What the FDA Isn't Telling You_SLATE

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Tue, 27 Sep 2005 17:18:23 -0400

[sSRI-Research] What the FDA Isn't Telling You_SLATE

 

 

 

 

 

 

What the FDA Isn't Telling You_SLATE

 

ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP)

Promoting Openness, Full Disclosure, and Accountability

www.ahrp.org

 

FYI

 

Writing in SLATE, Jeanne Lenzer has uncovered evidence demonstrating

FDA culpability in helping drug manufacturers conceal vital,

life-saving information from the public. In this case, undisclosed

suicides in clinical trials testing Eli Lilly's drug, duloxetine

(trade names: Cymbalta sold as antidepressant; Yentreve, when tested

for incontinence). The company and the FDA refused to disclose the

suicides that occurred in clinical trials testing duloxetine for

incontinence in non-depressed patients and volunteers-such as 19-year

old Traci Johnson who suicided at Lilly's laboratory.

Although the drug is sold for incontinence in Europe, Lilly withdrew

its application in the US and refused to divulge what happened in the

US trials. The scandal is that the FDA, a government agency, also

invoked " trade secret " as an excuse for failing to disclose a twofold

increased suicide risk in middle aged women taking duloxetine. Slate

reports: " middle-aged women taking duloxetine had a suicide attempt

rate of 400 per 100,000 person-years, more than double the rate of

about 160 per 100,000 person-years among other women of a similar age. "

 

Lenzer reports " In its Web-site database, Eli Lilly initially listed

no suicides and two deaths among patients enrolled in seven clinical

trials of Cymbalta for depression. "

 

Ironically, Lilly's database won the company praise in a May New York

Times article for being " the company that has gone furthest in

disclosing results. "

 

Lenzer finally obtained, under the Freedom of Information Act, " a

database that included 41 deaths and 13 suicides among patients taking

Cymbalta. Missing from the database was any record of Johnson, or at

least four other volunteers known to have committed suicide while

taking Cymbalta for depression. "

 

Today Lilly's Web site lists 10 clinical trials of Cymbalta and five

of Yentreve, with one suicide and five deaths combined. " Based on the

dates of the trials and the circumstances of the deaths, it's clear

that the Web-site numbers do not include any of the five suicides

missing from the FDA database. Lilly admits that it has never made

public at least two of those deaths. "

 

In another case, Lilly has yet to disclose the number of suicide

attempts in trials testing its number one selling drug, Zyprexa

(olanzapine). Dr. David Healy an international authority who has

examined both FDA and company data from both antidepressant and

antipsychotic drug trials has concluded that:

 

" The studies in adults with Zyprexa that Lilly submitted to the FDA

demonstrate, as far as I can establish, a higher death rate on Zyprexa

than on any other anti-psychotic ever recorded. In addition to this

Lilly have suppressed data on suicidal acts on Zyprexa from these

trials. The data are not available in the scientific literature, nor

from FOI requests to the FDA, nor from enquiries to the company.

Despite this Lilly are engaged in trials with this agent in children. "

See: Testing Psychotropic Drugs in Children, April 30, 2002 at;

http://www.ahrp.org/children/healy0402.php

 

Trade secret laws were not intended to conceal drug-related deaths and

serious adverse effects that threaten consumers' lives. To invoke

such laws in order to hide vital information subverts medical practice

and destroys public trust in medicine and physicians. Without public

trust neither manufacturers nor physicians can profit or function.

The FDA is betraying its mission which is to ensure that the public

health is protected and that physicians are provided accurate

information about the drugs they prescribe.

 

 

 

Contact: Vera Hassner Sharav

212-595-8974

veracare

 

 

 

 

SLATE

Drug Secrets

What the FDA isn't telling.

By Jeanne Lenzer

Posted Tuesday, Sept. 27, 2005

Traci Johnson's body was discovered on Feb. 7, 2004, hanging by a

scarf from a shower rod in an Indianapolis laboratory run by the drug

company Eli Lilly. The 19-year-old college student had been serving as

a test subject in a clinical trial of the experimental antidepressant

duloxetine. Investigators from the Food and Drug Administration rushed

to Indianapolis to determine whether the experimental drug was related

to her death. The probe was inconclusive.

 

This left researchers in a quandary: Was the drug safe or not? Could

duloxetine trigger suicide, as some experts suggested? Or was

Johnson's death an " isolated tragedy, " as Eli Lilly claimed? When drug

manufacturers fail to publish negative study results, as studies show

is often the case, the best source of information about these

questions is the FDA. The agency-which was rocked last week by the

sudden resignation of Commissioner Lester Crawford-requires companies

seeking approval for a drug to provide data from randomized controlled

trials, studies in which some patients are given the drug and others

are given a placebo. But when researchers and the press started asking

about duloxetine, the FDA didn't scour its database and go public. It

kept quiet. The FDA gave a legal rationale for its silence: Some

clinical trial data are considered " trade secrets, " or commercially

protected information, and thus are exempted from release under the

Freedom of Information Act. Since the FDA doesn't routinely perform

comprehensive reviews of drugs once they are on the market, when

uncommon but deadly side effects tend to be picked up, independent

researchers are often the only hope of catching such flaws. But the

trade-secrets rule can leave researchers in the dark about the most

worrisome data-negative results that support a failed application to

market a drug.

