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Eli Lilly
Drugs

Life Flow One
The Solution For Heart Disease

A Book by
Karl Loren

This page contains many separate reference articles, all about Eli Lilly, the most evil drug company on the planet.  Many of these articles are about one of its most profitable drugs, Prozac, probably the most evil single drug on the planet.  There are further links to other pages about Prozac.  It appears that, by now, this single page may have more references to Prozac than any other page on the web -- tell your friends to come look, and to inform the webmaster of other items to be published here.

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Articles On Drug Subjects
Click Here To Jump To The Article	Title Or Description	Comments
...1...	Links To The Corporate Home Pages For Eli Lilly
...2...	Books: Did Prozac pull the trigger? Anthony Daniels considers a case of mass murder, drugs and litigation
...3...	Putting Prozac on Trial
...4...	Stuck for Money: To Screen New Drugs For Safety, Lilly Pays Homeless Alcoholics
...5...	FDA Once Chastised Lilly for Using Alcoholics
...6...	NIH research ethics office questions study at Indiana University
...7...	Lilly Drug Clinic In U.S. Faces Scrutiny
...8...	Pharmaceuticals: Antidepressant Makers Study Kids' Market
...9...	Test Case: Drug Makers Relied On Two Researchers Who Now Await Trial
...10...	Children Who Kill-- On Prozac
...11...	Side Effects of PROZAC & Ritalin
...12...	Talking Back To Eli Lilly
...13...	Man Asserts Prozac® Defense at Bombing Trial
...14...	THE DANGERS OF PROZAC: Part 1
...15...	THE DANGERS OF PROZAC: Part 2
...16...	Photograph Of Prozac
...17...	PDR Article About Prozac Click Here For Publisher	Find the dangers admitted by the Manufacturer
...18...	Freedom Magazine Comments about Prozac
...19...	Plaintiff's Attorney For Attacking Prozac
...20...	FDA Issues Warning Letter To Eli Lilly's Italian Unit	Wall Street Journal Article
...21...	Eli Lilly & Co. Says Trial Of Heart Drug Was Stopped	Wall Street Journal Article
...22...	Revealed: the danger of taking Prozac	Article In the Guardian
...23...	Drugs & Guns Ritalin & Prozac Create Killers
...24...	Use of Mood-Altering Drugs to Control Toddlers' Behavior Jumped in the '90s
...25...	Mike's Personal Fight With Anti-Depressants
...26...	Drug Firms Treat PMS As a Mental Disorder	Wall Street Journal Article
...27...	Lilly at Trial -- Second Time In History That Lilly Faces Trial In Wrongful Death Because of Prozac
...28...	An Irish Student Asks Karl Loren For Help In His Research About Prozac
...29...	Wall Street Journal Article	To put that into some perspective, the nonsedating antihistamine Claritin costs about $83 for one month's supply; the antidepressant Prozac costs about $95 for a 30-day supply of 20-milligram pills.
...30...	Drug Makers Find a Windfall Testing Adult Drugs (including Prozac) on Kids	Wall Street Journal Article
...31...	Prozac For PMS = A Sick Fraud -- A Lilly Drug	From Eli Lilly, Itself
...32...	Drug Firms Treat PMS As A Mental Disease	Wall Street Journal
...33...		The Shooting Drug
...34...	Eric Harris was taking Luvox  (a Prozac-like drug) at the time of the Littleton murders	by Peter R. Breggin, M.D.
...35...	PROZAC: PANACEA OR PANDORA?	Author:  Ann Blake Tracy
...36...	Did Drugs Distort Mother’s Nature?
...37...	Petition To Convene Grand Jury To Investigate Eli Lilly and the FDA for Allowing Prozac To Be On The Market
...38...	Prozac Possible 'Link' to Brain Tumors
...39...	APLASTIC ANEMIA LINKED TO PROZAC
...40...	Prozac Profit Ploy- Rename and Sell Under "Sarafem"
...41...	The Insanity Continues as More U.S. Kids Are Taking Drugs for Behavior and Depression

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Here is a link to the Corporate Home Pages:

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Books: Did Prozac pull the trigger? Anthony Daniels considers a case of mass murder, drugs and litigation
ANTHONY DANIELS
 
09/08/96
The Sunday Telegraph London
Page 15

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(1996 (c) The Telegraph plc, London)

Harm: Mind, Medicine
and Murder on Trial

by John Cornwell
Viking, pounds 18

IN SEPTEMBER 1989, in Louisville, Kentucky, a man called Joseph Wesbecker went into the works of a printing company called Standard Gravure and shot 20 people before committing suicide. He had worked for the company for many years, but had found it so stressful that he had been off sick for a year. He was under treatment from a psychiatrist, and shortly before the fatal incident he had been prescribed the antidepressant fluoxetine, better known as Prozac.

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America being America, the survivors of the shooting, and the relatives of those who died, sued the manufacturers of Prozac, the giant pharmaceutical corporation Eli Lilly and Company, claiming that it was its drug which had turned Wesbecker into a homicidal maniac.

Their case was flimsy: Wesbecker had talked of blasting people at the company away, and had accumulated guns, well before he ever took Prozac. The plaintiffs chose to sue Lilly because, of all the conceivable defendants to sue (Wesbecker's doctor, Wesbecker's estate, the printing company, the company which provided security for the printing company), the pharmaceutical giant had by far the most money.

The worst that could be proved against the company was that, in its anxiety to corner the market (Prozac was soon to become the highest-selling drug in the world), its testing of its product was less than thorough. But in the end the company paid large sums of money to the plaintiffs in order to avoid the introduction into the court of evidence concerning its carelessness about another of its drugs, the anti-inflammatory agent Oraflex, which was responsible for many deaths in the early 1980s.

The payment made by Lilly was most unusual, in that it was not a settlement of the case as such: the company needed public vindication in court if the value of its stock was not to fall, and it eventually received that vindication. In effect, however, it had bribed the plaintiffs and their lawyers not to introduce emotive (but strictly irrelevant) evidence into the court about the company's past practices.

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Mr Cornwell's book is an examination of the multiple ironies of the case. Eli Lilly , whose product is based upon the premise that many mental disorders are the result of defective brain chemistry which Prozac then corrects, was forced to argue that Wesbecker's conduct was the result of his social upbringing and his untrammelled free will; while the principal psychiatrist for the plaintiffs, Dr Peter Breggin, who is a well-known exponent of the view that psychiatric disorders are the result of a defective way of life and cannot be cured by simply taking pills, was forced to argue that Wesbecker's conduct was largely the consequence of his having taken the drug Prozac.

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There was a great deal at stake in this case: for if Lilly had been found liable, it would not only have had serious consequences for Lilly itself, but for the entire pharmaceutical industry, upon which medical advance largely depends. The risks of pharmaceutical innovation would have become simply too great for any company to take.

Oddly enough, an aversion to risk becomes itself a risk: it is just as well that the antibiotic era preceded the era of litigation, otherwise we should in all probability have been denied these life-saving drugs. They would have been too risky to produce.

But the focus of Mr Cornwell's book is elsewhere. He is concerned to point out the inadequacy of seeing Wesbecker as either a man with defective brain chemistry, or as a man who simply chose to do wrong. He argues that one should see him in a wider social and psychological context: born into an unhappy home, he worked in an increasingly stressful and violent environment, was eventually shunned by society and was able to buy guns and ammunition freely. Mr Cornwell implies that the correct response to the Wesbecker story is communitarian, though he does not descend to concrete detail as to what this means in practice.

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The case illustrates the degree to which the idea of personal responsibility - the only conceivable basis for the rule of law - has been eroded in America. And the only people who can now be held responsible for their actions are those with a lot of money to pay others in compensation. So the rich really are different, after all: unlike the rest of us, they are responsible for what they do.

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Putting Prozac on Trial
Thomas Maeder
 
10/21/96
The Washington Post
FINAL
Page D02
Copyright 1996, The Washington Post Co. All Rights Reserved

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THE POWER TO HARM

Mind, Medicine, and Murder on Trial

John Cornwell

Viking. 321 pp. $24.95

Around 8:30 a.m. on Sept. 14, 1989, Joseph Wesbecker walked into the Standard Gravure printing plant in Louisville carrying an AK-47 assault rifle and hundreds of rounds of ammunition. Within 30 minutes, he killed eight people and wounded 12 others before pulling a pistol from his belt and shooting himself in the head.

Until going on long-term disability a year earlier, Wesbecker had worked as a pressman at Standard Gravure, a company where conditions were, by all accounts, appalling, with employees routinely working nine eight-hour shifts per week amid extremely unpleasant, even dangerous circumstances. An undercurrent of misery and violence permeated the company generally.

Wesbecker felt that he was mistreated by the supervisors at work, with some reason. In addition, however, he suffered from definite emotional problems. He had twice attempted suicide, and for five years psychiatrists had treated his manic-depressive and "schizoaffective" disorders with more than a dozen psychoactive medications. A year before the killings, Lee Coleman, the last in a series of psychiatrists, put Wesbecker on Prozac. Wesbecker did not like the effects of the drug and stopped taking it after two days. A year later, Coleman tried it again. This time he was disturbed by the agitation and volatile moods it seemed to produce in his patient. Wesbecker, however, insisted that it helped him. Two days later he ran amok.

