Drug Companies' Tests in Poor Countries Raise Ethical Questions

Joe Stephens Washington Post Service

Monday, December 18, 2000

Some Risky Experiments Are Done With Little Oversight

KANO, Nigeria By the time word of the little girl's death reached the United States, her name had been replaced by numerals: No. 6587-0069.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 (18.6 kilograms). 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, Medecins Sans Frontieres, 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 could not 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 n Experiment No. 154-149. They gave her 56 milligrams of Trovan. A day later, the girl's strength was evaporat- ing, 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 alternative 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 U.S. 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 Food and Drug Administration 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 lifesaving 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 government backing.

"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."

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

Dr. George McCracken, a Texas pediatrician and leading meningitis specialist who co-authored the guidelines, said he was surprised that 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 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 that its practices were validated - especially given the horrendous conditions it found - by the number of children who showed improvement and by a fatality rate of about 6 percent, which compares favorably with 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 her on the test drug for too long as her health declined. Generally, if 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 fee 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 Medecins Sans Frontieres 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.

Dr. Yola 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 that 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 Dr. Lodi, who watched the experiment unfold from across the compound, "I would take away their medical licenses."