By Duff Wilson and David Heath
Seattle Times staff reporters

Copyright © 2001 The Seattle Times Company

THE BEDROCK ETHIC of any human research is that a patient must fully understand an experiment before participating in it.

Yet the nation's top enforcer of human-research ethics says that the biggest problem in research today is that, often, this is not happening.

"Too often individual research participants will enter a study believing that they are perhaps being treated when in fact they need to understand that if they are participating in research, treatment might not be part of that," said Dr. Greg Koski, director of the federal Office for Human Research Protections.

Studies bear this out, suggesting that patients often don't understand what they are getting into when they sign up for clinical trials. They often don't realize that there is little chance the experiment will benefit them.

A survey of cancer patients at the University of Chicago found that 93 percent said they understood what they were told about the trial in which they were enrolled. Yet only a third were able to explain the main purpose of their trial accurately.

It's the job of researchers and institutional review boards to make sure patients understand their studies. Critics say they often fail to do an adequate job.

The federal Office for Protection from Research Risks (the former name of the Office for Human Research Protections) found that 90 percent of the cases it investigated had problems with informed consent.

Written in 'gobbledygook'

Abbey Meyers, founder of the National Organization for Rare Disorders, a patient-advocacy group, reviewed scores of informed-consent documents from research centers throughout the country. She was appalled at how incomprehensible they were.

"They are often written in scientific gobbledygook," Meyers said. "The rules say that they are supposed to be written in plain English, but people just ignore the rules."

Meyers was particularly appalled that many of the consent forms she reviewed held out the hope of a cure to terminally ill patients even in trials designed only to test for a safe dose of an experimental drug.

In the first phase of drug trials, researchers are testing doses that have never been tested in humans before. So they don't know if the drugs will be effective.

Even when a cancer drug is effective, it usually works only at a precise dose. Give a patient too little and nothing happens. Give too much and it can kill.

Phase-one trials a real concern

Studies have shown, and experts agree, that the chances of a patient getting better in a phase-one study are remote. A major review of 211 phase-one cancer trials involving 6,639 patients found that tumors responded to the experimental drugs less than 5 percent of the time.

Yet patients don't seem to understand this. According to surveys, people enroll in phase-one trials not for the good of science but for their own good. One study reported that 85 percent of patients signed up because they expected the treatment to make them better, 11 percent acted on the advice of a doctor and 4 percent felt pressured by their family.

If patients enrolled in dose-escalation trials for altruistic reasons, there would be less of an ethical dilemma, says Christopher Daugherty, the University of Chicago oncologist who conducted the study.

For that reason, he and others insist, researchers should be more blunt.

"It should really be put in terms that you will not benefit from your participation in this study," said LeRoy Walters, a bioethicist at the Kennedy Institute of Ethics at Georgetown University. "You will be taking part for the benefit of others."

Sprinkled throughout the informed-consent document that Kathryn Hamilton signed at The Hutch were suggestions that she could be saved by it.

"This new treatment program has been designed with the hope that it will prove to be much more effective than standard treatments now available. We hope that your life will be lengthened by this treatment," the consent form reads.

In fact, this study was designed to see how much chemotherapy patients could tolerate. Patients had already died from doses lower than that Hamilton was to be given.

Not all ethicists agree

Not all ethicists agree that patients have to be told they are enrolling only for the benefit of others. Even if the chances are remote that a patient will benefit, that may be better than the certainty that they will die if they don't enroll, said R. Alta Charo, professor of law and medical ethics at the University of Wisconsin.

"When you've got a disease that is absolutely untreatable by all measures, and you've got a patient who's willing to try anything instead of giving up, there's a strong libertarian bent that says why should anyone tell me no," she said.

Some research advocates worry that emphasizing the dangers might discourage anyone from signing up for clinical trials, bringing medical research to a halt.

"But that's all right," said Georgetown's Walters. "I'm all for medical progress, but only if it's done in an honest way. If that's the upshot of being honest to patients, I'm willing to accept that.

"We can't be hoodwinking people about what they are getting into."