Without Prozac, the killings would have been just another horrifying instance of the senseless mass killings that seem to plague modern life. With Prozac, they became a cause celebre.

At the time of Wesbecker's rampage, Prozac was just beginning to take the world by storm. It soon became one of the top-selling drugs of all time, contributing more than one-fourth of Eli Lilly and Co.'s total 1995 sales of $6.5 billion. Some doctors hailed it as a miracle drug that could cure otherwise intractable cases of depression and restore a full life to patients who had lost all hope. Others insisted that it was grossly misused and overprescribed, and a small but growing number of reports linked Prozac to catastrophic personality changes leading to suicide and sudden violent outbursts.

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By 1990, 54 civil and criminal suits concerning Prozac had been filed against Lilly , including one by the survivors of Wesbecker's killing spree and the families of the dead. The victims claimed that a reaction to Prozac, not Wesbecker's inherent mental illness, had caused the act and that Lilly had consistently misrepresented Prozac's safety to the Food and Drug Administration and the medical community. Lilly chose to go to court. Evidently the company lawyers believed that Wesbecker's history of mental illness and violent proclivities would reveal a man who was ready to explode, with or without Prozac, and that victory in this case would discourage other potential litigants.

The Wesbecker case offers an opportunity to explore a fascinating set of intertwined questions about human nature, corporate ethics and the testing and monitoring of new drugs by pharmaceutical companies and the FDA. What is a person's identity, and where does personal responsibility end and control by chemical or other factors begin?

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John Cornwell, a journalist and director of the Science and Human Dimension Project at Cambridge University, originally covered the Wesbecker case for the London Sunday Times Magazine. "The Power to Harm" is a longer piece of courtroom reporting that aspires, but fails, to address the large scientific and social issues raised by the crime and the trial.

The object of a trial is to win. Opposing sides present evidence and witnesses calculated to sway the jury. Right or wrong, this is how trials work. But in consequence, the last place to look for comprehensive, dispassionate, objective science is in the adversarial setting of a trial. It therefore seems unfortunate that Cornwell rarely ventures outside the Louisville courtroom in search of information -- even, apparently, to read the professional literature on the possible relationship between Prozac and violence or to consult other authorities for more information or a broader perspective on what is otherwise just an isolated case. His discussions of the chemical nature of the brain, the nature of psychopharmacology, the process of drug testing and approval, and our knowledge of Prozac itself are drawn almost exclusively from partisan information chopped up and shaped by legal rules and the tactics of opposing counsel.

How do the notions of responsibility applied in Wesbecker's case compare with those in other trials? How does Lilly 's behavior compare with that of other corporations rightly or wrongly sued by innocent victims? If the Prozac clinical trials were less than ideal -- perhaps even fishy -- were they worse than any others? How much can we know about psychoactive drugs (a useful point to decide before saying that we don't know enough)?

The Wesbecker case, which eventually ended in Lilly 's favor, is fascinating and troubling, and some of the weird turns of events and twists in trial strategies make for an interesting story. In the end, though, we are left with few answers and with the dissatisfied feeling that the best questions were never asked.

The reviewer, who is the author of "Adverse Reactions" and "Children of Psychiatrists," is completing a book on the discovery and development of the magainin antibiotics.

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Stuck for Money:
To Screen New Drugs
For Safety, Lilly Pays
Homeless Alcoholics
---
It's `Quick Cash' to Habitues
Of Indianapolis Shelters;
It Vanishes Quickly, Too
---
How to Mask a Recent Binge
By Laurie P. Cohen
 
11/14/96
The Wall Street Journal
Page A1
(Copyright (c) 1996, Dow Jones & Company, Inc.)

 
Corrections & Amplifications

BLACK MEN involved in experiments in Tuskegee, Ala., that began in the 1930s had already been infected with syphilis but then unknowingly went untreated for 40 years so that doctors could learn how the disease took its course. A page one article Thursday about clinical drug studies said incorrectly that the men were unwittingly infected with syphilis during the experiments. (WSJ Nov. 18, 1996)

INDIANAPOLIS -- Sitting in a drab hospital room at the Lilly Laboratory for Clinical Research, his home for 57 days, Louis Checchia lifts the sleeve of his navy-blue scrubs to display a right arm that is badly bruised and scarred from being pierced dozens of times.

Homeless and a hard drinker, Mr. Checchia can't say what kind of drug is being tested on him, although he has signed an informed-consent form. Nor has Eli Lilly & Co.'s "Subject No. 7" reported to the researchers any of the head and muscle aches he has suffered in recent weeks, as Lilly requires. He reckons these are simply the price of quitting drinking cold turkey to get into the study, not the possible side effects of Lilly 's experimental drug, known only as LY315920.

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For the 51-year-old ex-convict, any short-term discomfort seems well worth it. When he leaves in five days, Mr. Checchia, who has lived on the streets of Indianapolis for the past 14 years, will take with him $4,650 -- "in hundred-dollar bills," he emphasizes.

Mr. Checchia is what Lilly calls a "healthy volunteer." Each year, some 40,000 ostensibly healthy individuals are used by U.S. pharmaceuticals companies to participate in so-called Phase I drug tests. The Food and Drug Administration requires companies to do such tests to find out whether experimental drugs are safe enough to give to actual patients in Phase II testing .

For the pharmaceuticals industry, persuading able-bodied people to sample untried and potentially dangerous drugs is a tough sell. To woo their human subjects, most companies have to advertise heavily and shell out $125 or so a day, occasionally as much as $250; SmithKline Beecham PLC even pays referral bonuses. By contrast, Lilly advertises less frequently and, at $85 a day, pays what competitors believe is the lowest per diem in the business.

Alone among its peers, Lilly has become a potent magnet for homeless people. For more than two decades, Lilly 's testing clinic has drawn from the ranks of the homeless, often alcoholic men who drift in and out of Indianapolis's church-run inner-city missions. Some mission directors privately express misgivings about this but say they are reluctant to speak up because they receive funding from a foundation built on Lilly stock, even though the foundation is independent of the company and its clinic.

Word of mouth about testing at Lilly -- a company best known for the blockbuster drug Prozac -- has gradually spread through soup kitchens, prisons and shelters from coast to coast. Today, so many homeless men come to Indianapolis seeking admittance to Lilly 's research clinic that Matias Vega, medical director of the local Homeless Initiative Program, credits the clinic with creating a "shadow economy." One veteran nurse at the Lilly Clinic says that the majority of its subjects are homeless alcoholics.

A Lilly official describes that notion as "completely inaccurate." In a written response to questions, T. Dwight McKinney, executive director of clinical pharmacology, says that "the vast majority of our volunteers (roughly 94%) have a residential address."

Earlier, in a face-to-face interview in July, Dr. McKinney described the volunteers as "retired or temporarily employed." Test subjects welcome the free physical exams and the money they get, Dr. McKinney said, and, above all, are driven to participate "by altruism . . . . These individuals want to help society."

But Vaughn Bryson, who was Lilly 's chief executive officer for 20 months before being ousted in 1993, says the company's use of homeless drinkers is "no secret." Two homeless-shelter officials concur, as do another former Lilly executive and two staffers at Indiana University Medical Center, where Lilly doctors teach. Moreover, The Wall Street Journal interviewed 12 men who described themselves as homeless people who drank daily and who said that they, and many others like them, had participated in Lilly 's Phase I tests.

In many ways, the practice is mutually beneficial. For Lilly , it is efficient and limits the risk that subjects will sue if harmed by an experiment or divulge particulars of a drug, say former Lilly employees and advocates for the homeless. As for the subjects, they get several weeks or months of free room and board, and in interviews they express voluble gratitude for what they often call "easy money."

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Still, Lilly 's approach raises unsettling questions. Under FDA rules governing Phase I trials, drugs can be tested only in people who are able to make a "truly voluntary and uncoerced decision" to participate. Roger Williams, deputy director of the FDA's Center for Drug Evaluation, contends that using the homeless creates the very situation the rules were designed to prevent. He says the regulatory intent was to discourage disadvantaged people from participating in studies simply to escape "the horrible situation of their daily lives."

In addition, some public-health officials and test experts say the use of heavy drinkers in Phase I tests risks giving a distorted picture of an experimental drug's safety, which has to be ascertained before the drug can be given to actual patients in Phase II testing . "Alcoholism is a confounding feature," Dr. Williams says. "When something goes wrong, instead of saying this is a problem with our drug, you can say this is due to his alcoholism."

John Arnold, a pioneer of Phase I research who founded one of the nation's first clinics for such tests, is more outspoken. " Lilly isn't getting the safety it needs to take drugs into Phase II trials," he contends. "It's for the safety of Phase II patients that you even do Phase I."

