B Y J A N E T S P E N C E R K I N G

Transcription

1 The Effect B Y J A N E T S P E N C E R K I N G placebo is a pretend drug or a look-alike therapy, best known today for use in clinical trials of new treatments. It might be a sugar pill packaged to look exactly like an oral drug being tested. Or it might be a dummy injection intended to provide the experience except for the active ingredient of receiving a shot. The purpose of using a placebo is to compare the experience of the trial volunteers receiving the test drug with the experience of those not receiving it. In a blind clinical trial, none of the trial volunteers know who is receiving the placebo and who is getting the real drug. In a double-blind trial (considered the gold standard of clinical trials), the researchers and their assistants don t know either. This is done to remove any expectations that could color the results. The only difference between the two groups is the use of a test agent in one of them, so any differences in the outcomes can be attributed to the agent alone. You might be wondering what possible value there could be in pitting a real drug 14 InsideMS n

2 The Power of Suggestion By Mary Ann O Driscoll against a placebo. A sham treatment should have no impact at all. Amazingly enough, placebos have a record of success in clinical trials, including those in MS. Placebos actually work better than doing nothing at all. In other words, simply by swallowing a dummy pill or taking a dummy injection some people will do better for a time. In a number of studies, improvement in the placebo group which is called the placebo effect has been in the 30% to 40% range, and there have been a few trials in which a placebo group reported 70% effectiveness. This means two things: First, the actual value of a new agent has to be established not by comparing it with no treatment at all but by comparing it with an identical experience without the active agent. Second, the power of a treatment experience is measurable, even when there is no active agent. Why does a placebo work at all? Allen C. Bowling, MD, PhD, director of the Rocky Mountain MS Center and author of Alternative Medicine and Multiple Sclerosis, points out that placebos tend to do particularly well in trials that relate to subjective factors such as the amount of pain experienced by participants. Placebos have a much lower response rate in clinical trials for illnesses that are especially aggressive or present measurable changes the shrinking of tumors, for example. And, we should all remember, the result of active treatment always exceeds the placebo effect in the therapies that gain scientific approval. October December 2004 n InsideMS 15

3 But the plot thickens because not all placebo effects depend on subjective reporting by trial participants. There are examples of measurable biological or physiological changes as a result of placebos. As an example, Dr. Bowling described an MS trial in which the investigators were measuring the activity of natural killer cells, an immune system component. The placebo group showed increases in natural killer-cell activity that were close to those in the medicated group. How could taking an inert placebo produce a change in immune-system activity? The nervous system and the immune system were once thought to operate independently of each other, Dr. Bowling said. But we ve learned that they communicate regularly and indeed each can alter the activity of the other. The placebo effect in this trial may be an example of such communication, he speculated. The patient s brain thinks there is a drug at work, and the immune system responds accordingly. Dr. Dennis Bourdette, chair of Neurology at Oregon Health & Science University and associate director of the Oregon Center for Complementary and Alternative Medicine in Neurological Disorders (which goes by the provocative name of Vexing problems for scientific investigations Ideally, clinical trials eliminate anything that might obscure the trial s purpose: to measure the effect of a specific treatment. A placebo group that receives exactly the same attention and experience as the active treatment group levels the playing field for the test. But the nature of MS creates a messy playing field. John H. Noseworthy, MD, professor and chair of Neurology, Mayo Clinic College of Medicine, explained that because MS is such a highly variable disease, it s nearly impossible to predict how it will progress. A trial could have a placebo group made up of people whose MS symptoms just coincidentally begin to even out. They begin to do better than expected. If this happens, it creates a high placebo effect and lowers the rating of the real drug, even though the real drug might be genuinely helpful. The opposite can happen, too. A placebo group might contain many individuals who do worse than expected, making a not-so-good drug look better than it is. But in both examples, the changes may simply be the natural course of MS among these individuals. Dr. Noseworthy calls the situation vexing. As Dr. Fred D. Lublin, director of the Corinne Goldsmith Dickinson Center for MS at Mount Sinai School of Medicine in New York, pointed out, Every trial is a universe unto itself, and you can t predict how a placebo group will behave. Dr. Nancy Holland, vice president of Clinical Programs at the National MS Society, has this advice: People with MS need to view the results of clinical trials in context. A few percentage points of advantage in a single trial probably mean very little. Your physician should be guided by the preponderance of evidence and by your individual response to treatments. JSK and Martha King 16 InsideMS

