In 1998, 24 critically ill patients died after being given a blood substitute without their informed consent. The FDA had recently granted approval for companies to conduct clinical trials without informed consent for certain emergency room products. Baxter Healthcare Association was trying to glean data for their product, HemAssist, but when results showed more patients died in the HemAssist group than in the group receiving donated blood, the company stopped the trial.
In September 1999, 18-year-old Jesse Gelsinger died after undergoing experimental gene therapy treatment at the University of Pennsylvania. Gelsinger had suffered from a rare liver disorder, but had been relatively healthy before undergoing the test trial. His father claimed the researchers failed to reveal all the risks involved in the procedure.
"I encouraged my son to do this," Paul Gelsinger told a Senate Subcommittee on Feb. 2., 2000. "But I wasn't given all the information."
And last June, Ellen Roche, a healthy 24-year-old woman, died after inhaling a drug known as hexamethonium for a drug trial at Johns Hopkins University. An investigation later revealed the consent form Roche had signed didn't mention that the drug had never been approved for inhalation.
Children and Trials
Wolpe explains doctors on IRB's are often underpaid and under qualified to make sound judgments. Since drug trials often involve very specialized fields of medicine, risks can be overlooked during assessment.
Woodward is particularly concerned about children in drug trials. She points out a 1997 FDA mandate encourages drug companies to test their products on children. The mandate rewards companies that do so by extending their patent on a drug by another six months — a term that can be highly profitable for companies selling a popular product.
"It's a very dicey issue because you're dealing with people who cannot really give their informed consent," said Woodward.
But researchers counter that parents are very capable of making such delicate decisions for their children and that review boards pay extra attention to safety when considering tests on children.
"The parents are made sure they understand all the possible benefits and risks and are encouraged to ask questions," said Laurence Greenhill of the New York Psychiatric Institute. Greenhill is principal investigator for a clinical trial testing the use of the psychiatric drug, Ritalin, in pre-schoolers.
Greenhill adds that if clinical trials do not include children, then doctors will never have access to research to guide their treatment of juveniles.
Money and Judgment
One skewing factor in the clinical trial system, Wolpe argues, is money. He's concerned that healthy people like Roche might overlook the risks involved in a particular experiment if the pay is high enough. Helms is clear that pay is a main factor when considering which trials to enter — he won't work for less than $150 a day.
"The IRBs determine at what point are you using money to defeat people's better judgment," said Wolpe.
Money might also compromise doctors' judgments, he says. Drug companies often pay doctors for every new patient they recruit to undergo drug trials.
But John Plachetka, president and CEO of Pozen, a Pharmaceutical Development Company based in Durham, N.C., claims this pay is only designed to cover the costs a doctor adopts when entering a patient in a trial.