Lilly asserts that any prior use of alcohol by volunteers has no significant effect on its drug data. It says that most people who either are undergoing alcohol withdrawal or have liver disease severe enough to skew the data will have abnormal physical exams and laboratory screening tests, and thus will be excluded.

But on the streets, Lilly 's confidence in its subjects hardly seems justified.

At 6 o'clock on a muggy Thursday morning, Joseph LaDuke, Mark Slone and seven others leave the Salvation Army's Harbor Light Center, a mission where they spent the night, trekking a little more than a mile to the Lilly Clinic. Two days earlier, when Messrs. LaDuke and Slone showed up at the clinic to inquire about their prospects, the recruiting nurse had taken down their Social Security numbers and local residences (a day shelter for the homeless called Horizon House from Mr. LaDuke and an outdated address from Mr. Slone). The nurse then instructed them to return for a screening.

Mr. LaDuke says he heard about Lilly 's studies from an acquaintance on the streets of Nashville, Tenn. A cocky 23-year-old who has been wandering the country for two years, Mr. LaDuke says he used to be a crack addict but now just drinks. "The only reason I came here is to do a study so I can buy me a car and a new pair of shoes," he says.

Mr. Slone, a soft-spoken former truck driver who is 34, also heard of the Lilly studies from a homeless buddy, a man in Louisville, Ky. Mr. Slone says alcoholism forced him into poverty. He hopes Lilly 's bounty will enable him to "get my life back."

At 6:45, a Pinkerton security guard admits the pair to the Lilly Clinic, housed on the sixth and seventh floors of Wishard Memorial Hospital in downtown Indianapolis. Lilly nurses take blood and urine samples from about a dozen potential volunteers. Three hours later, the screening is over. One candidate is rejected on the spot because he is overweight. The rest are told to return on Monday morning at nine to be examined by a Lilly doctor. (All but one will end up getting into a five-week safety study of a schizophrenia drug.)

Outside, Mr. LaDuke reports that Pattie Patrum, the recruiting nurse, had admonished the group to stay off alcohol for the next four days. But Mr. LaDuke and Mr. Slone will later recall that they wound up guzzling a stash of Budweiser 36 hours before getting admitted to Lilly .

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No matter: Hard-drinking test subjects pride themselves on their skill at hiding the evidence of their binges. Regulars of Lilly studies spend much time sampling and swapping all manner of "detoxifiers" they insist guarantee entry to the clinic. Some swear by Herbal Clean, a tea, or golden seal, an herb grown in the Ozarks. Others say imbibing mineral oil or vinegar does the trick. James Picco, 57, who claims to have logged about 30 Lilly studies in 18 years but now is too old, downed "raisins, spinach and liver -- anything with iron."

Most of those interviewed use more mundane techniques to mask their addictions. James Hart recalls that he would quit drinking anywhere from three to 10 days before a screening and fudge those dates to Lilly staffers. "I might tell them I'd been sober for two months when it was only three or four days," says Mr. Hart, who hasn't been able to get into a Lilly study since 1994, when he was diagnosed with hepatitis. Jerry Bienz, a 39-year-old who is sitting outside the Lilly Clinic waiting to be screened, confides this: "The night before you come in, drink a gallon or two of water 'cause that will get your liver count down."

While elevated levels of certain liver enzymes are, in fact, a dead giveaway for alcohol in the system, Lilly 's homeless subjects generally manage to quit drinking long enough to pass the blood test the clinic gives.

Experts on the liver, where most drugs are metabolized, are divided on whether the tests are especially risky for heavy drinkers. Many say no, so long as the subjects have been off booze for a week or more and are eating a healthy diet. But some doctors who run Phase I tests argue that alcoholics do face a higher risk from the testing because they are more likely to suffer from certain diseases that standard blood screening doesn't detect. "Big-time boozers may have diseases that others don't; giving them untested drugs could harm them," says Diane Jorkasky, who heads SmithKline's Phase I test site in Philadelphia.

In any case, such subjects are hardly ideal drug-test candidates, the FDA and critics say. The biggest problem is that homeless alcohol abusers aren't always reliable when it comes to reporting adverse reactions. Sometimes they worry about being thrown out of a study, and sometimes they confuse the reasons for their symptoms, doctors who conduct Phase I tests say. "If a drug makes them dizzy or gives them a headache, they may think it comes from detoxification so they won't tell you, so you're potentially skewing the safety profile of the drug," says Philip Brown, a physician at Pharmaceutical Research Associates, a contract research organization in Charlottesville, Va.

Lilly says it continually tests and questions subjects for side effects, and knows what to watch for because of its preclinical data. "Although it is impossible to be 100% certain that every volunteer will report every side effect, there is no reason to believe that any characteristic of Lilly 's Phase I study population increases the likelihood of unreported or undetermined side effects," Dr. McKinney says.

Heavy drinkers also may metabolize a test drug more slowly than other people do, even if the drinkers' liver dysfunction is too mild for the screening test to detect. Doing safety tests on heavy drinkers thus may give an inaccurate read of a drug's half-life, the time it takes for it to be eliminated from the body -- essential data for figuring out dosages. Lilly 's Dr. McKinney says that "if this had any effect, it would be that trials of this drug would be more cautious (i.e., slower dose escalation or less drug exposure) in the future."

In any event, the admissions criteria at other Phase I testing clinics are more stringent. Other clinics don't accept smokers. They also typically insist that subjects give a local address and telephone number, and recruiters often call or write to them there before a study begins. By contrast, Lilly drug-test subjects interviewed said it was sufficient if they supplied the address and phone number of a shelter or relatives. Rick Posson, until recently the director of Horizon House, says his shelter never fielded any follow-up calls from Lilly Clinic staffers. Lilly acknowledges that it doesn't try to confirm addresses before testing , but says that in the rare cases where it has needed to reach a volunteer after a study, it has been able to do so.

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Lilly is accommodating to the homeless in other ways. Unlike other test centers, its clinic always houses subjects for the entire period of a Phase I study. It is willing to store subjects' possessions during studies.

Lilly also now issues photo ID cards to subjects, making it easier for them to cash checks. The clinic says it recently began paying by check rather than in cash, largely for record-keeping reasons.

Elsewhere, showing up dirty and fetid will get a volunteer booted out. Poor hygiene would "nuke" a potential test subject at PPD Pharmaco, a contract research organization in Austin, Texas, says Jerry Merritt, who oversees Phase I research. At the Lilly Clinic, nurses simply point slovenly test subjects to the shower, two subjects say. A Lilly spokesman explains, "We think it's a good idea to offer someone a shower if they need one."

The drug industry's dependence on human subjects has long been a lightning rod for controversy. Until the early 1960s, most companies simply guessed at dosage levels of new medications, and researchers would casually distribute experimental drugs to their physician friends to try on patients. In 1962, after large numbers of pregnant women in Europe were given thalidomide, a sedative that turned out to produce birth deformities, Congress passed new laws. These required companies, under FDA supervision, to test drugs on animals and healthy people to establish maximum dosage levels for the next phase of testing , on sick patients.

A dearth of volunteers led drug companies to turn to the nation's prisoners, who soon furnished virtually the entire Phase I pool. Lilly followed suit. But by 1974, in the wake of criticism focused on the poverty of prisoners and the frequent promise of early parole, the FDA required "informed consent" from subjects who could make a "truly voluntary and uncoerced decision." Though the new rules didn't specifically bar prison research, drug companies stopped it.

By this time, finding a steady supply of healthy people had gotten even more difficult because the Tuskegee experiments in Alabama, in which blacks were unwittingly infected with syphilis, had come to light, indelibly etching an unsavory side of human testing into the public imagination. One legacy of Tuskegee is that many blacks still shun human studies, which today are dominated by white men under 40.

Weary of the continual scramble for recruits, most companies turned to -- and continue to rely on -- university hospitals and contract research organizations to do their Phase I work. For reasons related to its history, Lilly took a different route.

In 1926, Lilly became the first drug company to operate its own clinic. J.K. Lilly Sr., then chairman, used it to understand more about his wife's severe anemia by conducting tests on ailing patients, according to an official company history. After severing its ties to prisons in the mid-1970s, Lilly set about expanding this clinic to include healthy subjects, too.

But even as others filled their Phase I studies mostly with college-age males, Lilly hung back. Many clinic physicians taught part time at Indiana University's medical school, and Lilly feared that students would feel pressured to enlist, says W. Leigh Thompson, who retired as Lilly 's chief scientific officer in 1995. He says that out of similar concerns, Lilly also barred its employees from studies. "If you're not going to use students and you won't use employees, you're restricting the population," Dr. Thompson says. ( Lilly 's Dr. McKinney confirms that the company bars its employees from participating but says it doesn't exclude students.)

Dr. Thompson says the practice of using homeless people was well under way when he arrived at Lilly in 1982. "We were constantly talking about whether we were exploiting the homeless," he recalls. "But there were a lot of them who were willing to stay in the hospital for four weeks."

