The Washington Post 

December 17, 2000, Sunday, Final Edition 

SECTION: A SECTION; Pg. A01 

LENGTH: 6614 words 

HEADLINE: Where Profits and Lives Hang in Balance; Finding an Abundance of
Subjects and Lack of Oversight Abroad, Big Drug Companies Test Offshore to
Speed Products to Market 

SERIES: THE BODY HUNTERS: Exporting Human Experiments; Pg. 1/6 

BYLINE: Joe Stephens , Washington Post Staff Writer 

DATELINE: KANO, Nigeria 

BODY: 

By the time word of the little girl's death reached the United States, her
name had been replaced by numerals: No. 6587-0069. 

She was 10 years old and a scant 41 pounds. She lived in Nigeria, and in
April 1996 she ached from meningitis. 

An epidemic raged and scores lay dying in this frenetic city of amber dust.
Somehow the girl found a refuge: a medical camp where foreign doctors had
arrived to dispense expensive medicines for free. 

Behind a gate besieged by suffering crowds stood two very different
clinics. A humanitarian charity, Doctors Without Borders, had erected a
treatment center solely in an effort to save lives. Researchers for Pfizer
Inc., a huge American drug company, had set up a second center. They were
using Nigeria's meningitis epidemic to conduct experiments on children with
what Pfizer believed was a promising new antibiotic--a drug not yet
approved in the United States. 

The experimental drug was a potential blockbuster: Wall Street analysts
said Pfizer might reap $ 1 billion a year if Trovan, as it was known, won
approval for all its potential uses. Pfizer also wanted to test the drug
for use against meningitis, including an epidemic strain. The company
couldn't find enough patients in the United States, so its researchers had
come to Kano, among the dying. 

Doctors working with Pfizer drew spinal fluid from the girl, gauged her
symptoms and logged her as patient No. 0069 at testing site No. 6587 in
experiment No. 154-149. They gave her 56 milligrams of Trovan. 

A day later, the girl's strength was evaporating, Pfizer records show, and
one of her eyes froze in place. 

On the third day, she died. 

Pfizer records are explicit. Action taken: "Dose continued unchanged."
Outcome: "Death." 

Nobody can know for certain if the girl would have lived had she been taken
off experimental Trovan; perhaps she was beyond all hope. Yet the
circumstances of her death--while taking an unapproved drug, with alternate
treatments at hand, in a hurriedly established private sector
experiment--suggest much larger problems. 

A Washington Post investigation into corporate drug experiments in Africa,
Asia, Eastern Europe and Latin America reveals a booming, poorly regulated
testing system that is dominated by private interests and that far too
often betrays its promises to patients and consumers. 

Experiments involving risky drugs proceed with little independent
oversight. Impoverished, poorly educated patients are sometimes tested
without understanding that they are guinea pigs. And pledges of quality
medical care sometimes prove fatally hollow, The Post found. 

Drugmakers hop borders with scant government review. Largely uninspected by
the Food and Drug Administration--which has limited authority and few
resources to police experiments overseas--U.S.-based drug companies are
paying doctors to test thousands of human subjects in the Third World and
Eastern Europe. 

The companies use the tests to produce new products and new revenue
streams, but they are also responding to pressure from regulators, Congress
and lobbyists for disease victims to develop new medicines quickly. By
providing huge pools of human subjects, foreign trials help speed new drugs
to the marketplace--where they will be sold mainly to patients in wealthy
countries. 

The FDA requires that patients in such tests, no matter where they live,
consent fully to the experiments if the results are to be used to win
marketing approval in the United States. And, in fact, many tests conducted
in the Third World are conducted carefully and serve to expedite the
creation of life-saving drugs. But the Post's investigation found that in
other instances, the rules are poorly enforced or ignored. 

The experiments raise questions about corporate ethics and profits on a
frontier of globalization where drug companies wield enormous influence,
and where doctors paid by U.S.-based corporations sometimes perform
experiments on ill-informed patients in authoritarian societies. 

A Nigerian physician who said he was present during the Kano experiment,
for instance, felt it was "a bad thing," but he did not object because
Pfizer's test appeared to have backing from the government. "I could not
protest," said the physician, Amir Imam Yola. "The system you have in
America and the system we have here, there is a wide gap. Freedom of speech
is still not here." 

At the time, Nigeria was run by a military government that had one of the
world's worst human rights and corruption records. 

