What is the placebo response?
The "placebo response" occurs when a person who is ill perceives an improvement or actually experiences an improvement in symptoms or overall health from the psychological effect of receiving treatment rather than from the treatment itself. Many factors influence the generation of a placebo response. Some scientists believe that certain psychological factors actually cause the body to produce hormones called endorphins, which act as the body's own pain killers, resulting in reduced levels of pain or discomfort.
The placebo response may be due to a person's profound desire to get better, increased medical attention as result of being in an experimental study of a new treatment, or even an unconscious wish by the person to please the physician by getting better.
Some improvements triggered by the placebo effect can be measured objectively. To that extent they are as real as any other improvement. But studies have demonstrated that placebo effects are usually not as strong or long-lasting as a medical treatment response.
The use of placebos in clinical trials
Using placebo as a control had until recently been the historic “gold standard” for clinical trials in MS, and it permits potential benefits – or safety issues – of an experimental treatment to emerge in high relief against a control group that receives the same amount of physician care except for inactive therapy. But ethical concerns exist when there are approved, effective disease-modifying therapies, such as those available for people who have relapsing forms of MS.
To tackle this issue, in 2001 the National MS Society held a summit and published recommendations related to the ethical use of placebos in MS clinical trials. These guidelines were revised in 2008 (Neurology 2008;70:1134
When are placebo-controlled trials ethically justifiable?
When are placebo-controlled trials ethically justifiable? According to the consensus guideline for ensuring that placebo-controlled trials are conducted ethically, placebo-controlled trials can be justifiable:
When established effective therapy is not available, such as for people with primary-progressive MS, or secondary-progressive MS in which relapses are no longer occurring.
When participants refuse established effective therapy. Careful informed consent is essential to ensuring that the subject is aware of the MS treatments available.
When subjects have not responded to established effective therapy. If one treatment has failed, but others are available, these should be suggested to the subject before participating in a placebo-controlled study.
In areas where resources are restricted and established effective therapy is not readily available. Trial sponsors are increasingly conducting studies in such areas of the world. For these studies to be considered ethical, special effort must be made to understand what treatments are available, as well as reimbursement policies and patient assistance programs. Sponsors should make a commitment to pursue registration (regulatory approval) of any proven drug in any country in which it is tested.
In short-term phase II proof of concept studies. There is no evidence that short-term deprivation (less than 6 months or so) of approved MS therapies can cause long-term differences in clinical outcome. If sound scientific reasons exist for doing a short-term study, the nature and rationale for the study should be carefully explained to participants.
When the outcomes of placebo therapy do not increase serious or irreversible harm, such as clinical trials of symptomatic treatments.
Alternatives to placebo-controlled trials: There are many trial design options that can avoid the use of control groups given only inactive placebo. One potential solution is to conduct “add-on” trials (where participants take a standard treatment plus either a new therapy or placebo version of the experimental therapy). Alternatively, “superiority” trials (where participants receive either a standard therapy or the new therapy) can be considered.