He says an independent board that oversees the clinic approved the practice. Both the board and Lilly 's top executives felt that employing the homeless was a philanthropic act, Dr. Thompson explains, adding that he, too, took this position. "Providing them with a nice warm bed and good medical care and sending them out drug- and alcohol-free was a positive thing to do," Dr. Thompson says.

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Lilly has persisted in this approach despite drawing regulatory censure following a 1993 disaster with an experimental hepatitis drug called FIAU. But as for Lilly 's overall safety record, the FDA has no way of knowing, because oversight of Phase I testing is limited. Robert Temple, an official of the FDA's Center for Drug Evaluation and Research, says: "We haven't seen anything that makes Lilly look worse [than other drug companies], but we haven't looked."

Mr. Checchia's 57th day at the Lilly Clinic officially begins at five in the morning, when the lights go on in his room and he must produce a urine sample. Actually, Mr. Checchia says he awoke two hours earlier and smoked a cigarette, violating clinic rules. At 6 a.m., a nurse takes his temperature, blood pressure and pulse, steps that will be followed later in the morning by an electrocardiogram and blood draws.

He is blase about them, as well as about "dosing days," the five separate days in which Lilly will inject its test drug into four male subjects aged 21 to 55. Mr. Checchia recalls that during his last dosing experience he had to report, on an empty stomach, to the Study Room for the first of about 18 blood draws that day. Then, at 10 o'clock sharp, a catheter stuck into his arm began sending LY315920, an experimental drug for severe infections, through his body. (Some subjects may get a placebo instead.) The repeated needle stabs have created deep, discolored scars in the crooks of Mr. Checchia's arms. But he later boasts, "I don't feel nothing."

For Lilly 's volunteers, scars are, in fact, a macho badge. Regulars are wont to show them off as proof of participation in multiple studies. They also like to be stuck repeatedly in the same place, because, they believe, nerves in the scar tissue are deadened, making blood draws painless.

During the long interludes between medical sessions, subjects kill time watching TV and playing pool in the clinic's recreation room. Small talk centers on what they will do with the money they get. Buying alcohol and cars (which can double as shelter) tops the list.

Other drug makers let Phase I subjects in long-term studies leave their facilities between dosings. But at Lilly , volunteers often remain in the clinic for weeks or months, largely to guarantee they abstain from drinking, says Dr. Thompson, the former chief scientific officer.

Lilly 's Dr. McKinney supplies a different rationale, explaining that the freedom to come and go could "compromise the safety of volunteers" in certain studies and that an in-patient setting makes data collection "more complete and reliable." He says that as a result, the study population for many trials is limited to people who can make the time commitment.

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In any event, Lilly grants its recruits certain perks not found elsewhere. For example, drug companies typically bar smokers because tobacco may change the way the liver metabolizes drugs, and smokers are at greater risk for certain diseases. "You don't want them," says SmithKline's Dr. Jorkasky.

For Lilly 's volunteers, however, cigarette breaks are a high point. Three times each day, usually after meals, they get to leave the clinic for a public area outside to smoke for half an hour. Their cigarette packs are kept by a clinic guard, and subjects are supposed to return them to his desk after breaks.

Mr. Checchia stows an extra pack of Pall Malls, keeping them in the drawer of his bedside table. Whenever he gets the urge between official smoking breaks, he says, he sneaks a cigarette in the bathroom. He uses a technique volunteers favor to avoid detection: standing on the toilet and blowing smoke into a ceiling vent.

When cigarette supplies dwindle, volunteers prevail on clinic nurses to buy more with funds unwittingly provided by Lilly . Each week, to help its subjects pass the time, the clinic provides them with hobby kits to make plastic car models and leather belts and wallets. Mr. Checchia says the kits bore him. Like many others, he sells the kits to a guard for about $20 of cigarette money.

Lilly says subjects are allowed outdoor smoking breaks if a drug protocol permits it, adding that if a volunteer smokes, the clinic records this, enabling it to study how cigarette smoking affects drug metabolism. Lilly says violations of the smoking policy can result in dismissal from a test. It denies that volunteers sneak smokes in the bathroom.

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For all the apparent monotony of life in a controlled environment, almost every Lilly subject seems to have a war story involving peril or pain. Whether or not they bring bad reactions to the staff's attention, they tell their friends.

David Pryor, a former homeless alcoholic who is trying to establish a detox facility in Indianapolis called Guttr Inc., describes a 120-day asthma study he was in in the late 1980s that, he says, "caused irregular heartbeats and high blood pressure" in four of its six participants. Mr. Checchia says that seven years ago, an experimental Lilly drug gave him a heart problem so bad "they had to put things on my chest to start my heart up again." He says the same thing happened to another subject, leading to their hospitalization for a short time after the study ended. Lilly "quit messing with that drug," Mr. Checchia says.

More recently, Mr. LaDuke, the young man who took part in the schizophrenia study this summer, says the drug made him fall asleep for two days straight. Mr. Slone chimes in that he got excruciating headaches from it. He says he reported the headaches.

All of the homeless test subjects interviewed tell of slipping, after the tests, into the shadowy recesses of urban life, gathering at Indianapolis haunts like the Relax Inn.

Sitting behind the front desk there, manager Doug Phillips confides that over the years he has routinely rented rooms to guests he refers to as "the guinea pigs." Over the din of pinball machines, he relates how these men typically arrive flush with $2,500 or so in cash, staying for about a week. "The guinea pigs go to the lounge next door, get drunk and buy the house a round," he says. "The idea is, they can party for a couple of weeks and go back to Lilly and do the next one." Lilly requires at least 30 days between studies.

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Mr. Checchia, nearing the end of his 62-day study last June, was ready to celebrate his first day of freedom by making a beeline for the Dollar Inn, a $24.95-a-day motel near the Indianapolis airport. "I'll get a case of Miller and an escort girl and have sex," he said. "The girl will cost me $200 an hour."

Mr. Checchia figured his $4,650 would last about two weeks.

Some Lilly subjects have blown through their bankroll more quickly. Mr. Hart tells how after a 1994 study, he left the clinic with five other subjects, whom he had hung out with on the streets. The group rented a couple of rooms at the Relax Inn (then called Chariot House). After a day-long vodka binge, Mr. Hart fell asleep. "When I got up, my pockets were inside out and I was missing $1,600," says the former Lilly Clinic regular. None of his buddies confessed.

Lilly 's volunteers have performed these distinctive rites for years. But their routines, not to mention their boom-and-bust economic cycles, have drawn scant notice. Some shelter directors and homeless advocates privately attribute their silence to their concern about the clout of the Lilly Endowment, whose philanthropy has helped define civic and religious life in Indianapolis.

Established in 1937 by the Lilly family with gifts of company stock, it now holds 16% of Lilly 's shares -- valued at more than $6.5 billion -- making it the company's biggest shareholder and one of the nation's largest charitable foundations. Lilly officials emphasize that the company doesn't meddle in the gift-giving decisions of the Endowment, which has its own board. A spokeswoman for the Endowment also says it operates independently, adding that its officials know nothing of the clinic's use of homeless alcoholics.

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But over the years, the Endowment has helped every one of Indianapolis's missions for men, and some mission staffers think of the charity and the company as interchangeable. Asked about Lilly 's use of homeless alcoholics, a director of one of the city's largest missions says: "I have to be careful with how I deal with this . ... Lilly has funded us and we're going to need to go back to them this year."

At the Lighthouse Mission, director Dick Craig says he often tries, though with scant success, to dissuade boarders from participating in Lilly 's studies. "These men need to deal with their spiritual needs and emotional problems, and they can't do that sitting in a hospital vegging out on drug tests." But he adds: "Eli Lilly is a big community supporter and I'd never be critical of the company."

The independent board charged with ensuring the safety of Lilly 's subjects also takes a benign view. Although the board meets every two weeks, Dr. McKinney, the clinic's chief, says members "rarely reject" Lilly 's blueprints for drug studies. The Rev. Harold Kallio, who was on the board for 10 years until 1994, says that if subjects drank, "that was their own personal life." As he puts it: "When I met the subjects at the clinic they were sober. On the outside, I don't know."

Late one afternoon, on an unseasonably warm Wednesday in October, Mr. Slone and Mr. LaDuke can once more be found sitting outside the Harbor Light mission with their pals.

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Mr. LaDuke recounts how after he was released from the Lilly Clinic at 2:30 p.m. on Sept. 3, he cashed a check for $2,250 and hit a bar. Then he went to a mall to buy the jeans and black Nikes he now wears, as well as a shirt he has since lost. With a fellow Lilly subject and another homeless acquaintance in tow, Mr. LaDuke made his way to several more saloons, ending his odyssey at the Red Garter, a dank topless bar. There he polished off shots of Jack Daniels and a cinnamon schnapps called Aftershock. Mr. LaDuke is hazy about the details of what happened next, except that at about 11 that night he "blacked out."

The next morning, Mr. LaDuke says, he woke up in the Marion County Jail "in a rubber room with no clothes on." Gone, too, was the rest of his Lilly loot -- some $1,700 -- which he believes was filched by his drinking companions. A court clerk confirms Mr. LaDuke's arrest for disorderly conduct and public intoxication.

