Hutch: Times' reports were 'blatantly false'
Seattle Times staff reporters
The president of the Fred Hutchinson Cancer Research Center said yesterday that published reports the center had failed to fully inform patients of medical risks and potential financial conflicts in two clinical trials were "blatantly false."
But Dr. Lee Hartwell brought few new details to a general rebuttal of the investigative articles that appeared this week in The Seattle Times. Instead, he focused on the nature of clinical trials, saying unexpected deaths do occur but patients and medicine itself benefit from experimental treatments.
Likewise, he said, medicine has benefited from a situation in which research centers such as "The Hutch" and its doctors have financial connections to biotechnology firms that help fund experiments.
Hartwell and Dr. Fred Appelbaum, director of the clinical-research division, held a news conference on the day of the fifth and final article in the series, "Uninformed Consent: What patients at 'The Hutch' weren't told about the experiments in which they died."
"Since the alleged events occurred between eight and 20 years ago, I have taken considerable effort to review the historical documents and interview relevant faculty, to satisfy myself of the truth," Hartwell said in a prepared statement.
"The center has been accused of enrolling patients on clinical trials that were known to be ineffective; accused of failing to inform patients of the risks of their treatment; and accused of taking these egregious actions for personal gain."
"I am here to state categorically that I have found all of these accusations to be blatantly false."
Hartwell and Appelbaum repeatedly denied there was a potential for researchers profiting from the experiments described in the newspaper. However, Appelbaum acknowledged that "in retrospect, we should have been more careful in avoiding even the possibility of misunderstanding."
In one experiment between 1981 and 1993 - which Appelbaum said was a series of related but different clinical trials - at least 20 of 82 blood-cancer victims seeking bone-marrow transplants suffered graft failure, which normally occurs about 1 percent of the time.
Hartwell said conduct of the trials was "thoroughly investigated" by the federal government and the center was "completely exonerated."
However, The Times found the federal investigation languished for a year after a staff person left, with many questions unanswered, and was then closed without interviews of any patients, doctors, review-board members or the primary complainant, a former Hutch doctor. Rather than exonerating the center, the federal investigation ended up with narrow findings, saying it was the internal review board's responsibility to curb the study if it had wanted to.
In the other study examined by The Times, four of 68 breast-cancer victims died from high doses of chemotherapy in a study that included experimental rescue drugs to prevent organ damage.
Appelbaum admitted it was an error that one patient, Kathryn Hamilton, was told she would be given the intravenous form of a rescue drug if she could not keep down the pill.
Her son, Chris Addicott, says the availability of the IV was critical to her decision because she feared, based on past experience with chemotherapy, that she would throw up the rescue drug and die from the high-dose chemo. During the experiment, Hamilton repeatedly threw up the drug and eventually gave up trying to swallow it.
"It made me feel very badly that in this one case there was a mixup," Appelbaum said yesterday. But he said that the rescue drug, pentoxifylline, "did not prove to be useful whatsoever, and so whether she got it or not would not have changed her course."
The Times series reported that Hamilton was told in her informed-consent statement that studies had shown that pentoxifylline was effective at preventing kidney, lung and liver damage, even though Hutch doctors had already completed a more authoritative study showing that the drug didn't work and might make some patients sicker.
The series also noted doctors' decision to escalate the dose of chemotherapy after previous patients had died from it. But Hartwell said that there was no evidence that escalating the dose led to the patients' deaths.
"It was a very low rate of four out of 68 people," he said.
Hartwell said he feared that patients with no hope of survival with standard treatment would avoid clinical trials as a result of the articles.
"Will they be deterred from their only remaining hope, a clinical trial?" he asked. "Moreover, since therapeutic outcome is so dependent on the patient's confidence in their caregivers and their hope for a favorable result, will outcomes be damaged?"
Appelbaum said he has talked with patients who recently got bone-marrow transplants from The Hutch. Some are organizing to state that they've received impeccable care and were fully informed of the risks.
Hartwell and Appelbaum flatly denied misleading any patient on the true risks of the clinical trials.
Appelbaum agreed with The Times' account of seven people dying from graft failure in one stage of Protocol 126, the blood-cancer experiment. He said there were about 10 fatal graft failures in later stages, for a total of about 17.
The Times' account had showed at least 13 later graft failures for a total of at least 20, based on Hutchinson records.
Drs. John Hansen, Paul Martin and William Bensinger, principal investigators on the clinical trials in question, also spoke at the news conference. Dr. E. Donnall Thomas, a 1990 Nobel Prize winner, attended but did not speak.
Hansen, Martin and Thomas held stock in Genetic Systems, a company that had paid royalties to The Hutch for an exclusive commercial license to rights for three of the drugs being tested in Protocol 126.
Hartwell and Appelbaum insisted the doctors could not have benefited from a successful clinical trial. But asked whether the company's stock might have benefited from its drugs even being placed into a trial at an institution as respected as The Hutch, Hartwell launched into a defense of the marriage of for-profit business and medical research.
"If there were not those incentives for start-up companies to commercialize products that were developed here at the center and at other institutions, they wouldn't get developed," he said.
Hansen, who was listed as an investigator on Protocol 126 while employed by Genetic Systems as medical director, said he had "no regrets" about it.
However, he conceded that if he could have done one thing differently, it would have been to remove himself completely because of the perception of conflict of interest. Hansen held 250,000 shares of stock now worth about $9 million.
Despite that, Appelbaum said, no doctors at the center have ever substantially profited from clinical trials there.
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