Lawsuits over clinical trials have doctors wary, but not quitting research yet

Although the potential for high awards in recent litigation has heightened attention to the clinical trials process, the long-term effect on medical research is unclear.

By Vida Foubister, amednews staff. April 16, 2001.

Alan Milstein is quickly becoming a household name among physicians involved in medical research.

In less than seven months, the Pennsauken, N.J.-based lawyer has filed three lawsuits on behalf of clinical trial participants that name physician investigators as defendants.

Case at a glance
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His most recent target is the Fred Hutchinson Cancer Research Center in Seattle. Two previous cases were filed against the University of Oklahoma Health Sciences Center in Tulsa and the University of Pennsylvania in Philadelphia. And he told AMNews that more cases will follow.

"I'm hoping to achieve a focus on the [oversight] system that's in place now that's not working," he said.

Milstein believes that neither institutional review boards nor the federal Office for Human Research Protections are doing an adequate job of protecting human subjects. Instead, the ethical nature and safety of clinical trials "depends solely" on the doctors and scientists who conduct them.

"In our major institutions, where you've got Nobel scientists and Nobel doctors and well-regarded professors, the IRBs more or less simply rubber-stamp whatever protocol one of these men put before them," he said.

More lawsuits that name physician investigators as defendants are expected.

To many involved in medical research, Milstein's statements smack of a "plaintiff's lawyer looking for business."

"I'm not saying the system is perfect," said David Korn, MD, senior vice president for biomedical and health sciences research at the Assn. of American Medical Colleges. "But there's an extraordinary degree of oversight right now and great scrutiny of what you're going to do and how you're going to do it."

So much scrutiny, in fact, that it has dissuaded many physicians from pursuing research. "There's not enough clinical investigators going into the field," Dr. Korn said.

The three lawsuits filed by Milstein have raised considerable attention in research circles.

But Philip Reilly, MD, CEO of Interleukin Genetics Inc. in Waltham, Mass., does not believe they've yet had a chilling effect on research.

"Patient groups that are hungry for a cure understand there are risks associated with clinical trials," he said.

Instead, these lawsuits pose a threat to the human subjects protection system because they are another "disincentive to serve as an IRB member," said Robert J. Levine, MD, professor of medicine at Yale University in New Haven, Conn. Other disincentives include the high-profile shutdowns at several research institutions and recent government reports critical of IRBs.

So far, only one case has been resolved. The lawsuit brought in September 2000 on behalf of the family of Jesse Gelsinger -- the teenager who died in a gene therapy experiment at Penn -- was settled out of court.

Although there is a tendency to assume that a settlement represents an admission of wrongdoing, that's not always the case.

"The fact that people settled typically is an acknowledgement that it costs them more to defend the suit than the settlement demands," Dr. Levine said.

However, Ernest Prentice, PhD, associate vice chancellor for regulatory compliance and co-chair of the IRB at the University of Nebraska Medical Center in Omaha, believes that the damages could be significant if these cases do come to trial.

"Any time you bring a malpractice lawsuit in the context of clinical research, juries are going to be much more sympathetic than they would be in a traditional malpractice case," Dr. Prentice said. "They expect experiments to be conducted at a much higher standard."

Even so, insurance coverage isn't expected to become a significant issue. Physician investigators engaged in research are typically covered both by their institution's insurance policy and their individual liability insurance, said Dr. Reilly, a former malpractice defense attorney.

Conflicts of interest

As in the Gelsinger case, the physician investigators named in the William Lee Wright Sr. v. Fred Hutchinson Cancer Research Center complaint filed March 26 had a financial interest in an outside firm -- Genetics Systems Corp., now Seattle Genetics Inc., based in Bothwell, Wash.

"This is also a case where the patients had an alternative therapy that would've probably given them a 20% to 50% chance of survival," Milstein said. To date, 80 of the 82 patients who participated in the failed blood-cancer trial between 1981 and 1993 have died.

Milstein filed the case as a class action lawsuit, but it has not yet been certified by the court. It draws heavily on a series of articles that ran in the Seattle Times beginning March 11.

The allegations against the Hutchinson Center include that it violated participants' "right to be treated with dignity" as established by the Nuremberg Code and the Declaration of Helsinki; violated federal laws controlling investigational drugs and the protection of human subjects; breached ethical principles outlined in the 1979 Belmont Report, which outlines the federal guidelines for the protection of human subjects in research; committed common law fraud "in intentionally misrepresenting the risks of participating"; and violated the Washington Health Care Provider Act by failing to provide participants with the information necessary to make an informed medical decision.

Despite the magnitude of these claims -- most of which have been refuted in the Hutchinson Center's response to the Seattle Times series -- those involved in the research enterprise still believe there are better ways to change the system.

"My preference overwhelmingly is not to have [these issues] settled by class action lawsuits and the courts, but by self-policing or, if necessary, by government regulation," said Jerome P. Kassirer, MD, editor-in-chief emeritus of the New England Journal of Medicine.

Investigators, however, do need to be held accountable for their actions.

"We live and die on public confidence in our institutions," Dr. Korn said.

Added Dr. Prentice: "When you lose that trust, the clinical research enterprise is going to shut down and we won't be able to advance research for the betterment of mankind."

ADDITIONAL INFORMATION:

Case at a glance

William Lee Wright Sr. v. Fred Hutchinson Cancer Research Center et al.

Venue: Kitsap County Superior Court, Washington
At issue: Whether research subjects enrolled in a cancer clinical trial sustained personal injury and death as a result of experimental treatment they received at the Seattle cancer center. The complaint alleges that the 82 participants were not fully informed of the trial's risks and that the investigators were unduly influenced by their potential for financial gain.
Potential impact: If successful, other lawyers are likely to file similar cases on behalf of clinical trial participants.