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VA Hospital’s Ethical Nightmare

TIMES MEDICAL WRITER

Twice, the patient told doctors at the West Los Angeles Veterans Affairs Medical Center that he did not want to be a guinea pig. But they went ahead anyway, keeping him on an operating table with an electrophysiology probe inserted in his heart for an extra 45 minutes to collect research data.

Another patient, a veteran so disturbed by mental illness that he was hiding bullets in his hospital room, also had his heart catheterization treatment prolonged for research purposes, though he did not give his legally required permission either.

Then there was Robert Hanson, a stocky World War II veteran who dropped dead of a heart attack in the hospital parking lot after taking an experimental heart drug. Hanson signed consent forms agreeing to be in a study of the drug, but some caregivers and his daughter insist the 71-year-old did not realize he was forgoing standard therapy to be in an experiment, with all the uncertainty and risk that implies.

These cases, involving a top cardiologist at the hospital, are among the most dramatic informed consent problems documented in recent years. Even now, nearly four years later, this conflict of morality and medicine continues to plague cardiology researchers at the nation’s largest VA health care facility.

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Ironically, the incidents were apparently unknown to Veterans Affairs officials who this week suspended research activities at the medical center to protect patients in clinical studies.

The suspension order, the first time the VA has taken such drastic action against one of its 173 hospitals, was based on dissatisfaction with hospital administrative procedures for ensuring the safety of human and animal research subjects. The agency began reviewing the medical center’s research practices in 1997.

In a related move, the federal Office for Protection from Research Risks on Monday canceled the medical center’s contract to do clinical research funded by the U.S. Department of Health and Human Services for similar reasons. The risk office first notified the hospital of possible research violations in 1993 and put the facility on probation in 1994.

But the hospital itself found much more specific and apparently more serious problems in an extraordinary investigation of cardiology research in 1995, according to an internal report obtained by The Times. The report cites several cases in which research regulations were violated and patients were put at risk in cardiology research.

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Officials at the hospital, recently renamed the West Los Angeles VA Healthcare Center, said the report was placed in proper agency channels. But Dr. John R. Feussner, the Veterans Affairs chief of research and development in Washington, said Wednesday that he was not aware of the research ethics violations in cardiology. He suggested that agency investigators should have been informed of the findings. “I will now get this report and make my own determination and see if it has any implications for our subsequent actions,” he said.

High Principle at Stake

At the core of the controversy is informed consent, the preeminent moral principle of human experimentation. With few exceptions, U.S. law mandates that researchers obtain prior written informed consent from people to protect them from exploitation and undue injury. And a state law makes it a crime to do risky research on people against their will.

The hospital’s internal investigation focused on research by Dr. Philip T. Sager, an internationally known clinical scientist who remains chief of cardiac electrophysiology at the medical center. Over several months of 1995, he conducted or oversaw potentially harmful catheterization research procedures on four patients without first obtaining proper consent, including one who refused his permission, the hospital’s internal report states. Those patients were not physically harmed.

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Overall, “quality assurance monitoring of human research with respect to informed consent appeared . . . to be basically nonexistent,” says the 40-page report, which was procured through the Freedom of Information Act.

Sager said in an interview he accepted the panel’s findings: “I have made mistakes. . . . I take them extremely seriously, greatly regret them, and have made major efforts to be certain these things don’t happen again.”

Though the report by a panel of five medical center employees and one VA medical official was sometimes scathing, several physicians and nurses close to the events were not appeased. They say the panel whitewashed serious incidents to protect the hospital and physicians involved.

“There is a loss of faith in the institution,” one VA caregiver said of the probe and its aftermath. “There is a feeling it has failed in monitoring the problem and getting justice for the violations.”

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Hospital officials have a different view. Responding to the investigation, they say that they reorganized the cardiology division, modified consent procedures, stepped up monitoring of patients’ rights, and briefly suspended Sager. “We’ve learned a lot from this and we’ve made this place a safer environment,” Dr. Dean C. Norman, the medical center’s acting chief of staff, said before this week’s action by the VA.

