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4 subjects challenge Lilly over drug trial
Outside overseer says he found no indication that suicide victim was depressed.

March 4, 2004
 

Four participants in an Eli Lilly and Co. drug trial in California said the clinic's staff told them that Traci Johnson, who committed suicide last month during the same study in Indianapolis, had a history of depression.

But Dr. Rafat Abonour, chairman of the institutional review board that reviews all Lilly drug trials at Indiana University-Purdue University at Indianapolis, said his review of Johnson's records showed no such history.

The conflicting contentions put Lilly in a difficult position. The company may have to defend its screening process for trial participants if Johnson was depressed and allowed into a study designed for healthy volunteers. Or it might have to fend off suspicions raised by Johnson's friends and family that withdrawal from the experimental antidepressant duloxetine caused a healthy Johnson to commit suicide.

The four California trial participants, all women, said they learned of Johnson's suicide from Dr. Mark Leibowitz, the lead physician for the California Clinical Trials Medical Group, which is conducting part of the duloxetine study on Lilly's behalf. They said he told them that Johnson had a history of depression.

A few days later, they said, Leibowitz brought in other clinical staff members to provide them with more information about the suicide. They said they were told that Johnson's depression wasn't uncovered during screening and that she shouldn't have been allowed in the study.

The women spoke to The Indianapolis Star in separate telephone interviews, and all described Lilly's screening process for depression as weak.

Phone calls to Leibowitz and Dr. Larry Ereshefsky, the chief scientific officer at California Clinical Trials, were not returned. Steve Sims, another clinic staff member, declined to comment.

Lilly officials this week declined to comment on Johnson's medical information, citing patient confidentiality. They defended screening methods and noted that even if clinic applicants acknowledge depression in their past, they may participate in a trial for healthy volunteers.

The institutional review board for the Lilly trial in Indianapolis announced Wednesday that it was satisfied with Lilly's responses to the suicide, which included hiring an independent psychiatrist to evaluate participants every day for depression and submitting a plan for dealing with subjects who start showing signs of depression.

Abonour said he had no idea why trial participants in California would be told that Johnson had a history of depression.

"To my knowledge, in reviewing the records, there is no history of (depression)," Abonour said. "In talking to Lilly, there is no evidence of prior history (of depression)."

Abonour said he reviewed documents Lilly provided regarding Johnson and the clinical trial. Pam Perry, spokeswoman for the IU medical school, said the documents consisted of information gathered during Lilly's screening of Johnson and during the trial.

Police said Johnson hanged herself with a scarf Feb. 7 in the bathroom of her room at the Lilly Laboratory for Clinical Research on the campus of IUPUI.

Lilly has said she was a healthy volunteer in a high-dosage study of duloxetine, a potential blockbuster drug that Lilly intends to offer to treat both depression and stress urinary incontinence. At the time of her death, Johnson had been taking a placebo for four days after being gradually phased off duloxetine.

Carmellia Wright, 38, is one of the four California trial participants who said clinic staff told them that Johnson was depressed. "They said, 'There was a young, depressed woman who committed suicide,' " Wright said. "They said that she was already depressed and that she shouldn't have been in the study in the first place."

Later, Wright wrote in her diary, which she provided to The Star, that "the young woman had a past of depression which was discovered later upon medical background."

Michelle Hermit, 48, said that officials at the clinic "clearly said she had a history of trying to commit suicide, a history of depression, and they didn't catch it in the screening."

Two other participants, Nisha Patel and Tatiana Sikic, said they were told that Johnson had a history of depression and had attempted suicide in her early teens.

The Rev. Joel Barnaby, a Philadelphia pastor and spokesman for the Johnson family, said he has no knowledge of any history of depression or attempted suicide. Such things would have been out of character for Johnson, he said.

"I've known her all her life," Barnaby said. "She's a vivacious, fun-loving, spirited, uplifting person."

Johnson's family has declined to discuss her death, except through Barnaby.

Dr. Eiry Roberts, Lilly's vice president in charge of early clinical development, said this week that company physicians gave Leibowitz and the staff of the California clinic medically relevant information about Johnson's death without naming her.

John Hayes, a clinical psychiatrist who leads Lilly's duloxetine team, declined to say what information was passed along but called the California participants' statements about Johnson conjecture and speculation.

"I believe that the information that we transferred to the staff at California Clinical Trials was accurate and appropriate and absent the speculation that you've heard," Hayes said Monday. The clinics "get a set of facts, and they draw conclusions from those facts."

In a written statement, Lilly promised swift action if the participants were misled.