After a brief stint in jail, Mr. LaDuke managed to reunite with Mr. Slone, who got out of the Lilly Clinic two days later. Both spent a few weeks in Louisville, working at minimum-wage, temporary jobs. Now the two are back in Indianapolis and down and out.

Determined to scare up some "quick cash," Mr. LaDuke places a call to Ms. Patrum, the Lilly recruiting nurse. At the crack of dawn on Monday morning, he strides into the Lilly Clinic to participate in another human trial.

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    Copyright © 1998 Dow Jones & Company, Inc. All Rights Reserved.

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FDA Once Chastised Lilly for Using Alcoholics
 
11/14/96
The Wall Street Journal
Page A10
(Copyright (c) 1996, Dow Jones & Company, Inc.)

In 1994, the Food and Drug Administration issued an unusual rebuke to Eli Lilly & Co. for using alcoholics in a drug study that triggered the company's most public drug- testing disaster.

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The experimental drug, known as FIAU, was intended to treat hepatitis B. In early 1993, two subjects who took FIAU in a trial at Lilly 's Indianapolis clinic experienced liver abnormalities, and one was hospitalized. The drug also was given to 15 people with hepatitis, who were enrolled in a Phase II trial at the National Institutes of Health. Five later developed toxic liver reactions and died.

In the aftermath, the FDA took Lilly to task for using two supposedly healthy test subjects who turned out to be alcoholics. In a previously undisclosed warning letter to Lilly Chairman Randall Tobias, the FDA told Lilly that "the use of volunteers with a history of daily alcohol intake . . . is not in keeping with good clinical investigational practice."

Lilly says its informed-consent form in the study stated that subjects shouldn't have abused alcohol or drugs in the preceding six months. That caveat, as well as its screening and monitoring, gave Lilly "no reason to question the medical history information" supplied by the alcoholic subject who was hospitalized, it says.

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The FDA also chastised Lilly for failing to report within 10 days the hospitalization of one test subject. Lilly said it didn't do so because his adverse reaction wasn't "serious" or "unexpected." It said he was hospitalized so Lilly could observe him in an alcohol-free environment until his liver returned to normal. The FDA, however, described the subject's reaction as serious and said it "could not exclude FIAU as the cause."

(See related article: "Stuck for Money: To Screen New Drugs For Safety, Lilly Pays Homeless Alcoholics --- It's `Quick Cash' to Habitues Of Indianapolis Shelters; It Vanishes Quickly, Too --- How to Mask a Recent Binge" -- WSJ Nov. 14, 1996)

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NIH research ethics office questions study at Indiana University

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PAUL RECER
 
12/20/96
The Associated Press
(Copyright 1996. The Associated Press. All Rights Reserved.)

WASHINGTON (AP) - Federal officials have sent a letter to Indiana University seeking more information on allegations that medical researchers there are using homeless people as test subjects.

Gary B. Ellis of the office of Protection from Research Risk at the National Institutes of Health said Friday that the letter was prompted by media reports that homeless and alcoholic people were being recruited for clinical studies at a hospital affiliated with Indiana University. Use of such "vulnerable people" is restricted by federal regulations.

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Inquiry letters like that sent to Indiana are usually the first step in an investigation by the NIH agency, Ellis said. He noted, however, that only a small percentage of such letters results in follow-up investigations.

The issue at Indiana University, said Ellis, is whether or not proper informed consent has been obtained from test subjects recruited for Phase I drug tests conducted at Wishard Memorial Hospital at the Indiana University medical school. The studies are connected to drugs being developed by Eli Lilly & Co., an Indianapolis pharmaceutical firm with close ties to the university.

Under federal regulations, Ellis said, informed consent is only possible if there is no undue influence or coercion of test subjects. The regulations specifically warn against influencing "certain vulnerable populations," that include the economically disadvantaged, such as homeless people, he said.

Ellis said no investigation is under way and the agency is awaiting an answer from the university to a series of questions in the letter.

"This letter is part of an ongoing evaluation," he said.

Before a pharmaceutical company can start human drug tests, it has to receive approval from the federal government. A part of the process is an evaluation of the proposed experiment by an independent board of scientists. The committee giving approval to tests of Lilly drugs often is the Indiana University Institutional Review Board.

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For that reason, Ellis said, the letter of inquiry was sent to Indiana University instead of to Lilly .

Calls for comment from two offices at the Indiana University medical school were not returned on Friday.

On Nov. 14, The Wall Street Journal reported that Eli Lilly routinely uses homeless people to test drugs in the Lilly Clinic at Wishard Memorial. The newspaper said Lilly has been rebuked by the Food and Drug Administration for using alcoholics in a study testing a liver drug. The study design specifically excluded people with alcohol abuse problems.

An official of Eli Lilly denied that the company uses homeless people to test drugs, noting that 94 percent of the test participants have residential addresses.

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Technology and Health

Lilly Drug Clinic
In U.S. Faces Scrutiny
 
12/23/96
The Asian Wall Street Journal
Page 10
(Copyright (c) 1996, Dow Jones & Company, Inc.)

WASHINGTON -- The National Institutes of Health is looking into how Eli Lilly & Co. recruits human subjects for initial safety tests of experimental drugs at its Indianapolis clinic.

The move comes in response to a page-one article in the Nov. 15-16 edition of The Asian Wall Street Journal saying that, in so-called Phase I testing , Lilly largely relies on homeless people who drink. Gary B. Ellis, an official of the NIH, said it is "evaluating the protection of human subjects."

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The Lilly Clinic is housed at Wishard Memorial Hospital on the campus of the Indiana University medical school. Isaac Levy, an associate dean at the university, said the school has received an NIH list of questions and will respond to it next month. One concern of the NIH is to make sure the human test subjects are capable of informed, uncoerced consent.

If the NIH isn't satisfied with the response, it could pursue a formal investigation, which could lead to more strin gent steps.

Lilly has denied that most of its subjects in initial drug tests are homeless drinkers or that the tests are in any way compromised. Company officials last week weren't available to comment.

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Pharmaceuticals:
Antidepressant Makers Study Kids' Market
By Elyse Tanouye
 
04/04/97
The Wall Street Journal
Page B1
(Copyright (c) 1997, Dow Jones & Company, Inc.)

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The makers of Prozac, Zoloft, Paxil and other antidepressants are taking aim at a controversial new market: children.

Currently, no medications are approved by the Food and Drug Administration to treat depression in patients under 18 years old. But drug companies are racing to compile data on whether their drugs are safe and effective in children, hoping to present the results to federal regulators.

Already, Pfizer Inc. has submitted pediatric test data on its drug, Zoloft; SmithKline Beecham PLC is conducting two large tests of its antidepressant, Paxil, on children. Bristol-Myers Squibb Co. and American Home Products Corp. are preparing to begin large-scale tests of their drugs, Serzone and Effexor respectively. Eli Lilly & Co., meanwhile, has submitted children's data compiled from several independent researchers regarding its entry in the antidepressant market, Prozac.

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Drug makers also are preparing their medications in easy-to-swallow forms that will be more palatable to even the youngest tykes: Lilly 's Prozac is already available as a minty liquid; Pfizer is working on a liquid version of Zoloft and an orange-flavored liquid Paxil is nearing approval from the FDA.

Advocates say the drug makers are responding to an urgent need. An estimated three million to four million children and adolescents in the U.S. suffer from depression and obsessive-compulsive disorder, according to various sources; the American Academy of Child and Adolescent Psychiatry says about 5% of children and adolescents suffer from significant depression, and drug maker Solvay Pharmaceuticals Inc. and Pharmacia & Upjohn Inc. say another one million kids have obsessive-compulsive disorder. Many of these young patients now are inadequately treated, experts say, often leading to long-term emotional and behavioral problems, drug abuse, or even suicide.

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But prescribing antidepressants to the young raises tough issues. There isn't any sure-fire test for depression, forcing parents and physicians to decide whether a child is clinically depressed or simply riding the roller-coaster emotions of growing up. Critics worry about aggressive marketing tactics and consequent overuse. And safety concerns linger. Antidepressants often are used daily for many years, yet researchers haven't conducted longterm studies to see how the chemicals affect still-growing bodies.

Yet doctors prescribe them for kids anyway; physicians may legally do so, even though the drugs are not approved for youths. About 580,000 children and adolescents received a prescription for Prozac, Paxil or Zoloft last year, according to IMS America Ltd., a research firm. "Parents are in a very difficult situation of having to make the best judgment with their physician, without data," says Peter Jensen, an official at the National Institutes of Health, which is funding research on antidepressants for kids.

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"This is a largely undertreated, understudied patient population in which drug studies need to be performed," adds Darlene N. Jody, a research official at Bristol-Myers Squibb Co.

Antidepressant makers also need a new market as growth slows in the adult segment. IMS America says some 28 million Americans took the heavily-marketed drugs last year. Estimates vary widely, but the American Psychiatric Association says that in a given year, only 16 million adults suffer from depression, obsessive-compulsive disorder and panic disorder, the major conditions that antidepressants treat.

