Lawsuits Attack Medical Trials
As claims arise, some fear tests will lose public support
By Maureen Milford, The National Law Journal August 20, 2001
Less than a year has passed since Alan C. Milstein brought a suit on behalf of the family of Jesse Gelsinger, symbolically filing on the anniversary of the 18-year-old's death during a gene-therapy experiment at the University of Pennsylvania.
From that point on -- for Milstein and the clinical research community -- it became a brave new world. The Gelsinger case took Milstein, of Sherman, Silverstein, Kohl, Rose & Podolsky in Moorestown, N.J., from handling low-profile insurance cases to leading a highly visible crusade for a new constitutional right guaranteeing dignity in human experimentation.
"This is the first time in my career that it's not just about money," says Milstein, 47. "It's about changing a system that has gone terribly wrong."
Milstein is pursuing his cause through the courts, bringing (or consulting on) half a dozen lawsuits against big-name medical research institutions during the past year. Recently, he filed two wrongful-death suits against the prestigious Fred Hutchinson Cancer Research Center in Seattle, for clinical trials involving treatments for leukemia and breast cancer.
"This is something that never happened before," says William Hirschhorn, director of the Office of Clinical Trials at Temple University School of Medicine in Philadelphia. "Lawyers for the first time are seeing a lot of problems. Milstein opened the door for doctors to be held accountable."
Every year, at least 100,000 new volunteers enroll in clinical trials. At any given time, about at least 14,000 such trials are being conducted on humans at research institutions, universities and hospitals.
The experiments administered by physicians and other clinical investigators usually involve new drugs, devices and surgical procedures. Sometimes they involve new applications of existing drugs.
Experiments can be therapeutic -- that is, they are conducted on people who are suffering from an illness -- or nontherapeutic -- in which case the volunteers are healthy. In a "challenge study," researchers examine the physiological effects on the body by the introduction of a foreign substance.Experiments Vary
The protocols for an experiment can vary. Many people are familiar with the practice of giving one group a drug and another a placebo, but in reality, placebo trials are rarely undertaken today, Milstein says. In some cases, placebo trials are considered unethical if an existing therapy is known to work.
The experiments can be sponsored by private-sector pharmaceutical companies or public institutions, such as the National Institutes of Health and the Veterans Administration. Nonprofit health organizations, such as cancer foundations, also sponsor such research.
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 one in 1,000 chance or a one in 10,000 chance of a so-called adverse event, such as injury or death. Critics, Milstein among them, say that the informed consent forms are, at best, dense and written in clinical language. At worst, the informed consent process can be fraudulent, critics say.Source of Theories
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, there has been widespread underreporting 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 14th Amendment, which states, that "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 outweigh the 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 1949 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.
None of Milstein's cases has gone to trial, but the suits have sent shudders through the biomedical community. For instance, Gelsinger v. University of Pennsylvania, No. 1885, in state court in Philadelphia, was settled confidentially only a month after the complaint was filed.
"Alan has really hit a nerve," says Kendra L. Dimond, a partner at Arent Fox Kintner Plotkin & Kahn in Washington, D.C., who represents institutions and researchers. "I've been receiving a lot phone calls from institutions about what's going to happen next" with the Hutchinson case in Seattle, she says.
The litigation comes as public confidence in clinical trials has been shaken, Surgeon General David Satcher told the National Human Research Protections Advisory Committee in April, according to a report in the Seattle Times.Fueling Debate
In June, Ellen Roche, a healthy 24-year-old, died during an asthma study at Johns Hopkins University in Baltimore. Such events have prompted a debate over the role of litigation in human experimentation.
"I think there should be 100 more of the lawsuits," says Adil Shamoo, a professor at the University of Maryland School of Medicine and a member of the Department of Health and Human Services' National Human Research Protection Advisory Committee. "The law community has really been delinquent -- it's been way behind because lawyers don't understand" clinical trials.
Meanwhile, the volume of human experiments has grown enormously in the past 20 years, with about 48,000 clinical researchers practicing today.
Some experts in the biomedical field believe the litigation will have a chilling effect on research that benefits humankind through scientific advancement. They also worry that volunteers will dry up.Wide Net
Experts are also 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," says Arthur Caplan, who heads the Center for Bioethics at Penn and was a defendant in Gelsinger. "This is not a good trend because research 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 says.
Milstein also filed a wrongful-death suit against the chief bioethicist at the University of Oklahoma Health Sciences Center in Tulsa, claiming that patients' constitutional rights were violated during experiments for a melanoma vaccine. Robertson v. McGee, No. 10-CV00 GOH.
Jonathan Moreno, director of the Center for Biomedical Ethics at the University of Virginia, says this type of litigation could stifle academic freedom at a time when bioethical scholarship is most needed.
COURT TEST AHEAD But other lawyers say it's still too soon to sound the alarm because Milstein's dignity claims have yet to be tested in court.
"He hasn't won anything," says Leonard H. Glants, a law professor Boston University's School of Public Health. "I would love to see one of the cases go to trial. I can't imagine a judge agreeing with him on a constitutional basis. I mean, these are private [research] organizations."
Lawyers watching from the sidelines believe that the Hutchinson cases, both in federal court in Seattle, are likely to go to trial. One case, Berman v. Fred Hutchinson Cancer Research Center, No. C01-O727 R, involves a clinical trial in which at least four women died after being treated with a drug to protect them against the effects of high-dose chemotherapy. The other, a proposed class action, Wright v. The Fred Hutchinson Cancer Research Center, No. C01-5217 L, involves an experimental treatment in which at least 20 leukemia patients died.
"The Hutchinson Center believes that its physicians acted correctly and out of the interest of patients. We intend to establish that at trial," says Joseph M. Hassett of Hogan & Hartson in Washington, D.C.
Because Wright potentially involves dozens of plaintiffs and at least 32 physicians who will need to be deposed, lawyers predict that it will be a long and costly action.Motion Pending
Meanwhile, Milstein is optimistic that the judge in the Robertson case in Oklahoma will deny a defense motion to dismiss and award his client a big victory by affirming, for the first time, that the dignity of volunteers in a medical experiment is protected by the Constitution.
"These are embryonic theories ... Alan is doing good work in further advancing them," says Stephen F. Hanlon, a partner in the Tallahassee, Fla., office of Holland & Knight, who raised the human dignity issue in a case in which high-risk pregnant women were experimented on without their consent. The case settled last year for $3.8 million.
As lawmakers begin to take a closer look at human experimentation, critics say not enough has been done. A hearing called by Senator Edward M. Kennedy, D-Mass., before the Health, Education, Labor and Pension committee in September will look at strengthening oversight and regulation of clinical trials. Kennedy has yet to introduce legislation, but many believe litigation will be an important precursor of future public policy.
"The best way to change the regulations is to get lawsuits," says Abbey Meyers, president of the National Organization for Rare Disorders. "There is no penalty now."