Recent clinical trial deaths suggest imbalances
Troubles point to assessment problems
There have been some high-profile deaths of research participants in the past decade that have led to federal scrutiny of IRBs and their roles in protecting human research subjects. Some of the studies in which people died clearly show some problems with informed consent and an assessment of potential risks and possible benefits. Here’s a thumbnail sketch of some of these cases:
• Tony LaMadrid: According to testimony given Sept. 18, 1997, at a meeting of the human subjects subcommittee of the National Bioethics Advisory Commission of Silver Spring, MD, LaMadrid died in 1991 after jumping off an engineering building. LaMadrid had been a participant in a schizophrenia research project at the University of California-Los Angeles (UCLA) in which a large percentage of participants suffered worsened symptoms a year into the study. A father to another participant in the UCLA schizophrenia study testified that his own son lost intellectual functioning and became violent during participation in the same study. These negative outcomes were never discussed or revealed by researchers. "The researchers told us at that time that Greg might not even have to take antipsychotics medication, and it was recommended that he participate in the crossover and withdrawal protocol," testified Robert Aller, the father of research participant Gregory Aller. Aller further stated that the study’s consent forms were ambiguous, misleading, and contained no ranking or assessment of risks.
• Kathryn Hamilton: 48-year-old Hamilton chose to participate in a clinical trial, called Protocol 681, involving an experimental drug that she had hoped would help her survive a recurrence of breast cancer. The research was conducted at the Fred Hutchinson Cancer Research Center in Seattle. However, in 1993, Hamilton became one of four study participants who died from the high-dose experimental treatment, according to media reports. Hamilton’s family told reporters that she had never been given adequate informed consent, including information regarding a change in how the drug was to be administered and disclosure that the drug already had caused one woman’s death.
• Gage Stevens: A 3-month-old infant suffering from reflux, Stevens was enrolled in a clinical trial for Propulsid, a heartburn medicine that had only been approved for adults and had already been linked to heart problems and adult deaths. After being given Propulsid for four months, Gage died in 1999, according to media reports. The physician who encouraged the baby’s parents to enroll him in the Propulsid study did not disclose the potential risks or the deaths associated with the drug, and the consent form erroneously said the drug had been approved for use in infants, according to news articles. Hundreds of people have died from heart problems associated with Propulsid use, and the drug has been taken off the market.
• Jesse Gelsinger: Suffering from a rare genetic defect in the liver, ornithine transcarbamylase disorder, Gelsinger was enrolled in an experimental gene therapy at the University of Pennsylvania in Philadelphia. Gelsinger had not expected to receive any personal benefit from the therapy, but he volunteered so that future babies might receive a cure. The therapy resulted in the 18-year-old’s death following a coma in 1999, according to news reports. Gelsinger’s parents say the young man had not been adequately informed of the health risks and that he had not been told of two previous volunteers who suffered from temporary liver toxicity, news reports say.
• Ellen Roche: A healthy volunteer in a Johns Hopkins University research study of asthma, Roche died in 2001 as a result of her research participation, according to a public statement by Edward D. Miller, MD, of Johns Hopkins. A July 19, 2001, letter addressed to Baltimore-based Johns Hopkins, by the Office for Human Research Protections (OHRP), states that the study had used a toxic chemical called hexamethonium that is not approved by the Food and Drug Administration for use in humans and that the IRB did not ask investigators for any information about the pharmacology and toxicity of the inhaled hexamethonium. The OHRP letter also says that investigators changed the research protocol without obtaining IRB approval and that the informed consent document, which was approved by the IRB, failed to adequately describe the research procedures. The informed consent even referred to hexamethonium as a medication, and the consent document did not adequately describe the research risks.
• Nicole Wan: A University of Rochester in New York student, Wan volunteered to participate in a research project that involved performing bronchoscopy on healthy individuals, according to a report from the State of New York Department of Health in Albany. Wan died two days after the bronchoscopy from lidocaine toxicity, and blood level tests taken at the time she was brought into the emergency room indicated that she apparently had received four times the amount of lidocaine during the procedure than the maximum dosages established in previous research protocols, the New York Department of Health states. In addition, the research protocol had no mechanism in place to limit the amount of lidocaine available during the procedure, and there was no documentation of the amount of lidocaine administered, all suggesting that IRBs should take an active role in ensuring researcher compliance with regulations and laws involving human subject protection, the report says.
Some high-profile deaths of research participants in the past decade have led to federal scrutiny of IRBs and their roles in protecting human research subjects. Heres a thumbnail sketch of some of these cases.
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