Industry guidelines for conducting meningitis experiments never envisioned
testing an antibiotic amid a terrible epidemic in a squalid, short-staffed
medical camp lacking basic diagnostic equipment. 

Texas pediatrician George McCracken, a leading meningitis specialist who
co-authored the guidelines, said he was surprised Pfizer's researchers had
attempted such a venture. "I just wouldn't do a study that way myself," he
said. "I know they wanted to get the data. They wanted to go fast. They
wanted to move ahead. I'm not sure they made a smart decision." 

Among the 200 stricken children enrolled in its experiment, 11 died and
others suffered meningitis-related symptoms such as deafness, lameness,
blindness, seizures, disorientation and, in one case, an inability to walk
or talk, company records show. 

Pfizer said its goal was to study the safety and effectiveness of its
antibiotic while simultaneously pioneering a breakthrough treatment for the
Third World. The company contends its practices were validated--especially
given the horrendous conditions it found--by the number of children who
showed improvement and a fatality rate of about 6 percent, which compares
favorably to those reported for bacterial meningitis victims treated at
U.S. hospitals. The Trovan experiment, a company spokeswoman said, was
approved by a Nigerian ethics board and "was sound from medical,
scientific, regulatory and ethical standpoints." 

Pfizer researchers prepared the study over six weeks, instead of the year
or longer common in the United States. And while American meningitis
patients generally receive fast-acting intravenous medicines, the
researchers gave most of the Nigerian subjects an oral form of Trovan that
the company said had never been tested in children. 

Ten doctors interviewed about Patient 0069's death--including
pediatricians, meningitis specialists and physicians who have practiced in
developing countries--said they were troubled by her case. Their questions
focused in part on whether doctors left the child on the test drug for too
long while her health declined. Generally, if human subjects are not
responding to an experimental treatment, they are removed from the test and
given proven medicines. 

Industry guidelines governing meningitis experiments urge that researchers
conduct a second spinal tap a day or so after treatment begins to see if
the medication is working. Pfizer researchers chose to make such exams
optional in Nigeria and Pfizer said they did not perform one on Patient
0069, leaving her on the experimental drug until her death. 

"It could be considered murder," said Evariste Lodi, the Doctors Without
Borders physician who led the charity's efforts against meningitis in Kano,
after he reviewed a Pfizer description of Patient 0069's death. Added Agwu
Urondu, a Nigerian physician still working in the city: "The patient died
because [the doctor] refused to help." 

In a written statement, a Pfizer spokeswoman said a death such as Patient
0069's could occur during treatment with any antibiotic and that
researchers had no reason to suspect the experimental medicine was not
working. 

Abdulhamid Isa Dutse, a Nigerian doctor hired by Pfizer to run the
experiment, agreed that physicians should alter the medication of a patient
who is not improving. "To be very, very honest, in retrospect, maybe we
should have done something about that," he said of the girl. 

Yola, the Kano doctor, and others who battled the epidemic said patients
did not understand they had been in an experiment. "The patients did not
know if it was research or not," agreed a Nigerian laboratory technician
who took part. "They just knew they were sick." 

Pfizer disputes that, saying local nurses explained the research to
families, even though the company has no signed consent forms to prove it. 

Although Pfizer eventually won approval to sell the drug to adults in the
United States, in the end its push to bring Trovan to market turned out
badly. Authorities never approved marketing the antibiotic for use by
children in the United States or Nigeria. U.S. regulators discovered dozens
of discrepancies in the Kano test results. Last year, they advised doctors
to restrict Trovan's use in adults because patients had suffered liver
damage and death. European regulators suspended sales altogether. 

Pfizer's Nigerian clinic opened and closed in a relative eye blink: About
three weeks after the company's team roared in with a chartered DC-9, the
team roared out. Pfizer's doctors returned once to examine the patients but
did not track their long-term recovery. 

"If I had the power," said Doctors Without Borders physician Lodi, who
watched the experiment unfold from across the compound, "I would take away
their medical licenses." 


A Desperate Time 


Pfizer's path to Kano began on the Internet. 

Pfizer physician Scott Hopkins was on the World Wide Web when he learned of
a meningitis epidemic racing across northern Nigeria. The often-deadly
infection of the brain and spinal cord had begun to kill hundreds upon
hundreds in a region already staggering under epidemics of cholera and
measles. Some victims lay prone on bare ground in convulsions, physicians
recalled. By February 1996, 120 new patients were arriving at Kano's poorly
equipped, feces-stained infectious disease hospital every day. 