The experience at the West Los Angeles medical center raises questions that are fundamental to America’s vast and growing clinical research enterprise.

How should charges of unethical research practices be investigated? Who should set and enforce penalties for violations? And who represents the interests of patients whose rights may have been trampled?

Roughly one out of every three clinical studies poses ethical problems, according to scholarly analyses of research programs, federal inspection reports, and a 1998 government-funded survey of hospital ethics committees. Most often, the concern is nonexistent or inadequate consent from study participants.

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“When there are problems in human research, they often center on poorly informed consent, which is not consent at all,” said Gary Ellis, director of the federal risk office.

Probe Started in 1995

The internal probe of cardiology research began in October 1995, in response to allegations by staff members that Sager had done research on patients without their permission or knowledge.

Sager, 43, is a graduate of the Yale Medical School, a fellow of the American Heart Assn. and the American College of Cardiology and an official of the National Assn. of Pacing and Electrophysiology. He has authored or co-authored 50 articles in the medical literature.

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For its investigation, the VA panel conducted 28 depositions of medical staff and others, analyzed 10 patient cases, reviewed thousands of pages of documents and audited two months’ worth of 1995 cardiology patient records.

VA lawyers in Washington redacted the names of patients and staff members from the copy of the panel’s report provided to The Times. A search of Los Angeles County death records identified the patient Robert Hanson. A dozen current or former physicians and nurses at the West Los Angeles VA hospital agreed to be interviewed if their names were not published.

The most important charge the panel substantiated, according to the report, involved a heart patient subjected to research against his will. The man had heart disease and was hospitalized for a catheterization procedure to measure his heart’s electrical activity. That entails inserting a plastic-coated wire into the heart through an incision in a blood vessel in the groin.

The infraction took place when Sager and co-workers prolonged the patient’s 105-minute treatment by 45 minutes to gather data for research purposes, according to the report. The hospital classified the research as “medium to high risk,” the most serious category.

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Though doctors told Sager that the patient had “refused to consent” to the research on at least two occasions, Sager said “they would proceed anyway,” the report says.

The panel concluded that Sager “violated research ethics by performing a research protocol in the face of the patient’s overt refusal” the report says, adding that he apologized to the panel for “improper behavior.”

“Afterwards, I realized this was really wrong, and I deeply regretted it,” Sager said in an interview.

The VA panel criticized other doctors who went along with the research, saying they showed a “clear lapse of ethical behavior,” the report says.

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Outside experts in medicine and ethics said the violation appeared unusually flagrant. It was “unconscionable,” said Ruth Faden, director of the Bioethics Institute at Johns Hopkins University. “There is no justification for going forward over an expressed refusal.”

Some critics of the panel’s report say that the infraction was more than just “improper behavior” or an “ethics” violation.

The California Medical Experimentation Act of 1978 specifies a range of penalties for violating informed consent. The maximum is a $10,000 payment to the victim and a year in jail if a researcher “willfully fails to obtain the subject’s informed consent . . . and thereby exposes a subject to a known substantial risk of serious injury, either bodily harm or psychological harm.”

Norman, the chief of staff, said he discussed the infraction’s possible “criminal implications” with VA lawyers. “They would have brought up any if there were any,” he said. Norman said the hospital did not notify law enforcement or medical licensing authorities of the investigation findings.

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Vivian Hersch, a supervising attorney in the state attorney general’s health quality enforcement section, said hospital officials should have reported the incident--and possibly others--to the state, as mandated by the business and professions code. And a spokeswoman for the California Medical Board, Candis Cohen, said the findings “sound like something that should be reported to our board.”

Consent Not in Writing

The VA investigation turned up three other patients subjected to research procedures who did not provide prior written consent.

Sager said that another physician was supposed to get the patients’ informed consent for the research. The physician spoke with the patients and got consent and just failed to get it in writing, Sager said.

