Question

TESTING DRUGS IN THE DEVELOPING WORLD

The drug development process is long, risky, and expensive. It can take ten 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 is New York–based Pfizer. Developing a new drug involves risks and costs, and pharmaceutical companies will jump at opportunities to reduce both; in 1996 Pfizer thought it saw one such opportunity.

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 favourable 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 on whom to test the drug. Then, in early 1996, 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 had given 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. Critics alleged 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.

Trovan was approved by the FDA for use in adults in 1997, but it was never approved for use in children. Launched in 1998, by 1999 there were reports that up to 140 patients in Europe 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. In 2003, two dozen Nigerian families sued Pfizer in a federal court in New York. The families claim their children either died or were injured because Pfizer did not adequately inform them of the risks and alternatives for treatment with Trovan. The case was ultimately settled out of court.

Did Pfizer behave unethically by rushing to take advantage of an epidemic in Nigeria to test an experimental drug 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? And did doctors keep patients on Trovan too long, when they should have switched them to another medication? Is it ethical to test an experimental drug 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? These questions are all raised by the Pfizer case, and they remain unanswered, by the company at least.

Questions

1. 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. Sometimes such consent cannot be easily obtained due to language barriers or literacy problems (meaning the parents can't read and/or sign consent). Should the trials proceed anyway if there is a chance of benefit to the children?

2. If it is true that between 80 and 90 percent of drug candidates fail in clinical trials, should we wait until advances in the “technological environment” remove the need for human testing trials, even if thousands could die from treatable diseases in the meantime?

Answer 1

1. No, the trials should not proceed until and unless a consent of the patient has been taken into consideration. Whatever the language barriers might be, obtaining consent of the patient is necessary. The patient should be communicated about the trials, the components and side-affects of the drug. Even if the drug may or may not benefit the children in the future, the company conducting the trials may face ethical and legal issues.

2. According to my opinion, even if drug candidates fail in the clinical trials, it is necessary to keep on conducting trials till it is successful as waiting for change in technological environment may take a very long time, which might cause loss of life of many people.