4 Placebo Dreams By Mary Ann O Driscoll ORCCAMIND), has looked at some of the placebo effects in trials of the MS disease-modifying drugs. He noticed a connection between the placebo response level and the intensity and invasiveness of the fake procedure. For instance, the placebo group in the Phase III trial of glatiramer acetate had a 42% reduction in relapse rate while they were on the daily placebo injections compared with their relapse rate before entering the study. The placebo group in the Phase III interferon beta-1a trial who were receiving a weekly injection had only a 28% reduction. Thus a dummy injection given every day may have produced a much higher placebo effect than a dummy injection given once a week. Placebos cause real physiologic changes and many things including patient beliefs, frequency of administration, even the color of placebo pills can affect the strength of the placebo effect, Dr. Bourdette said. Placebos and alternative therapies Obviously, the power of the mind is not to be dismissed. Until the dawn of scientific medicine, much medical treatment worked because of the placebo effect. Medicines were given that we now know couldn t possibly affect the physiology of an illness, but the sick person often felt better and sometimes got well. Today, Dr. Bowling points out, modern medicine, with its reliance on data and drugs proven to be effective, removes much of the placebo effect that might spring from personal doctor patient interactions. Many people feel they aren t getting the October December 2004 n InsideMS 17

5 caring relationship they want from medical visits and they go looking for it elsewhere, he continued. Elsewhere can mean the assorted venues of complementary and alternative medicine (called CAM). Popular CAMs include visualization, spirituality practices, massage, meditation, homeopathy, acupuncture, yoga, tai chi, and more. Appointments with CAM practitioners often span an hour s time in a relaxed environment, allowing practitioners and patients to develop a real rapport. Part of the effectiveness of CAM treatments may well be a placebo effect, and if a treatment is not harmful, it is important for conventional health-care professionals not to pull that support out from under their MS patients, Dr. Bowling said. Multiple sclerosis is not yet curable. The best and most effective of MS therapies available to date help control the disease for many people, but there is still a big gap between what the proven therapies can accomplish and what people with MS want and need. There are many things that we do not understand about placebo effects, Dr. Bourdette commented. Placebo effects represent an aspect of mind body medicine. For this reason, the National Institutes of Health (NIH) through the The Society publishes two booklets to help people explore CAM: Clear Thinking about Alternative Therapies and Vitamins, Minerals, and Herbs in MS. Contact your chapter for copies or visit Living with MS on the National MS Society Web page. National Center of Complementary and Alternative Medicine is encouraging research scientists to apply for funding to investigate the mechanisms of action of placebo effects. The response to any treatment I prescribe for a patient involves both a placebo effect and the specific effect that the treatment provides, Dr. Bourdette said. While we are not going to cure MS with a placebo and it is not ethical to give a placebo as a treatment, understanding better how placebos induce changes in the immunologic and central nervous systems would help us enhance responses to active treatments. Embracing the placebo effect with caution Dr. Bowling concurs. His first recommendation is never to replace conventional medical therapies with CAM treatments. However, people with MS can embrace the placebo effect and use it to their own advantage, he said. Provided that individuals take care when and how they do so. There is a wide range of CAM therapies. Some of them are totally whacko and might hurt you, Dr. Bowling cautioned. Thoroughly investigate any you are considering. Get good information so you can make wise choices. What you select may even have some real therapeutic effect and it might stimulate a placebo effect. Both would be good. Janet Spencer King is a freelance writer and the editor of Hemalog, a magazine for people living with hemophilia. This is her first article for InsideMS. 18 InsideMS n