For Pfizer, the timing was oddly fortuitous. The New York-based, then-$ 11
billion-a-year corporation was pushing to submit Trovan for FDA approval. A
bacteria fighter, Trovan had shown promise against a broad range of
infections--sinusitis, bronchitis, gonorrhea and pneumonia. Thousands of
patients had enrolled in international drug studies in the company's
biggest testing program ever. Wall Street analysts predicted that Trovan
could be one of the most financially successful new drugs of its kind in
years. 

There were worries, however, about possible side effects in children.
Trovan belonged to the quinolone class of antibiotics, and quinolones had
caused joint damage in experiments on young rabbits and puppies. 

Pfizer knew that the company needed extensive, convincing tests that proved
Trovan was safe and effective in order to gain approval for the drug's use
on children. But illnesses such as bacterial meningitis were relatively
rare in the United States. 

"We had to move quickly" after spotting the epidemic, explained Pfizer
spokeswoman Betsy Raymond. "You would not be able to find those numbers of
children with spinal meningitis in the U.S." 

Hopkins, who then headed Trovan development, said he proposed leading a
six-person team into the epidemic in an attempt to establish that Trovan in
oral form could work as well in children as a fast-acting intravenous
antibiotic. If successful, oral Trovan would mark a breakthrough in
battling epidemics in the Third World. Children could simply swallow a pill
once a day, eliminating risky injections. 

Hopkins said he was confident of Trovan's potency and that he pitched the
plan to senior Pfizer executives by arguing, in part, that a humanitarian
thrust in Nigeria could create a "halo" over their newest product. 

Pfizer said it authorized the venture solely to win FDA approval for Trovan
use in meningitis epidemics, which occur mainly in developing nations.
Hopkins says today that this designation proves that the experiment was
philanthropic, not a cheap way to get the drug approved for American
children. 

But McCracken, who later conducted Trovan tests for the company, calls that
argument "a little bit disingenuous. They do gain from it. They gained
knowledge about how the drug works. It's not 100 percent altruistic." And
under U.S. law, once the drug won FDA approval for any purpose, American
pediatricians would be free to prescribe it. 

One Pfizer child disease specialist, Juan Walterspiel, complained that the
experiment was too risky--oral Trovan had never been tested on a child, he
later alleged in a lawsuit. The suit ultimately was dismissed at the
request of the physician and Pfizer; neither side would comment on the
litigation for this article. 

Hopkins, who has since left Pfizer, recalled in an interview that when he
launched the experiment, he had data showing children had readily absorbed
oral Trovan. Pfizer spokeswoman Kate Robins disagreed. 

In fact, Robins said, only one child had taken the oral form of Trovan at
the time. Pfizer has no knowledge of how that child fared, she said. But
previous tests of the oral form on adults, and of an intravenous
formulation of Trovan on children, showed it was well absorbed, she said. 

Gary Overturf, a New Mexico child disease specialist, said that without
oral studies in children, support for using oral Trovan on perilously ill
Nigerian children would appear to have been "at best . . . thin." Another
specialist, Creighton University pediatrics department Chairman Stephen
Chartrand, said use of the oral drug under those circumstances would be
"unconscionable." 

Yet the experiment quickly won clearance in Nigeria after what company
records call an "independent review" by authorities there and the approval
of a Kano hospital ethics committee. 

"That was kind of a desperate time for them--they were happy to have anyone
come in and do just about any kind of work," Hopkins recalled of the
Nigerian regime then in power. 

Pfizer did not require FDA approval to conduct the trial, he said. The
company gave regulators a copy of their plan anyway, he said, and the
agency granted permission to export Trovan to Nigeria. 

Within six weeks of his discovery of the meningitis outbreak, Hopkins
recalled, Pfizer had chartered a DC-9 and he was jetting toward the
epidemic's center. 

Treatment and Tensions 

The ancient walled city of Kano is an impoverished metropolis of 2 million
people that sprawls across a scorched savanna. A choking white fog of
pollution pumped by decrepit cars and speeding mopeds shrouds a labyrinth
of buildings tacked together with corrugated metal and russet-baked earth. 