New prescriptions for Prozac and drugs like it rose 17% last year and have increased even more slowly in recent months, far below the 58% increase in 1994, according to IMS numbers. U.S. sales rose 24% to $3.77 billion last year, compared with a 63% increase in sales in 1994.

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Kids accounted for only about 4% of antidepressant prescriptions last year, according to research firm Scott-Levin Inc. Some desperate parents say antidepressants can provide a much-needed rescue. JoAnne Myers of Houston says Prozac has stopped the violence in her nine-year-old son, Michael, who has been diagnosed with multiple problems. He now has friends for the first time in his life and was even invited for a sleepover recently. "I feel it's a miracle drug," she says.

In other patients, however, the benefits aren't as clear. Ramona Donnino of Duncanville, Texas, says her teenage daughter, Maritza Munoz, "was smiling again" while on Zoloft, but the already-thin teen began to lose weight and her doctor switched her to Prozac. Then Maritza started eating voraciously and gained weight too quickly, and her mood swings returned along with headaches. Now she takes Paxil but hasn't yet felt any improvement. "I just wish the results were faster," the 19-year-old student says.

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Approval of such drugs to treat other pediatric illnesses is further along. Last week, Luvox, sold by Solvay Pharmaceuticals Inc. and Pharmacia & Upjohn Inc., won FDA approval to treat obsessive-compulsive disorder in children. Luvox is a "serotonin-reuptake inhibitor" in the same class as Prozac, Zoloft and Paxil. Pfizer has submitted data on the use of Zoloft in children with OCD to regulators; SmithKline is testing Paxil for the same purpose.

The makers of antidepressants generally decline to comment on their strategies and other issues. They don't want to be seen as promoting children's use of their drugs before they have won federal approval to do so. They also say they must wait to see the results of the clinical trials, which will quantify whether and how well their pills work on the young. In the past, drug companies had shied away from testing chemicals on children, but the FDA encouraged them to proceed because so many doctors are prescribing Prozac and its rivals to kids anyway.

So far, one major children's trial indicates the drugs may work, but only in some patients.

The study compared Prozac and a placebo in 96 children ages 8 to 18; about half of the kids on Prozac showed improvement. Then again, a third of those on a placebo also improved, says Graham Emslie, professor of psychiatry at the University of Texas Southwestern Medical Center in Dallas, which conducted the research. And about 17 patients on Prozac had recurrences of depression within a year. Dr. Emslie also found that three kids taking Prozac developed mania, or excessive feelings of euphoria.

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Findings like that give some critics pause, as do the aggressive tactics that marketers use to pitch antidepressants to adults, such as mounting consumer ad campaigns and marketing drugs far beyond the narrow ranks of psychiatrists. Other critics worry that once the drug makers' marketing machinery hits high gear, doctors may prescribe the products to kids who don't really need them. "If all you have is a hammer, everything begins to look like a nail," says Gilbert Fuld, a pediatrician in Keene, N.H.

"It is the case that antidepressants are sometimes prescribed too quickly and without adequate critical thought. I see it myself," says Michael Strober, a clinical psychologist at the University of California Los Angeles medical school. "But we've also seen the reverse problem -- teenagers with severe and persisting depression who received surprisingly minimal treatment."

Some symptoms of depression are clear-cut: overwhelming sadness and recurrent thoughts of death or suicide. Others are more vague: changes in appetite or sleeping patterns, a loss of energy and interest in activities, feelings of hopelessness and low self-worth, an inability to concentrate, headaches or stomachaches. If a child suffers several of these symptoms for two weeks or longer, a parent should seek professional help, the American Psychiatric Association advises.

Prescribing the drugs "is a safeguard and a way of feeling like we're doing something," says Joyce Breasure, a counselor in Dover, Del., and immediate past president of the American Counseling Association. "Most of us who do this for a living spend part of our day asking whether we made the right call."

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Similar concerns have been raised about using Ritalin for children with "attention-deficit hyperactivity disorder." Prescriptions for Novartis AG's drug and generic versions soared to 12.1 million last year from 6.5 million in 1993.

Ritalin is "terribly overused," says Peter Goldenthal, a King of Prussia, Pa. psychologist. He says the disease occurs in 3% to 5% of children, but he hears reports of classrooms with 20% of their children taking the drug. The controversy prompted Ritalin's maker to run an anti-abuse campaign last year. Dr. Goldenthal and others worry that antidepressants for the very young could become a similar fad.

Even when an antidepressant works, it must be accompanied by counseling, experts say. Brenda Mouri of Plano, Texas, says her 16-year-old daughter, Marlo Lawrence, brightened considerably after going on Prozac. But the teenager was disappointed the drug didn't solve all of her problems and turned to cocaine and other illegal drugs to feel better, before her parents could get her in a counseling program.

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"I kind of expected [Prozac] to fix all my problems instantly," Marlo says, and she felt even worse after learning that not even medicine could fix everything. Prozac worked some, Marlo's mother notes, "but it doesn't take away any insecurities, or any low self-esteem."

Dr. Jensen of the NIH concurs that depressed children also need help with self-esteem, social skills and other problems that no medication can treat. "Pills don't create skills," he says.

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(See related letters: "Letters to the Editor: Psychopharmacology and Children" -- WSJ May 7, 1997)

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Test Case:
Drug Makers Relied
On Two Researchers
Who Now Await Trial
---
The Americans Are Accused
Of Endangering Patients
And Stealing $10 Million
---
`Checks and Balances' Failed
By Steve Stecklow and Laura Johannes
 
08/18/97
The Wall Street Journal Europe
Page 1
(Copyright (c) 1997, Dow Jones & Company, Inc.)

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AUGUSTA, Georgia -- For most of this decade, many pharmaceutical companies relied heavily on two distinguished clinical researchers, Richard L. Borison and Bruce I. Diamond, to test new mental-health drugs. Now, the two men are awaiting trial in Richmond County, Georgia, after pleading not guilty to 172 criminal charges.

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Georgia state investigators accuse the two men of running a secret, renegade drug- testing operation, recklessly endangering patients and stealing from Georgia's only state medical school more than $10 million in drug-company payments. They contend that Dr. Borison, a 47-year-old medical doctor, was rarely around the test sites and left unqualified employees to treat patients and that Dr. Diamond, 52, a pharmacologist, routinely forged Dr. Borison's signature on patient and test records. Former employees of the pair say they were pressured to enroll large numbers of patients, whether eligible to participate or not. The doctors deny all the charges.

Prosecutors and medical-college officials are incredulous that none of the drug companies appeared to notice anything wrong. The companies, which are required to monitor clinical trials to ensure integrity of the data and patient safety, overlooked or ignored obvious signs that the two professors at the Medical College of Georgia here didn't follow proper procedures, investigators say.

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"The checks and balances that are in place didn't work," says Georgia Assistant Attorney General David McLaughlin. The two men "were doing this for years and didn't get caught."

The companies say they trusted Drs. Borison and Diamond to follow proper procedures and medical-college rules. They say they hired the two because they were prominent in their field and could sign up test subjects quickly -- an important consideration because of the companies' growing need for human test subjects to satisfy regulatory requirements. In addition, pharmaceutical companies testing similar drugs often compete fiercely for the same limited pool of patients.

The two researchers "had been active in the development of many successful drugs, and they were good recruiters," says William Kennedy, vice president of Zeneca Inc., of Wilmington, Delaware, which hired them in 1990 to test Seroquel, a schizophrenia drug.

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Among other companies, Johnson & Johnson hired the men to test Risperdal, its new schizophrenia medicine, and SmithKline Beecham PLC had them evaluate Paxil, a now-popular antidepressant. Their dozens of other clients also included Bristol-Myers Squibb Co., Eli Lilly Co. and Glaxo Wellcome PLC.

Some drug companies acknowledge they complied with Dr. Borison's requests to send payments to companies he controlled or even to his house, instead of the medical college. The companies also didn't question the researchers' practice of obtaining approval from outside human-test review boards, including one 4,000 kilometers away, instead of the one across the street that the college says they were supposed to use. "That should raise a red flag to anybody," says Manuel Casanova, an Alzheimer's researcher at the school.

And when one inspector from a test-monitoring company hired by Sandoz AG aggressively questioned the authenticity of Dr. Borison's signatures on patient records, the inspector was abruptly taken off the case after Dr. Diamond complained to the man's superiors, three former employees say.

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Drs. Borison and Diamond decline to be interviewed. Their attorneys say they didn't commit any crime and term the entire matter a contractual dispute with the school. "Whether Borison or Diamond owe the Medical College of Georgia money is a matter of contractual interpretation, not criminal law," says Michael C. Garrett, who represents Dr. Borison.

The attorneys also say the drug studies were performed appropriately and dispute any former employees' claims to the contrary. "Some persons may feel there were shortcuts taken," says Donald F. Samuel, Dr. Diamond's attorney. "That's maybe because they don't have the knowledge to properly evaluate what was going on."

