Lilly's 'Quick Cash' to Habitues
Of Shelters Vanishes Quickly
By LAURIE P. COHEN
Staff Reporter of THE WALL STREET JOURNAL
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.
Return To The Article
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.
Return To The Article
'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.
Return To The Article
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.
Return To The Article
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."
Return To The Article
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."
Return To The Article
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.
Return To The Article
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.
Return To The Article
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.
|