Amid the clamor sits the Kano Infectious Disease Hospital, a compound of
crumbling cinder-block bunkers. International aid workers call it one of
the world's most fetid and overburdened hospitals. Rats chew on neglected
corpses and patients defecate on the ground. Many wards lack water and
electricity; walls are encrusted with excrement and blood. 

Stunned, Pfizer's researchers reportedly confessed to locals they had
expected a rural village, not urban chaos and squalor. 

Doctors Without Borders, more accustomed to such conditions, had already
begun improvements. The Nobel Peace Prize-winning charity, which races free
care to public health disasters worldwide, had arrived weeks earlier with
an inexpensive antibiotic called chloramphenicol. Its volunteers had
organized patient screening and treatment, grouping the sick by the
severity of their illnesses. The sickest patients slept inside in the
compound's few battered beds and on benches; the less seriously ill
occupied mats in tents. 

Tension surfaced immediately--starting with control of the beds. Hospital
officials gave the researchers two of the best-maintained patient wards,
including much of the compound's coveted bed space, charity workers said. 

"Very, very sick people were outside who could have had a bed inside,"
except that researchers wanted the beds for the experiment, complained
Karin de Jonge, a Belgian nurse and the Kano field coordinator at the time
for the charity. 

Pfizer's test also drained away the most experienced Nigerian doctors and
nurses, she said. The paycheck was tempting: One lab technician said the
study, in effect, doubled her pay. 

"That made us very angry," de Jonge said. 

Hopkins called the Doctors Without Borders complaints "paranoid," saying
the charity wanted sole credit for taming the epidemic. "I wouldn't give my
dog" chloramphenicol, which he said had serious side effects. Hopkins also
said that Pfizer upgraded conditions at the camp. 

Pfizer said patient care was not "compromised" by the trial and that its
physicians, support staff and equipment "substantially improved" the level
of care. 

But Lodi, of Doctors Without Borders, described Pfizer's disruptions as so
serious that they alone may have contributed to patient deaths. 

"In an epidemic, where you have a very high number of cases who will die,
you don't go and experiment," added de Jonge. "You are talking about human
beings, after all." 

The Experiment Begins 

At first, the Pfizer researchers wanted only the most treatable children,
not those near death. But once confronted with the tumult of the epidemic,
any child who arrived at its wards was treated, Hopkins said. 

Over two weeks, the Pfizer researchers assumed care of 198 children, most
underweight and some only a few months old. The children were stricken with
various stages of bacterial meningitis, which can escalate rapidly from
fever to coma, convulsions, and death. 

The experiment's plan called for half of the patients to get Trovan, either
in a tablet, an oral solution or in an intravenous formulation that
bypassed the digestive tract. The other half of the patients would receive
an injection of the comparison antibiotic ceftriaxone, an effective
meningitis treatment already approved for American children. Unlike the
quinolones, ceftriaxone had never been associated with arthritis in lab
animals. 

Problems arose as soon as the experiment began. Children were supposed to
have their blood tested on arrival and again after five days. But that plan
was generally abandoned "due to the shortage of medical staff," according
to an internal Pfizer report on the experiment. 

Ceftriaxone was to be given by injection into a vein or muscle. But because
of the shortage of skilled workers, the report said, the drug was almost
always injected into the youngsters' buttocks or thighs to save time and
trouble. The shots were severely painful, leading to "great fear and
sometimes dangerous struggles with children," according to the report. 

To reduce the pain after initial injections, the report said, researchers
cut the volume of antibiotic given to children who were improving to
one-third of the recommended amount. Pfizer said available data indicated
the dose remained more than sufficient, but the drug's manufacturer,
Hoffmann-La Roche, said the reductions could have sapped the drug's
strength and skewed any comparison to Trovan. 

"A high dose is essential," Hoffmann-La Roche medical director Mark Kunkel
said, stressing that he had no independent knowledge of the experiment.
"Clinical failures . . . and perhaps deaths of children could have resulted
from the low dosing." 

Deaths in Kano 

Deaths were inevitable across the compound, regardless of who provided
care. In January 1996, the death rate in the Kano region peaked at about 20
percent, according to Doctors Without Borders statistics. The rate
plummeted as humanitarian groups airlifted in medicine, but by the end of
the outbreak an estimated 15,800 Africans had perished. 

In Pfizer's wards, the mortality rate was at least as low, if not lower,
than in the charity's wards, Hopkins said. The questions that surfaced
later focused on specific medical choices, especially the decision to use
an unapproved oral antibiotic on very young, very ill children. 

