April 10, 2001
view or print this bulletin in its original format, click here
(requires Adobe Acrobat Reader)
Summary: An international task force convened by the National MS Society has developed guidelines for the ethical use of inactive placebos in future clinical trials for MS:
Background: In placebo-controlled studies, a placebo -- an inactive compound that is designed to look just like the test drug -- is administered to a “control” group of subjects to evaluate the benefits and liabilities of the test drug, which is administered to an “experimental” group of subjects. This type of study is widely acknowledged as the most efficient, cost effective, and decisive means of testing the safety and effectiveness of a therapy.
However, since the approval of the first treatment for relapsing-remitting MS in 1993, and with the approval of additional agents in subsequent years, debate has been ongoing about whether placebo-controlled trials are still ethical and practical in people who have forms of MS for which there are approved treatments.
To address this concern, the National MS Society convened the International Task Force on Placebo-Controlled Clinical Trials in Multiple Sclerosis in New York City in early 2000. The group of clinicians, statisticians, ethicists and regulators debated the issues relating to the use of placebo-controlled trials for MS and developed a consensus opinion about the ethics and practicality of future placebo controlled clinical trials in MS. The pros and cons of other types of controlled trials, such as active control-arm, natural history, and add-on studies, were also discussed as alternatives to placebo-controlled trials. The task force developed its recommendations based on the need to protect people who participate in clinical studies and on the need to develop improved therapies.
Recommendations: The task force considered a series of questions related to this issue and developed a series of recommendations, summarized below:
1. Placebo-controlled trials are only ethical for forms of MS where treatments are widely available when participants formally decline the use of available treatments. The researcher conducting the study must inform the participant of the approved treatments – fully and clearly – and should actively recommend use of these agents. The participant should decline the use of available medication in writing, as part of the “informed consent” process, and the researcher should continue to apprise the participant of medications that become available during the course of the trial.
2. It is ethical to offer participation in a trial to a person for whom available therapy has failed. If multiple therapies are available, these should be stressed to the person as an alternative before offering participation in a placebo-controlled trial.
3. It is ethical to offer participation to individuals who have forms of MS for which there are no approved or available treatments.
4. Shortening a clinical trial or reducing its sample size – to minimize time on placebo or numbers of people exposed to placebo – does not justify a placebo-controlled trial if the people enrolled have other treatment options.
5. It is not ethical to conduct placebo-controlled trials in resource-poor countries where approved treatments are not available because of financial, political or reimbursement barriers. There must be reasonable and achievable expectation that any drug found to be safe and effective in a placebo-controlled trial will be made available to the residents of the countries in which the trial was done after completion of the trial.
6. While placebo-controlled trials may be difficult to undertake for forms of MS where treatments are available, they remain the most efficient and easily interpretable of trial designs.
It is anticipated that these recommendations will be used as guidelines for the conduct of future MS clinical trials. As new therapies are developed, these guidelines may be reconsidered and modified.
Research Programs Department