"If we discover that any inappropriate or inaccurate information was spread about Traci Johnson, we will take aggressive action to protect her memory and her family," Lilly spokesman Rob Smith said in the statement.

Hayes and Smith declined to say if the company had told the clinic whether Johnson was depressed, citing the privacy of participants. In an interview and in a new consent form issued to 100 participants after Johnson's death, Lilly officials called her a "healthy volunteer."

Shortly after Johnson's suicide, Lilly disclosed that four participants who were depressed committed suicide during previous trials of the drug, a number the company said was below the level of those who were not taking the medicine and lower than suicide rates for another class of antidepressants, which includes Paxil, Zoloft and Prozac.

Participants screened

Researchers at the Lilly Clinic in Indianapolis deemed Johnson healthy during the initial screening for the duloxetine study in January, Lilly officials said. In such a screening, participants fill out a survey of their medical history and are interviewed by the medical staff. If an answer raises a red flag, the medical staff probes further, perhaps administering a psychiatric exam, Hayes said.

Sikic said she had to undergo a psychiatric exam after she told researchers in California that she had been depressed about eight years ago after her grandmother died. But she said she left out the fact that she had tried to kill herself with sleeping pills.

"I didn't tell them about that. I needed the money too bad," she said. Most participants in the trial are hard up for money, Sikic said.

In the duloxetine trial, participants were paid about $100 a day and provided with a room and meals.

Johnson, who had been a student at the Indiana Bible College last fall, signed up for the study to earn money to return to school next term, friends have said.

California clinic researchers gave Sikic a short written psychiatric test and she met with a psychiatrist, who determined she was fit for the program, she said.

They also approved Hermit, who said she told researchers that she had suffered from depression after her mother died and took medication for it. She said she was asked a few follow-up questions.

Hermit called the screening for depression "sloppy."

Wright said she was asked whether she had a history of depression. When she answered "no," the researcher moved on, she said.

John Callaghan, Lilly's director of U.S. exploratory medicine, said that in a screening for depression, the company's researchers look to see whether a person's depression is urgent or calls for immediate action. They also look for any evidence that a person is considering harming him or herself, Callaghan said.

Both Callaghan and Hayes said that past instances of depression would not necessarily disqualify a person from being a "healthy volunteer."

"Whether their personal history would have precluded them from the study would have been a judgment call," Hayes said. He said Lilly does not perform a psychiatric evaluation on every potential participant in order to weed out those with depression.

Fred Cohen, who has run clinical trials for Eli Lilly and Johnson & Johnson, said that if researchers do not expect the drug to cause a particular problem, they often don't push beyond the participant's initial answers.

"There has to be a rationale for your screening, " said Cohen, now president of Crownstone, a pharmaceutical research and consulting firm in Pennsylvania. "Why would they want to plant ideas in people's heads?"

Researchers take that precaution because mentioning a condition such as depression almost guarantees a higher reported incidence of it among trial applicants, he said.

Implications for Lilly

After Johnson's death, most of her friends described her as sunny and upbeat.

However, one recent acquaintance, Angelica Diez, said Johnson sometimes would become upset over a male student at the Bible College.

"Sometimes, he ignored her," Diez said. "She was into the guy so much. . . . She'd start crying."

The student declined to comment.

Like many of Johnson's other friends, Diez said she finds it hard to believe that Johnson would take her own life.

"I don't think she hurt herself," Diez said. "It was the reaction (to the drug)."

John Crompton, a friend of Johnson's from Pennsylvania who said he talked with her three times a week by phone, said that during the drug study she often complained of fatigue and other small things.

"If there was something really heavy bothering her, she would have told," Crompton said.

Barnaby, Johnson's pastor in Philadelphia who recommended her for the Bible College, said he saw no signs that Johnson was depressed.

He said he last saw Johnson two weeks before her death, when she came to Philadelphia to sing in his church choir. He said he remains convinced "that there are some risks involved in the drug."

A coroner's report, released Monday, ruled Johnson's death a suicide and did not cite duloxetine or any other drug as a factor.

The U.S. Food and Drug Administration is reviewing Johnson's suicide.

The agency's findings could have huge implications for Lilly.

If the FDA approves duloxetine, Lilly hopes to release it as an antidepressant this summer. Cymbalta, as the drug would be called, could generate annual sales as high as $2 billion, Wall Street analysts estimate.

Johnson was participating in a study of duloxetine for its stress urinary incontinence application, which could eventually yield $1billion in annual sales.

Star reporter Jeff Swiatek contributed to this report.

Call Star reporter J.K. Wall at (317) 444-6287.

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