"It would never be used like that in the United States," Hopkins said. "The
standard is IV [intravenous] therapy." 

Pfizer Vice President Paul S. Miller defended the decision in a written
statement that he sent to a lawyer for Walterspiel, the former Pfizer
doctor. The oral formulation was safe, Miller argued. Nonetheless, he said,
the researchers had given critically ill Nigerian children antibiotic
injections instead of the oral drugs. Doctors also could halt or modify
treatment if the oral Trovan failed, he said. 

Pfizer's internal report on the experiment showed children did die shortly
after taking oral Trovan. 

On April 6, 1996, a 7-year-old boy whose facial muscles had ceased
functioning entered a Pfizer ward, the report said. Doctors labeled him
patient No. 0054 and, despite his paralysis, gave the 39-pound boy 50
milligrams of oral Trovan. 

Within nine hours, the report said, Patient 0054 was dead. 

It also happened with Patient 0069, the 10-year-old girl. She grew worse
over three days while taking no antibiotic except oral Trovan, confirmed
Dutse, the Nigerian doctor who led the Pfizer test. 

"Oh my God!" Urondu, the Kano physician, said after a reporter showed him
Pfizer records recounting the girl's death. "It was an experimental drug
for meningitis! You change--or even use two drugs, for God's sake!" 

Marc Gastellu-Etchegorry, a Doctors Without Borders official who has helped
evaluate drugs for use in developing countries, read the report at the
charity's Paris headquarters and shook his head. "This is a mistake," he
said. "When the patient is declining step-by-step, you try to give them a
fighting chance. It can look like a murder if you don't." 

McCracken, the meningitis specialist, said that when he helped Pfizer
conduct a subsequent experiment with injectable Trovan in the United
States, Africa and Latin America, he crafted written rules to protect
failing patients. 

"That wouldn't have happened in our study," McCracken said of Patient
0069's treatment. "Generally, if they don't improve over the first 48
hours, they are switched out." 

Robins, the Pfizer spokeswoman, said in a written statement that things
were different in the Nigerian epidemic, where 48 hours was "too early to
judge a response to therapy." The meningitis bacteria there had never
proven resistant to quinolone antibiotics, she added, so no one was
concerned the Trovan was not working. Robins also said that doctors gave
the girl intravenous fluids after 48 hours, which she said satisfied
industry guidelines that recommend changing a failing patient's
"therapeutic regimen." 

Pfizer also pointed out that the fatality rates in Nigeria were about equal
among the patients who received oral Trovan, Trovan by injection and the
comparison drug. 

Hopkins stressed that no child would have been given the oral formulation
unless he or she appeared well enough to swallow. Patient 0069 may have
appeared relatively stable, he speculated, and then suddenly worsened on
the third day, perhaps from complications set in motion before treatment
began. 

And yet, Dutse confirmed that he, like the physicians from the charity,
considered it necessary to modify treatment of failing children. "You can't
jeopardize a patient's life," he explained. Handed the report describing
Patient 0069's death, Dutse confirmed he had written it, then stared at it
silently. "I recollect this one," Dutse finally said. "She just died." 

Dutse read the report again and then shrugged. "I don't know what happened.
If a patient isn't doing well, you change the treatment. . . . 

"Why we didn't do that, I don't know." 

Missing Signatures 

In the United States, researchers are required to carefully apprise
patients of the risks of an experimental medicine. They describe its
purpose and explain alternative treatments. Then the patient, their parents
or an impartial witness must sign a written approval statement. 

In Nigeria, the researchers crafted a consent form approved by a Nigerian
committee, but most of the families streaming in from rural villages were
illiterate. The doctors used local nurses to talk to the families. Yet
neither the parents, the nurses nor any other witnesses signed the sheets,
the company said. 

Pfizer described the lapse as a procedural error but stressed in a written
statement that "verbal consent was obtained." 

Nonetheless, Hopkins and Dutse said that the nurses did not translate the
full consent form. 

"To be honest with you, it was a general explanation," Dutse said. "It is
very complicated for them. You explain to them it's a new medicine and you
have a right to say no." 

In many instances, Dutse recalled, parents scanned the American faces and
then begged him to make the decision. His reply: "That's the only thing to
do." 

"I take the responsibility at the end of the day," Dutse said. Given their
poverty and lack of access to decent medical care, "Honestly, did they have
a choice?" 

