'The Hutch' begins presenting defense

For a month now, the ethics of a failed medical experiment conducted 20 years ago have been dissected in a small Seattle courtroom.

Sitting in the front row on hard wooden benches are the spouses of five patients who died in the controversial experiment at the Fred Hutchinson Cancer Research Center. They claim "The Hutch" withheld crucial information about the risks of the experiment known as Protocol 126.

Sitting only a few feet away are three doctors who supervised the research. One of them, a slight, 83-year-old man dressed each day in a plain blazer and slacks, is E. Donnall Thomas, who received the Nobel Prize in 1990 for his pioneering work in bone-marrow transplants.

Thomas began testifying yesterday about the history of bone-marrow transplants. He and his team persevered long after most other researchers in the 1960s gave up on transplants because they didn't seem to work. This revolutionary form of treatment now offers a cure for once-incurable diseases, such as leukemia.

As the trial passes its midpoint and The Hutch began presenting its defense this week, experts say that patient lawsuits against cancer centers are rare.

"This is a very unusual case," said Joel Cunningham, a Seattle attorney who handles malpractice cases. "I also think this is a very important case."

He thinks it could have a chilling effect on research should The Hutch lose.

The Hutch denies anyone was misled or any information withheld. The center's attorneys will emphasize The Hutch's leading role in research that has saved more than 150,000 lives. They also plan to show that cancer centers around the world were doing similar research, and they will call expert witnesses to testify that Protocol 126 was a worthy and ethical experiment.

Protocol 126 was intended to find a way to prevent graft-versus-host disease, a serious and potentially fatal complication of a bone-marrow transplant. But it relied on an entirely new form of transplant with no track record. Researchers wondered from the start whether the technique might increase fatal complications, such as graft failure and cancer relapses.

As it turned out, Protocol 126 was a disaster, according to Dr. Paul Martin, who was in charge of the protocol. In one version of the experiment, roughly half the 22 patients had a disease with at least a 50 percent chance of survival with a conventional transplant. All but one died. Including all versions of the protocol, which ran from 1981 to 1993, at least 83 of the 85 patients enrolled died (the fate of at least one other patient is in dispute).

A key question in the case — one of the most basic ethical issues in medical research — is whether the patients gave informed consent.

All five patients decided to get a bone-marrow transplant long before being admitted to The Hutch. But most of the patients were not told about Protocol 126 until hours before their treatment was to begin.

Joe Fisher, whose wife, Ruth, died in the experiment, tried to contain his grief and anger on the witness stand as he looked at his handwritten notes from the meeting with the doctor. All it said about Protocol 126 was that it was a "good procedure."

"I felt they gave us the treatment they wanted to give us, and you can call it what you want, bait and switch, sales job, whatever, and that's how I feel as I sit here today," Fisher testified.

Patients would usually come to The Hutch to meet with a doctor weeks or months before scheduling a bone-marrow transplant.

But Martin, the lead researcher on Protocol 126 and one of the defendants, acknowledged that patients weren't told about the experiment until a meeting with doctors hours before treatment was to begin.

David Breskin, an attorney for the families: "The patients who come to The Hutch, they do not come to The Hutch because they want to be human subjects in research. They come to The Hutch because they are a patient who needs a transplant to cure their leukemia, correct?"

Martin: "That's certainly the starting point for their coming to Seattle to see us at the cancer research center, yes."

Breskin: "And in fact, it isn't until the family conference that a protocol or any sort of research is presented to them, correct?"

Martin: "That's usually the case back then, and even today it's still true."

Arthur Caplan, a bioethicist at the University of Pennsylvania who is not a witness in the trial, said in an interview last week that the practice of waiting until so late to tell the patients about a clinical trial "makes no ethical sense."

The Hutch, however, contends that all patients were well informed before they enrolled in Protocol 126. In cross-examining surviving spouses, attorneys for The Hutch, who wouldn't comment on their case outside of court, have painstakingly gone through a stack of consent forms each patient had to sign before getting treatment.

Patients knew from The Hutch's name that it was a research center, said the center's attorney, Bill Leedom, in his opening statement. Also, the doctors who sent them to The Hutch "knew they were sending patients to a research center to be on a research trial where the results were unproven and unknown."

