Wednesday, September 17, 2008

Why cost benefit analysis will always be unacceptable

A rotavirus vaccine is developed and the vaccine goes to clinical trials. (Full details here - preview only.)

In 1991 the Food and Drug Administration granted the pharmaceutical company Wyeth Ayest (later Wyeth Pharmaceuticals) permission to make and test this vaccine, which they named RotaShield. Over the next five years it launched large-scale clinical trials in the U.S., Finland and Venezuela, verifying RotaShield's safety, ability to induce a protective immune response and lasting efficacy. ... Over the next nine months months more than 600,000 children received an estimated 1.2 million does of RotaShield. ...

The disaster struck. In 1999 several infants suffered a serious complication within two weeks of receiving the vaccine: a segment of the intestine folded into a nearby region (like part of a telescope collapses into another), creating a blockage called intussusception. The condition can be excruciatingly painful and must be quickly reversed with either an air or fluid enema or fixed surgically. In rare cases, the intestine perforates and the infant dies. The CDC, which was monitoring experience with RotaShield, called for an immediate halt to the immunization program, thereby sinking a vaccine that had taken 15 years and several hundred million dollars to launch.

The agency initially estimated the risk to be one intussusception in 2,500 vaccine recipients, which was considered unacceptable. Later studies pegged the probability at only one in 11,000. Then Lone Simonsen of the NIH correlated risk with age: infants younger than three months were in less danger than older ones. If the vaccine were given only to young babies, the likelihood of intussusception could drop 10-fold to perhaps one in 30,000.

The new data raised new questions. Was this risk acceptable in the U.S., where children are often hospitalized but rarely die of rotavirus? Were the odds more palatable in the developing world, where one child in 200 dies of rotavirus? If 150 lives could be saved for each complication from intussusception, might the risk be justified? Given these statistics, was it unethical, in fact, to withhold a vaccine that might save half a million lives a year? Or no matter what the risk-benefit analysis showed, was it unethical to market a vaccine in the developing world that had been withdrawn from use in the U.S.?

The CDC and the WHO called a meeting of policymakers from developing countries. After heated discussion, science bowed to politics. As a high-ranking Indian official said, "I know this vaccine would save 100,000 children in my country. But when the first case of intestinal blockage occurred, I would not be forgiven for allowing a vaccine that had been withdrawn in the United States to be used in my country."

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