20% volunteers drop out after suicide in Eli Lilly’s duloxetine trial

20% volunteers drop out after suicide in Eli Lilly’s duloxetine trial

Thu, 12 Feb 2004

The Associated Press reports that nearly a fifth of the volunteers testing Eli Lilly’s antidepressant drug, duloxetine, dropped out after Traci Johnson, a 19-year old student committed suicide at a company laboratory. “Three participants in the study in Indianapolis and 16 volunteers in Evansville have quit.” See: http://abcnews.go.com/wire/US/ap20040212_723.html

The Philadelphia Inquirer reports (below) that “the Institutional Review Board (IRB), a body of the Indiana University School of Medicine, which has been monitoring the clinical trial, moved to tighten the duloxetine study.” And the Inquirer reports that IRB “ordered Lilly to accept no new subjects for the trial, ordered an independent psychiatrist to evaluate the current subjects, and required that they sign a new consent form.”

Did the FDA approved informed consent form signed by Ms. Johnson and the other subjects disclose the fact that there had been 4 suicides in prior duloxetine clinical trials?

The New York Times finally saw fit to report the suicide of this healthy volunteer but buried the report on p. A30. The report provides Eli Lilly an opportunity to present the company’s spin. For example, “the company did not believe that duloxetine …caused the suicide.” That assertion is premature, inasmuch as Lilly’s chief medical officer and former senior researcher at the National Institute of Mental Health, Dr. Alan Breier, acknowledged that Ms. Johnson had been screened by Lilly before the trial and found her not to be “healthy and had no mental problem.” The test did require Ms. Johnson and the other volunteers to take “larger than therapeutic doses.” How then can the company exonerate the drug out of hand?

A classic example of PHARMA spin follows: When confronted with the revelation that there were not one but 5 completed suicides in duloxetine clinical trials, a Lilly spokesman, Robert Smith, is quoted stating: “The drug has been studied in 9,000 patients ….and we have not been able to discern any signal between duloxetine and suicidal ideation.”

But when confronted with the revelation that there was a two-to three fold increased incidence of suicidal ideation and suicidal acts by children who tested antidepressants compared to those given a dummy pill, drug manufacturers and FDA officials claim– “but there was no death from suicide in pediatric antidepressant trials.” See: www.ahrp.org

What did the FDA know and when did it know about the suicides? What, if anything, does the FDA do to ensure that patients and volunteers are protected from harmful drug tests?

http://www.philly.com/mld/inquirer/news/local/7932602.htm
PHILADELPHIA INQUIRER
Feb 12, 2004
Drug test altered in wake of suicide
By Walter F. Naedele

Colleen Jacoby last spoke to Traci Johnson on Friday, the night before Johnson is reported to have committed suicide.

“On the phone, she was laughing, she was happy,” Jacoby said of her call from Northeast Philadelphia to her best friend in Indianapolis.

At 9 p.m. Saturday, a doctor at Indiana University Hospital pronounced Johnson dead, a suicide, according to an incident report from the Indianapolis Police Department.

Johnson, 19, a 2002 graduate of Bensalem High School, had been found hanging by a scarf from a bathroom shower rod in the Lilly Laboratory for Clinical Research.

Since early last month, after leaving studies at the Indiana Bible College in Indianapolis, Johnson had been categorized a “healthy subject” by Eli Lilly & Co. in a trial of the drug duloxetine, which a spokesman for the pharmaceutical company said would be used to treat depression and for urinary incontinence caused by stress.

Jacoby, 20, who lives in the Oxford Circle neighborhood of Northeast Philadelphia, said that “80 percent of [Johnson’s] life, she was with me; we were her second family.”

Johnson “would never hang herself,” Jacoby said. “Never, ever. She was full of life.”

David Shaffer, an Eli Lilly spokesman in Indianapolis, said that four of more than 8,500 people in previous trials of duloxetine had committed suicide.

But, he said in an interview yesterday, they were “studies of people who actually had depression.”

“And that rate is in line with what you’d expect in a population of that size who were depressed,” and who weren’t taking the drug, he said.

Shaffer said Johnson’s trial consisted of healthy persons “in which the patient doesn’t know, the doctor doesn’t know, whether they’re on the medication or sugar pills.” There are about 100 subjects currently.

Johnson had been given duloxetine early last month but was taking sugar pills at the time of death, Shaffer said. He called this “a high-dose study.”

“It’s higher than the dose we expect to be used in clinical practice, once the drug is approved and doctors are using it in the real world.”

Yesterday, the Institutional Review Board, a body of the Indiana University School of Medicine, which has been monitoring the clinical trial, moved to tighten the duloxetine study.