Urondu said the researchers should have stressed that there was an
alternative: Walk a few yards to a Doctors Without Borders tent. 

Today, it is impossible to ask the Nigerian families how much they
understood, Dutse said, because there is no way to locate "rural people
with no address." 

Lodi, the physician from Doctors Without Borders, said he believes they did
not comprehend what was happening. He said he treated some of the children
after Pfizer's researchers left. As he explained in an e-mail: "All those
patients and their families came back saying that they had never been
informed that they were used in experimentation with an unproved medicine." 

Yola, the Kano physician, stressed that such questions about consent would
never arise in America, where "they have everything to protect a patient
from a doctor." 

Side Effects 

Many American doctors remain leery of giving quinolone antibiotics to
children for fear they might develop arthritis. Some researchers have used
joint specialists and sophisticated electronic equipment to search for
damage during studies. 

The Kano medical camp had neither specialists nor expensive equipment--even
the hospital's X-ray machine was broken, Dutse said. 

As they arrived, 60 children showed signs of joint pain, a common result of
meningitis, according to the experiment's final report. Dutse worried that
the pain could mask swelling or erosion caused by Trovan. "Honestly, I was
very scared of that," Dutse said. "What if anything happened? I could not
forgive myself." 

Dutse inspected knees and ankles, hoping to discern any damage caused by
Trovan. His final report concluded that the antibiotic harmed none of the
children in this way. (The later Trovan experiment, which was only
partially completed, also found no evidence of joint damage.) 

Yet, Dutse said, "Did we miss some quinolone arthritis? It's possible." 

Statistics accompanying the experiment's final report showed that seven
children who took Trovan and seven who took the comparison drug had
full-blown arthritis. Fifteen children who took Trovan showed signs of
joint pain during the experiment, a rate three times that of children who
took the comparison drug. 

Hopkins called the statistics insignificant, and Pfizer said there is no
data to suggest that Trovan is associated with joint pain. But Hopkins said
the European Union later balked at marketing Trovan to children--in part
due to the Nigerian joint pain figures. 

Aftermath in Kano 

Pfizer's researchers departed Kano after treating victims for about two
weeks, leaving each child with a list of medications taken. Any child who
remained ill was transferred across town to a better-equipped hospital, the
company said. 

But Lodi contends that Doctors Without Borders assumed care of some of the
children and saw no medical records. The physicians could only guess how to
continue treatment, he said. 

Researchers asked the children to return in four to six weeks to ensure
they remained healthy and free of side-effects. Less than half showed up,
Dutse said. 

Although U.S. medical guidelines governing meningitis experiments recommend
long-term follow-ups, Pfizer's experiment called for no additional checks.
The company said medical literature supported a six-week follow-up period
for the type of meningitis in Kano and that it saw no unusual side effects
among the children who did return. 

The experiment's final report concluded that Trovan and the comparison drug
were equally safe and effective. It also disclosed that 45 children
received treatment deviating from the experiment's preapproved plan. 

Pfizer said the errors did not compromise patient care. 

Despite the problems, Dutse said he believes children benefited from
Pfizer's visit. But he also voiced concerns. If a corporate giant landed in
Kano again, Dutse said, he would want solid guarantees of continuing
assistance from the company. 

"In the future, we will have clear terms," Dutse said. "These things have
opened our eyes.. . . You are dealing with human beings, whether they are
American children or they are Nigerian children. They are entitled to the
best." 

Fallout and Failure 

By December 1996, Pfizer had tested oral and intravenous Trovan on 13,000
people in 27 countries. Late that month, the company applied to the FDA for
approval to market Trovan. 

Six months later, FDA inspectors traveled to Pfizer's Groton, Conn.,
research campus to examine documents from Nigeria. Sorting through raw
results recorded in Kano, inspectors discovered nearly four dozen
discrepancies. 

One document listed a child's white blood cell count as 68; another pegged
it at 680. Other records showed that some lab tests had been conducted in
Kano when they actually were done in Connecticut, the FDA said, and Pfizer
could not recall who recorded some of the data. 

Pfizer said any discrepancies noted by FDA "did not compromise the validity
of the trial or its conclusions." 

The FDA would not discuss why it never approved marketing Trovan for
children--such specifics are considered corporate secrets. But Pfizer said
that it withdrew its request to use the drug against "epidemic meningitis"
after regulators indicated they would deny it based on a range of
concerns--including the failure to conduct adequate follow-up exams. 