Drs. Borison and Diamond made the lucrative switch from scholarship to entrepreneurship after collaborating for years, first at the University of Health Sciences/The Chicago Medical School (an independent institution now called Finch University of Health Sciences/The Chicago Medical School), where both earned doctorates in pharmacology. Dr. Borison also went to medical school at the University of Illinois in Chicago.

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By the time Dr. Borison finished his residency in 1981, he had published 85 articles in scholarly journals. Beginning in the mid-1970s, he and Dr. Diamond, who isn't a physician, had collaborated on more than 50 research projects. They got job offers in Augusta, where Dr. Borison went to work for a Veterans Affairs hospital and Dr. Diamond at the college. Both chose to specialize in research on how chemicals affect the brain just as scientific breakthroughs were expanding pharmaceutical treatments for the mind.

Some of Dr. Borison's research was criticized by regulators. In a paper delivered in May 1985 before the American Psychiatric Association, he reported that the generic version of Thorazine, a SmithKline schizophrenia drug, wasn't as effective as the brand-name medicine. Patients on Thorazine at the VA hospital in May 1984 became agitated and hostile, he said, when they were switched to generics the following month.

But when the U.S. Food and Drug Administration examined Dr. Borison's claims, it found that the VA hospital hadn't stocked Thorazine in May 1984 and had been using a generic equivalent exclusively for months. In addition, three of the 11 patients supposedly taking Thorazine that month weren't in the hospital then, the FDA said. In response, Dr. Borison said he had altered the time periods to protect patient confidentiality. But the FDA said a review of all possible time periods also failed to corroborate his data. It publicly rebuked him.

In a speech before pharmaceuticals manufacturers in June 1986, James C. Morrison, then deputy director of the FDA's office of drug standards, said of Dr. Borison's claims, "We conclude it is shameful that serious allegations about the performance of generic drugs have been made and widely repeated based on such faulty data." But the FDA had no disciplinary power because the incident didn't involve data submitted to it.

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Dr. Borison, defending himself to the VA, complained that the FDA criticism had prompted companies to withdraw research work. But any setback was brief. In 1988, he was promoted to a full professorship at the medical college and later became chairman of its psychiatry department. Between 1988 and 1996, companies including Abbott Laboratories Inc., Hoechst AG, Warner-Lambert Co., Pfizer Inc. and Sandoz showered him and Dr. Diamond with contracts for more than 160 studies.

Drug companies either say they didn't know about the FDA's harsh criticism of Dr. Borison or discounted it because no formal action was taken. "I have never heard of it," says Ravi Anand, who was in charge of the clinical trials performed by Dr. Borison for Sandoz (now part of Novartis AG). Dr. Anand, who joined Sandoz in 1989, says that if he or his predecessors had known, "we would drop that person like a hot potato."

With business booming in early 1994, Drs. Borison and Diamond opened a new drug- testing site across the street from the medical college, in the BioTech Park office complex. Its entrance was only marked Suite 7. "I kept asking when are we going to get a sign out," says Debra Brown, drug-study coordinator who worked there until June 1996 and left of her own volition. "They just skirted the issue."

Former employees and patients say they believed the test site, which used medical-college employees, supplies and appointment cards, was connected to the school. But the college says it didn't know about the operation. Like most medical schools, Medical College of Georgia requires faculty members to get its approval for all research and is supposed to collect all research money, using some for overhead. But in many Borison-Diamond trials, it says, it got no funds. It also concedes it did a poor job of tracking the studies.

The FDA requires that clinical research be approved by institutional review boards -- self-regulatory oversight entities -- and academics typically go through review boards on campus. But in at least 44 trials, Drs. Borison and Diamond went outside the college to find a review board, including one in Olympia, Washington.

Some Borison-Diamond staffers had no medical training before arriving at the clinic, but were asked to do sophisticated tasks, the FDA and former employees say. Two of their study coordinators had been hired after working as Girl Scout administrators; another had recently been a Delta Airlines flight attendant. At Suite 7, the office secretary became the staff pharmacist, keeping track of experimental drugs; she had no professional training.

Christy Hernandez, who began working at BioTech Park as a study coordinator in December 1994, also had no medical training, yet was put to work interpreting electrocardiograms and blood tests -- tasks normally done by physicians. She says she was deciding whether Alzheimer's patients could safely continue taking an experimental Sandoz drug. "There are many intricacies in reading medical data, and I didn't know how to do it," she says. Answering the telephone, she adds, is "all I should have been doing."

Dr. Borison, meanwhile, was rarely in, several former employees say. "He was never at BioTech Park other than for, like, a birthday," says Angela Touey, another former study coordinator.

The FDA, which launched its own investigation of the test operation last year, says Dr. Diamond performed medical tasks and "routinely" forged Dr. Borison's signature on patient charts and other documents. Prosecutors and former employees say the nonphysician even forged prescriptions -- a violation of state law. Ms. Touey says that prior to scheduled visits from drug-company inspectors, employees would place yellow stickers on documents that required Dr. Borison's signature and give them to Dr. Diamond. "We would tote these books to Bruce's office, and he would just sign away," she testified to a VA investigative board last year. Attorneys for the two men decline to comment on these accounts.

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Rigorous FDA standards require that new drugs be tested on large numbers of human patients. But because many people are reluctant to participate, drug companies, anxious to beat competitors to market with new products, prize researchers who excel at recruiting. Drs. Borison and Diamond were masters, able to round up dozens of willing patients within weeks.

An August 1994 letter from Abbott complimented Dr. Borison on his "impressive" enrollment for trials of the schizophrenia drug Sertindole, adding: "For your efforts, we will purchase a fax machine for the high-enroller award for the month of May." When sign-ups reached 20, the letter promised "an enrollment bonus of $3,000, with which you may purchase a computer." Abbott terms the compensation "appropriate."

Ms. Hernandez and other former employees say that Dr. Diamond pressured them to recruit large numbers of test subjects quickly, including some who may not have qualified, and that their pay depended on it. The employees' low pay was supplemented by frequent bonuses -- of $500 or more -- that were partly based on the number of patients they recruited.

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Ms. Brown says Dr. Diamond once wrote on a cocktail napkin that "he would double my salary that year" if she recruited 30 new patients for a Sandoz Alzheimer's study. Ms. Brown says she barely missed the quota. A contract shows the drug company had offered to pay $19,380 per subject -- one of the highest amounts ever offered in an Alzheimer's trial.

"It became like a game to Bruce Diamond," Ms. Brown says. "He was just crazy about enrolling all of these patients, and it became more and more obvious that this isn't right." Dr. Diamond's attorney acknowledges that employees were paid recruiting bonuses, but says, "If the incident with the cocktail napkin occurred, it was obviously a joke."

Paige Horan, who coordinated Borison-Diamond drug trials at the VA hospital, says Dr. Diamond pushed her so hard to recruit and retain subjects for a Sandoz study of a schizophrenia drug that she misled patients -- claiming the experimental medicine may be the "next wonder" drug. The recruiters "were promising them things that we knew were wrong," she says in an interview. "I was very wrong for doing it."

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Ms. Hernandez says Dr. Diamond "just wanted us to recruit as many people as possible, and whether we thought they would be eligible or not." Dr. Diamond's attorney says some unqualified patients may have been enrolled but denies his client knew at the time that anybody was ineligible.

Eligibility requirements for drug studies are designed to make sure that drugs are tested on patients they are most likely to help. The studies' rules usually specify the type and stage of disease the test subjects must have, and they exclude people with other health or substance-abuse problems. The results could be skewed if researchers enroll ineligible patients, and patients could suffer because they pass up opportunities to try other therapies that might be more helpful.

When Nancy Sisk brought her husband, Leroy, to BioTech Park in June 1995, intrigued by an experimental Sandoz drug for Alzheimer's, the retired minister couldn't even remember what state he lived in. At Dr. Borison's clinic, Mrs. Sisk says a staff member, whom she can't identify, took her husband into a back room and administered a mental-acuity test with a scale from zero to 30. "She came and told us, `He made an eight, but we'll give him a 12,' " Mrs. Sisk says. A score of 10 was needed to enroll in the study, which was aimed at people who still retained much of their cognitive ability.

Three months into the study, Mrs. Sisk, concerned that her husband wasn't improving, took him to Edward Zamrini at the VA hospital. Dr. Zamrini gave him the same acuity test. Mr. Sisk's score was two. "There was no way he could have legitimately been admitted or enrolled in the Sandoz study," Dr. Zamrini later testified to the VA investigative board. Because Mrs. Sisk had said her husband hadn't deteriorated significantly since the first test, Dr. Zamrini added, "In my opinion, their initial score of 12 is suspect." Mr. Sisk ultimately quit the study.

Dr. Diamond, his attorney says, didn't perform the test on Mr. Sisk or order any employee to put him in the study.

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As activity at Suite 7 picked up, rumors began circulating around the college that Drs. Borison and Diamond were making a killing by running drug studies on the side. Dr. Borison amassed a collection of antiques, including suits of armor, and made plans to build a full-scale castle outside Augusta. Dr. Diamond bought a Mercedes. Dr. Borison, who earned $154,000 at the college, reported gross income of $1.2 million on his 1995 federal tax return. Dr. Diamond, who earned $65,000 at the school, reported $1.1 million. (The tax returns were attached to the indictments.) In both cases, most of the money came from PharmEd Inc., their research company.