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Again, the research in question was cardiac catheterization, but these patients were exposed to an additional risk: During the research measurements, they received an intravenous dose of the drug isoproterenol to make their hearts race.

One of these patients had a mental illness. He had been diagnosed with “delusional disorder” and “major depressive disorder with psychotic features,” the report says. Around the time the research was performed on him, the report said, he “had contraband including bullets in his room, and was put on 72-hour hold as a danger to others.”

The panel scolded Sager for poor management in this case, saying “there was considerable carelessness and negligence in the supervision of advanced trainees who were assigned the task of obtaining informed consent.”

After the VA investigation, Sager tried to contact the four patients found to be subjected to research procedures without consent. He reached two, met with them separately at the hospital and obtained what he called “retroactive” consent for the research.

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The hospital’s internal panel also strongly suggested that some patients who did give their consent may not have fully understood what they were doing.

And it documented a “fairly loose process” of winning patients’ cooperation to participate in studies supervised by Sager. A physician working under him was singled out for “thoughtlessness and careless disregard for patient autonomy,” the report says.

That physician and another doctor “were not very familiar with the studies for which they were obtaining informed consent,” the report says. They “rarely gave the patient copies of the consent forms.” Such an approach is in stark contrast to federal and professional guidelines, which recommend leaving a complete informed-consent document with a prospective research subject to review in depth.

Faden, the Johns Hopkins ethics specialist, said she was “troubled” that physicians “didn’t know very much about the studies that they were approaching people to participate in. . . . That is not good standard practice. That’s a no-brainer.”

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Meanwhile, the panel also took up a “minor” ethics charge, as Norman called it, against Dr. Bramah Singh, an expert on heart drugs and then the chairman of cardiology. The panel ruled that Singh was a co-leader of a research study that included a patient who was confused about the study when he consented to it.

Allegations by Doctors, Nurse

Hanson’s death was the most dramatic case. VA physicians and a nurse alleged that he did not belong in the study of the experimental anti-arrhythmia drug dofetilide and that his consent to participate was so poorly informed as to be meaningless.

Hanson’s daughter, Cheryl Alvarado, believes that researchers pushed him into the study. “I think they took advantage and they put him in this thing and they killed him,” she said in an interview.

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After reviewing the case, the panel ruled that the research was ethical and Hanson’s care was appropriate. However, two of the six panel members dissented and had “serious reservations about entering this patient in the . . . study,” the report says.

The ruling inflamed the dispute among some of the cardiology staff members, prompting allegations of a cover-up. The ensuing controversy touches on several of the major ethical and moral questions in clinical research today:

Are elderly patients appropriate candidates for experimental treatments when standard therapies are available? Are researchers justified in putting a seriously ill person in a clinical study where he has a good chance receiving a placebo, or no medication? Do poor people who rely on government health care feel unduly obligated to participate in risky clinical studies when approached to do so?

“He ain’t nobody,” Alvarado said of her father. “He ain’t got no money. If he did, he wouldn’t be going to that VA in the first place.”

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Born and raised in Wisconsin, Robert Lowell Hanson did not get past the eighth grade. In 1941, he joined the Navy at 17 and served for four years, largely in the Pacific. After the war, he settled in the Los Angeles area, working as a painter and property manager.

For the last few years of his life, the ailing septuagenarian slept in a listing trailer parked in the patchy yard behind his daughter’s rented North Hollywood house.

He had a history of coronary artery disease as well as ventricular arrhythmia, a disorder in which the heart’s largest pumping chamber beats chaotically, leading to dizziness, fainting spells or death. In the 1980s, his daughter said, doctors outfitted him with a defibrillator, an electronic device implanted in the body that shocks the heart when it beats out of control.

In the spring of 1995, he went to the West Los Angeles VA facility seeking treatment for dizzy spells. Sager and other physicians attributed his dizziness to an anti-arrhythmia medication he was then taking, sotalol, the investigation report shows.