 

The argument for secrecy is that failed efforts at drug development

need protection lest entrepreneurs suffer a competitive disadvantage

when other companies aren't forced to expend the same time and money

exploring dead ends. And at first blush, there would appear to be

little need for clinical data on a drug that isn't in use. The problem

is that many drugs have multiple uses. Duloxetine, for example, is

marketed under the brand name Cymbalta to treat depression. Traci

Johnson committed suicide while taking duloxetine during tests for

selling the drug to treat stress urinary incontence, under the brand

name Yentreve. If a drug is on the market for one use and studies

about another use suggest disquieting risks-as the death of Traci

Johnson may-do the benefits of keeping the study data secret outweigh

the costs?

 

The FDA approved Cymbalta to treat depression in August 2004. By the

end of that year, Cymbalta sales topped $61.3 million. At some

point-the date is undisclosed-Eli Lilly began testing Yentreve. In

January 2005, as Cymbalta sales climbed to $106.8 million for the

first quarter, Lilly announced that it was withdrawing its application

for Yentreve. Then it cited the trade-secret rule in refusing to

disclose why the drug did not win approval. Perhaps the rationale was

harmless-the drug didn't work for incontinence. But duloxetine has

been approved as a treatment for incontinence in Europe since August 2004.

 

Over four months beginning in January, I filed several Freedom of

Information Act requests on behalf of the Independent on Sunday, a

British newspaper, for all safety data related to Cymbalta and

Yentreve. I received a database that included 41 deaths and 13

suicides among patients taking Cymbalta. Missing from the database was

any record of Johnson, or at least four other volunteers known to have

committed suicide while taking Cymbalta for depression.

 

When I asked the about the missing results, FDA officials cited a

federal regulation that they said prohibited the agency from releasing

study data-or acknowledging the existence of an application-for a drug

that fails to win FDA approval. Since the FDA never approved Yentreve,

all the data about it were off limits. The agency may have used a

similar rationale in failing to release safety data about the pain

reliever Bextra, which Pfizer, its manufacturer, withdrew from the

market in April for fear of links to an increased rate of heart attack.

 

In its Web-site database, Eli Lilly initially listed no suicides and

two deaths among patients enrolled in seven clinical trials of

Cymbalta for depression. (Lilly's database won the company praise in a

May New York Times article for being " the company that has gone

furthest in disclosing results. " ) Today the Web site lists 10 clinical

trials of Cymbalta and five of Yentreve, with one suicide and five

deaths combined. Based on the dates of the trials and the

circumstances of the deaths, it's clear that the Web-site numbers do

not include any of the five suicides missing from the FDA database.

Lilly admits that it has never made public at least two of those

deaths. Lilly spokesman David Shaffer said that data was unavailable

because some of the studies were still in progress. He also said that

two of the suicides " took place in depression studies run by another

company, " and that " the decision about how and when to disclose such

information rests with that company. " Shaffer was referring to the

Japanese firm Shionogi & Co., which partners with Lilly to market

duloxetine in Japan.

 

Meanwhile, my sources (sorry, they're gun-shy and anonymous) were

telling me that duloxetine caused suicidal tendencies in patients who

took the drug for incontinence-and who were not depressed. That news

was potentially explosive. In the face of questions about a link

between antidepressants and suicide, industry experts have long

insisted that it's depression, not the drugs used to treat it, that

causes patients to kill themselves. Johnson's death appeared to call

that claim into question. She entered the clinical trial as a healthy,

nondepressed volunteer in order to help pay her college tuition. And

she was only approved for the study after undergoing thorough medical

testing to screen out depression or suicidal tendencies.

 

Because one patient's reaction can't prove anything one way or the

other, it was critical for researchers to analyze the results of all

the patients in Lilly's duloxetine studies. Instead, the FDA's

interpretation of the trade-secrets rule left only the positive data

from the Cymbalta trials available for review.

 

In June, after the Independent article, the FDA (without issuing a

press release) noted on its Web site that one suicide " was reported in

a Cymbalta clinical pharmacology study in a healthy female volunteer. "

The agency added that new data from stress urinary incontinence trials

showed that middle-aged women taking duloxetine had a suicide attempt

rate of 400 per 100,000 person-years, more than double the rate of

about 160 per 100,000 person-years among other women of a similar age.

These findings had been withheld from the public, and the researchers

asking for them, for five months after the FDA had reviewed data

showing the increased risk.

 

The FDA claims it has no choice but to resist releasing information

about drugs it doesn't approve. " My hands are tied, " said Dr. Robert

Temple, FDA's director of medical policy. " This is something only

Congress can change. " That may be as much a matter of the FDA's

interpretation as it is of the law, however. Experts disagree about

whether congressional action or a federal court ruling is needed to

make data like Johnson's death available, or whether the FDA could

choose to disclose more itself.

 

The voluntary guidelines promoted by the drug industry, however, are

not a solution. These guidelines encourage companies to list every

clinical trial they initiate. Registration would be helpful. But it

would not compel companies to release the data from, or even the

outcomes of, their trials, as long as they companies can argue that

this information is " commercially protected. "

 

The use of trade-secret laws to conceal deaths and serious side

effects linked to drugs has the obvious flaw of putting profits before

public health. It also subverts the covenant between researchers and

study volunteers. Subjects like Traci Johnson are told that even if

they do not personally benefit from a new drug, the scientific

knowledge gained from the study in which they've participated will

benefit others. The volunteers should be told instead that scientists

will learn about their experience only if it's good news for the drug

they're helping to test.

 

Jeanne Lenzer is a freelancer whose work appears regularly in the

medical journal BMJ. Her e-mail address is jeanne.lenzer.

 

 

 

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