Shaffer said the board ordered Lilly to accept no new subjects for the trial, ordered an independent psychiatrist to evaluate the current subjects, and required that they sign a new consent form.

The Lilly spokesman said that enrollment for this trial was completed before Johnson’s death, that the subjects had undergone psychiatric evaluation before the trial, and that the new form asks their consent in light of the apparent suicide.

Shaffer said that “the steps that the [review board] took, we feel, are appropriate in this case.”

Jacoby said she and Johnson had been friends since grammar school, and longtime members of the Greater Church of Philadelphia, a nondenominational Pentecostal church in Kensington.

The Rev. Joel Barnaby, the pastor there, said that since Johnson’s death, the young woman’s relatives “just walk around numb. They’re just devastated.”

He said they “come to me and lean on my shoulder and [ask], ‘How did this happen to our little girl?’ ”

Barnaby said that Johnson came to him last year, asking for names of Bible schools.

“I asked why, and she said, ‘Because I want to sharpen my skills and understanding of the Scriptures, so that I could be a vessel of honor that the Lord might use.’ ”

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http://www.nytimes.com/2004/02/12/health/12SUIC.html?pagewanted=print&position=
THE NEW YORK TIMES
February 12, 2004

Student, 19, in Trial of New Antidepressant Commits Suicide
By GARDINER HARRIS

A 19-year-old college student who had shown no outward signs of depression killed herself over the weekend at an Eli Lilly & Company laboratory in Indianapolis where she had been participating in a company drug trial for an experimental antidepressant.

The student, Traci Johnson, was one of 25 healthy patients at an Eli Lilly clinic who were being given larger than therapeutic doses of duloxetine, which will be known as Cymbalta if it is introduced as an antidepressant. Four days before her death, Ms. Johnson was taken off Cymbalta and given a placebo.

While Eli Lilly asserted that it had properly screened Ms. Johnson before the study started to ensure that she was healthy and had no mental problems, her death is being used by critics of a popular class of antidepressants to bolster their case that the widely used drugs carry the risk of suicidal tendencies for a small number of people, particularly young people.

Four other patients who were given the drug during earlier trials also committed suicide, the company said. The drug is being tested not only as an antidepressant but also as a possible treatment for stress urinary incontinence.

Ms. Johnson’s death came less than a week after a federal advisory panel concluded that the Food and Drug Administration should issue stronger warnings to doctors that this class of antidepressants may be linked to suicide and violent behavior in children and teenagers.

A review board has told Eli Lilly to stop entering new patients into the trial, and to have all the current participants evaluated by an independent psychiatrist.

Robert Smith, a Lilly spokesman, said the company did not believe that duloxetine, the drug’s generic name, caused the suicide.

“This drug has been studied in 9,000 patients, in depressed and nondepressed healthy people, and we have not been able to discern any signal between duloxetine and suicide or suicidal ideation,” Mr. Smith said.

Ms. Johnson had not shown signs of depression, distress or mood swings throughout about a month in the trial, said Dr. Alan Breier, Lilly’s chief medical officer.

Patients who abruptly stop therapy with some antidepressants often experience withdrawal symptoms that can include severe agitation, unusual dreams and night sweats. This is especially true of antidepressants like Paxil, made by GlaxoSmithKline, that leave the bloodstream quickly. Cymbalta also leaves the blood stream quickly.

Dr. Breier said Ms. Johnson did not appear to be suffering any withdrawal symptoms. He said the company might never be able to answer why Ms. Johnson killed herself.

“Most people who commit suicide in the general population leave people asking these kinds of questions,” Dr. Breier said. “And just because this happens while someone is taking a drug doesn’t mean the drug caused it.”

Ms. Johnson did not leave a suicide note. She hanged herself in a shower stall Saturday night in the bathroom of Lilly’s dormlike laboratory on the top two floors of the Indiana University Medical Center.

She had been attending nearby Indiana Bible College but left school to participate in the study because it paid $150 a day plus meals.

Whether antidepressants cause some people to commit suicide was an issue that flared briefly in the early 1990’s but had been largely dismissed by mainstream researchers until last summer. That is when GlaxoSmithKline warned that a series of studies had found that children and teenagers given Paxil were more likely to attempt or think about suicide than those given a placebo.

Wyeth soon followed with a warning suggesting that its antidepressant, Effexor, should not be given to children. British and American drug regulators set to work studying the problem. The British soon concluded that most antidepressants in this class should not be used in children and teenagers since they have not proved effective in that population and could be linked to suicide.

The F.D.A. continues to study the issue, said Susan Cruzan, an agency spokeswoman. The agency is aware of Ms. Johnson’s death and will evaluate its implications once the agency receives all of the needed information about it, Ms. Cruzan said.

Copyright 2004 The New York Times Company

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