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.
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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.
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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.
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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.
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