This is rather old news, but one can imagine how Lilly ran its tests for Humulin, in 1979-80.

There are numerous other articles of interest where this came from and the  source is:


We know that Aventis did similar testing for Lantus' clinical trials in 1997-8 and we know that Lilly didn't remove Iletin I mixed beef-pork insulin from the world market until 2 years after this blast was published.

I thank Lauri Veneri for directing us to it and to the list of other interesting articles at the end of this article. You may wish to compare it with the October 1996 WSJ article in which ADA's Phil Cryer complains about the over 13% of diabetics dying from iatrogenic hypoglycemia at:
<click here>

Maybe the Journal was shorting Lilly Stock in '96? (NOT likely!)

Lilly's 'Quick Cash' to Habitués Of Shelters Vanishes Quickly


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.

The Food and Drug Administration chastised Lilly in 1994 for using alcoholics in a drug study.

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.


Day Rates

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.


'Temporarily Employed'

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.


Room and Board

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."

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.


From the Salvation Army Mission

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 Wished 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.

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.


A Question of Risk

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.

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."


A Lightning Rod of Controversy

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.

Lilly has persisted in this approach despite drawing regulatory censure following a 1993 disaster with an experimental hepatitis drug called FIAU. (See article below.) 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."


Testing at the Lilly Clinic

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.

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.


Swapping War Stories

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.

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.


Boom-and-Bust Cycles

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.

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 .Eli 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.

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 $1,700Ñwhich 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.

Copyright © 1997 Dow Jones & Company, Inc. All Rights Reserved.

Ms. Veneri also provided us with this information regarding the "causes" of diabetes: This is the flip side of the debate.  NCIRS states there is no link to vaccines and Juvenile Diabetes. US officials state that Dr Claussen’s finding are irrelevant because they were conducted on other countries population as well This is interesting reading linking Diabetes to cow’s milk fed to infants Studies linking the rotavirus vaccine to Diabetes  This article has some great facts linking vaccines and diabetes and some interesting statistics Vaccines and Immune Suppression Rubella and its link to Diabetes Interesting article written by a “nonmedical”  medical and medical historian, siting the link between pertussis and diabetes along with other vaccine related illnesses Another article linking rotavirus and Diabetes the incidence of type 1 diabetes among children in Finland that coincided with the introduction of immunisation against Haemophilus influenzae Explains autoimmune disease and their link to vaccines HIB vaccine and its link to Diabetes