Attorneys for The Hutch plan to call expert witnesses to testify that cancer centers around the world were asking the same research questions as those asked in Protocol 126.

The Hutch says that Dr. Richard J. O'Reilly of Memorial Sloan-Kettering Cancer Center in New York will testify that these types of clinical trials were well designed and in the mainstream of clinical research.

Other expert witnesses include Drs. Richard Champlin, director of the M.D. Anderson Cancer Institute in Houston, and David G. Nathan, president emeritus of the Dana-Farber Cancer Institute in Boston.

Robert Levine, a bioethics expert from Yale University, is expected to testify that the consent forms and doctors' meetings on Protocol 126 satisfied the requirements for informed consent.

Jurors will have to weigh those statements against expert testimony presented on the plaintiffs' behalf.

Gwen L. Nichols, director of the hematological malignancy program at Columbia University's medical school, testified The Hutch should not have enrolled patients with good chances of being cured in Protocol 126 since it was so risky. Ken Cheung, a statistician at Columbia, testified that Protocol 126 should have been stopped when the second patient developed graft failure, a fatal complication.

Expert witnesses can be critical in malpractice cases, but they're often less important in informed-consent cases, said Cunningham. That's because jurors don't need experts to decide whether patients were told everything they needed to know or whether the patients would have acted differently if they had known more, he said.

Superior Court Judge Douglas McBroom ruled before the trial began that the experiment caused the deaths of four patients in the case and that The Hutch was negligent in the treatment of the fifth patient.

The Hutch's institutional review board, charged with protecting patients, grappled with all of these same ethical issues in 1981 when they rejected Protocol 126. The board later reversed itself.

In detailed minutes of the meeting, review-board members expressed concern that the protocol was a radical departure from conventional transplants, that there hadn't been adequate testing of animals, that it could have led to increases in cancer relapses and graft failures, and that the consent form didn't spell out the risks.

One member said if the risks were spelled out, "I would be very hesitant at this point to sign the consent."

But evidence presented by the plaintiffs shows that the language about risks in consent form given to patients remained unchanged.

Jurors have been allowed to ask questions during the trial. Some questions suggest that jurors have sympathy for The Hutch doctors. One juror asked the brother of a patient who died, "Do you think your brother was the type of person that would be part of a research study in order to help other people?"

The witness, Dan Mahler, responded, "If his life depended upon it, no."

But jurors had tough questions for Martin, such as how many graft failures it would take before he would stop Protocol 126.

There are 15 jurors, three of whom will be dismissed before deliberations begin. The families need 10 jurors to win their case.

New facts have emerged as the case has progressed.

For example, pre-trial discovery exposed a laboratory accident that may have played a role in the death of one patient, David Yingling. Most of his brother's bone marrow was lost as it was being processed, yet The Hutch acknowledged during the trial that it never told the family. The judge ruled before the trial that the center was negligent in that case; testimony now will help determine damages.

There's also evidence that Yingling was treated in the protocol before it was approved by the center's review board, a violation of federal rules.

And there's been testimony that The Hutch's director, Dr. Robert Day, agreed to stop enrolling patients with a good prognosis into the experiment, though Martin said Day never passed that on.

As The Hutch in the coming three weeks brings its leading doctors and expert witnesses to the stand, its challenge will be to overcome four weeks of emotional accounts told to the jury.

Stories like that of Paul Mahler, who was told for the first time about Protocol 126 the day before his treatment would begin.

Mahler, an anthropology professor at Queens College in New York, had spent months researching his options before deciding on a bone-marrow transplant at The Hutch. With a transplant, Mahler learned, patients like him had a 50 percent chance of a cure; The Hutch had a better cure rate — up to 70 percent. His wife, Marian Dagosto, testified that the doctor never made it clear those odds did not apply to Protocol 126.

Mahler consented. He died of graft failure nine months later.

"It would never occur to me to ask them if they were withholding any information," Dagosto testified. "Why would we think that way? We weren't going in there to be suspicious. We were going in there to be helped."

David Heath: 206-464-2136 or dheath@seattletimes.com