Wanda Swinamer learned that she had breast cancer in the spring of 1984. Her treatment was decided by the flip of a coin.
She is one of 20,000 patients who participate each year in a form of medical experimentation known as randomized clinical trials, in which patients are assigned to a treatment group on a random basis to avoid any bias in the study. These trials are used to evaluate the effectiveness of new drugs and surgical procedures, particularly in the field of cancer research.
Supporters of randomized trials argue that they are essential for objectively determining the best therapy for a given disease. But for some doctors the trials raise ethical questions, centering on a concern that patients may be deprived of the best available treatment in the interest of the scientific validity of the study.
The study in which Swinamer participated was conducted at the National Institutes of Health. Its purpose was to determine whether breast cancer could be effectively treated by a lumpectomy (in which only the tumor is removed) combined with radiation therapy, as compared with the traditional but more disfiguring mastectomy, in which the breast is amputated.
Doctors at NIH explained to her that they did not yet know which treatment had a better prognosis. The randomization was used to obtain an unbiased assignment of patients into two groups. She had an equal chance of receiving either treatment. Once the computer decided which treatment was to be used, she had the right to leave the study any time before surgery.
In Swinamer's case, the computer assigned a lumpectomy with radiation.
"If I knew which one was better I would have chosen that," Swinamer said. "But I didn't, and neither did they."
In principle, randomized trials are performed only when there is no clear evidence as to which therapy is best. There are usually preliminary data, however, from earlier nonrandomized testings and animal experiments.
Dr. Samuel Hellman, physician-in-chief at Memorial Sloan Kettering Cancer Center, is concerned that patients in randomized trials are not being fully informed. "If I say to you I don't know for certain which treatment is better, does that mean I'm likely to believe that there is no difference?" said Hellman. "That's a serious error of omission."
"No physician who knows what is best should participate in clinical trials," said Dr. Bernard Fisher, head of the National Surgical Adjuvant Project for Breast and Bowel Cancers. "But for those of us who have so many doubts and questions about what is best, we find no philosophical or ethical constraints."
The appeal of randomized clinical trials, at least to medical researchers, is that they are experiments -- quantifiable, controlled and scientific. Fisher contends that randomized studies are one of the most important advances in medicine of the 20th century.
"Just as sterile technique becomes a way of life for surgeons, so must all physicians be indoctrinated with the clinical trial mechanism," he said.
Some, however, question the validity of this technique. Dr. Emil Freireich, professor of medicine at M.D. Anderson Hospital in Houston, asserts that randomized studies are widely overused.
"The heterogeneity of human beings is so enormous that it is pretentious to assume that by randomly assigning patients you are going to get comparable groups," he said. "It works very well with pure-bred mice, but not with people."
Dr. Thomas Chalmers, former dean of Mount Sinai School of Medicine, contends that it is still the best method available. He believes that a randomized study should be used to test every new treatment developed.
"Doctors ought to be investigators and appreciate that they don't know all of the answers," said Chalmers.
"The only way to test out the new is to confess to the patient, who's come to us with a life and death decision, that we don't know whether it's the new or standard treatment that's better," said Dr. Ronald Blum of the Department of Oncology at New York University Medical Center. "This is what the randomization implies. Then we have to destroy the myth that we know the answer, and that's upsetting to people."
Patients agree to participate in randomized trials through a process known as informed consent, in which the study's purpose and the patient's options are explained. "The patients in the clinical trials we do are very well informed, relative to what their diseases and therapies are all about," said Fisher. "People who have strong preferences are really not patients who can participate in clinical trials. No trials should intimidate or mandate. It must be of the patient's own free will."
It may be difficult, however, to discern exactly what is of the patient's own free will. "When you're sick, you're vulnerable, and you want somebody to help you," said Carol Levine, editor of the Hastings Center Report, a magazine that examines ethical questions in medicine. "You want to make that physician think of you as good patient, and so your inclination is to do whatever is suggested."
At issue is whether these studies pose a conflict of interest for the physicians involved -- a conflict between accruing scientific data and doing what is best for the particular patient.
"The doctor-patient relationship is in my judgment one of complete confidence," said Hellman. "You come to me, I might be wrong, but I'm not going to be motivated by other than your best interest."
Dr. John Bennet, head of the Eastern Cooperative Oncology Group, said randomized studies "may not be in the best interest of the patients you are treating at that particular point in time, but they're surely in the best interest of the generation of patients to come with that disease."
"My feeling was that as long as I had to go through this, I wanted to contribute something," said Swinamer. "Maybe it will be my daughter down the line that I'm helping."
Perhaps the most controversial question about randomized trials is when to stop a study. When can one treatment definitively be said to be better than another?
Supporters of these studies worry that physicians enrolling their patients will develop opinions about which treatment is better before the results are statistically valid. In a number of studies, including the one in which Swinamer participated, the ongoing results are not made available to doctors and patients until a committee overseeing the study decides it is time to stop the trial.
"To me, this is morally difficult to deal with," said Hellman. He believes that when one treatment starts looking better than another, it is wrong to tell the patients there is no difference.
"Hiding the results doesn't make the ethical question less," he said. "It just means you have to be more of a detective to figure it out."
"We look at the trials very carefully," said Bennet, "and if one treatment seems quite superior to the other, then we stop the trial."
One alternative to randomized studies is to compare patients from physicians using different treatments, matching groups after treatment, instead of before.
This method, according to Hellman, allows the individual physician to do what he or she thinks is best and not violate the patient's confidence. Other medical researchers, however, assert that such studies would give biased results.
It is difficult to gain funding and acceptance by the medical community for studies that are not randomized. "The problem is a regulatory one," said Levine. "Many new drugs cannot be marketed without having first gone through a randomized trial. Everybody wants the best science, but is randomization the only way to go?"