The drug companies complied when Dr. Borison asked that money be sent directly to PharmEd or his home rather than to the college. A Warner-Lambert spokesman says one company unit sent a $10,000 check to PharmEd at Dr. Borison's request because it trusted him and the request came on medical-college stationery. The U.S. unit of Japan's Otsuka Pharmaceutical Co. also sent payments this way. "We were relying on his representations as a prestigious person," Scott Willoughby, Otsuka's U.S. general counsel, explains. The company has adopted controls to prevent a recurrence, he says.

In January 1996, Drs. Borison and Diamond opened a new research site to prospect for subjects in Charlotte, North Carolina. John Stokes, an inspector from Quintiles Transnational Corp., visited it a few months later. Sandoz had hired Quintiles, a medical-research contractor in Research Triangle Park, North Carolina, to help oversee its Alzheimer's studies, and Mr. Stokes questioned how Dr. Borison could sign records for patients seen in Charlotte on a day when he was nearly 320 kilometers away in Augusta. "The more questions he asked, the more nervous Dr. Diamond got," says a former study coordinator.

A person familiar with the matter says Dr. Diamond complained to Mr. Stokes's superiors at Quintiles. The next business day, Mr. Stokes was off the case. "Poor guy, he got in trouble," says Sharad Mogul, who managed the Charlotte office for Drs. Borison and Diamond at the time and had formerly worked at Quintiles. The drug- testing inspection system, he says, "is a joke, and what happened to John Stokes is a classic example." He says drug companies treat researchers like "kings" and are reluctant to antagonize them because they supply the study data. Mr. Stokes and Quintiles decline to comment.

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Things began to unravel for the two researchers when Ms. Touey left her job in Suite 7 to go to graduate school. A few months later, in the autumn of 1995, she took a part-time job with David Hess, a neurologist and researcher at the VA hospital. Dr. Hess told the VA investigative board that Ms. Touey asked him, on her first day on the job, how she should obtain a patient's consent to participate in a stroke study. He testified that when he explained that as the principal investigator, only he was supposed to obtain consent, she said it didn't work that way at her previous job.

Alarmed by this and other accounts from Ms. Touey, Dr. Hess spoke to other former employees and alerted officials at the medical college and the VA hospital, he testified. Days later, in June 1996, Drs. Borison and Diamond resigned their medical-school positions and are no longer testing any drugs; drug companies either stopped the trials or transferred them to other researchers. In February, the two men were indicted on state criminal charges. No trial date has been set.

Meanwhile, a court-appointed receiver is overseeing assets of the testing operations -- including equipment, files, money and bank accounts -- which, if the two are convicted, are subject to state forfeiture.

George Schuster, chairman of the medical school's institutional review board, says he is still disturbed by the drug companies' response to the scandal. He notified about two dozen companies in June 1996 that Drs. Borison and Diamond had resigned their positions after allegations of research misconduct and wrote that the school was "very concerned" about patients' welfare. But many of the companies "didn't seem particularly concerned" about patients, Dr. Schuster says, adding that most were interested only in whether data had been faked. Told there was no immediate evidence of that, "most of them seemed to lose interest," he says.

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Ms. Brown recalls a time when Sandoz did show some concern. Two years ago, it sent a representative to Augusta after discovering that she was dispensing medication at a time of day before most doctors' offices had opened -- suggesting that Dr. Borison wasn't around. Sandoz says its representative told the clinic to stop dispensing medication without a physician present. But employees say the practice continued anyway. Ms. Brown says the Sandoz representative never asked her any questions and left Augusta saying that if she "had a mother with Alzheimer's disease, [she] would want her to come to our clinic."

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Personal Thoughts

Editor's Say:

Children Who Kill--
On Prozac

Hi Folks,

Most of you who know me or follow my editorials know that I do not especially like firearms. But, I'm not foolish enough to think that it's possible to rid America of guns without upsetting the delicate balance that has long existed in this country. Although I actually dislike guns, I know that they are quite necessary if we expect to remain a free people.

Recently there have been a rash of copy-cat murders involving children and firearms. Although I am much saddened by these tragic deaths and injuries, I am not at all persuaded to legislate away our 2nd Amendment rights. There are those, however, who have used these unfortunate incidents to jerk at the strings of peoples' hearts in an attempt to legislate additional gun control. Because the millions of well-trained children who have long held a gun in this country have never gone on a rampage before, I have to ask myself why did these handful?

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Maureen Sielaff recently brought to my attention an interesting fact that never made it into the main stream media. If you read her editorial carefully, you will see that it's not the guns that these children used that are at fault, but possibly the drugs these children were on when they did these terrible things. Incidentally, one particular drug was common to all of them, according to Sielaff. Read it for yourself:

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>     SPRINGFIELD, OREGON - Before going on a wild shooting spree at his
>Springfield Oregon high school that left 2 dead and 22 injured, Kip Kinkel
>had been attending anger control classes and was taking a prescription drug
>called Prozac. This particular drug has factored in almost all wild
>shooting sprees which have taken place in the last ten years. Eli Lilly of
>Indianapolis, Indiana was recently sued over the homicidal tendencies this
>drug is alleged to induce in patients. Prozac is commonly given to youth as
>a treatment for depression.
>
>     In the book "Prozac and other Psychiatric Drugs," by Lewis A. Opler,
>M.D., Ph.D., the following side effects are listed for Prozac: apathy;
>hallucinations; hostility; irrational ideas; and paranoid reactions,
>antisocial behavior; hysteria; and suicidal thoughts.
>

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>     Though many are demanding stricter gun control laws as a solution to
>this sudden increase in homicidal shootings, these events do not appear to
>correlate to a sudden increase in firearm ownership. But when the
>percentage of these killers that are on Prozac is compared to the
>percentage of the general public on Prozac, a very disturbing pattern
>emerges. Though Prozac does indeed help many people suffering from
>depression, it appears that it does indeed also drive many into homicidal
>rages.
>
>     When Kip Kinkel's home was investigated several bombs that he had
>constructed were discovered. With a ban on bombs already in place, he
>nevertheless managed to have several in his possession that he might well
>have taken to school instead of guns. So the question arises, if guns had
>been banned like bombs, would the danger have been averted? The
>unmistakable answer is that it would not. And with the shootings
>correlating far more closely with the psychiatric drug Prozac, why is the
>public put in such great danger by its widespread use, while efforts are
>directed instead toward something that shows no correlation?
>
>     Apparently it is easier to drug our youth, to fill their bodies with
>drugs that many times have worse side effects on their minds and spirits
>than the problems they have. You name the attitude and there is a drug to
>supposedly help or cure it.
>

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>     It may be time to take the War On Drugs to where it can really be
>effective; getting these society cop-out drugs out of our children's lives.
>It may be time we rise and help our children through productive activities
>and quit drugging them senseless.  --Maureen Sielaff
>

185 Side Effects
of PROZAC & Ritalin

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Best Regards,  Al Colombo

 

---

Personal Thoughts

Editor's Say:

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Side Effects
of PROZAC & Ritalin

Folks,

The following list of side effects associated with Prozac should open anyone's eyes. If all of this is true, why are we giving this stuff to our kids for? I honestly can not understand the psychology behind drugging our kids with substances like this.

Al Colombo

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>Sender: Jackie Patru <104645.452@compuserve.com>
>To: Blind.Copy.Receiver@compuserve.com
>
>Received a forwarded message some time ago regarding a gentleman's request
>for info on Prozac. Just pulled it out of my "TO ANSWER" file. After
>listing all these effects of PROZAC, thought you would like to have the info.
>
>The man's wife is pregnant and taking PROZAC. Naturally he is concerned
>and with good cause. From the PDR (Physician's Desk Reference) Family
>Guide to Prescription Drugs, here's what it says about PROZAC:
>
>"More Common Side Effects may include:
>
>Abnormal dreams, agitation, anxiety, bronchitis, chills, diarrhea,
>dizziness, drowsiness and fatigue, hay fever, inability to fall or stay
>asleep, increased appetite, lack or loss of appetite, light-headedness,
>nausea, nervousness, sweating, tremors, weakness, weight loss, yeawning.[21]
>
>Less Common Side effects may include:
>

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>Abnormal ejaculation, abnormal gait, abnormal stoppage of menstrual flow,
>acne, amnesia, apathy, arthritis, asthma, belching, bone pain, breast
>cysts, breast pain, brief loss of consciousness, bursitis, chills and
>fever, conjunctivitis, convulsions, dark tarry stool, difficulty in
>swallowing, dilation of pupils, dimness of vision, dry skin, ear pain,
>exaggerated feeling of well-being, excessive bleeding, facial swelling due
>to fluid retention, fluid retention, hair loss, hallucinations, hangover
>effect, hiccups, high or low blood press