U.S. Agency Investigates Cancer Trials at Hutch

By Duff Wilson and David Heath Seattle Times staff reporters

The federal agency charged with protecting patients in clinical trials is investigating complaints against Seattle's Fred Hutchinson Cancer Research Center.

The Office for Human Research Protections (OHRP) has asked Hutchinson Center officials to respond to complaints about two experiments in which at least 20 people died. Those clinical trials were featured earlier this year in a Seattle Times series entitled, "Uninformed Consent: What patients at `The Hutch' weren't told about the experiments in which they died."

Dr. Greg Koski, director of OHRP, confirmed there is an investigation but said agency rules prevent him from discussing the details. In April, Surgeon General David Satcher called for a federal investigation.

In March, The Times reported that patients had died prematurely in a blood-cancer experiment called Protocol 126, conducted from 1981 to 1993, and a breast-cancer experiment called Protocol 681, conducted from 1991 to 1998.

In both cases, Hutchinson Center doctors had financial interests in drugs being tested. And in both cases, patients were not fully informed about risks, alternatives and financial conflicts of interest.

Center spokeswoman Susan Edmonds yesterday acknowledged the investigation, saying OHRP had sent a letter to The Hutch asking specific questions about the experiments and seeking supporting material.

OHRP has broad powers when it finds that human subjects are endangered. Last Thursday, the agency suspended clinical research at Johns Hopkins University in Baltimore, jolting the medical-research community.

The action came in response to the recent death of a healthy 24-year-old woman, Ellen Roche, who had volunteered to inhale an unapproved drug, hexamethonium, as part of an experimental trial studying the causes of asthma. Roche died June 2.

OHRP partially lifted its suspension this week in response to proposals made by Johns Hopkins to beef up its protections.

The Hutch says it did nothing wrong in treating cancer patients in Protocol 126, but admitted it had given incorrect information to one patient in Protocol 681.

Families in both cases have filed lawsuits in U.S. District Court in Seattle.

Protocol 126 was an attempt to prevent graft-versus-host disease in bone-marrow transplant patients by removing T-cells from the marrow. It led to patient deaths from graft rejections, cancer relapses and new cancers. As a result of the failed experiment, The Hutch today is a leading opponent of T-cell depletion.

Family members say they were not properly informed of the risks, safer alternatives, or financial conflicts of interest by the three principal doctors in the trial, each of whom owned stock in a company that held the commercial rights to three antibodies being tested in T-cell removal.

In 1993, the federal oversight agency, then named the Office for Protection from Research Risks, began to investigate Protocol 126 in response to complaints from Dr. John Pesando, a former Hutch doctor and internal review-board member. The federal investigator left in the middle of his probe to take another job. The office, chronically understaffed, closed the case without further investigation, failing to interview anyone, visit Seattle or review medical records.

Protocol 681, an experiment in the safety of high-dose chemotherapy drugs for breast-cancer patients, has not previously been investigated by government agencies.

In that experiment, 48-year-old health-care administrator Kathryn Hamilton, of Spokane, died after being told the drug pentoxifylline, available intravenously, might reduce the toxic side effects of chemotherapy. But The Hutch had lost the right to use the intravenous drug, and nausea and vomiting prevented Hamilton from being able to hold down the pill version of pentoxifylline.

At the time, Hutch researchers were just about to publish a new study showing that pentoxifylline wasn't effective anyway. Hamilton died from the toxic side effects of the chemotherapy drugs.

As the federal investigation begins, The Hutch continues its own assessment of research policies. A committee comprised mainly of Hutch donors and supporters is working to finish up its review of the center's practices in patient consent, financial conflicts of interest, internal review and safety monitoring.

The group, known as the Committee on Patient Protection in Research Trials, is basing its work on four consultant reports.

The Rev. William Sullivan, chairman of the committee, said in an e-mail that the committee plans to deliver its report plus the reports of the outside experts to the center's Board of Trustees by the end of August.

One committee member, Jon Fine, president and chief executive officer of United Way of King County, said, "The group is working hard and clearly taking its role seriously and is approaching it with an unbiased, independent perspective."

Fine said the work is proving "worthwhile," but declined to be more specific. He said the committee will not go outside its charge, which is to focus on current practices only.