The Future of Medical Trials in America
Bioethics Legal Review
July 2005
By Maureen Milford
Four years have passed since the landmark Gelsinger case, in which attorney/modern-day crusader Alan Milstein of Sherman, Silverstein, Kohl, Rose & Podolsky, Pennsauken, NJ (and a member of this newsletter's Board of
Editors) successfully brought suit on behalf of the family of Jesse Gelsinger, who died during a gene-therapy experiment at the University of Pennsylvania. From that point on, it became a brave new world. According to William Hirschborn, director of the office of Clinical Trials at Temple University School of Medicine in Philadelphia, who commented at the time: "Milstein opened the door for doctors to be held accountable." The Case According to the suit, the facts are these: On Sept. 17, 1999, 18-year-old Jesse Gelsinger died while participating in a gene transfer experiment at the Institute for Human Gene Therapy (IHGT) located at the University of Pennsylvania. At the time of his death, Gelsinger suffered from a mild form of ornithine transcarbamylase deficiency (OTC), a rare metabolic disorder, which was controlled with a low-protein diet and drugs. He volunteered to participate in the experiment, knowing it would not benefit his own condition, because he was led to believe his participation held little risk and would directly benefit yet-to-be-born infants with OTC. While at IHGT, Gelsinger was infused with trillions of particles of an adenovirus vector, which was developed at the University for the purpose of transferring OTC genes. According to the suit, the vector was known to be more toxic than other vectors used in gene transfer. After receiving the vector, Gelsinger suffered a chain reaction including jaundice, a blood-clotting disorder, kidney failure, lung failure and brain death. Milstein's suit declared that Gelsinger died as a direct result of the carelessness, negligence, recklessness and wanton and willful conduct of defendants. The University of Pennsylvania reached an out-of-court settlement with the Gelsinger family, the amount of which was not disclosed. A subsequent investigation by the FDA found numerous breaches of federal research rules, in addition to an apparent financial conflicts of interest through which one of the principal investigators, stood to profit from the experiment through a biotechnology company he had founded. Protocols and Controversy Much of the controversy surrounding clinical trials today involves informed consent. Volunteers for experiments are supposed to be informed of the risks of the drug or procedure, including whether those risks are significant -- for instance, whether there is a 1 in 100 chance or 1 in 10,000 chance of a so-called adverse event, such as injury or death. Critics, Milstein very vocal among them, say that the informed consent forms are, at best, dense and written in clinical language. At worse, the informed consent process can be fraudulent or misleading, critics say. In the past several years, federal regulators have restricted or shut down research at 20 institutions for violations of rules designed to protect participants. According to The New America Foundation, "The crackdown has come at a time when funding for biomedical research has been skyrocketing, many more clinical trials are being conducted and an already-weak oversight system of institutional review boards (IRBs) has been staggering from the strain of too much work." And Milstein is on the front lines. In the past 2 years, he has filed three major lawsuits against university-affiliated research centers. These include a suit against the Fred Hutchinson Cancer Research Center in Seattle, a world-renowned cancer institute affiliated with the University of Washington; a class-action suit filed jointly with Oklahoma lawyer Robert Seacat against the University of Oklahoma for experiments with a melanoma vaccine; a recent suit on behalf of soldiers ordered to be inoculated with anthrax vaccine; and more. He is also greatly concerned about medication given for ADHD, ADD and related behavioral disorders in children. The Suits Milstein's lawsuits are garnering a lot of attention because, historically, suits involving human experiments tended to be brought as malpractice cases, which stayed off the public's radar screen. What's more, critics say, before these lawsuits, there had been widespread under-reporting of adverse events.
The novel claims in Milstein's lawsuits build on theories that have been evolving for more than 30 years and center on U.S. and international standards covering the rights of people who are the subjects of scientific experiments. According to Milstein, the right to be free from unethical experimentation is guaranteed by the Fourteenth Amendment, which states, "nor shall any State deprive any person of life, liberty, or property, without due process of law." The new generation of experimentation litigants raises the claims that volunteers' rights to dignity include the right to be told the risks and benefits of an experiment; the right to an ethical experiment in which the benefits outweightthe risks; the right to be fully apprised of conflicts of interest (including financial stakes); and the right to be assured that the research is valid and valuable. International standards, including the 12949 Nuremberg code, a response to Nazi medical experiments, also set forth basic human dignity principles, the lawsuits say. The suits also draw on the so-called common rule, a common set of regulations for about 20 federal agencies that governs human subject protection in research. Bioethicists Caught in the Net Many are concerned because Milstein has included as defendants in his lawsuits bioethicists as well as members of institutional review boards, the volunteers charged with reviewing and approving clinical trials. "It's terrifying," said Arthur Caplan at the time he was a defendant in Gelsinger. "This is not a good trend be-cause reserrch can prove risky no matter how careful you are in reviewing or monitoring it." Caplan was later dropped from the suit, but not before it cost him about $10,000 in legal fees, he said. Milstein also filed a wrongful-death suit against the chief bioethicist at the University of Oklahoma Health Scien-ces Center in Tulsa, mentioned above, claiming that patients' constitutional rights were violated during experiments for a melanoma vaccine (Robertson v. McGee).
Maureen Milford is a reporter for The National Law Journal, a sister publication of this newsletter. Look for articles by Alan Milstein, a member of this newsletter's Board of Editors, in upcoming issues.
