More MS news articles for Sep 2001

Ethics storm rumbling around placebo use in clinical trials

By BETSY MASON / The Dallas Morning News

For more than half a century, placebos have helped researchers test potential new therapies. But some people now say this is unethical.

Many scientists argue that in some cases placebos are perfectly safe and ethical, and are essential to determine how effective a new treatment is. Without a placebo group for comparison, scientists can't be sure any positive results are not due to patients' expectations of benefit rather than the actual treatment a phenomenon known as the placebo effect.

But some people say it is never acceptable to allow patients to forgo treatment for the sake of a clinical trial.

The debate about placebos in trials was reignited last year when the World Medical Association revised the Declaration of Helsinki its recommendations for research involving humans. The new version condemns the use of placebos in trials when a proven treatment exists.

The medical community agrees that patient safety is of the utmost importance. But many scientists, including Dr. Robert Temple of the U.S. Food and Drug Administration, believe the Declaration of Helsinki is too hard on placebo use. "They basically banned it anywhere there's an existing therapy. We think that's wrong," he says.

An important role for placebos is to "blind" a study. This means that patients do not know whether they are receiving the treatment or the placebo. In a "double-blind" study, the doctors don't know what the patients are receiving, either. This way, the results aren't as vulnerable to bias from what the doctor expects to happen.

Dr. Temple agrees that it is unethical to use placebos when they would increase the risk of death or the incidence of disease. But the FDA follows guidelines that identify cases where placebos can be used safely. "If there is no harm to the patients, then you can ask them to participate in a placebo-controlled trial," he says.

One such case would be a trial for an antihistamine where patients not taking an active medication would merely suffer allergy symptoms, says Dr. Temple. "It's not unethical to do that trial. There's no conflict."

Dr. Temple also points out that any trial can be risky, even if there isn't a placebo group. "When you put a person on a new drug instead of the proven therapy, they are taking a risk," he says. "The safety of the new drug is unknown."

But Kenneth Rothman, an epidemiologist from Boston University, supports the revision of the Declaration of Helsinki. He says it is completely unethical to use placebos in any trials when there is an existing treatment. It doesn't matter if the trial is for allergy medication or cancer therapy, he says. Dr. Rothman contends that the FDA, by requiring placebo groups in many trials, encourages scientists to compromise their ethics to get drugs approved.

Currently in the United States, the decision about how much risk is acceptable is up to the patients. Scientists doing research involving humans must get "informed consent" from the participants before beginning a trial. The patients are told they could receive a placebo and are informed about the potential risks involved so they can decide whether they are willing to participate. "I would be perfectly happy to volunteer for a trial if no harm would come to me," Dr. Temple says.

Studies are under way to help establish when it is acceptable to use placebos. In May, the National Multiple Sclerosis Society set up a task force to determine whether placebo groups should be included in trials, even though partially effective treatments exist. The resulting report in the Annals of Neurology concluded that MS patients could ethically be given placebos as long as the patients were educated about benefits of the existing treatments.

A recent review in Science of short-term trials involving high blood pressure found no increased risk for patients receiving a placebo for a short time. Dr. Sana Al-Khatib, a cardiologist at Duke University in Durham, N.C., and an author of the study, says the results show that the Declaration of Helsinki is too black-and-white. "We really prefer that these general edicts leave some room for the use of placebos where it has been proven it is safe," she says.

Jonathan Moreno, a bioethicist at the University of Virginia in Charlottesville, agrees. "A blanket rule will always be short-sighted and inadequate," he says. "There needs to be a much more nuanced approach."

Dr. Rothman says a nuanced approach is unnecessary because placebos aren't essential to clinical trials, anyway. Any new treatment, he says, should be tested against the existing treatment. "What we really want to know is if the newest treatment is better than the current treatment," he says. "The argument that they absolutely have to have a placebo is ridiculous."

The doctors doing the research need to determine the best trial design, which in some cases involves a placebo group, Dr. Temple says. Sometimes even a proven treatment won't be effective in a given trial because of the particular conditions of the trial, such as the patient group involved. So showing that a new treatment is just as good as an old treatment may just mean they were both ineffective in that trial, he says. Using placebos gives the researchers a control group to help them interpret the results.

Also, many more people are needed in trials that test against existing treatments than in trials that use a placebo group in order to get the necessary statistical information. This exposes more people to risk from the trial, Dr. Temple says. Placebo trials are the most efficient, cost-effective and decisive way to test new treatments, he contends.

© 2001 The Dallas Morning News