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So he was asked to be in a study of dofetilide. The Food and Drug Administration and the hospital’s ethics committee endorsed the design of the dofetilide study. It carried the FDA designation of Phase Two, meaning the drug was in an intermediate stage of development.

The drug, made by Pfizer, recently received preliminary FDA approval for a heart disorder other than the one tested in the research Hanson was subjected to.

Over several days at the hospital in June, Hanson underwent extensive cardiac testing before he received the experimental drug. After being released from the hospital, he crossed the parking lot to his car and was found on the pavement.

There is debate over the drug’s role in Hanson’s death. The hospital autopsy concluded that the most plausible cause of death was “cardiac arrhythmia,” but said nothing about whether the drug was involved. Sager said he doubted it.

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But one VA physician said: “He died of a drug reaction.” The tragedy prompted another VA physician to begin referring to dofetilide as “the death drug,” sources say.

Following Hanson’s death, VA health care providers challenged the medical decisions that led him into the research program and said it was “inhumane” to put a sick old man in a study where he had a 50% chance of receiving a placebo, or no medication.

Finally, some questioned whether Hanson realized he was in an experiment. Two VA health care providers who saw him during his hospitalization said in interviews that Hanson did not know what was going on.

But Sager and another caregiver disputed that version of events, saying Hanson understood what he was getting into. Hanson’s medical record, Sager said, contains “multiple documentations” that “the patient understands and is aware. . . . I feel really comfortable in my heart that this patient did understand.”

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As for Alvarado, she said her father never mentioned being a research subject before or during his five-day hospital stay. And it would have been out of character for him to keep that news from her, she said. “My dad did not know he was in a clinical study program,” she said. “No, he did not.”

He must have mistaken the consent form for routine hospital paperwork, she said, adding that he needed reading glasses that he did not have with him during his hospital stay.

The panel declined to pursue the charge that Hanson was inadequately informed about the study, presumably because he signed the study consent form, which said dofetilide “has been associated with sudden death in patients with arrhythmias and heart disease.”

Independence of Panel Doubted

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Despite the investigation’s many harsh findings, a number of current and former VA caregivers argue that the panel was a “kangaroo court” and that the hospital’s response to it was “an obstruction of justice.”

Fueling skepticism of the panel’s independence was a potential conflict of interest: At the time of the probe, the panel’s highest-ranking member, and the only one with cardiology expertise, was collaborating with Sager on a research project.

Dr. Pamela Steele was then chief of cardiovascular diseases and acting chief of medicine at the VA central office in Washington. Along with five other VA researchers, Steele and Sager co-authored a defibrillator study presented at a 1996 American Heart Assn. meeting.

Norman, who created the panel, disputed that the collaboration tainted the panel’s work. Steele “claimed no conflict and in fact if I remember correctly . . . she was very upset with Dr. Sager,” he said.

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In a brief interview, Steele said emphatically that there was no conflict of interest. Sager agreed, adding that he had minimal or no personal contact with Steele while the study they co-authored was being prepared.

But Ellis, director of the Office for Protection from Research Risks, said it is not good practice for a collaborator to be among those probing a researcher’s alleged wrongdoing. “Co-authors are not as independent of one another as they need to be to have one credibly investigate the other,” Ellis said.

In addition to Steele, the VA panel consisted of the West Los Angeles hospital’s associate chief of psychiatry, who chaired the proceeding; a hospital administrator; a physician specializing in geriatrics; a clinical nurse; and a pharmacoeconomics specialist.

Summarizing its findings, the internal hospital panel noted that Sager “has had an illustrious career thus far as an academic cardiologist” and “responded rapidly and responsibly to feedback regarding lapses in research procedures.” It recommended that the hospital take a “measured” response in reprimanding him.

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Sager said the ordeal has made him a better doctor and researcher. The investigation “really improved the research environment at this medical institution,” he said last week.

“I think it’s been a very positive thing. It’s been painful for me emotionally, personally and professionally. But I think it’s been appropriate.”


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