Nonetheless, the FDA authorized marketing Trovan for use against 14 adult
illnesses on Dec. 19, 1997. Later, the European Union approved Trovan but
specifically advised that "Trovan tablets . . . should not be given to
children." 

Pfizer sponsored a February 1998 launch meeting in Orlando. More than 1,800
sales people rhythmically chanted "Tro-van, Tro-van, Tro-van," a company
magazine recounted. The company emblazoned its annual report with a photo
of Hopkins and other Trovan team members. 

The drug quickly became one of the most prescribed antibiotic brands in the
United States. Pfizer reported that sales topped $ 160 million in Trovan's
first year and roughly 2.5 million adults had taken it by mid-1999. 

But just as suddenly, regulators announced bad news. During 16 months on
the market, there had been 140 reports of liver problems in Trovan
patients. At least 14 suffered liver failure and six died. 

Pfizer said no serious liver problems had surfaced in its experiments,
including the Nigeria tests. 

U.S. regulators advised doctors to restrict Trovan use to patients with
serious diseases whose need was great enough to outweigh the risks of liver
damage. European regulators suspended Trovan sales altogether. 

In the aftermath, at least 16 patients and family members have filed
lawsuits claiming liver injuries and one death. Pfizer aborted an
international pediatric meningitis experiment and told stockholders it had
suffered "a disappointment" with Trovan. 

Since then, Pfizer has acquired Warner-Lambert Co. to become the largest
drug maker in the world. Hopkins left Pfizer to become an independent
consultant. Dutse ascended to dean of the Kano medical school. Lodi now
works with refugees in Guinea. No one is quite sure what became of the
rural children in the experiment. 

And, as of last fall, Urondu remained at the Kano Infectious Disease
Hospital, working 70-hour weeks among the cholera victims laid low by the
latest epidemic to sweep across the arid plains of northern Nigeria. 

"I love this job; I work every day," Urondu explained recently while on
rounds. "They see you," he said of his emaciated patients, and "after God,
you are the next person." 

And as for Pfizer? Urondu smiled without humor. 

"They left before the party was over," he said. 

Why Go Overseas? 

Q: Who is conducting human drug experiments in the developing world? 

A: Major drug companies, small biotech firms, universities and the U.S.
government. 

Why do drug companies go to developing countries to do experiments? 

Drug companies can find large numbers of sick people on whom to test
unproven medicines. Experiments can be done cheaper and faster, and with
less red tape. People in developing countries sign up more readily because
they need access to health care. Altogether, that means less promising
drugs can be abandoned and profitable ones pursued sooner. 

Does that violate any U.S. law or regulation? 

No. The authority of U.S. regulators stops at the border. Regulators may,
however, question the test results if they are submitted as evidence a drug
is safe and effective enough to market to Americans. By that time, however,
the experiment may have been concluded for years and the test subjects
unavailable for interviews. 

How many human experiments do U.S. companies do in the developing world? 

Many drug companies refuse to say. While the percentage of experiments done
in the developing world remains small compared to that in the U.S. and
Europe, available statistics suggest that the number is increasing at a
much faster rate. 

How reliable are the results brought back to the United States? 

U.S. regulators say inspections in developing countries uncover more
problems with data integrity and informed consent than inspections in the
United States. 

Trovan's Troubled History 

Early Development 

A team led by Pfizer researcher Katherine Brighty synthesizes Trovan
(trovafloxacin) for the first time in a laboratory. A broad-spectrum
antibiotic, Trovan attacks bacteria responsible for a wide range of
illnesses. Pfizer eventually launches the biggest clinical trial program in
company history, encom-passing 13,000 patients in 87 studies in 27 countries. 

1996: Tests in Nigeria, 

Approval Request 

April 3 to May 15: Pfizer researchers conduct human experiment in Kano,
Nigeria, to compare the drug to another antibiotic in treating 200 children
with bacterial meningitis. Researchers say the trial is a success. 

Dec. 30: Pfizer files for approval to sell Trovan in the U.S. for a variety
of infections. 

1997: Inspection, 

FDA Approval 

June: FDA inspects Pfizer's files on the Nigerian Trovan experi-ment, later
cites numerous record-keeping deficiencies. 

October: Pfizer withdraws FDA application for use of Trovan to fight
bacterial meningitis in children in an epidemic. 

