The drug development process is long, risky, and expensive. It can take 10 years and cost in excess of $500 million to develop a new drug. Moreover, between 80 and 90 percent of drug candidates fail in clinical trials. Pharmaceutical companies rely upon a handful of successes to pay for their failures. Among the most successful of the world?s pharmaceutical companies in New York?
based Pfizer. Given the risks and costs of developing a new drug, pharmaceutical companies will jump at opportunities to reduce them, and Pfizer thought it saw one.
Pfizer had been developing a novel antibiotic, Trovan, that was proving to be useful in treating a wide range of bacterial infections. Wall Street analysts were predicting that Trovan could be a blockbuster, one of a handful of drugs capable of generating sales of more than $1 billion a year. In 1996, Pfizer was pushing to submit data on Trovan?s efficacy to the Food and Drug Administration (FDA) for review. A favorable review would allow Pfizer to sell the drug in the United States, the world?s largest market. Pfizer wanted the drug to be approved for both adults and children, but it was having trouble finding sufficient numbers of sick children in the United States to test the drug on. Then a researcher at Pfizer read about an emerging epidemic of bacterial meningitis in Kano, Nigeria. This seemed like a quick way to test the drug on a large number of sick children.
Within weeks a team of six doctors had flown to Kano and were administering the drug, in oral form, to children with meningitis. Desperate for help, Nigerian authorities gave the go-ahead for Pfizer to give the drug to children (the epidemic would ultimately kill nearly 16,000 people).
Over the next few weeks, Pfizer treated 198 children. The protocol called for half the patients to get Trovan and half to get a comparison antibiotic already approved for the treatment of children. After a few weeks, the Pfizer team left, the experiment complete. Trovan seemed to be about as effective and safe as the already approved antibiotic.
The data from the trial were put into a package with data from other trials of Trovan and delivered to the FDA.
Questions were soon raised about the nature of Pfizer?s experiment. Allegations charged that the Pfizer team kept children on Trovan, even after they failed to show a response to the drug, instead of switching them quickly to another drug. The result, according to critics, was that some children died who might have been saved had they been taken off Trovan sooner. Questions were also raised about the safety of the oral formulation of Trovan, which some doctors feared might lead to arthritis in children. Fifteen children who took Trovan showed signs of joint pain during the experiment, three times the rate of children taking the other antibiotic. Then there were questions about consent. The FDA requires that patient (or parent) consent be given before patients are enrolled in clinical trials, no matter where in the world the trials are conducted. Critics argue that in the rush to get the trial established in Nigeria, Pfizer did not follow proper procedures, and that many parents of the infected children did not know their children were participating in a trial for an experimental drug. Many of the parents were illiterate, could not read the consent forms, and had to rely upon the questionable translation of the Nigerian nursing staff. Pfizer rejected these charges and contends that it did nothing wrong.
The FDA approved Trovan for use in adults in 1997, but it has not approved the drug for use in children. Trovan was launched in 1998, and by 1999 there were reports that up to 140 patients in Europe had suffered liver damage after taking Trovan. The FDA subsequently restricted the use of Trovan to those cases where the benefits of treatment outweighed the risk of liver damage. European regulators banned sales of the drug. 29 ?What are the different phases that a Drug Company goes through in order to bring a new drug product to market in the U.S. and Europe?
?Did Pfizer behave unethically by rushing to take advantage of an epidemic in Nigeria to test experimental drugs on children?
?Should it have been less opportunistic and proceeded more carefully?
?Were corners cut with regard to patient consent in the rush to establish a trial?
?Did doctors keep patients on Trovan too long when they should have switched them to another medication?
?Is it ethical to test experimental drugs on children in a crisis setting in the developing world where the overall standard of health care is so much lower than in the developed world and proper protocols might not be followed?
