Re: GEN: FDA's Integrity?
From: Anna Meenan, MD (annam@uic.edu)
Fri May 18 14:03:53 2001
I'm not sure I'd blame the FDA entirely. I read that irritable bowel
syndrome support groups are demanding that this stuff be put back on the
market.
--
Anna Meenan, MD, FAAFP
At Fri, 18 May 2001, art fougner, md wrote:
>
>This in today's Reuters -
>
>Lancet questions FDA integrity, claiming drug industry influence
>
>Last Updated: 2001-05-17 19:01:18 EDT (Reuters Health)
>
>By Richard Woodman
>
>LONDON (Reuters Health) - Patients taking a controversial new drug for
>irritable bowel syndrome may have died because the US Food and Drug
>Administration has become the "servant of the drug industry," the Editor
>of The Lancet claimed on Thursday.
>
>In a devastating editorial, Richard Horton said that although
>GlaxoSmithKline voluntarily withdrew alosetron (Lotronex) 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," Horton said.
>
>The 2-page editorial, entitled "Lotronex and the FDA: a fatal erosion of
>integrity," accuses the FDA of receiving hundreds of millions of dollars
>in 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.
>
>The editorial also alleges that negotiations between the FDA and
>GlaxoSmithKline on Lotronex's future involved a "two-track process, one
>official and transparent, one unofficial and covert."
>
>Lotronex, a new 5-HT antagonist class of drug for irritable bowel
>syndrome, 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 cases of severe constipation, including
>instances of obstructed and ruptured bowel, were reported. In addition
>to 5 deaths, 34 patients required admission to hospital and 10 needed
>surgery.
>
>Horton writes 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 editorialist also points out that FDA scientists knew that the
>medication guide, which advised 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," he continues. "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."
>
>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 28
>meeting between GlaxoSmithKline and FDA officials. Rather than reject
>the company's risk management proposal and withdraw Lotronex, the FDA
>offered several conciliatory options including voluntary withdrawal
>pending further discussion.
>
>Horton claims "many within the FDA leadership now want to bring Lotronex
>back. An advisory committee meeting set up to do so is being planned
>for June or July."
>
>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 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 analyse 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 an extremely
>unpleasant condition, but is not life-threatening. To approve a drug
>that can lead to ruptured bowel and death is 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 GlaxoSmithKline "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.
>
>In his current Lancet editorial Horton recommends that:
>
>- Lotronex should be reclassified as an investigational new drug,
>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 epidemiological advice provided
>to advisory committees.
>
>- There should be an independent congressional audit of the FDA's drug
>approval processes.
>
>- Pharmacovigilance should be removed from CDER's control because safety
>cannot be overseen by a centre that receives 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.
>
>GlaxoSmithKline spokesman Martin Sutton told Reuters: "We regard the
>editorial as misleading. There have been discussions between FDA and
>GlaxoSmithKline 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."
>
>Sutton 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.
>
>GlaxoSmithKline chief executive Jean-Pierre Garnier said in April 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.
>
>However, industry analysts who have met R&D head Tachi Yamada more
>recently told Reuters that the company now appeared to be more
>optimistic about a Lotronex relaunch.
>
>-London Newsroom +44 20 7542 7986
>
>Perhaps when the FDA licenses a drug, any suit alleging that the drug is
>unsafe should be brought in Federal Court against the FDA itself.
>There's a tort reform sorely needed.
>
>just my opinion - i could be wrong.
>
>art
>
>--
>art fougner, md
>
>A series of 1000 cases begins with but a single anecdote.
>