Dec. 18: Pfizer physician Juan Walterspiel sends letter to Pfizer's
chairman, alleging unethical practices in the Nigerian experiment. 

Dec. 19: FDA approves Trovan for combating 14 bacterial infections in
adults. Human experiments for other possible Trovan uses continue. 

1998: Sales Launch, 

A Death Reported 

February: Pfizer sponsors a launch meeting for Trovan in Orlando. The drug
quickly becomes one of the most prescribed antibiotic brands in the United
States. Pfizer reports sales top $ 160 million in Trovan's first year; 2.5
million prescriptions are written by mid-1999. 

Also that month, Pfizer responds that after an extensive review of the
Nigeria experiment, Walterspiel's claims determined unfounded. Walterspiel
terminated. 

May 15: Walterspiel sues Pfizer, claiming he was fired for raising ethical
questions about the Nigeria experiment. Pfizer denies claim; suit later
dropped. 

July 3: The European Union approves sale of Trovan for adults. 

September: FDA approves adding wording to Trovan labels in the United
States that note that liver abnormalities and hepatitis have occurred in
Trovan patients, and that "liver failure . . . has also been reported
rarely." 

Dec. 1: FDA receives report of the death of a Trovan patient that the
agency says is associated with liver injury. 

1999: Call for Ban, 

New Restrictions 

May: Pfizer warns European doctors that 140 Trovan patients have suffered
liver damage. 

June 3: The non-profit group Public Citizen asks the FDA to ban Trovan,
arguing liver problems surfaced in animal and human experiments even before
it was approved for sale. 

June 9: FDA advises that Trovan's use be restricted to patients with
serious diseases in institutional settings. Agency reports more than 100
cases of liver damage among Trovan patients, including six deaths. Pfizer
later suspends pediatric experiments. 

July 6: Lawsuit filed against Pfizer in South Carolina on behalf of Trovan
patient. Other suits follow in Illinois and New York. Cases pending. 

About This Series 

Today: Nigeria 

In sub-Saharan Africa, an American pharmaceutical giant tests an unapproved
drug on desperately ill children in an epidemic. The experiment illustrates
a booming, poorly regulated system of international drug testing that far
too often betrays its promises to patients and consumers. 

Monday: Regulation 

The global boom in overseas drug testing means some of the newest drugs
coming to U.S. consumers are tested far from the scrutiny of Food and Drug
Administration investigators in countries that may have few inspectors and
little history of examining drugs for safety and effectiveness. 

Tuesday: Informed Consent 

Testing in far-flung countries has weakened basic protections for naive,
impoverished or uneducated human subjects who try experimental drugs
because they are desperate for medical treatment. 

Wednesday: China 

A massive blood harvest among Chinese peasants yields precious genetic
material that means millions for a U.S. company and Harvard University. But
the impoverished participants say they didn't get what they were promised. 

Thursday: Latin America 

The dramatic increase in huge drug trials has left domestic and U.S.
regulators struggling to keep up. It also has left open the possibilities
for mistakes, mismanagement and outright fraud. 

Friday: Thailand 

Staggering under an HIV epidemic, Thailand opens itself to experiments by
foreign researchers. But what do the Thai people have to risk and what do
they get in return? 

Contributors 

"The Body Hunters" is the result of an 11-month reporting effort on five
continents led by reporters Joe Stephens, Deborah Nelson and Mary Pat
Flaherty of The Washington Post's investigative staff. 

In addition to reporting from Washington and other U.S. locations, Stephens
visited test sites in Nigeria and Bulgaria, Nelson reported from Hong Kong
and Costa Rica and Flaherty traveled to Thailand and Hungary. Other
reporting was provided by associate editor Karen DeYoung in Costa Rica and
Argentina, and staff correspondents John Pomfret in China, Sharon
LaFraniere in Estonia, Russia and Switzerland, and Doug Struck in Thailand.
Reporters Joby Warrick and David Ottaway also contributed from Washington.
Photography was provided by staffers Michael Williamson in Nigeria, Lois
Raimondo in Thailand, Carol Guzy in Hungary and Michael Robinson-Chavez in
Costa Rica. Researchers Alice Crites, Robert Thomason and Lynn Davis also
contributed. Sarah Cohen provided data analysis. 



Louis Proyect
Marxism mailing list: http://www.marxmail.org/

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