be an epidemiologically trained

physician experienced in conducting clinical trials and independent of

industry.

SOURCE: The Lancet 2001;357:1544-1545.