Better Safeguards Sought for Research Subjects : Medicine: Ethicists note that newer regulations focus heavily on informed consent, which was often absent in Cold War radiation experiments. But some want more scrutiny.
Each week the ads pop up in the help-wanted sections of newspapers around this hub for medical research: “Reap the Rewards of Research.” “New Year’s Cash Flow Low?” “Earn Up to $150.”
The ads seek paid volunteers for medical studies, be it a closer look at toenail fungus or how the elderly sleep. Elsewhere, subjects come from the ranks of the sick; their payment is the hope of a cure for their illness.
Thousands of people take part each year, and most of them are fully informed of risks involved, unlike the unwitting subjects of radiation research during the Cold War.
But most contemporary research on humans goes on behind tightly closed doors, with scrutiny mainly by scientists’ peers.
“We know more about how many mice, cats, dogs and monkeys are involved in experiments than we do about people,” said Arthur Caplan, director of the Center for Biomedical Ethics at the University of Minnesota.
In fact, the federal guidelines on use of laboratory animals are 83 pages long, while its guidelines on human research subjects cover 19 pages.
Protecting the right of patient privacy, the medical community says, is what mitigates against more information being collected on people.
Nobody knows exactly how much research is performed on humans. But the federal Department of Health and Human Services, the biggest single backer of research on humans, funds nearly $5 billion worth of projects annually at about 1,000 institutions.
Who keeps track of the roughly 15,000 HHS projects each year?
That and all medical research on humans is guided by the so-called Nuremberg Code, principles of informed consent drawn up after disclosures about Nazi medical experiments conducted during World War II.
Under federal regulations enacted only in the 1970s, the Office for Protection from Research Risks is charged with overseeing all research on humans.
But the OPRR actually reviews research proposals for 600 of the hospitals, schools and businesses doing HHS research.
The 400 other institutions, considered the biggest and best in the country, get approval for research from their own institutional review boards, composed largely of people who work there.
“We rely on the integrity of our investigators, and we have no real reason to believe they would violate the regulations,” said Paula Knudson, coordinator of an institutional review board at the University of Texas Health Sciences Center in Houston.
“Every hospital or medical school is like a jungle; there are drums beating all the time,” she said. “There are lots of eyes around.”
She said that her board checks out about 1,000 research proposals a year, and that in her 17 years on the board the worst violation involved a researcher who failed to get all of his consent forms signed by participants.
Most complaints seem to center on what is known as “informed consent,” that is, fully telling patients of the experiment and its risks.
For example, paralyzed patients at a Boston hospital contended last year that they were falsely promised they would be able to walk if they underwent an experimental spinal operation. And an independent review last year of a major women’s health study found that study procedures did not give participants enough information on risks or benefits.
The lack of informed consent was at the heart of the controversy over radiation experiments at the Fernald State School for the Mentally Retarded in Waltham after World War II. That, and other recently disclosed Cold War studies with radiation, prompted investigations by the Clinton Administration and by some members of Congress.
Ethicists note that regulations since the 1970s focus heavily on informed consent and make a repeat of the Fernald School experiments highly unlikely.
But as recently as a 1992 congressional hearing, questions were raised about whether women in a breast cancer prevention study were being adequately informed about a drug they would take.
And late last month, the National Cancer Institute ordered the University of Pittsburgh to temporarily stop enrolling new patients in 14 cancer studies, including that of tamoxifen, which aims to test whether women susceptible to breast cancer can avoid developing the disease if they take the drug. Before enrollment can resume, the university and the cancer institute must examine the university’s oversight procedures and safeguards. The suspension is expected to last at least a month.
Gary Ellis, director of the Office for Protection from Research Risks, said his office has investigated 115 complaints about research on humans in the last four years, leading to corrective actions in 90% of the cases. Most of them related to informed consent of research participants.
After the uproar over the post-World War II radiation experiments, some people want even more scrutiny.
There are no disclosure regulations for strictly private research, leading some to call for a law covering all research on humans, just as the Federal Animal Welfare Act does for laboratory animals.
Also, drug company research increasingly is carried out by companies that specialize in testing, and those tests can escape the scrutiny they might get in a major teaching hospital, some critics say.
Dr. H. Jack Geiger, a past president of Physicians for Social Responsibility, adds that more oversight is needed on human experiments by the military and intelligence agencies, for which there still is no independent review.
George Annas, chairman of the health law department at the Boston University Schools of Medicine and Public Health, said there should be more protections for experiments on children and the institutionalized disabled.
The medical community resists these pressures.
Michelle Scarlatelli, a spokeswoman for Brigham and Women’s Hospital in Boston, wouldn’t list research projects there, saying: “Our obligation is to report to various government agencies. Our obligation is not to report out to the press.”
“The system is based on trust,” said Ellis, the regulator.
“If I told you there were no problems at 1,000 institutions and 15,000 projects, you would have strong reason to conclude that I was either blind or looking in the wrong place,” he said.
But, he said, the complaints his office gets give evidence of “a monitoring program that is vigorous and healthy.”
